In vitro histoculture of human tumors with fluorescent dye end-points measured by confocal microscopy: high correlation of in vitro and in vivo chemosensitivity.
Tumors from 40 patients and 7 established human xenograft tumor lines were grown in three-dimensional histoculture. A Viable-Cell-Index (VCI) based on fluorescent dyes and Growth Fraction Index (GFI) based on [3H]thymidine incorporation were measured by confocal microscopy and histological autoradiography, respectively, after treatment with cytotoxic agents. Chemosensitivity in vitro with the two methods was correlated with chemosensitivity of the same set of human xenografted tumor lines grown in nude mice. The percent accuracy of in vitro to in vivo correlation with VCI (73%) was higher than GFI (63%). The number of false positives with VCI was 12.1% (4/33), and with GFI was 31.3% (10/32). The results thus indicated that in vitro histoculture with fluorescent vital-dye end-points to measure cell viability is of potential use to determine tumor chemosensitivity.


Properties of a new crystal form of the complex of concanavalin A with methyl alpha-D-glucopyranoside.
The complex of concanavalin A with methyl alpha-D-glucopyranoside crystallizes as regular rhombic dodecahedra containing 35% protein by weight. The crystal is of space group I23 with a = 167.8 A (1 A = 0.1 nm) and contains one concanavalin A dimer per asymmetric unit. It diffracts to a resolution of 1.9 A and is suitable for crystallographic investigation of the structure of the saccharide-binding site.


Clinical pharmacology of amikacin sulphate: blood, urinary and tissue concentrations in the terminal stage of pregnancy.
Within a broad programme of research into the pharmacokinetics of various antimicrobials in gynaeco-obstetric patients, with a view of determining its concentrations in the different compartments and reproductive organs, we administered 7-5 mg/kg of amikacin sulphate to eleven women in the terminal stage of pregnancy one hour before collecting the specimens studies. The concentrations in the maternal blood and urine was similar to that obtained during the first weeks of gestation, and to that achieved outside pregnancy. The low determinations observed at the level of the foetal blood and urine and the anniotic fluid, as well as in the placenta and oviducts, is in our view due to the fact that the passage of this drug into the 'compartments' mentioned takes place slowly; this hypothesis is, however, subject to corroboration or refutation by further studies on this question. The concentration of this compound found was, nonetheless, bactericidal in all the parameters studied.


BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells.
The use of BMP-2 in orthopedic surgery is limited by uncertainty surrounding its effects on the differentiation of mesenchymal stem cells (MSCs) and how this is affected by cellular aging. This study compared the effects of recombinant human BMP-2 (rhBMP-2) on osteogenic and adipogenic differentiation between senescent and non-senescent MSCs. Senescent and non-senescent MSCs were cultured in osteogenic and adipogenic differentiation medium containing various concentrations of rhBMP-2. The phenotypes of these cells were compared by performing a calcium assay, adipogenesis assay, staining, real-time PCR, western blotting, and microarray analysis. rhBMP-2 induced osteogenic differentiation to a lesser extent (P < 0.001 and P = 0.005 for alkaline phosphatase activity and Ca2+ release) in senescent MSCs regardless of dose-dependent increase in both cells. However, the induction of adipogenic differentiation by rhBMP-2 was comparable between them. There was no difference between these two groups of cells in the adipogenesis assay (P = 0.279) and their expression levels of PPARγ were similar. Several genes such as CHRDL1, NOG, SMAD1, SMAD7, and FST encoding transcription factors were proposed to underlie the different responses of senescent and non-senescent MSCs to rhBMP-2 in microarray analyses. Furthermore, inflammatory, adipogenic, or cell death-related signaling pathways such as NF-kB or p38-MAPK pathways were upregulated by BMP-2 in senescent MSCs, whereas bone forming signaling pathways involving BMP, SMAD, and TGF- ß were upregulated in non-senescent MSCs as expected. This phenomenon explains bone forming dominance by non-senescent MSCs and possible frequent complications such as seroma, osteolysis, or neuritis in senescent MSCs during BMP-2 use in orthopedic surgery.


A clinical study of the efficacy of topical corticosteroids on dry eye.
To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluorometholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.


LINC01711 promotes transforming growth factor-beta (TGF-β) induced invasion in glioblastoma multiforme (GBM) by acting as a competing endogenous RNA for miR-34a and promoting ZEB1 expression.
GBM is the central nervous system's most aggressive and malignant tumor. TGF-β expression is elevated in GBM, and it promotes invasion and EMT. TGF-β regulates the expression of several lncRNAs, which promote glioma pathogenesis. Here we characterize the role of TGF-β-induced lncRNA- LINC01711 in glioma pathogenesis. We show that LINC01711 expression is significantly upregulated in GBM tissues and is associated with poor overall survival of GBM patients. Loss-of-function studies illustrate that LINC01711 promotes proliferation, migration, and invasion in GBM. In addition, LINC01711 depletion sensitizes glioma cells to Temozolomide (TMZ) induced apoptosis by inhibiting ZEB1 expression. LINC01711 functions as a competing endogenous RNA for miR-34a and promotes ZEB1 expression to regulate invasion. Our findings suggest that LINC01711 is an attractive therapeutic target for GBM.


Quality appraisal of clinical guidelines for surgical site infection prevention: A systematic review.
Surgical site infections (SSI) occur in up to 10% of surgeries. Wound care practices to prevent infections are guided by Clinical Practice Guidelines (CPGs), yet their contribution to improving patient outcomes relies on their quality and adoption in practice. We critically evaluated the quality of CPGs for SSI prevention during pre-, intra- and post-operative phases of care. We systematically reviewed the literature from 1990-2018 using the Cochrane Library, CINAHL, EMBASE, MEDLINE, ProQuest databases and five guidelines repositories. We extracted characteristics of each guideline using purposely-developed data collection tools. We assessed overall quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Combined searches of databases and repositories yielded 5,910 citations. Of these, we reviewed 215 full text documents. The final sample included 15 documents: 6 complete CPGs, 3 CPG updates, and 6 supplementary documents. The overall %mean scores across AGREE II domains for CPGs were: 1) scope and purpose (%mean ± SD = 86.3±23.5); 2) stakeholder involvement (%mean ± SD = 64±31.0); 3) rigour of development (%mean ± SD = 68.7±30.6); 4) clarity and presentation (%mean ± SD = 88.5±16.7); 5) applicability (%mean ± SD = 44±30.2); and, 5) editorial independence (%mean ± SD = 61±37.6). Based on individual AGREE II domains and overall scores, we appraised 4 out of 6 CPGs (inclusive of updates) as "recommended" for use in practice. Overall agreement among appraisers was excellent (ICC 0.86 [95%CI 0.73-0.94] - 0.98 [95%CI 0.96-0.99]; p <0.001). International interest in CPG development has resulted in refinements to methodologies, which has led to improvements in the overall quality of the product. Given the domains that received the lowest scores, it is clear that we need more consumer involvement and better consideration of the implementation challenges with CPG uptake and sustainability.


COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARdelta activation.
Although cyclooxygenase (COX)-2 inhibitors (coxibs) are effective in controlling inflammation, pain, and tumorigenesis, their use is limited by the recent revelation of increased adverse cardiovascular events. The mechanistic basis of this side effect is not well understood. We show that the metabolism of endocannabinoids by the endothelial cell COX-2 coupled to the prostacyclin (PGI(2)) synthase (PGIS) activates the nuclear receptor peroxisomal proliferator-activated receptor (PPAR) delta, which negatively regulates the expression of tissue factor (TF), the primary initiator of blood coagulation. Coxibs suppress PPARdelta activity and induce TF expression in vascular endothelium and elevate circulating TF activity in vivo. Importantly, PPARdelta agonists suppress coxib-induced TF expression and decrease circulating TF activity. We provide evidence that COX-2-dependent attenuation of TF expression is abrogated by coxibs, which may explain the prothrombotic side-effects for this class of drugs. Furthermore, PPARdelta agonists may be used therapeutically to suppress coxib-induced cardiovascular side effects.


Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism.
Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has historically been associated with warm freshwater exposures at lower latitudes of the United States. In August 2010, a Minnesota resident, aged 7 years, died of rapidly progressive meningoencephalitis after local freshwater exposures, with no history of travel outside the state. PAM was suspected on the basis of amebae observed in cerebrospinal fluid. Water and sediment samples were collected at locations where the patient swam during the 2 weeks preceding illness onset. Patient and environmental samples were tested for N. fowleri with use of culture and real-time polymerase chain reaction (PCR); isolates were genotyped. Historic local ambient temperature data were obtained. N. fowleri isolated from a specimen of the patient's brain and from water and sediment samples was confirmed using PCR as N. fowleri genotype 3. Surface water temperatures at the times of collection of the positive environmental samples ranged from 22.1°C to 24.5°C. August 2010 average air temperature near the exposure site was 25°C, 3.6°C above normal and the third warmest for August in the Minneapolis area since 1891. This first reported case of PAM acquired in Minnesota occurred 550 miles north of the previously reported northernmost case in the Americas. Clinicians should be aware that N. fowleri-associated PAM can occur in areas at much higher latitude than previously described. Local weather patterns and long-term climate change could impact the frequency of PAM.


Biotination of proteins in vivo. A post-translational modification to label, purify, and study proteins.
Post-translational modification of proteins with biotin provides the means to specifically label proteins in vivo and to purify proteins from crude cell lysates. The carboxyl-terminal protein segments modified by reaction with biotin ligase are strongly conserved in nature. We have demonstrated that the proteins encoded by translational gene fusions of a number of heterologous proteins to these carboxyl-terminal sequences become biotinated in vivo. The minimum size of the protein segment needed to allow biotination of fusion proteins is 75 amino acids. This biotination sequence, although of bacterial origin, functions in Saccharomyces cerevisiae as well as in Escherichia coli. Fusion proteins are readily labeled with [3H]biotin in vivo and the labeling is highly specific due to the scarcity (less than 5) of biotinated protein species. Biotinated fusion proteins can be readily purified in native form by binding to columns of monomeric avidin followed by elution with buffers containing biotin. Alternatively, proteins can be purified in a denatured form in presence of 1% sodium dodecyl sulfate or 8 M urea. Thus, this technology allows purification by affinity chromatography of any protein to which a biotination sequence can be attached. The ability to specifically label a protein in vivo should have utility in studies such as intracellular protein trafficking and cytoskeletonal dynamics.


"Becoming the man you always wanted to be": Exploring the representation of health and masculinity in Men's Health magazine.
Men's health and lifestyle magazines are a popular medium through which hegemonic ideals of masculinity are displayed, influencing the way men behave and think about health (Crawshaw, 2007, Soc Sci Med, 65, 1606; Stibbe, 2004, Men Masc, 7, 31). This study conducted a critical discourse analysis of Australia's most popular men's health and lifestyle magazine, Men's Health, in order to understand how health is presented to men. Six issues were examined, from April 2016 to September 2016. Three themes supporting hegemonic masculine discourses were revealed: a forged physique, (hetero)sexual prowess and career dominance. A fourth theme, the new man, was also identified revealing a shift in attitudes towards nutrition and style. Despite this shift in the representation of masculinity, hegemonic ideals remain dominant in the construction of Australian masculinity in this popular men's health and lifestyle magazine. SO WHAT?: This study highlights the utility of Men's Health magazine in promoting health and brings into question whether the current representation of masculinity works towards improving or decreasing the health of Australian men.


High hydrostatic pressure perturbs the interactions between CF(0)F(1) subunits and induces a dual effect on activity.
Chloroplast ATP-synthase is an H(+)/ATP-driven rotary motor in which a hydrophobic multi-subunit assemblage rotates within a hydrophilic stator, and subunit interactions dictate alternate-site catalysis. To explore the relevance of these interactions for catalysis we use hydrostatic pressure to induce conformational changes and/or subunit dissociation, and the resulting changes in the ATPase activity and oligomer structure are evaluated. Under moderate hydrostatic pressure (up to 60-80 MPa), ATPase activity is increased by 1.5-fold. This is not related to an increase in the affinity for ATP, but seems to correlate with an enhanced turnover induced by pressure, and an activation volume for the ATPase reaction of -23.7 ml/mol. Higher pressure (up to 200 MPa) leads to dissociation of the enzyme, as shown by enzyme inactivation, increased binding of 8-anilinonaphthalene-1-sulfonate (ANS) to hydrophobic regions, and labeling of specific Cys residues on the beta and alpha subunits by N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylene-4-diamine (IAEDANS). Compression-decompression cycles (between 0.1 and 200 MPa) inactivate CF(0)F(1) in a concentration-dependent manner, although after decompression no enzyme subunit is retained on a Sephadex-G-50 centrifuge column or is further labeled by IAEDANS. It is proposed that moderate hydrostatic pressures induce elastic compression of CF(0)F(1), leading to enhanced turnover. High pressure dissociation impairs the contacts needed for rotational catalysis.


The Pivotal Role of Pediatric Psychology in Chronic Pain: Opportunities for Informing and Promoting New Research and Intervention in a Shifting Healthcare Landscape.
In the context of new efforts to formulate more comprehensive diagnostic and treatment processes for chronic pain conditions, this review aims to provide an overview of some of the most salient developments in the diagnosis and clinical treatment of pediatric chronic pain and to delineate the current and future role of clinical pediatric psychologists in these efforts. The acceptance and promotion of the multidisciplinary approach to pediatric pain management has had an especially significant impact on the field of pediatric psychology. Though chronic pain was historically conceptualized as a biomedical problem, psychology is increasingly viewed as a routine, integral, and component part of treatment. With this evolving biopsychosocial paradigm, pediatric psychology is poised to help shape the development of this field, contributing to emerging conceptual and diagnostic frameworks via consultation, research, clinical care, and education. This review discusses the role of pediatric psychologists as collaborators in emerging diagnostic and assessment frameworks, leaders in pain-related research, drivers of clinical care, and educators for providers, patients, and the lay public. With increased opportunities to enhance the conceptualization and treatment of pediatric pain, pediatric psychologists have an important role to play in reducing the prevalence and persistence of pediatric pain.


A phase I study of intravenous RMP-7 with carboplatin in patients with progression of malignant glioma.
RMP-7, a nine amino acid peptide bradykinin agonist, increases the delivery of hydrophilic compounds across the blood-tumour barrier. In this dose ranging study, 14 patients with progressing malignant glioma (9 glioblastoma multiforme, 4 anaplastic astrocytoma, 1 anaplastic oligodendroglioma; age range 31-68 years, baseline Karnofsky range 60-90%, 5 having had prior chemotherapy) were treated with intravenous RMP-7 and carboplatin to assess the safety, tolerability, and side-effect profile of increasing doses of this combination. Carboplatin dosing was by target area under the curve (AUC) according to the Calvert protocol. Patients were allocated to one of five treatment regimes: cohort A (n = 2) received 50 ng/kg RMP-7 and target AUC 5 mg/ml/min carboplatin; cohort B (n = 3) 100 ng/kg RMP-7 + AUC 5; cohort C (n = 2) 100 ng/kg RMP-7 + AUC 7; cohort D (n = 2) 200 ng/kg RMP-7 + AUC 7; cohort E (n = 5) 300 ng/kg RMP-7 + AUC 7. Treatment was given once every 4 weeks with magnetic resonance imaging scans every 2 months. Patients received 37 cycles in total (median 2, range 1-7). The drug combination, as a cancer treatment, was tolerated in all groups. Effects possibly related to RMP-7 included flushing, nausea, headache and mild increase in heart rate, all transient. 3 patients in cohort E experienced grade 3/4 neutropenia and thrombocytopenia. These toxicities are consistent with known effects of carboplatin at this dose range. In cohort E (n = 5) 1 patient improved and another remained stable for > or = 6 months. In summary, the dose was escalated to the maximum dose of RMP-7 given to volunteers without additional related side-effects. The side-effects of the combination were consistent with giving the two drugs alone and would merit further study for efficacy.


Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta.
The transmembrane protein CD33 is a sialic acid-binding immunoglobulin-like lectin that regulates innate immunity but has no known functions in the brain. We have previously shown that the CD33 gene is a risk factor for Alzheimer's disease (AD). Here, we observed increased expression of CD33 in microglial cells in AD brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (Aβ42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble Aβ42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of Aβ42 in microglial cell cultures. Finally, brain levels of insoluble Aβ42 as well as amyloid plaque burden were markedly reduced in APP(Swe)/PS1(ΔE9)/CD33(-/-) mice. Therefore, CD33 inactivation mitigates Aβ pathology and CD33 inhibition could represent a novel therapy for AD.


[Acute macular neuroretinopathy--case report].
The aim of this study is to present rare retinal disease of unknown origin. 27-years-old man was diagnosed because of poor vision in the left eye, which lasted 4-5 weeks. Following examinations were performed: Visual acuity, contrast sensitivity, color perception, visual field, fluorescein angiography (AF), visual evoked potentials (VEP), full-field flash electroretinography (flash ERG), focal-foveal electroretinography (focal ERG), multifocal electroretinography (multifocal ERG). Follow-up 1.5 year. Visual acuity of right eye was 1.25 (-0.1 log MAR) and left eye 1.0 (0.0 log MAR). In left eye between optic disc and macula irregular lesion with dots of retinal pigment epithelium atrophy and little edema was seen. AF revealed small "window" defects. In visual field of the left eye paracentral relative scotoma occurred and in stereokampimetry central relative scotoma was found about 5 degrees from the fixation point. In VEP latency of P100 was delayed and amplitude was reduced in both eyes. In flash as well as focal ERG small reduction of cone function and delayed implicit time of b-wave were found in left eye. In general examination no focal inflammation and no abnormalities in laboratory tests were found. The patient was treated with steroids for 3 weeks. After ten days of general steroid treatment visual acuity improved to 1.25 and subjective improvement of vision occurred. Control examination after 1.5 year revealed no patient's complains, visual acuity 1.25, no change in visual field, VEP improvement. In left eye flat irregular area with pigment epithelium atrophy was seen. Acute macular neuroretinopathy may be diagnosed after detail examination. Prognosis is generally good, recovery is slow, but despite of local retinal atrophy subjective complains disappear completely.


Peri-ictal heart rate changes in patients with epilepsy.
Heart rate (HR) changes associated with seizures are promising biomarkers in epilepsy. The aim of our study is to reveal possible HR changes in the peri-ictal period. Long-term video-EEG monitorization records of generalized and focal epilepsy patients were reviewed. HRs were calculated in the pre-ictal (2 min before the first seizure activity in EEG), ictal (the time from the first seizure activity on the EEG to the end of the seizure), and in the interictal period (at least 2 h before or 12 h after the seizure). Interictal, pre-ictal, and ictal HRs were compared with each other. In addition, it was investigated whether peri-ictal HR changes differ between generalized and focal seizure patients. Focal motor seizures were observed in 21, and generalized tonic-clonic seizures were observed in 18 of 39 (22 female and 17 male) patients studied. HRs in the pre-ictal and ictal periods were significantly higher than in the interictal period. This significant increase in HR was validated separately in both focal and generalized seizure groups and was not different between the two groups. Our study supports previous studies showing the presence of increased peri-ictal HR and also provides new insights by comparing focal and generalized motor seizures. We think that our findings may contribute to the development of early warning signs in epilepsy patients.


Upregulation of protein S by progestins.
Users of progestin-only contraceptives have raised protein S (PS) levels compared with baseline. This contrasts with the reduction in PS levels observed in users of combined oral contraceptives, which contain both a progestin and an estrogen. To determine the effect of progesterone and other progestin isoforms on the expression of PS and to describe the mechanism involved. Promoter activity of the PROS1 gene that encodes PS was assessed in vitro using breast and liver carcinoma cell lines grown in the presence of various progestins, with and without the addition of excess progesterone receptors. An electromobility shift assay (EMSA) was also performed to identify the progesterone receptor binding element. PROS1 transcriptional levels were directly upregulated by 25% by progesterone via a mechanism that was progesterone receptor isoform B (PR-B)-dependent. The process was blocked by the progesterone receptor modulator RU486. Results for the EMSA demonstrated that a probe comprising nucleotides -397 to -417 of the PROS1 promoter bound to ligand-activated PR-B, suggesting that the domain is a progesterone response element (PRE). The type of progestin isoform greatly influenced the level of PROS1 promoter upregulation, with medroxyprogesterone able to stimulate a > 2-fold stronger response compared with progesterone. The PROS1 promoter is responsive to progesterone and other progestins via a mechanism involving PR-B interacting with a PRE. The type of progestin is important as some elicit stronger upregulatory effects than others, which may influence the choice of progestin used for hormonal contraception by PS-deficient individuals.


Catalytic decomposition of gaseous PCDD/Fs over V2O5/TiO2-CNTs catalyst: Effect of NO and NH3 addition.
There is a strong need for a control technology that simultaneously achieving the abatement of PCDD/Fs (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans) and nitrogen oxides (NOx) emissions in waste incineration industry. TiO2 and carbon nanotubes (CNTs) were used as composite carriers to support vanadium oxide as an innovative catalyst to simultaneously control PCDD/Fs and NO emissions. The removal efficiencies (RE) of PCDD/Fs by V2O5/TiO2-CNTs catalyst under a space velocity (SV) of 20,000 h(-1) reaches 99.9% at 150 °C and adsorption is supposed to be the main mechanism at this temperature. The influence of NONH3 reaction on PCDD/Fs catalytic reaction is investigated. The kinetics analysis exhibits that the addition of NO and NH3 reduces the activation energies for OCDD (octachlorodibenzo-p-dioxin) and OCDF (octachlorodibenzofuran) decomposition to 3.6 kJ/mol and 5.4 kJ/mol respectively.


Evaluation of alternative confidence intervals to address non-inferiority through the stratified difference between proportions.
The confidence interval (CI) for the difference between two proportions has been an important and active research topic, especially in the context of non-inferiority hypothesis testing. Issues concerning the Type 1 error rate, power, coverage rate and aberrations have been extensively studied for non-stratified cases. However, stratified confidence intervals are frequently used in non-inferiority trials and similar settings. In this paper, several methods for stratified confidence intervals for the difference between two proportions, including existing methods and novel extensions from unstratified CIs, are evaluated across different scenarios. When sparsity across the strata is not a concern, adding imputed observations to the stratification analysis can strengthen Type-1 error control without substantial loss of power. When sparseness of data is a concern, most of the evaluated methods fail to control Type-1 error; the modified stratified t-test CI is an exception. We recommend the modified stratified t-test CI as the most useful and flexible method across the respective scenarios; the modified stratified Wald CI may be useful in settings where sparsity is unlikely. These findings substantially contribute to the application of stratified CIs for non-inferiority testing of differences between two proportions.


Toward a Model of Human Information Processing for Decision-Making and Skill Acquisition in Laparoscopic Colorectal Surgery.
To create a human information-processing model for laparoscopic surgery based on already established literature and primary research to enhance laparoscopic surgical education in this context. We reviewed the literature for information-processing models most relevant to laparoscopic surgery. Our review highlighted the necessity for a model that accounts for dynamic environments, perception, allocation of attention resources between the actions of both hands of an operator, and skill acquisition and retention. The results of the literature review were augmented through intraoperative observations of 7 colorectal surgical procedures, supported by laparoscopic video analysis of 12 colorectal procedures. The Wickens human information-processing model was selected as the most relevant theoretical model to which we make adaptions for this specific application. We expanded the perception subsystem of the model to involve all aspects of perception during laparoscopic surgery. We extended the decision-making system to include dynamic decision-making to account for case/patient-specific and surgeon-specific deviations. The response subsystem now includes dual-task performance and nontechnical skills, such as intraoperative communication. The memory subsystem is expanded to include skill acquisition and retention. Surgical decision-making during laparoscopic surgery is the result of a highly complex series of processes influenced not only by the operator's knowledge, but also patient anatomy and interaction with the surgical team. Newer developments in simulation-based education must focus on the theoretically supported elements and events that underpin skill acquisition and affect the cognitive abilities of novice surgeons. The proposed human information-processing model builds on established literature regarding information processing, accounting for a dynamic environment of laparoscopic surgery. This revised model may be used as a foundation for a model describing robotic surgery.


Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.
A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70.0% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid and of no detectable amounts of cell wall components such as alpha, epsilon-diaminopimelic acid and hexosamine, was found to possess strong antitumor activity. Repeated intralesional injection of this fraction, designated MY-1, without attachment to oil or a single intralesional injection of MY-1 emulsified in mineral oil caused the IMC carcinoma of CDF1 mice and line 10 tumor of strain 2 guinea pigs to regress and/or prevented metastasis very effectively. MY-1 after digestion with RNase, which contained 97.0% single-stranded DNA with a guanine-cytosine content of 69.8%, was more effective than undigested MY-1 against IMC and line 10 tumor, while MY-1 digested with DNase, which contained 97.0% RNA, had reduced activity, suggesting that the DNA from BCG possessed strong antitumor activity under certain conditions. Details of the extraction procedures and physicochemical characterization of MY-1 were also described.


Unilateral Cleft Lip Nasal Deformity: Foundation-Based Approach to Primary Rhinoplasty.
Cleft lip results in disruption of the nasal foundation and collapse of tip structures. Most approaches to primary rhinoplasty focus on correction of lower lateral cartilages; however, recurrent deformity is common, and secondary revision is frequently required. The authors describe an alternate approach that focuses on the foundation to "upright the nose," without any nasal tip dissection. This study assessed changes with surgery and with growth. Secondary goals were to compare methods of sidewall reconstruction and septoplasty and to identify predictors of relapse. Consecutive patients undergoing repair (n = 102) were assessed. Images were captured preoperatively, postoperatively, and at 5 years of age (when available) using three-dimensional stereophotogrammetry. Standard anthropometric and contemporary shape-based analysis (volume ratio, dorsal deviation, and alar-cheek definition) was performed to assess longitudinal changes. Images of age-matched normal control subjects were used for comparison. Significant changes in anthropometric and morphometric measurements occurred following surgery. Postoperative form was similar to controls immediately after surgery and at 5 years. Nasal corrections were satisfactory, and only two patients have elected to undergo revision. When subjects were grouped according to cleft type, we found the same trends. When comparing different methods of nasal sidewall reconstruction or septoplasty, we found no differences. Alveolar cleft width was a significant predictor of worse preoperative and postoperative form. Significant nasal correction can be achieved by means of reconstruction of nasal foundation, without nasal tip dissection. Preservation of tissue planes may allow for easier secondary revision, if necessary. Therapeutic, IV.


High-throughput, single-cell NF-κB dynamics.
Single cells in a population often respond differently to perturbations in the environment. Live-cell microscopy has enabled scientists to observe these differences at the single-cell level. Some advantages of live-cell imaging over population-based methods include better time resolution, higher sensitivity, automation, and richer datasets. One specific area where live-cell microscopy has made a significant impact is the field of NF-κB signaling dynamics, and recent efforts have focused on making live-cell imaging of these dynamics more high-throughput. We highlight the major aspects of increasing throughput and describe a current system that can monitor, image and analyze the NF-κB activation of thousands of single cells in parallel.


Action research study on advance care planning for residents and their families in the long-term care facility.
Research in Taiwan has indicated that advance care planning is rarely undertaken in long-term care facilities. The purpose of this study was to develop an advance care planning interview guideline and care model to facilitate the process of advance care planning for residents and their families in long-term care facilities. This study follows an action research design. Cycles of planning, action, observation, and reflection were planned and modified based on the results of interviews with residents and their families as well as meetings with staff. To establish the interview guideline and care model through this action research study, residents and their families were interviewed separately. The researcher subsequently held meetings with staff members to evaluate the results and identify problems during each advance care planning process. This information was synthesised and used to modify the care model for implementation with the next resident-family pair. This process was performed a total of ten times. This study included residents (N = 10), their families (N = 20), and medical staff (N = 4) at a long-term care facility. The interviews and meetings were audio recorded, transcribed, and subjected to a simple thematic analysis together with the field notes and reflection logs. Four themes emerged from the data related to: opening the conversation with the interview guidelines about the life story of residents; continuing life stories to the quality of remaining years of the residents; gradually changing the topic to the end-of-life care issues; and concluding the conversation by explaining the content of advance directives and hospice care. The advance care planning care model was implemented following logical thinking from a Chinese perspective. This consisted of opening, developing, changing, and concluding through the views of Confucianism, Buddhism, and Taoism. The research findings indicate that the model successfully facilitated the process of advance care planning for residents and their families.


A pilot study comparing protein expression in different segments of the normal colon and rectum and in normal colon versus adenoma in patients with Lynch syndrome.
Lynch syndrome (LS) is a common inherited predisposition to colorectal cancer (CRC). In LS patients, CRC is predominantly located in the right colon, as opposed to sporadic CRC, which usually affects the left colon or rectum. Previous studies have demonstrated a clear distinction in gene expression between sporadic CRC and normal colon at different locations in the colorectum. However, little is known about LS gene expression profiles in different areas of the colorectum. Here, we compared the protein expression profiles for normal colorectal samples among different locations as well as between adenomas and matched normal tissue in LS. Protein from 33 tissue samples (27 normal tissues and 6 adenomas) from 9 patients with LS was extracted for reverse-phase protein array (RPPA) analysis. The antibody panel used for RPPA included 109 key proteins involved in various cancer-related pathways. Cluster 3.0 was used for unsupervised and supervised clustering analysis. IGF1R and COL6A1 were expressed significantly differently between the normal right and normal left colon (q < 0.05); FN1, COL6A1, and IGF1R were expressed significantly differently between the normal right colon and normal rectum (q < 0.05). In the adenomas and matched normal tissue, PEA-15 was the only protein with significantly different expression (q < 0.05). We found differences in protein expression between normal tissues from the right colon, left colon, and rectum as well as between adenomas and matched normal tissue. However, those differences should be further confirmed in a larger sample size.


Separation of basic drug enantiomers by capillary electrophoresis using chicken alpha1-acid glycoprotein: insight into chiral recognition mechanism.
Recombinant chicken alpha(1)-acid glycoprotein (alpha(1)-AGP) was prepared by the Escherichia coli expression system and completely deglycosylated alpha(1)-AGP (cd-alpha(1)-AGP) was obtained by treatments of native alpha(1)-AGP with a mixture of endoglycosidase and N-glycosidase. The average molecular masses of chicken alpha(1)-AGP, cd-alpha(1)-AGP and recombinant alpha(1)-AGP were estimated to be about 29 200, 21 700 and 20 700, respectively, by matrix-assisted laser desorption-time of flight-mass spectrometry. We compared the chiral recognition ability of chicken alpha(1)-AGP, cd-alpha(1)-AGP and recombinant alpha(1)-AGP using them as chiral selectors in capillary electrophoresis. The chicken alpha(1)-AGP showed higher resolution for eperisone, pindolol and tolperisone than cd-alpha(1)-AGP or recombinant alpha(1)-AGP. Recombinant alpha(1)-AGP still showed chiral recognition for three basic drugs tested. By addition of propranolol as a competitor in the separation solution in CE, no enantioseparations of three basic drugs were observed with chicken alpha(1)-AGP, cd-alpha(1)-AGP or recombinant alpha(1)-AGP. These results reveal that the protein domain of the chicken alpha(1)-AGP is responsible for the chiral recognition ability, and that the chiral recognition site(s) for basic drugs exists on the protein domain.


Separation and determination of oleic and cis-vaccenic acids by gas-liquid chromatography mass spectrometry using a polar cyanopropylsiloxane liquid phase.
The separation and quantification of the monoenoic isomeric oleic (cis-9-octadecenoic) and cis-vaccenic (cis-11-octadecenoic) acids as their pyrrolidine derivatives, was studied with a gas chromatograph mass spectrometer system using mass chromatography. By monitoring the characteristic ions of the pyrrolidine derivatives of oleic (m/z 208 and 222) and cis-vaccenic (m/z 210 and 224) acids, both derivatives were separated. The ratio of m/z 210 to 208 was proportional to the relative amounts of cis-vaccenic to oleic acid. By this method, the content of cis-vaccenic acid in choline phosphoglycerides from rat liver and Yoshida ascites hepatoma (AH 7974) was determined.


The clinical characteristics and quality of life of 248 pediatric and adult patients with Congenital Adrenal Hyperplasia.
Congenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East. This case-control study included patients with CAH aged >5 years from two tertiary centers (2020-2021). The patients were matched to a healthy control group and were then divided into pediatric and adult groups. Data were collected from their electronic medical records. Additionally, the EQ-5D-5L QoL questionnaire was completed by both the patients and control group to assess five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The study included 248 patients with CAH (females: 58.8%), with a family history of the condition (57.3%) and/or parental consanguinity (68.1%). The most frequently reported gene defect was CYP21A2, while the most commonly reported symptoms/signs were ambiguous genitalia and obesity. Almost all female patients had received corrective surgery. The questionnaire response rate was 86.3% (n=214/248). The CAH patient group's mean total QoL score was 85.2 compared with 99.8 in the control. Further, CAH patients had lower QoL scores in all domains compared to those in the control group (p ≤ 0.0001-0.0023). The pain/discomfort and anxiety/depression domains were affected significantly more than the other domains were, with 47.7% and 44.4% participants, respectively, p<0.0001. Additionally, obesity was found to be a predictor of reduced mobility following a logistic regression analysis (p ≤ 0.04, OR (0.18-0.98)). Patients with CAH reported lower QoL overall, particularly in the pain/discomfort and anxiety/depression domains. Based on this, we recommend the early involvement of psychologists in a multidisciplinary team approach, pre-marital screening, and the implementation of awareness programs for people diagnosed with CAH in communities with high consanguineous mating.


High burden of self-reported sexually transmitted infections among female sex workers in Togo in 2021.
Sexually Transmitted Infections (STI) remain a public health challenge, especially for Female Sex Workers (FSW) who are particularly vulnerable. In sub-Saharan Africa where the overlapping epidemics of STI and HIV are concentrated among key populations, epidemiological data are needed in order to better understand STI trends in this population. The aim of this study was to assess the prevalence of self-reported STI symptoms and their risk factors among FSW in Togo in 2021. A cross-sectional study was completed in June and July 2021 among FSW in two cities of Togo: in Lomé (capital city, south of Togo) and in Kara (north of Togo). A snowball sampling method was used and after consent, a standardized questionnaire was administered by trained research staff to collect information on STI. A multivariate logistic regression model was used to identify factors associated with self-reported STI. A total of 447 FSW, 300 in Lomé and 147 in Kara participated in this study. Median age was 30 [IQR: 24-38] and STI symptoms in the previous 12 months were reported by 191 FSW [42.7%, 95% CI: (38.1-47.5)], among whom 116 (60.7%) sought medical care. The most common reported symptoms were abnormal vaginal discharge (n = 78; 67.2%) and vaginal itching (n = 68; 58.6%). Current STI symptoms (at the time of the survey) were reported by 88 FSW (19.7%). In multivariable logistic regression, self-reported STI symptoms in the previous 12 months was negatively associated with living in the Lomé and older age and positively associated with having more than 15 clients in the previous week and being victim of violence. Findings from this study reveal that the self-reported STI burden is relatively high among FSW Togo. Additional strategies are needed at the structural, medical, political and social levels to curb this trend and effectively aim at the elimination of STI epidemics by the year 2030.


Median arcuate ligament syndrome.
Median arcuate ligament syndrome (MALS) can cause a range of symptoms, including abdominal pain, nausea, vomiting, and weight loss. Because all patients have some degree of celiac artery compression by the median arcuate ligament (MAL), it may be difficult to discern which patients have a pathologic compression. Based on the multiple theories of MALS etiology, it is unlikely that we know the true cause of this syndrome. In fact, there are many physicians who question the validity of the diagnosis of MALS. Before offering intervention for MALS, a thorough gastrointestinal evaluation should be performed, including consideration of diagnostic temporary percutaneous celiac ganglion block. Patients who are on chronic narcotics preoperatively have a lower likelihood of postoperative symptom relief and therefore should be evaluated by a pain specialist preoperatively. The most reliable treatment comprises open surgical treatment with division of the MAL, removal of surrounding celiac ganglion, evaluation of the celiac artery with pressure measurements or ultrasound, and celiac artery reconstruction if indicated. Laparoscopic and endovascular interventions are novel treatments and may be considered in select patients who cannot undergo an open surgical procedure.


Early-life determinants of excess weight in children born heavy.
Infants born heavy are vulnerable to later obesity, but it is unknown whether obesity-related risk factors present between conception and delivery predict their postnatal weight trajectory. We modelled the weight trajectories of infants born high birth weight (HBW, greater than or equal to 4000 g) and/or large for gestational age (LGA, greater than 90th percentile) using data from the Infant Feeding Practices Study II (N = 371). A high percentage of infants were both HBW and LGA, but the trajectories were modelled separately. Weight of infants born heavy begins high, gradually decreases, and then levels off by 12 months. Delivery method was the only predictor of weight. Caesarean-delivered HBW infants were heavier than vaginally-delivered HBW infants although this effect disappeared by 12 months. Findings indicate that early-life influences are not necessarily deterministic of the postnatal weight trajectory of infants born heavy. Future research is needed to examine postnatal behaviours that may be implicated in the relationship between large size at birth and later obesity.


Magnetic Resonance-Guided focused ultrasound surgery for Parkinson's disease: A mini-review and comparison between deep brain stimulation.
Magnetic resonance-guided focused ultrasound (MRgFUS) is a new surgical treatment for Parkinson's disease (PD). Previous experience with radiofrequency lesionectomy and deep brain stimulation (DBS) has identified several candidate targets for MRgFUS intended to alleviate the motor symptoms of PD. The main advantage of MRgFUS is that it is incisionless. MRgFUS has certain limitations and is associated with adverse effects. The present study reviews the literature on conventional surgical interventions for PD, discusses recent studies on MRgFUS, and the comparison between DBS and MRgFUS for PD. The reviews aims to provide an essential reference for neurologists to select the appropriate treatments for patients with PD.


Influences of exercise-stress and adrenaline upon intra- and extracellular acid-base status, electrolyte composition and respiratory properties of blood in tench (Tinca tinca) at different seasons.
Exercise-stress in tench resulted in severe acidosis in both the red cells and the extracellular fluid in vivo. These coincident pH decreases conformed to the in vitro pHi-pHe relationship for tench blood in the oxygenated state. The extracellular acidosis was primarily respiratory in winter and metabolic in spring and summer. This was due to more effective buffering of metabolic protons in winter by an elevation in [HCO3-] levels, rather than to differences in the lactic- and carbonic acid loads. A good correspondence was found between buffered metabolic protons and increases in [lactate]. There was no evidence for beta-adrenergic red cell swelling and associated red cell pH changes in tench both after exercise and adrenaline infusion. Arterial O2 transport was, however, improved in exercise by pronounced increases in PO2. This increase was not of adrenergic origin, as adrenaline alone caused a decrease in arterial PO2. Large increases in plasma potassium concentration and small elevations of chloride and calcium levels occurred in exercise. Hematocrit and blood [Hb] also increased, probably due to an adrenergic release of erythrocytes from the spleen, but these increases were small and appeared unimportant for blood O2 transport. Seasonal differences were found in exercise-induced changes in [lactate], in the magnitude of electrolyte and PO2 changes, as well as in resting values for pHe, pHi, [HCO3-], [Cl-] and [Ca++]. The origin and importance of these are discussed.


Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells.
Traditional Mongolian medicine (TMM) uses preparations from herbs as one form of medication for the treatment of a diversity of diseases including diabetes mellitus (DM). We evaluated the effect of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat typical symptoms of type 2 DM, on insulin secretion, electrophysiological properties, intracellular calcium concentration and cell proliferation of INS-1E insulinoma cells under standard cell culture conditions (SCC; 11.1mM glucose). Insulin secretion was measured by ELISA, electrical properties were assessed by whole cell patch clamping, intracellular calcium concentration (Cai) by Fluo-4 time lapse imaging, insulin receptor expression was verified by RT-PCR and cell proliferation assessed by CellTiter-Glo® cell viability assay. Insulin released from INS-1E cells into the culture medium over 24h was significantly increased in presence of 500 mg/L aqueous LS extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS OWE resulted in a depolarization of the cell membrane potential paralleled by an initial increase and subsequent decline and silencing of action potential frequency, by KATP channel inhibition, persisting depolarization and an increase in Cai. The electrophysiological effects were comparable to those of 100 μM tolbutamide, which, however failed to elevate insulin secretion under SCC. Furthermore all LS extracts stimulated INS-1E cell proliferation. The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM.


Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils.
Rituximab, a chimeric CD20 monoclonal antibody (mAb), is widely used in the treatment of patients with low-grade non-Hodgkin's lymphoma. Possible anti-tumour mechanisms involve complement-mediated lysis and/or antibody-dependent cellular cytotoxicity (ADCC). Because G-CSF greatly enhances the cytotoxicity of neutrophils (PMN) in ADCC, the clinical efficacy of rituximab might be enhanced by the addition of G-CSF. Therefore, we investigated the neutrophil-mediated CD20-dependent cellular cytotoxicity in B cell lines. In contrast to previous studies by others, we found that G-CSF-primed PMN are capable of functioning as effector cells in CD20-dependent cellular cytotoxicity. However, HLA class II mAbs were far more effective. The differences between HLA class II- and CD20-mediated PMN-ADCC were not due to: (1) the use of chimeric (hIgG1) mAbs vs mIgG2a mAbs; (2) HLA class II-induced apoptosis as an 'ADCC-sensitising' mechanism; (3) CD20-induced inhibition of ADCC; (4) inferior membrane mobility of CD20. Analysis of Fcgammareceptor (FcgammaR) involvement showed that although CD20-induced ADCC was mediated mainly via FcgammaRI, for optimal lysis FcgammaRI and FcgammaRII were both required. In contrast, in HLA class II-dependent ADCC both FcgammaRI and II were capable of independently inducing maximum lysis. The mechanism underlying these differences in FcgammaR-binding and activation remains to be elucidated.


Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use.
During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95. This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.


Creutzfeldt-Jakob disease after liver transplantation.
We report a 57-year-old woman who died from Creutzfeldt-Jakob disease 2 years after a liver transplantation. The liver donor had no history of neurological disease. In one albumin donor, possible Creutzfeldt-Jakob disease developed 3 years later. The patient initially had cerebellar symptoms. Neuropathology included "Kuru-type" plaques and prion protein (PrP) deposits involving the cerebellum predominantly. The patient was homozygote valine at codon 129 of the PrP gene while the liver was homozygote methionine. This observation raises the possibility of transmission of Creutzfeldt-Jakob disease by the graft itself or the associated albumin transfusions and, on a wider extent, by nonneural tissue.


The influence of the dopaminergic system on cognitive functioning: A molecular genetic approach.
Many pharmacological and clinical studies have demonstrated the importance of the dopaminergic (DA) system for cognitive functioning but little is known about the genetic basis of general cognitive ability that has been demonstrated to be highly heritable. Attempts to detect associations between certain gene loci and endophenotypes of general cognitive ability have turned out to be more promising. Therefore, the aim of the present study was to investigate two dopaminergic candidate genes (COMT VAL158MET and DRD2 TAQ IA) for endophenotypes of cognitive functioning i.e. attention, vigilance, interference, time estimation and sensoric and motoric reaction times. Out of a gene data bank of more than 600 healthy Caucasian participants, 96 subjects (n = 48 males and n = 48 females) were recruited according to their genotype/allele pattern, resulting in six independent groups (COMT: VAL/VAL, VAL/MET, MET/MET)x(DRD2: A1-, A1+) of n = 16 subjects each. Results showed associations of the COMT gene with attention and with time estimation but most noteworthy was an interaction effect DRD2xVAL on interference performance as measured by the STROOP-test explaining 13% of the variance. Findings suggest that a balance between DA related catabolic enzyme activity and receptor density are good predictors for the endophenotype of cognitive interference and that the COMT gene is in accordance with previous studies related to cognitive functioning.


Carrageenan oedema in copper-deficient rats.
Carrageenan-induced hind paw oedema has been studied in rats deprived of copper for different lengths of time. A common feature observed in normally fed and copper-deficient rats was the rise of serum copper levels occurring between 10 and 24 h after the injection of the irritant. After 1 month of copper-deficient diet no differences are seen in the oedema developed by controls and copper-deprived animals, while after 3 months the oedema developed by copper-deficient rats was significantly greater compared with the controls.


Discovery and development of palmatine analogues as anti-NASH agents by activating farnesoid X receptor (FXR).
Sixty-one palmatine (PMT) derivatives, of which twenty-eight were new, were synthesized and evaluated for their anti-fibrogenic activities via collagen type I α 1 (COL1A1)-promoter based luciferase model in LX-2 cells, taking 2,3,10-trimethoxy-9-p-isopropyloxyprotopalmatine bromide (1) as the lead. Among them, compound 3a exerted the highest potency with the IC50 value of 8.19 μmol/L and SI value of 8.59, and reduced the expressions of multiple fibrogenic biomarkers, including COL1A1, TGF-β1, α-SMA and TIMP1 in a dose-dependent manner. In addition, it significantly reduced liver steatosis and inflammation, and especially attenuated the degree of liver fibrosis in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-induced NASH mice model in vivo. Mechanism study indicated that it significantly ameliorated liver injury by activating farnesoid X receptor (FXR). BDL-induced fibrosis rats model further verified its liver-protective and anti-fibrosis activities. Therefore, PMT derivatives constituted a new family of non-steroidal FXR agonists as anti-NASH candidates, with the advantage of good safety profile, and are worthy for further investigation.


Aloperine protects beta-cells against streptozocin-induced injury to attenuate diabetes by targeting NOS1.
Type 1 diabetes (T1D) is a metabolic dysfunction characterized by the selective destruction of islet β-cells, with oxidative stress playing an essential role in the manifestation of this disease state. Aloperine (ALO) represents the main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides L. and features outstanding antioxidative properties. In this study, T1D was induced by a single high dose streptozotocin (STZ, 150 mg/kg, intraperitoneal) in mice. Diabetic animals were intragastrically administered ALO at a dose of 50 mg/kg/day. Notably, treatment of ALO (50 mg/kg/day) for seven consecutive days could observably reverse the onset of diabetes induced by STZ accompanied by weight gain, lower blood glucose levels, and relief of β-cells damage. Our in vitro study further demonstrated that ALO protected β-cells from STZ/hydrogen peroxide-induced oxidative damage as manifested by increased expression of MnSOD and CAT. Furthermore, a network pharmacology study revealed that NOS1 represented the main target of ALO. Mechanistic studies subsequently showed that treatment of ALO increased the expression of NOS1, whereas NOS2 was decreased. Moreover, a docking study carried out suggested that ALO could fit into the binding pocket of human NOS1 and molecular dynamics simulation further validated this docking event. Collectively, the administration of ALO prior to diabetes could be a viable approach to the prevention of β-cell injury. This study may offer a novel potential herbal medicine against T1D and may further help improve the understanding of the underlying molecular mechanisms of ALO-mediated protection against oxidative stress.


Comparison of bone scintigraphy and Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography in the detection of bone metastases of prostate carcinoma.
This study aims to assess the diagnostic performance of Ga-68 prostate-specific membrane antigen PET/computed tomography in the comparison of planar bone scintigraphy in the detection of bone metastases. Another purpose is to define the additional benefit of bone scintigraphy subsequent to prostate-specific membrane antigen PET/computed tomography and the role of prostate-specific membrane antigen PET/computed tomography in the treatment planning. Forty-six patients with a median interval of 19 (range: 3-90) days between prostate-specific membrane antigen PET/computed tomography and bone scintigraphy included in the analysis. Diagnostic performance of both modalities was calculated and compared. Prostate-specific membrane antigen PET/computed tomography and bone scintigraphy were performed for initial staging in 25 (54%), for evaluation of biochemical recurrence in 11 (24%) and metastatic castration-resistant prostate carcinoma in 10 (22%) patients. In the patient-based analysis sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for bone scintigraphy for detection of bone metastases were calculated as 50%, 19-29%, 32-39%, 32-39%, and 33-39%, respectively, based on whether equivocal findings were classified as positive or negative. For prostate-specific membrane antigen PET/computed tomography, these values were found significantly higher as 100%, 95-100%, 98-100%, 96-100%, and 100%, respectively. The diagnostic performance of bone scintigraphy and PET/computed tomography in clinical subgroups was analyzed, prostate-specific membrane antigen PET/computed tomography was superior to bone scintigraphy in three groups. In this retrospective study, prostate-specific membrane antigen PET/computed tomography was found to be superior to planar bone scintigraphy in the detection of bone metastases. Additional bone scintigraphy seems to be unnecessary in patients who underwent prostate-specific membrane antigen PET/computed tomography within three months period without additional treatment.


Increase in antibiotic prescriptions in out-of-hours primary care in contrast to in-hours primary care prescriptions: service evaluation in a population of 600 000 patients.
The objective of this study was to describe the frequency and nature of antibiotic prescriptions issued by a primary care out-of-hours (OOH) service and compare time trends in prescriptions between OOH and in-hours primary care. We performed a retrospective audit of 496 931 patient contacts with the Oxfordshire OOH primary care service. Comparison of time trends in antibiotic prescriptions from OOH primary care and in-hours primary care for the same population was made using multiple linear regression models fitted to the monthly data for OOH prescriptions, OOH contacts and in-hours prescriptions between September 2010 and August 2014. Compared with the overall population contacting the OOH service, younger age, female sex and patients who were less deprived were independently correlated with an increased chance of a contact resulting in prescription of antibiotics. The majority of antibiotics were prescribed to patients contacting the service at weekends. Despite a reduction in patient contacts with the OOH service [an estimated decrease of 486.5 monthly contacts each year (95% CI -676.3 to -296.8), 5.0% of the average monthly contacts], antibiotic prescriptions from this service rose during the study period [increase of 37.1 monthly prescriptions each year (95% CI 10.6-63.7), 2.5% of the average monthly prescriptions]. A matching increase was not seen for in-hours antibiotic prescriptions; the difference between the year trends was significant (Z test, P = 0.002). We have demonstrated trends in prescribing that could represent a partial displacement of antibiotic prescribing from in-hours to OOH primary care. The possibility that the trends we describe are evident nationally should be explored.


Comparison of S9 fractions from rats, mice, and Chinese hamsters to metabolize dimethylnitrosamine and diethylnitrosamine to intermediates that induce sister-chromatid exchanges in V79 cells.
This study was designed to compare the ability of hepatic S9 preparations from rats, mice and Chinese hamsters to activate dimethylnitrosamine (DMN) and diethylnitrosamine (DEN) into intermediates capable of causing sister-chromatid exchanges (SCEs) in V79 cells. The results indicated that the hepatic preparations from the species studied differed in their ability to activate DMN while in the case of DEN no species difference in bioactivation was observed. For DMN, a dose-dependent increase of SCEs was seen in cultures treated with various concentrations plus rat, mouse or hamster S9 mix and the mouse S9 mix was the most effective activator of DMN and this was followed by the rat and Chinese hamster S9 mix with little difference noted for the latter 2 species. For DEN, an increase of SCE was seen in cultures treated with various doses plus S9 mix from any of the species studied but unlike DMN, the SCE rate did not increase in a significant dose-dependent manner and no species difference in bioactivation was observed.


SNVDis: a proteome-wide analysis service for evaluating nsSNVs in protein functional sites and pathways.
Amino acid changes due to non-synonymous variation are included as annotations for individual proteins in UniProtKB/Swiss-Prot and RefSeq which present biological data in a protein- or gene-centric fashion. Unfortunately, proteome-wide analysis of non-synonymous single-nucleotide variations (nsSNVs) is not easy to perform because information on nsSNVs and functionally important sites are not well integrated both within and between databases and their search engines. We have developed SNVDis that allows evaluation of proteome-wide nsSNV distribution in functional sites, domains and pathways. More specifically, we have integrated human-specific data from major variation databases (UniProtKB, dbSNP and COSMIC), comprehensive sequence feature annotation from UniProtKB, Pfam, RefSeq, Conserved Domain Database (CDD) and pathway information from Protein ANalysis THrough Evolutionary Relationships (PANTHER) and mapped all of them in a uniform and comprehensive way to the human reference proteome provided by UniProtKB/Swiss-Prot. Integrated information of active sites, pathways, binding sites, domains, which are extracted from a number of different sources, provides a detailed overview of how nsSNVs are distributed over the human proteome and pathways and how they intersect with functional sites of proteins. Additionally, it is possible to find out whether there is an over- or under-representation of nsSNVs in specific domains, pathways or user-defined protein lists. The underlying datasets are updated once every 3months. SNVDis is freely available at http://hive.biochemistry.gwu.edu/tool/snvdis.


Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer.
Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.


Testicular blood flow and a study of the testicular venous to arterial transfer of radioactive krypton and testosterone in the rhesus monkey.
1. Testicular blood flow (ml. 100 g(-1).min(-1); mean +/- S.E. of the mean) measured in monkeys by (133)Xe clearance was 15.9 +/- 1.2 (twenty-six estimations on three monkeys; six testes) within 15 min of anaesthesia and 7.5 +/- 0.8 (twelve estimates; four monkeys, eight testes), after 1-2 hr of anaesthesia; and, when measured by (85)Kr clearance in the second hour of anaesthesia was 9.1 +/- 3.7 (seven estimates; four monkeys, four testes). Testicular temperature was 32.9 +/- 0.2 degrees C (mean +/- S.E. of mean) when deep body temperature was 37.2 +/- 0.2 degrees C.2. Blood flow in the caput epididymidis was 27.4 +/- 2.1 ml. 100 g(-1).min(-1) (mean +/- S.E. of mean; four estimates).3. Radioactivity accumulated in the ipsilateral testis and epididymis but not in the contralateral tissues, during the infusion of (85)Kr saline into the testicular veins.4. During [(3)H]testosterone infusions into the testicular veins, radioactivity was consistently higher in ipsilateral testicular arterial plasma than in plasma withdrawn simultaneously from the aorta in four of five experiments with no difference in one. After two such infusions, the radioactivity was up to 5 times greater in the ipsilateral testis and epididymis than in the contralateral tissues.5. During one infusion of [(125)I]bovine serum albumin into the testicular veins, there was no accumulation of radioactivity in the ipsilateral tissues.6. Testosterone concentrations (ng.ml(-1); mean +/- S.E. of mean) in plasma from seven anaesthetized monkeys which were sexually experienced were: testicular vein 53.22 +/- 8.03 (eight estimates); testicular artery, 4.58 +/- 0.94 (14); saphenous vein, 3.81 +/- 0.68 (14). The corresponding values from four sexually inexperienced monkeys were 25.27 +/- 2.11 (12); 2.89 +/- 1.99 (12); aorta 2.76 +/- 0.57 (12).7. The results are discussed as evidence for vascular exchange of molecules between the testicular veins and artery in the spermatic cord.


Nasal mucus transportability in children with cleft palate.
Children with cleft palate (CP) have a high prevalence of sinusitis. Considering that nasal mucus properties play a pivotal role in the upper airway defense mechanism, the aim of the study was to evaluate nasal mucus transportability and physical properties from children with CP. Hospital for Rehabilitation of Craniofacial Anomalies, School of Dentistry, University of São Paulo, Bauru, SP, Brazil and Laboratory of Experimental Air Pollution, School of Medicine, University of São Paulo, São Paulo, SP, Brazil. Nasal mucus samples were collected by nasal aspiration from children with CP and without CP (non-CP). Sneeze clearance (SC) was evaluated by the simulated sneeze machine. In vitro mucus transportability (MCT) by cilia was evaluated by the frog palate preparation. Mucus physical surface properties were assessed by measuring the contact angle (CA). Mucus rheology was determined by means of a magnetic rheometer, and the results were expressed as log G* (vectorial sum of viscosity and elasticity) and tan delta (relationship between viscosity and elasticity) measured at 1 and 100 rad/s. Mucus samples from children with CP had a higher SC than non-CP children (67+/-30 and 41+/-24 mm, respectively, p<0.05). Mucus samples from children with CP had a lower CA (24+/-16 degrees and 35+/-11 degrees , p<0.05) and a higher tan delta 100 (0.79+/-0.24 and 0.51+/-0.12, p<0.05) than non-CP children. There were no significant differences in mucus MCT, log G* 1, tan delta 1 and log G* 100 obtained for CP and non-CP children. Nasal mucus physical properties from children with CP are associated with higher sneeze transportability. The high prevalence of sinusitis in children with CP cannot be explained by changes in mucus physical properties and transportability.


A study on the association of serum 1,5-anhydroglucitol levels and the hyperglycaemic excursions as measured by continuous glucose monitoring system among people with type 2 diabetes in China.
Blood glucose excursion is an important component of the glycaemic burden, but there are no indexes that can directly reflect them. The aim was to evaluate the values and significance of serum 1,5-anhydroglucitol (1,5-AG) in people with type 2 diabetes mellitus in China and to elucidate the relationship between 1,5-AG and traditional indexes of glycaemic excursions by continuous glucose monitoring. A total of 576 healthy adults and 292 patients were included, and their 1,5-AG, fasting blood glucose and postprandial blood glucose and glycated haemoglobin were measured. For the 34 patients, their mean blood glucose, standard deviation of blood glucose, mean amplitude of glucose excursion, mean of daily differences, low blood glucose M-value index and the area under the curve for blood glucose above 180 mg/dL were calculated by use of a continuous glucose monitoring system. Serum levels of 1,5-AG among healthy adults were 28.44 ± 8.76 µg/mL with a significant gender bias rather than age bias. The 1,5-AG levels in people with type 2 diabetes mellitus were 4.57 ± 3.71 µg/mL, which were lower than those seen in the healthy adults. There was a correlation between 1,5-AG and glycated haemoglobin, fasting blood glucose, and postprandial blood glucose (r = -0.251, -0.195 and -0.349, respectively; all had p < 0.05). The continuous glucose monitoring system demonstrated that 1,5-AG presents a negative correlation with mean blood glucose, standard deviation of blood glucose, mean amplitude of glucose excursion and mean of daily differences for 7 days and with the area under the curve for blood glucose above 180 mg/dL on the third, fourth and seventh days. 1,5-AG may serve as a marker of hyperglycaemia and 7-day hyperglycaemic excursions as well as being a useful adjunct to glycated haemoglobin for blood glucose monitoring in patients with diabetes.


Arrhythmic events in Brugada syndrome patients induced by fever.
The Brugada syndrome is associated with arrhythmic events, which may even lead to sudden cardiac death (SCD) as it causes arrhythmic events. A typical Brugada syndrome ECG type I can be triggered at fever situations. The aim of this pooled meta-analysis is to further explore the baseline characteristics and the association of fever to BrS-related arrhythmic events. We compiled data from a search of databases (PubMed, Web of Science, Cochrane Library, and Google Scholar). We included 17 studies including 14 case reports and a total of 53 patients. Our population including 53 patients showed a male predominance of 92% with a mean age of 40.6 ± 17.7 years. 58% of patients had a family history of SCD or BrS. Genetic screening was performed in 14 patients (26%) and revealed a SCN5A mutation in 21% of the patients. ICD implantation was initiated in six patients. 75% (n = 39) of patients did not have symptoms before the fever event. Symptoms at fever included life-threatening arrhythmia such as ventricular fibrillation (VF) or ventricular tachycardia (VT; 17%), syncope (13%), and cardiac arrest or aborted SCD (13%). One patient developed electrical storm which led to not aborted SCD. Fever is a great risk factor for arrhythmia events in BrS patients. Patients with known fever triggered Brugada syndrome should be surveilled closely during fever and be started on antipyretic therapy as soon as possible.


A new symmetrized solution for phase retrieval using the transport of intensity equation.
We propose a novel symmetrization method for solving the transport of intensity equation (TIE) using fast Fourier transforms for situations where the input images may or may not exhibit spatial periodicity. The method is derived from the analysis of intensity conservation law and the internal symmetry of the TIE, and is illustrated for both a computational and an experimental data set.


Time study on the uptake of four different beta-blockers in garden cress (Lepidium sativum) as a model plant.
The aim of this study was to investigate the uptake of four beta-blockers by the model plant Lepidium sativum (garden cress) and their possible metabolization over a time period of 8 days. Therefore, cress was grown hydroponically in tap water for a week until they were matured, following irrigation with drug-containing water over the course of another 8 days. Samples were taken at days 1, 2, 4, and 8 after irrigation started. All four beta-blockers were taken up by the plants and the different octanol-water coefficients (log P) of the drugs have an influence on the uptake speed in the roots of the plants. The log P seems to have no influence on the translocation of the drugs from the root to the shoots. Furthermore, neither phase I nor phase II metabolization occurred inside the plants.


Prevalence of erectile dysfunction: need for treatment?
Research examining the occurrence of sexual problems in nonclinical populations tends to be restricted to highly select populations. Recently, several population-based surveys surfaced in the international literature, triggered by the advent of effective pharmacological treatment for erectile dysfunction (ED). ED is a common disorder, especially among elderly men. The annual incidence in men 40-69 y of age is 26 per 1000 men. Although most of the difficulties are mild and do not totally prevent intercourse, about 26% of men experience moderate to complete ED. The impact of this category of ED on sexual activity among men is marked. The incidence of ED increases with age and the presence of concomitant conditions, such as diabetes mellitus, heart disease, hypertension, depression, pelvic surgery, negative mood, lack of self-esteem, problems with relationships, or just inadequate sexual experience. Vascular disease is thought to be the most common cause of organic ED, and it may be an early symptom of cardiac morbidity and mortality. Although one may expect that any man with ED who is motivated to continue sexual activity may seek current highly effective symptomatic medical treatment, only a few men are actually seeking help, and not every man seeking help appears to be a candidate for (symptomatic) medical treatment. The frequent association of sexual and medical problems, especially in the aged, and the high dropout rates for symptomatic ED treatment make counseling, adjustment of lifestyle, and modification of risk factors, such as medication, overweight, smoking, alcohol consumption, and lack of exercise, the primary steps in a holistic approach toward the treatment of ED. It is especially important to educate these men to remain physically and sexually as active as possible for as long as possible. The phrase 'use it or lose it' is particularly appropriate for the genitalia.


Papillary conjunctivitis presenting months after permanent eyebrow tattooing.
To present a case of tattoo side effects not limited to the tattoo site and rise an alarm regarding using non-FDA-approved products. A 30-year-old female presented with bilateral ocular pain, dryness, and itching. The ocular exam showed bilateral injection and edema of the superior palpebral and bulbar conjunctiva. Several 1-2 mm dark pigmented lesions and papillae coursing along the upper palpebral conjunctival lid margin and 5 mm above the margin were found in both eyes. The ocular surface was dry with diffuse superficial punctate keratitis. The biopsy report showed granular foreign material in the dermis. SOX-10 and MART-1 immunostaining highlighted melanocyte distribution and the sample was diagnosed as exogenous pigment consistent with tattoo ink by the pathologist. On further investigation following the pathology report, the patient stated that she got bilateral permanent eyebrow tattoos 4 months before presentation in a country other than the United States, and she was not aware about the standards of the ink used, nor the certification of the person performing the tattoo. The patient denied any type of tattoo or manipulation on the eyes or orbit, including sclera or conjunctivae. Importance: The complications of periorbital tattooing are not limited to the point tattoo location and can potentially spread to the nearby segments. It is notable that there is no FDA approved tattoo ink available, even with a certified tattoo artist performing the tattoo, the risks of inflammation, infection, and other side effects are still present.


Triterpenoid glycosides from Adina rubella.
Two new triterpenoid glycosides, quinovic acid-3 beta-O-beta-D- glucopyranosyl-(1-->4)-alpha-L-rhamnopyranoside and quinovic acid-3 beta-O-beta-D-glucopyranosyl-(1-->3)-beta-D-fucopyranoside (named rubelloside A and B, respectively), were isolated from roots of Adina rubella. Their structures were elucidated by spectral and chemical means. Rubelloside B exhibited immunological enhancement.


Covert neurological symptoms associated with silent infarcts from midlife to older age: the Atherosclerosis Risk in Communities study.
Unrecognized or unreported stroke-like symptoms, called covert symptoms, occur in persons free of clinical stroke. Whether covert symptoms are associated with subclinical brain infarcts (SBIs) is unknown. This study examined the association between covert stroke-like symptoms and SBI/stroke in persons with no history of stroke or transient ischemic attack. A total of 1881 Atherosclerosis Risk in Communities (ARIC) participants free of clinical stroke or transient ischemic attack (40% male, 50% black, 47-70 years) were queried for covert symptoms and underwent cerebral MRI during the baseline MRI visit. Symptoms were reassessed after 3 years at Visit 4 (n=1001; 39% male, 50% black) and approximately 10 years with a follow-up MRI (n=1006; 40% male, 50% black, 61-83 years). Covert symptoms were associated with prevalent SBI (OR, 1.94; 95% CI, 1.21-3.11; P=0.006). No support was found for associations between baseline MRI symptoms and SBI at the follow up MRI visit. In participants without SBI at baseline, symptoms at Visit 4 (OR, 2.96; 1.23-7.13; P=0.016) and symptoms at the follow-up MRI visit (OR, 4.29; 2.51-7.33; P<0.001) were associated with a combined outcome of new SBI/clinical stroke on follow-up MRI. Covert symptoms at follow-up MRI visit were also associated with having new SBI (OR, 2.26; 1.18-4.32; P=0.014) on the follow-up MRI that were not seen on the baseline MRI. Covert neurological symptoms were associated with prevalent SBI, and when ascertained at the time of follow-up MRI, with new SBI. Covert symptoms may reflect heightened risk for infarcts.


Polyclonal B-cell activation of rabbit Peyer's patch.
This study delineates the culture conditions and cellular requirements for pokeweed mitogen (PWM)-induced polyclonal B-lymphocyte activation of rabbit Peyer's patch cells for immunoglobulin secretion. This system was optimal with a cell density of 3 X 10(5) cells/ml and a culture duration of 7 days, in round-bottom containers. Although glass-plate-adherent cells did not appear to influence this process, the immunoglobulin responses to PWM were T cell dependent. This study supplies a foundation for further work on the mechanisms of polyclonal activation of B cells in the rabbit Peyer's patch.


Telepsychiatry in the Arab World: A Viewpoint Before and During COVID-19.
Telepsychiatry, a subset of telemedicine, has been increasingly studied to meet the growing demands for psychiatric care. The utility of telepsychiatry is relevant now more than ever as the world endures the COVID-19 global pandemic. This paper describes the prior state and the changes that the COVID-19 outbreak brought to telepsychiatry in a selected group of Arab countries of the Middle East and North Africa (MENA) region. We invited twelve early-career psychiatrists from different Arab nations to share information related to telepsychiatry in their respective countries before and during the COVID-19 pandemic. The information was collected using a semi-structured guide. This was complemented by a search for relevant articles in five search engines using terms such as "COVID-19," "telepsychiatry," and "Arab world". Before the pandemic, digital mental health services were provided in several Arab countries, mainly through hotlines and messaging services. The COVID-19 pandemic has marked a major shift in digital psychiatric services in the Arab MENA world, through the transformation of many clinics and some hospitals into digital mental health systems. Many non-governmental organizations also started remote initiatives for psychological support and psychiatric counseling. Three main barriers of patient-related, healthcare-related, and system-related hurdles of using telepsychiatry emanated from the analysis. The use of digital mental health services varies between different Arab countries. Even though some nations have laws that regulate the provision of such services, most struggle with multifactorial barriers. As affordable and attainable solutions cannot only rely on training and recruiting more psychiatrists, telepsychiatry would help meet the exceeding demands in the Arab world, particularly after the COVID-19 outbreak.


Study on personalized microbial formulation during high-temperature aerobic fermentation of different types of food wastes.
The rapidly growing generation of food wastes has attracted extensive attention. In this context, biochemical processors, using high-temperature aerobic fermentation, has become a beneficial method to treat food waste in situ. However, existing microbial agents do not vary the proportion of strains according to the different food wastes, with this approach affecting the degradation efficiency. In this study, high-temperature resistant strains, with high degradation efficiency, were isolated and screened, before establishing a novel method for preparing personalized microbial formulations. Using the degradation efficiency of wastes after three days as the evaluation standard, 12 groups of Plackett-Burman experiments were used to determine the main effect strains for different types of food waste. Fifteen groups of Box-Behnken experiments were then used to determine their best proportions at which the maximum degradation efficiency occurred. Finally, simulated fermentation experiments were used to check for improvement of the fermentation process by mixing strains according to the personalized proportions. Results of molecular identification and physiological assessments indicated that all the seven strains were Bacillus spp., with no antagonistic effects between them. Based on the Plackett-Burman and Box-Behnken tests, three personalized bacterial agents were obtained for different types of food waste. The fermentation results further showed that, compared with the use of equal proportions of strains, a maximum increase of 15.43% in organic matter degradation was achieved after adding personalized proportions. This study provides both theoretical and practical references for the use of personalized microbial agent formulations for high-temperature aerobic fermentation of food wastes, thus providing these microbial agents with good prospects and economic value.


Half blind superiority tests for clinical trials of anti-infective drugs.
This paper introduces a test of superiority of new anti-infective drug B over comparator drug A based on a randomized clinical trial. This test can be used to demonstrate assay (trial) sensitivity for noninferiority trials and rigorously tailor drug choice for individual patients. Our approach uses specialized baseline covariates XA ,XB , which should predict the benefits of drug A and drug B, respectively. Using a response surface model for the treatment effect, we test for superiority at the (XA ,XB ) point that is most likely to show superiority. We identify this point based on estimates from a novel half-blind pseudo likelihood, where we augment a blinded likelihood (mixed over the treatment indicator) with likelihoods for the overall success rates for drug A and drug B (mixed over XA ,XB ). The augmentation results in much better estimates than those based on the mixed blinded likelihood alone but, interestingly, the estimates almost behave as if they were based on fully blinded data. We also develop an analogous univariate method using XA for settings where XB has little variation. Permutation methods are used for testing. If the "half-blind" test rejects, pointwise confidence interval can be used to identify patients who would benefit from drug B. We compare the new tests to other methods with an example and via simulations.


Insights into the mechanism of erythrocyte Na+/K+-ATPase inhibition by nitric oxide and peroxynitrite anion.
Evidence shows that Na(+)/K(+)-ATPase from kidney, brain and liver is inhibited by nitric oxide (NO) and peroxynitrite anion (ONO(2) (-)), but the mechanism is unknown. The aim of the present work was to study the inhibitory effect of NO and ONO(2) (-) on erythrocyte Na(+)/K(+)-ATPase. Erythrocyte membranes were isolated from male Wistar rats by hypotonic washing. The membranes (free from haemoglobin) were incubated for Na(+)/K(+)-ATPase activity measurement at various concentrations of ATP in the presence or absence of 400 microM SNAP (an NO donor) or 100 microM SIN-1 (an ONO(2)(-) donor). At these concentrations, SNAP and SIN-1 released about the same amount (100 microM) of NO or ONO(2)(-), respectively, as monitored by measuring NO(2)(-) + NO(3)(-). Both SNAP and SIN-1 decreased V(max) by ca. 75% but they did not decrease the apparent affinity of the Na(+)/K(+)-ATPase for the substrate (a decrease of K(m) was even observed after SNAP treatment). The pattern of this inhibition is compatible either with oxidation of SH groups directly involved in ATP binding but in a way that is not surmountable by increasing the substrate concentration ("non-competitive") or with oxidation of SH groups located outside the active site of the enzyme but important for the activity of the enzyme.


Staphylococcal enterotoxins A and B share a common structural motif for binding class II major histocompatibility complex molecules.
A comparative site-directed mutagenesis study of staphylococcal enterotoxins A and B was undertaken to identify key amino-acid residues which govern interactions with major histocompatibility class II molecules. This involved generating a three-dimensional homology model for enterotoxin A in complex with the HLA-DR1 molecule, based on the reported X-ray crystal structures of enterotoxin B, both free and bound to HLA-DR1. A binding motif previously described for enterotoxin B was found to be conserved in enterotoxin A. An examination of the experimental data with the homology model clarifies how T-cell responses to enterotoxin A, and most bacterial superantigens, are likely to be mediated by variations of a structurally conserved HLA-DR alpha binding motif.


New insights into membrane fouling in submerged MBR under sub-critical flux condition.
This study investigated the membrane fouling in MBRs under sub-critical flux condition. Results showed membrane fouling at subcritical flux evolved through a three-stage process: a slow linear increase in transmembrane pressure (TMP) (stage I), followed by an exponential increase in TMP (stage II), and finally a rapid linear TMP rise was observed at stage III. It was found that bound EPS would play a significant role in fouling development at stage I, while SMPs appeared to be the major contributor to self-accelerating fouling phenomena observed at stage II. At stage III, the entire membrane was covered by a cake layer of flocs, as the result, the fouling rate was likely determined by floc characteristics. This study offers new insights into the fouling development under sub-critical flux condition.


Polymerase chain reaction of human cytomegalovirus from liver and urine compared with serological test in cholestasis infants.
The most common infection in cholestatic infants is caused by human cytomegalovirus (HCMV). The aims were to detect the presentation of HCMV in cholestatic infants and to evaluate the concordance, sensitivity, and specificity between serology and polymerase chain reaction (PCR) of HCMV from liver biopsy and urine specimens. A descriptive observational study with a cross-sectional approach was conducted on 35 cholestatic infants with ethical approval. Specimens were liver biopsy, urine, and anti-HCMV serology. Liver and urine specimens were performed to nested PCR, followed by statistical analysis. PCR from the liver biopsy and urine specimen were positive in 74.3% and 85.7%, respectively. There was no concordance between IgM with the liver PCR, but there was a concordance between IgM with the urine PCR and between IgG with the liver and urine PCR. The sensitivity and specificity of IgM with the liver PCR were 46 % and 56%, respectively, with a diagnostic accuracy of 49%. While IgG sensitivity was 96% with a diagnostic accuracy of 80%. IgG sensitivity and IgM specificity compared with the urine PCR were 93% and 100%, respectively, with a diagnostic accuracy of more than 60%. It demonstrates a high prevalence of HCMV DNA in urine and liver biopsy from cholestatic infants. HCMV PCR assay is more sensitive and specific than the anti-HCMV IgM, but IgG has high sensitivity and accuracy diagnostic. Therefore, serological examination is an option for diagnosing HCMV infection in cholestatic infants in developing countries with no PCR facilities.


Electrophysiological correlates of stuttering severity: An ERP study.
Although a variety of theories have been proposed to explain the etiology of stuttering, the exact neurological origin of it is still uncertain. The aim of this study is to investigate the correlation between stuttering severity and ERP measures. The population of this study consisted of 12 adults with moderate, 12 adults with severe stuttering, and 12 fluent speakers as the control group. ERPs were recorded during an auditory task in which subjects should determine an oddball stimulus. The result of mismatch negativity (MMN) amplitude analysis revealed significant differences between severe stuttering and fluent speakers groups and between two stuttering groups. Moreover, the result showed significant differences between the three study groups for P300 amplitude. The findings of the present study suggest that the differences in ERP components are existed not only between people who stutter and fluent speakers but also between people with different levels of stuttering severity.


Chorionicity determination in twin pregnancies: how accurate are we?
To determine the accuracy of antenatal prediction of chorionicity in twin pregnancies in our institution. Antenatal chorionicity was determined using the number of placental masses, the presence or absence of a twin peak sign and the fetal sex. The gestational age at assessment was documented. Postnatal diagnosis of chorionicity was determined by neonatal sex and placental pathology. Chorionicity was correctly determined in 95% of cases (n = 131); 91% of the monochorionic and 96% of the dichorionic pregnancies were correctly determined. If chorionicity was assessed prior to 14 weeks' gestation (n = 96) the correct diagnosis was made in all except one case. Ultrasound assessment of chorionicity has a high sensitivity and specificity. This is further improved if the assessment is performed prior to 14 weeks' gestation.


One-step construction of biosensor based on chitosan-ionic liquid-horseradish peroxidase biocomposite formed by electrodeposition.
A simple and controllable electrodeposition approach was established for one-step construction of hydrogen peroxide (H(2)O(2)) biosensors by in situ formation of chitosan-ionic liquid-horseradish peroxidase (CS-IL-HRP) biocomposite film on electrode surface. A highly porous surface with orderly three-dimensional network was revealed by scanning electron microscopy (SEM) investigation. The biocomposite provided improved conductivity and biocompatible microenvironment. The developed biosensor exhibited a fast amperometric response for the determination of H(2)O(2) and 95% of the steady-state current was obtained within 2s. The linear response of the developed biosensor for the determination of H(2)O(2) ranged from 6.0 x 10(-7) to 1.6 x 10(-4)M with a detection limit of 1.5 x 10(-7)M. Performance of the biosensor was evaluated with respect to possible interferences and a good selectivity was revealed. The fabricated biosensor exhibited high reproducibility and long-time storage stability. The ease of the one-step non-manual technique and the promising feature of biocomposite could serve as a versatile platform for the fabrication of electrochemical biosensors.


Hemostasis in Pediatric Surgery.
Hemostasis is an important concept in pediatric otolaryngologic surgery. This article details the considerations the otolaryngologist should take when it comes to clinical evaluation and surgical technique. It begins with the preoperative evaluation, and evolves into the use of different mechanical and chemical methods of operative hemostasis. We detail use of different hemostatic techniques in common pediatric procedures, and finally, we discuss indications for intraoperative and postoperative blood transfusion in pediatric patients if the surgeon encounters significant intraoperative hemorrhage. This paper gives a comprehensive look into the hemostatic considerations for the pediatric patient through the preoperative to postoperative period.