Effect of angiotensin-converting enzyme inhibition with perindopril and beta-blockade with atenolol on retinal blood flow in hypertensive diabetic subjects.
The effect of angiotensin-converting enzyme (ACE) inhibitors on the diabetic retinal circulation has not been studied previously. The aim of this study was to evaluate the effect of ACE inhibition and beta-blockade on retinal blood flow (RBF) in a group of 45 hypertensive diabetic subjects using a randomized double-blind trial over a period of 12 months. Laser Doppler velocimetry and computed image analysis were used to measure RBF. The changes in blood pressure over 12 months were comparable (perindopril [PE]: systolic [SBP] 152.1 +/- 3.3 and diastolic [DBP] 97.2 +/- 1.7 mm Hg to SBP 136.8 +/- 3.4 and DBP 85.8 +/- 2.1; atenolol: SBP 158.9 +/- 5.1 and DBP 97.5 +/- 1.6 mm Hg to SBP 137.9 +/- 3.4 and DBP 85.1 +/- 1.6; P = .607, mean +/- SEM). RBF decreased from 17.19 +/- 2.21 microL x min(-1) to 14.18 +/- 1.50 microL x min(-1) in the PE group (n = 15, P = .208) while it increased with atenolol from 15.80 +/- 1.24 microL x min(-1) to 16.99 +/- 1.18 microL x min(-1) (n = 17, P = .399). The comparison of percentage changes in RBF (PE -7.16% +/- 11.49%; atenolol, +15.31% +/- 9.51%) reached statistical significance (P < .05). There was an increase in RBF in 33.3% of subjects receiving PE and in 70.6% of those receiving atenolol. Similar trends were found for retinal conductance. There were no significant changes in the parameters of retinal vascular permeability. Albuminuria decreased to a greater degree with PE, but did not reach significance (PE, 112.1 +/- 39.5 mg/24 h to 88.6 +/- 30.5 mg/24 h; atenolol, 87.3 +/- 51.7 mg/24 h to 82.1 +/- 47.7 mg/24 h). This suggests that ACE inhibition therapy may promote a hemodynamic milieu in the hypertensive diabetic retinal circulation that serves to protect against the progression of diabetic retinopathy, whereas beta-blockade has the opposite effect.


DNA content analysis of insect cell lines by flow cytometry.
The DNA content of insect cell lines (6 lepidoptera, 1 coleoptera and 1 diptera) was determined by flow cytometry. The DNA profiles of the 8 cell lines tested were different. They were characterized by the presence of several peaks (2 to 7) corresponding to different ploidy levels, by differences in the fluorescence intensity of each peak and by the proportion of cells in each peak. Two cell lines (Cf124 and BmN) were constituted of 2 distinct populations of cells. The DNA profiles of the cell lines were stable among the passages and during the length of time culture. This technique was demonstrated to be useful for the detection of mixed cell lines and nucleopolyhedrovirus cell infection, using Autographa californica MNPV. The flow cytometry gives interesting results on the cell cycle and the ploidy level; it appears as a good tool for insect cell lines characterization.


Utility of thromboelastogram in cardiac surgery in Jacobsen syndrome associated with platelet dysfunction: a case report.
Jacobsen syndrome is a rare genetic disorder with multiple congenital anomalies and platelet abnormalities caused by chromosome 11 deletion. A 7-month-old boy with thrombocytopenia underwent ventricular septal defect closure. At the beginning of surgery, the platelet count was 168 × 103/μL, and heparinized kaolin with heparinase reaction time (HKH-R), which represents clot formation time, was prolonged at 30.4 min. Platelet transfusion was continued, and at the end of surgery, the platelet count and HKH-R values improved to 215 × 103/μL and 15 min, respectively. As anesthetic management of patients with abnormal platelet function, the viscoelasticity test might be useful in evaluating hemostatic capacity.


Isoelectric focusing of tryptic peptides from hemoglobin subunits by immobilized pH gradients.
The technique of isoelectric focusing on immobilized pH gradients (IPG) has been applied to the analysis of tryptic digests of alpha- and beta-chains of human hemoglobin. Using peptides purified by RP-HPLC as a reference, it was possible to create a peptide map in the single IEF dimension. Unfortunately, it was not possible to find experimental conditions (medium for migration and staining) which would allow the detection of peptides of less than 10-12 residues. Almost all the bands visible on the gel could be assigned to known peptides. In order to obtain these results the IPG runs were performed in 8 M urea containing 0.5% carrier ampholytes and the gel stained with colloidal Coomassie brilliant blue G-250, in the presence of a high-salt concentration and at acidic pH.


Bone Marrow Mesenchymal Stem Cell Therapy and Related Bone Marrow-Derived Orthobiologic Therapeutics.
The purpose of the current article is to review the available literature related to bone marrow-derived mesenchymal stem cell therapy in the management of musculoskeletal pathologies and demonstrate the critical need for additional well-designed clinical studies. In recent years, there has been a rapid increase in interest regarding the use of bone marrow-derived mesenchymal stem cells in the treatment of musculoskeletal injury and disease. The clinical use of BM-MSCs and other forms of stem cell therapy has far outpaced the basic and translational science evidence required to elucidate the potential efficacy of this orthobiologic treatment approach. Early studies have demonstrated potential clinical benefit of utilizing bone marrow-derived mesenchymal stem cell therapy in the management of knee osteoarthritis, focal chondral lesions, shoulder pathology including rotator cuff tears and glenohumeral arthritis, and degenerative disk disease in the spine. To date, most published studies are small case series often lacking a control group or a standardized method of treatment. Bone marrow-derived mesenchymal stem cell therapy is becoming an increasingly common treatment for musculoskeletal injuries and disease. Although early clinical studies have shown promising outcomes, methodological flaws and lack of standardization among trials have limited the conclusions that can be drawn from the existing literature. A better understanding of the underlying mechanism of action and more carefully designed clinical trials will help reveal the efficacy and utility of BM-MSCs as a treatment modality for various orthopedic pathologies.


Endocardial Radiofrequency Ablation vs. Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy: A Systematic Review and Meta-Analysis.
Septal myectomy (SM) has been the gold standard therapy for most patients with hypertrophic obstructive cardiomyopathy (HOCM). Endocardial radiofrequency ablation of septal hypertrophy (ERASH) is a novel treatment for septal reduction. We aimed to assess the efficacy and safety between two treatment strategies. We searched PubMed, Web of Science, Cochrane Library, and Embase databases to identify relevant studies published up to March 2021. Random-effect models were used to calculate standardized mean difference (SMD) and 95% confidence intervals (CIs) for resting left ventricular outflow tract gradient (LVOTG) and septal thickness. Twenty-five studies are included in this review, eighteen studies for SM and seven studies for ERASH. During follow-up, there were significant reductions of the mean resting LVOTG in adults (SM groups: SMD = -3.03, 95% CI [-3.62 to -2.44]; ERASH groups: SMD = -1.95, 95% CI [-2.45 to -1.45]) and children (SM groups: SMD = -2.67, 95% CI [-3.21 to -2.12]; ERASH groups: SMD= -2.37, 95% CI [-3.02 to -1.73]) after the septal reduction therapies. For adults, SM groups contributed to more obvious reduction than ERASH groups in interventricular septal thickness (SM groups: SMD = -1.82, 95% CI [-2.29 to -1.34]; ERASH groups: SMD = -0.43, 95% CI [-1.00 to 0.13]). The improvement of the New York Heart Association class was similar in the two groups (SM groups: 46.4%; ERASH groups: 46.7%). The periprocedural mortality in SM and ERASH were 1.1 and 1.8%, respectively. This systematic review suggests that SM is superior to ERASH in the treatment of HOCM. But for the patients who are at risk for open cardiac surgeries or prefer a less invasive approach, ERASH might be an optional approach.


Nonaqueous capillary electrophoresis in coated capillaries: an interesting alternative for proteomic applications.
This work brings together some contributions for the use of nonaqueous media for proteomic analysis, for both capillary electrophoresis (CE) separation and the preparation of tryptic digests. First, a ternary nonaqueous buffer consisting of 60/30/10 v/v methanol/acetonitrile/acetic acid with 12.5 mmol/L ammonium acetate was optimized for CE separation of the tryptic digest of lysozyme. Lysozyme was chosen as a model system for the protein digestion, which has also been prepared in an organic-rich medium with methanol/50 mmol/L NH(4)HCO(3), pH 8.0 (60/40 v/v). The separation results were compared to in silico (PeptideCutter program) digestion conditions, and high-efficiency peak separation (18 peaks) was obtained in 20 min with an electric field of 350 V/cm. In addition, we have evaluated the stability of a coated capillary with poly-N,N-dimethylacrylamide (60/30 cm total/effective length and 75 microm ID) for over 100 runs of tryptic digest with the nonaqueous background electrolyte solvent system. The migration times for ten selected peptide peaks presented 3-7% relative standard deviation.


The IT connection. An integrated health care system gets wired.
At the heart of PeaceHealth's IT infrastructure is the Community Health Record--a comprehensive medical record that links all patients served by any component of the integrated network to all PeaceHealth clinicians and staff. So far, satisfaction scores are soaring.


Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector.
This study evaluates the efficiency of herpes simplex virus (HSV) mediated gene transfer in human squamous cell carcinoma (SCC) cell lines in vitro and in vivo when delivered by selective intra-arterial perfusion. Human head and neck SCC were exposed to HSV-LacZ and HSV-interleukin-2 (IL-2) and gene transfer and expression assessed by X-gal staining and enzyme-linked immunosorbent assay, respectively. Hamster cheek pouch tumors were perfused with HSV-LacZ or HSV-IL-2, by microcannulating the external carotid artery, and gene transfer determined. A ratio of 5 viral particles per tumor cell achieved gene transfer rates exceeding 50%. Interleukin-2 levels of 287 +/- 17 to 424 +/- 8.4 ng per million cells were achieved at a ratio of 2 viral particles per tumor cell. Selective intra-arterial perfusion of the HSV-IL-2 vector yielded IL-2 levels of 45.8 +/- 17.0 pg per g tumor. HSV amplicon vectors are efficient vehicles for gene transfer in vitro in human head and neck SCC cell lines and in vivo when introduced by selective intra-arterial perfusion.


From classical psychodynamics to evidence synthesis: the motif of repression and a contemporary understanding of a key mediatory mechanism in psychosis.
The stress vulnerability model has proven to be a politically important model for two reasons. It has provided the framework that defines a temporal and dynamic process whereby a person's uniquely determined biopsychosocial vulnerability to schizophrenia symptoms interacts with his or her capacity to manage stress and the amount and type of stress experienced in such a way that the person experiences schizophrenia symptoms. Second, the development of this framework promoted the notion of inherited and acquired vulnerability. Implicit was that vulnerability was individually determined and that there was a role for psychosocial factors in the development/maintenance of schizophrenia symptoms. This proved to be a catalyst for the development of studies implicating psychosocial factors in the etiology of schizophrenia symptoms. Studies derived from cognitive-behavioral theories have proven the most successful in identifying thinking patterns, emotional disturbances, and neurocognitive and defensive vulnerability factors inherent in the development of schizophrenia symptoms. Historically, within the psychoanalytic school there has been debate regarding the role of repressive coping mechanisms in schizophrenia development. Psychoanalytic theories have always appeared incapable of providing etiologic explanations of schizophrenia symptoms, with the possible exception of Melanie Klein, than other more salient psychosocial schools. Mechanisms within the process of repressive coping are consistent with evidence and mechanisms supporting the stress vulnerability models and existing cognitive-behavioral theories regarding development of paranoid delusions. These mechanisms are less consistent with social cognitive explanations of schizophrenia symptoms.


Cloning of a cholesterol-alpha-glucosyltransferase from Helicobacter pylori.
O-Glycans of the human gastric mucosa show antimicrobial activity against the pathogenic bacterium Helicobacter pylori by inhibiting the bacterial cholesterol-alpha-glucosyltransferase (Kawakubo, M., Ito, Y., Okimura, Y., Kobayashi, M., Sakura, K., Kasama, S., Fukuda, M. N., Fukuda, M., Katsuyama, T., and Nakayama, J. (2004) Science 305, 1003-1006). This enzyme catalyzes the first step in the biosynthesis of four unusual glycolipids: cholesteryl-alpha-glucoside, cholesteryl-6'-O-acyl-alpha-glucoside, cholesteryl-6'-O-phosphatidyl-alpha-glucoside, and cholesteryl-6'-O-lysophosphatidyl-alpha-glucoside. Here we report the identification, cloning, and functional characterization of the cholesterol-alpha-glucosyltransferase from H. pylori. The hypothetical protein HP0421 from H. pylori belongs to the glycosyltransferase family 4 and shows similarities to some bacterial diacylglycerol-alpha-glucosyltransferases. Deletion of the HP0421 gene in H. pylori resulted in the loss of cholesteryl-alpha-glucoside and all of its three derivatives. Heterologous expression of HP0421 in the yeast Pichia pastoris led to the biosynthesis of ergosteryl-alpha-glucoside as demonstrated by purification of the lipid and subsequent structural analysis by nuclear magnetic resonance spectroscopy and mass spectrometry. In vitro enzyme assays were performed with cell-free homogenates obtained from cells of H. pylori or from transgenic Escherichia coli, which express HP0421. These assays revealed that the enzyme represents a membrane-bound, UDP-glucose-dependent cholesterol-alpha-glucosyltransferase.


[Development and validation of indicators relating to the quality of prevention and early management of postpartum haemorrhage (COMPAQ-HPST research project)].
To develop and validate a set of quality indicators (QIs) relating to the prevention and early management of postpartum haemorrhage (PPH) in maternity wards. The ultimate aim was to use these QIs for hospital comparison and public diffusion of results. In 2009, COMPAQ-HPST developed a set of five QIs from consensus guidelines with the aid of experts and professional associations, relating to: i) the prevention of PH (three QIs) and ii) the initial management of PPH (two QIs). We also tested a questionnaire about the presence of written protocols in maternity wards. Ninety-seven voluntary maternity wards were included in the study. All five QIs showed wide variations in implementation among hospitals, revealing substantial room for improvement. Results of the questionnaire were variable according to the item considered. We validated five process QIs relating to the prevention and early management of PPH. All these five QIs have been transmitted to HAS for nationwide generalization. They should allow hospitals to implement quality of care improvement in this setting, adapted to their individual and comparative results.


Diseases sometimes associated with psoriasis. I. Candidosis.
Of 5,033 patients who were seen between 1968 and 1975, 407 suffered from psoriasis (Ps) and 245 from candidosis (Cn). Of these, 38 patients (p less than 0.001) had both diseases. In 24 additional families, Ps was found in one member and Cn in another. The relationship of the two diseases is discussed.


Genetically-controlled severity of autoimmune thyroiditis in Obese strains (OS) chickens is expressed at both the humoral and cellular effector mechanism levels.
Two lines of Obese strain (OS) chickens of identical MHC (B) genotype, B5B5, bred over 10 years with different selection parameters, differ in their severity of spontaneous autoimmune thyroiditis. To determine whether alterations in immune responsiveness underly this discrepancy, the two lines were compared for their thyroiditis effector mechanisms. The OS B5B5 chickens, selected for high levels of serum thyroglobulin autoantibody, had correspondingly higher levels of thyroid-specific cytotoxic cells and also antibody dependent cellular cytotoxicity (ADCC) than the equivalent B5B5 line selected solely for the phenotypic trait of hypothyroidism. These results thus emphasize the importance of the non-MHC locus controlling immune responsiveness, in the 3 locus-model for this autoimmune disorder.


A systematic review of the effect of laughter yoga on physical function and psychosocial outcomes in older adults.
Laughter yoga is one of the increasingly used methods among complementary health approaches in the world. The aim of this study was to determine the effectiveness of laughter yoga on physical function and psychosocial outcomes in older adults. In this systematic review, electronic searches were performed in CINAHL, Web of Science, COCHRANE, Scopus, ProQuest databases from May 2010 to May 2020. The screening process was conducted by two authors independently and finally agreed together. The review was reported according to PRISMA guideline. A total of 3210 studies were examined, and seven publications (six quasi experimental and one randomized control trial), in accordance with the inclusion criteria were included in the study and evaluated. The results indicated that significant differences were found in the effectiveness of laughter yoga on physical function (blood pressure, cortisol level, sleep quality) and psychosocial health (life satisfaction, quality of life, loneliness, death anxiety, depression, mood, happiness) in older adults. Laughter yoga is a cost-effective and no adverse effect in older adults. It can be used for health promotion for older adults.


Quantitative distribution of GABA-immunoreactive neurons in cetacean visual cortex is similar to that in land mammals.
Sections of the anterior portion of the visual cortex in the lateral gyrus of the Black Sea porpoise were studied to determine the neuronal architecture and numerical density, and the distribution of neurons immunoreactive to gamma-aminobutyric acid (GABA). Cytoarchitecture and neuronal density are similar to those described in another cetacean, the bottlenose dolphin. GABA-positive neurons are distributed through all layers of the visual cortex but are especially dense in layers II and III, and comprise some 20% of the total neuronal population in this part of the cortex. The distribution of GABA-positive neurons is similar to that found in land mammals.


Offset analgesia: somatotopic endogenous pain modulation in migraine.
The complex mechanisms underlying migraine are not entirely understood. It has been suggested that descending endogenous pain modulation is an important contributing factor, although research is controversial. A frequently used method to quantify the inhibitory pain modulation system is offset analgesia (OA), defined as a disproportionally large decrease in pain perception in response to a small decrease of painful stimulation. The aim of this study is to evaluate the OA response in patients with migraine and healthy controls, measured at the forehead (trigeminal, V1) and forearm (extratrigeminal). Patients with episodic migraine during the headache-free interval (n = 26) and age- and sex-matched headache-free controls (n = 26) were included in this cross-sectional study. All participants underwent an individualized OA paradigm consisting of 3 stimulus offset trials and 3 constant temperature trials examined at both, a trigeminal and an extratrigeminal test site. Items from the quantitative sensory testing protocol were additionally included. In contrast to the extratrigeminal area, a reduced OA response was shown in the trigeminal area in patients with migraine compared with healthy controls (P < 0.01, mean difference: 13.7, 95% confidence interval: 3.8-23.6). Statistically significant differences between the trigeminal area and the extratrigeminal area were neither observed in healthy controls nor in patients with migraine (P > 0.05). Mechanical detection, mechanical pain threshold, warm detection, and heat pain threshold showed no significant differences between groups or test sites (P > 0.05). In summary, patients with episodic migraine in the headache-free interval exhibited somatotopically specific differences in endogenous pain modulation.


Hormonal control of alpha-amylase gene expression in barley. Studies using a cloned CDNA probe.
Starting with an enriched alpha-amylase mRNA preparation, cDNA was synthesized by reverse transcription and was cloned at the Pst I site of plasmid vector pBR322 by the "G-C tailing" procedure. Clones containing alpha-amylase cDNA sequences were identified among the recombinant clones by in vitro translation of hybrid-selected mRNA followed by immunoprecipitation of translation products with antiserum to alpha-amylase. The longest alpha-amylase cDNA clone isolated was 630 base pairs long and was characterized by digestion with restriction enzymes. Using this clone as a labeled nucleic acid hybridization probe, we observed that multiple bands of DNA with alpha-amylase sequences were present in restriction digests of barley embryo DNA. This indicates the presence of a family of barley alpha-amylase or alpha-amylase-like genes. Analysis of RNA blots with the cloned alpha-amylase hybridization probe indicated that alpha-amylase mRNA is synthesized de novo in barley aleurones after addition of gibberellic acid. The gibberellic acid-induced accumulation of alpha-amylase mRNA is blocked by cycloheximide which suggests the requirement of a newly synthesized protein factor for efficient expression of alpha-amylase gene.


Lyon phenomenon in ouabain-treated erythrocytes of Duchenne muscular dystrophy carriers as revealed by cell electrophoresis.
Using the cell-electrophoretic method, 0.1 mM ouabain/l Eagle MEM medium caused a moderate decrease in electrophoretic migration time (EMT) of erythrocytes in 19 out of 23 DMD-affected patients. In 8 out of 10 healthy boys, 0.1 mM ouabain induced an increase in erythrocyte EMT. Under the influence of 0.1 mM ouabain, the erythrocytes clearly showed a bimodal distribution of EMT in 9 out of 13 definite carriers and in 8 out of 17 possible carriers. In DMD patients, and in 10 healthy boys and 10 healthy women, no bimodal distribution of EMT was observed.


Genetics of cell-surface antigens: regional mapping of three components of the human cell-surface antigen complex, AL, on chromosome 11.
Cytogenetic analysis has been performed on a series of deletion mutations on human chromosome 11 of AL hybrid clones in which specific markers have been lost as a result of treatment with mutagenic agents. Such analysis has localized the three previously identified components of the AL cell-surface antigen complex to the indicated regions of chromosome 11: a1 and a3:11p13 leads to 11pter; a2:11q13 leads to 11qter. Using these methodologies human lactic dehydrogenase A localization on the short arm as reported by others has been confirmed. Evidence is presented provisionally assigning this gene to 11p13 leads to 11pter.


Imipramine inhibits adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells.
Imipramine (IM) has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells (MSCs) were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1 μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 (PPARγ2). Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in cells treated with IM at concentrations of 0.01, 0.1 and 1 μmol/L, suggesting that the suppression on PPARγ2 was involved in IM's inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor (AR) and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.


A qualitative exploration of the experiences of doctors, nurses and pharmacists regarding medication management in outpatient setting.
To understand how the medications are managed by the multidisciplinary team and their suggestions for nursing management, and to develop a framework for safe medication management in hospital-based outpatient. More than 80% of hospital-based outpatient visits involve medication prescriptions, indicating the importance of safe medication management there. This was a qualitative study with face-to-face interviews with physicians, nurses and pharmacists from 11 medical outpatient units. Four themes elicited were categorized as follows: unclear professional roles and functions in outpatient medication management; intertwined communications; moving from data to wisdom; and ambiguous culture of safety. The resulting model is a collaboration of physicians, nurses, pharmacists, and patients and families integrated with hospital administrative support and information technology in a culture of safety. Medication management in outpatient is critical but usually overlooked. Nursing leaders should develop a culture of safety and provide more support and training for nurses to provide comprehensive medication management for outpatients. It is important to develop outpatient nurses' role and competence in managing patient medication safety. Nurses in management would benefit from applying the 'framework of efficient and safe medication management for outpatients' to assess and identify weak areas for improvement.


Experimental system of care coordination for the home return of patients with metastatic cancer: a survey of general practitioners.
To promote improved coordination between general practice and hospital, the French clinical trial CREDO ("Concertation de REtour à DOmicile") is testing an innovative experimental consultation for patients with metastatic cancer who are returning home. This consultation involves the patient, the patient's referring GP (GPref) and a GP with specific skills in oncology (GPonc) in a specialized care center. The objective of our study is to explore the satisfaction of GPsref about this consultation, in the phase of interaction between GPonc and GPref. This observational, cross-sectional, multicenter study explored the satisfaction of GPsref who had participated in this type of consultation, via a telephone survey. One Hundred GPsref responded to the questionnaire between April and September 2019 (overall response rate: 55%). 84.5% were satisfied with the consultation, and the majority were satisfied with its methods. Half of the GPsref learned new information during the consultation, three-quarters noted an impact on their practice, and 94.4% thought that this type of coordination between the GPref and the oncology specialist could improve general practice - hospital coordination. For GPs, the CREDO consultation seems to be practical and effective in improving the coordination between general medicine and hospital. GPs would benefit from such coordination for all patients with cancer, several times during follow-up and at each occurrence of a medically significant event.


Chryseobacterium meningosepticum infection: antibiotic susceptibility and risk factors for mortality.
A limited range of antibiotic classes are available for treatment of Chryseobacterium meningosepticum infections. Although the role of C. meningosepticum in newborn infections and immunocompromised hosts has been recognized, clinical data detailing these infections remain limited. This retrospective study investigated the risk factors for mortality in patients with C. meningosepticum infections and the antibiotic susceptibility of clinical isolates. Information on demographic characteristics, clinical parameters, antibiotic treatment, and outcomes was collected. Statistical significance of potential prognostic parameters was analyzed by Fisher's exact test. The antimicrobial susceptibility of 19 isolates to seven antibiotics was determined, and susceptibility results were presented as minimal inhibitory concentration (MIC) range, MIC at which 50% of isolates were inhibited (MIC(50)), and MIC at which 90% of isolates were inhibited (MIC(90)). Hypoalbuminemia (<2.5 g/dL) [p=0.02] and increased pulse rate (p=0.008) at the onset of infection, and presence of an indwelling central venous line (p=0.04) were associated with poor outcomes. Use of appropriate antibiotics was not significantly associated with the clinical outcome (p=0.21). MIC values of levofloxacin (MIC(50)/(90), 0.12/2 microg/mL) were lower than those of ciprofloxacin (0.5/4 microg/mL). Hypoalbuminemia, increased pulse rate at the onset of infection and presence of central venous line infection were associated with a poor outcome in patients with C. meningosepticum.


Postoperative astigmatism after central vs eccentric penetrating keratoplasties.
Six patients with markedly eccentric penetrating keratoplasties had severe corneal astigmatism (mean, 10.38 +/- 2.91 diopters). In four of these patients the flat meridian was lying in the direction of graft displacement. Laboratory experiments disclosed no statistically significant difference in diameter between the major and minor axes of the corneal buttons in the centrally and eccentrically trephined eyes and we could not elucidate the mechanism of the severe astigmatism. However, in the eccentrically trephined eyes the longer axis consistently lay in the direction of decentration whereas in the centrally trephined eyes the long axis was oriented randomly.


Contents of tannins of cultivars of sorghum cultivated in Brazil, as determined by four quantification methods.
High tannin content in sorghum grains is an undesirable characteristic for poultry and pig feeding and represents a challenge for breeding programs. On the other hand, moderate content of tannins in sorghum may be beneficial in human diets because they exert anti-cancer, anti-inflammatory and reduced carbohydrate uptake effects, among others. The aim of this study was to compare tannin contents of twenty sorghum cultivars available in Brazil, as well as to compare results obtained with four methods of tannin quantification: butanol/HCl, vanillin/HCl, BSA/FeCl3 and PVPP/Folin-Ciocalteu. The results obtained with butanol/HCl and vanillin/HCl were higher than with BSA/FeCl3 and PVPP/Folin-Ciocalteu. A known amount of purified quebracho tannin was used to test the validation of methods of tannin quantification and vanillin/HCl stood out for its high accuracy degree. The sampling used reveals wide genetic diversity regarding tannin contents. The expectation of predicting tannin contents on basis of grain color seems unfeasible.


The concentration of lysozyme and secretory IgA in tears from healthy persons with and without contact lens use.
A comparison of tear lysozyme and tear secretory IgA, determined by micropipette sampling and immunoassay technique, between 18 long-term contact lens wearers (median age 35 years, median lysozyme concentration 1.93 g/l, median IgA concentration 0.72 g/l) and 42 non-contact lens wearers (median age 41 years, median lysozyme concentration 2.21 g/l, median IgA concentration 2.42 g/l) disclosed a significant decrease (P less than 0.01) of secretory IgA in the contact lens group. The decrease of secretory IgA was associated (P less than 0.01) with the presence of deposits on lens surface. No differences in lysozyme concentration was found between the two groups (P greater than 0.05). The duration of lens wear was 8.5 years in average ranging from 1 to 23 years. These findings of decreased secretory IgA might partly explain the fact that contact lens wearers are more exposed to infectious corneal and conjunctival complications than non-contact lens wearers.


DSM diagnosis and beyond: on the need for a hermeneutically-informed biopsychosocial framework.
While often dubbed "the bible of contemporary psychiatry" and widely hailed as providing "a benchmark" for the profession, on closer inspection the DSM is seen to be shot through with philosophical assumptions that restrict its theoretical cogency and limit it clinical efficacy. Hence, in the interests of enhanced patient-care it is important to think critically about the DSM, with a view to maximising its diagnostic strengths while minimising its weaknesses. The critical analysis undertaken in the present paper underscores the importance of not construing the DSM as a self-contained diagnostic tool but of viewing it, rather, as an indispensable component in a more comprehensive, multidimensional diagnostic process. More specifically, the contention is that the DSM's diagnostic limitations evoke a biopsychosocial framework of application as their necessary corrective, notwithstanding the entrenched tendency to construe these approaches as oppositional. Further, it is contended that a hermeneutically informed biopsychosocial template has particular advantages as an integrating framework.


Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS.
Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI). Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA. ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly. Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8. ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.


[Application of synovium-derived mesenchymal stem cells in tissue engineering].
To review the research application and advance of synovium-derived mesenchymal stem cells (SMSCs) in tissue engineering. The recent related literature was reviewed, concerning isolation method, characteristics of SMSCs, and its application in tissue engineering. SMSCs are multipotent cell population with characteristics of easy isolation and high proliferation, which have been applicated in the cartilage, tendon, ligament, and bone tissue engineering. SMSCs is a new member of mesenchymal stem cells family. It appears to be promising seed cells for tissue engineering, but further research is needed.


New and improved tools and methods for enhanced biosynthesis of natural products in microorganisms.
Engineering efficient biosynthesis of natural products in microorganisms requires optimizing gene expression levels to balance metabolite flux distributions and to minimize accumulation of toxic intermediates. Such metabolic optimization is challenged with identifying the right gene targets, and then determining and achieving appropriate gene expression levels. After decades of having a relatively limited set of gene regulation tools available, metabolic engineers are recently enjoying an ever-growing repertoire of more precise and tunable gene expression platforms. Here we review recent applications of natural and designed transcriptional and translational regulatory machinery for engineering biosynthesis of natural products in microorganisms. Customized trans-acting RNAs (sgRNA, asRNA and sRNA), along with appropriate accessory proteins, are allowing for unparalleled tuning of gene expression. Meanwhile metabolite-responsive transcription factors and riboswitches have been implemented in strain screening and evolution, and in dynamic gene regulation. Further refinements and expansions on these platform technologies will circumvent many long-term obstacles in natural products biosynthesis.


Predictive impact of low-frequency pretreatment T790M mutation in patients with EGFR-mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.
Low-frequency epidermal growth factor receptor (EGFR) T790M mutation could be detected by ultrasensitive methods in EGFR tyrosine kinase inhibitor (TKI)-naïve non-small cell lung cancer (NSCLC). However, the impact of pretreatment T790M (preT790M) on the efficacy of EGFR-TKIs and on resistance remains unclear. Two independent cohorts consisting of advanced EGFR-mutated NSCLC patients treated with first-line EGFR-TKIs, a derivation cohort that started treatment between August 2013 and July 2016 (cohort A, n = 44) and a validation cohort between August 2016 and December 2017 (cohort B, n = 22), were examined in this study. Among these, 28 patients underwent re-biopsy at disease progression. DNAs from pretreatment tumor biopsy samples and re-biopsy samples were assessed to detect T790M by the Cobas EGFR Mutation Test v2 (Cobas) and for quantitating T790M by droplet digital polymerase chain reaction (ddPCR). Detection rates of preT790M were 40.9% (18/44) in cohort A and 45.5% (10/22) in cohort B by ddPCR, and none by Cobas. A cutoff value of 0.3% for dividing into high- vs. low-preT790M allele frequency was determined by receiver operating characteristic curve analysis in cohort A. Progression-free survival (PFS) was significantly shorter in the high- preT790M group (n = 12) than in the low-preT790M (n = 6) and negative (n = 26) groups (combined low-preT790M) (median: 6.9 vs. 13.8 months, P = 0.00073). These observations were validated in cohort B [median: 6.2 (n = 5) vs. 15.3 months (n = 17), P = 0.0029]. In 28 paired biopsies, Cobas detected post-progression T790M in 60% (3/5) of the high-preT790M, in 57% (4/7) of the low-preT790M, and in 56% (9/16) of the negative-preT790M groups. EGFR-mutated NSCLC with high preT790M had significantly shorter PFS on EGFR-TKIs. However, preT790M abundance may not necessarily confer post-TKI T790M resistance.


Does monoclonal antibody treatment for COVID-19 impact short and long-term outcomes in a large generalisable population? A retrospective cohort study in the USA.
To explore whether monoclonal antibodies (MAb) administered to high-risk patients with COVID-19 during the first week of illness prevent postacute sequelae of SARS-CoV-2 infection. Retrospective cohort study. USA. A sample of 3809 individuals who received MAbs and a matched one-to-one comparison group from a set of 327 079 eligible patients who did not receive MAb treatment were selected from a deidentified administrative data set from commercial and Medicare Advantage health plan enrollees in the USA, including claims and outpatient laboratory data. Individuals who received MAb were 28% less likely to be hospitalised (HR=0.72, 95% CI 0.58 to 0.89) and 41% less likely to be admitted to the intensive care unit (HR=0.59, 95% CI 0.38 to 0.89) 30 days from SARS-CoV-2 diagnosis compared with individuals who did not receive MAb. A higher proportion of individuals given MAb therapy received care for clinical sequelae in the postacute phase (p=0.018). While MAb therapy was associated with benefits in the acute period, the benefit of therapy did not extend into the postacute period and did not reduce risk for clinical sequelae.


Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory.


Specific expression of human interferon-gamma controls hepatitis B virus replication in vitro in secreting hepatitis B surface antigen hepatocytes.
Interferon-gamma (IFN-γ) has been reported to have antiviral activity against Hepatitis B virus (HBV) and to suppress HBV replication noncytolytically in vivo. Since systemic administration of IFN-γ may cause severe adverse effects, studies of the effects of liver-specific IFN-γ expression from adenoviral vectors in vivo have been investigated. In this study, a novel strategy has been described that drives specific expression of human IFN-γ in HBsAg-secreting hepatocytes. A bicistronic expression vector has been developed, pcDNA3.1-HBV antisense S gene-HCV core protein gene-HCV internal ribosome entry sites (IRES)-IFN-γ (pcDNA-SCIγ), by inserting four DNA fragments into pcDNA3.1. Tight modulation of HCV IRES-dependent translation by the HCV core protein was achieved using an antisense RNA technique with a bicistronic expression vector. HepG2 cells and HepG2.2.15 cells stably expressing HBV were transduced with pcDNA-SCIγ to test the responsiveness of IFN-γ to HBsAg expression. Gene transfer resulted in a low background and a 30-fold induction of IFN-γ expression from pcDNA-SCIγ in a cell-specific fashion. Hepatocyte-specific IFN-γ expression controlled effectively HBV replication in HBsAg-secreting HepG2.2.15 cells without cell toxicity.


Unusual combination of genetic defects in a Sicilian family: beta-thalassaemia, haemoglobin Lepore Boston-Washington and heterocellular hereditary persistence of fetal haemoglobin.
This paper reports a Sicilian family in which beta-thalassaemia, haemoglobin Lepore Boston-Washington and heterotocellular hereditary persistence of fetal haemoglobin (HPFH) were present in various combinations. The most interesting combination was that of Hb Lepore and heterocellular HPFH, which has not been previously reported. This subject was clinically normal, with the haematological picture of Hb Lepore trait and an unusually high level of HbF due to an increased number of circulating F cells.


Nrf2 as a target for cancer chemoprevention.
Chemical insults, whether of endogenous or exogenous origins, play major roles in the etiopathogenesis of many cancers. As such, strategies to blunt their formation and limit their damage to biomolecules are a central aspect of chemoprevention. Cellular defenses against such insults are regulated in part by the transcription factor Nrf2. Nrf2, in turn, regulates gene expression through interactions with the ARE (antioxidant-response-element) found in the promoter regions of many cytoprotective genes. Under basal conditions, Nrf2 is tethered in the cytoplasm to an actin binding protein Keap1. Pharmacological and food-derived agents such as dithiolethiones and isothiocyanates trigger the release of Nrf2 from Keap1, allowing it to translocate into the nucleus and stimulate gene transcription. Studies using nrf2-deficient mice have revealed that Nrf2 regulates basal and inducible expression of multiple categories of genes, including xenobiotic-metabolizing enzymes, antioxidant enzymes, molecular chaperones/stress response proteins, as well as proteasome subunits, that collectively reflect the complex and important role Nrf2 plays in the cellular defense against carcinogens. Nrf2 knockout mice are greatly predisposed to chemical-induced DNA damage and exhibit higher susceptibility towards cancer development in several models of chemical carcinogenesis. Nrf2 also mediates protection against oxidative stress and influences inflammatory processes, both of which contribute to carcinogenesis. Observations that nrf2-deficient mice are refractory to the protective actions of some chemopreventive agents highlight the importance of the Keap1-Nrf2-ARE signaling pathway as a molecular target for prevention.


Reduction of brain stem pathology and transient amelioration of early cognitive symptoms in transgenic mice treated with a monoclonal antibody against α-synuclein oligomers/protofibrils.
Immunotherapy against alpha-synuclein (α-syn) is a promising novel treatment strategy for Parkinson's disease (PD) and related α-synucleinopathies. We have previously shown that systemic treatment with the monoclonal oligomer/protofibril-selective antibody mAb47 targeting cytotoxic α-syn leads to reduced central nervous system levels of such species as well as an indication of reduced late-stage symptoms in aged (Thy-1)-h[A30P] α-syn transgenic mice. Here, we performed an early-onset long-term treatment study with this antibody to evaluate effects on brain pathology and behavioral outcomes in the same mouse model. Compared to the placebo group, the treatment strongly reduced phosphorylated α-syn (pS129 α-syn) pathology in the upper brain stem. Moreover, a preserved recognition memory and risk assessment behavior could be seen in antibody-treated mice at six months of age, even although these effects were no longer significant at eleven months of age. Importantly, no evidence of inflammatory responses or other potential toxic effects was seen with the treatment. Taken together, this study supports the strategy to target α-syn oligomers/protofibrils with monoclonal antibodies to counteract early symptoms and slow down the progression of PD and other α-synucleinopathies.


Early effects of modulating nuclear factor-kappaB activation on traumatic spinal cord injury in rats.
Genes regulated by NF-kappaB play an important role on secondary damage and repair after spinal cord injury (SCI). To assess the early effects of the pharmacological inhibition and overactivation of NF-kappaB, pyrrolidine dithiocarbamate (PDTC) or lipopolysaccharide were given to rats before or after SC contusion. The amount of spared SC tissue was higher (P < 0.05) at 24 h postinjury in rats post-treated with PDTC; both PDTC-treated rats showed no significant trend to decrease polymorphonuclear infiltrate. p65 subunit was present in inflammatory cells, neurons, and astrocytes at the injury site. These data support further investigation on functional effects of NF-kappaB inhibition in acute SCI.


Basic characteristics and safety of donation in related and unrelated haematopoietic progenitor cell donors - first 10 years of prospective donor follow-up of Swiss donors.
Since July 2007 prospective life-long follow-up (FU) for unrelated (URD) and related donors (RD) is mandatory in Switzerland and data on every allogeneic haematopoietic progenitor cell (HPC) donation are collected prospectively. We report the real-world experience of HPC donation during a 10-year study period (01.07.2007-30.06.2017) with basic characteristics and FU data. 1105 donors underwent 1155 HPC donation procedures. Eighty percent of first donations performed by 802 (73%) RDs and 303 (27%) URDs were peripheral blood stem cells (PBSC), 20% bone marrow (BM). Male donors were over-represented as URD (60% male vs 40% female). Main differences between RDs and URDs concerned age and pre-existing health disorders. RDs were significantly older at first donation (median age 48 years) compared to URD (34 years, p < 0.0001) and had more pre-existing health problems: 25% vs 9% in URD (p < 0.0001). No fatal complications occurred, collection related severe adverse events (SAE) after first donation were not significantly different between groups (RD 1.2%, URD 0.99%), incidence rates for neoplastic and autoimmune diseases did not exceed the rates of the general population. RDs are a more heterogeneous and potentially more vulnerable group, but if donor evaluation is performed appropriately, HPC donation is still safe.


Role of Mycobacterium vaccae in the protection induced by first generation Leishmania vaccine against murine model of leishmaniasis.
Various Leishmania antigens showed to induce protection when used with IL-12 as an adjuvant in an animal model of leishmaniasis. Limitations in using IL-12 justify searching for an appropriate adjuvant to accelerate induction of a Th1-type immune response and protection. In this study, the role of Mycobacterium vaccae as an adjuvant mixed with either autoclaved Leishmania major (ALM) or freeze-thawed-killed L. major (KLM) in increasing protection in susceptible and resistant mice was studied. Nineteen groups of BALB/c and 19 groups of C57BL/6 mice, ten mice per group, were immunized three times in 45 days interval with different doses of either KLM or ALM alone or mixed with either BCG or different doses of M. vaccae. Immunized groups of mice and PBS-injected control group were challenged with 2 x 10(6) promastigotes of L. major at the base of the tail. The evolution of the lesion was monitored, and the size of the lesion was measured and recorded weekly. Anti-Leishmania total IgG Ab was titrated before and after challenge. The results showed that immunization of either susceptible or resistant mice with KLM or ALM mixed with low dose of M. vaccae increased protection defined by significantly smaller ulcer size in immunized mice compared with the PBS-injected control group.


The treatment of herpetic reinfection with levamisole.
The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls.


Neutrophils in preterm birth: Friend or foe?
Preterm birth is a serious global health problem that affects 5-18% of pregnancies worldwide. In addition to being the major cause of neonatal mortality and morbidity, preterm birth is associated with short term and long term complications in the offspring. Despite this, the causes and pathogenesis of preterm birth remain unclear. Neutrophils are innate immune cells that infiltrate the maternal-fetal interface during normal parturition and their accumulation is dramatically increased during preterm birth, especially in the presence of an infection. Indeed, a defining feature of chorioamnionitis (inflammation of the chorioamnionic fetal membranes) that is associated with more than 40% of preterm births, is neutrophil accumulation. While these cells may play an important role during normal term parturition as well as preterm birth, their functions at the maternal-fetal interface are unclear. This review will provide a broad overview of the relevant studies to enable a better understanding of the roles of neutrophils during normal parturition and preterm birth.


GZD856, a novel potent PDGFRα/β inhibitor, suppresses the growth and migration of lung cancer cells in vitro and in vivo.
Platelet-derived growth factor receptors (PDGFRα/β) play critical roles in the autocrine-stimulated growth and recruitment of cancer-associated fibroblasts (CAFs) of human lung cancer cells. We have identified GZD856 as a new PDGFR inhibitor that potently inhibits PDGFRα/β kinase activity and blocks this signaling pathway in lung cancer cells both in vitro and in vivo. GZD856 strongly suppresses the proliferation of PDGFRα-amplified H1703 (PDGFRβ(-)) human lung cancer cells and demonstrates significant in vivo antitumor efficacy in a xenograft mouse model. Although GZD856 displays only limited in vitro antiproliferative efficiency against PDGFRα(-)/PDGFRβ(+) A549 lung cancer cells, it efficiently inhibits the in vivo growth and metastasis of A549 cancer cells in xenograft and orthotopic models, respectively. The promising in vivo antitumor activity of GZD856 in A549 models may result from its suppression of PDGFR-related microenvironment factors, such as recruitment of CAFs and collagen content in stromal cells. GZD856 may be considered as a promising new candidate for anti-lung cancer drug development.


MiR-29b interacts with IFN-γ and induces DNA hypomethylation in CD4+ T cells of oral lichen planus.
Oral lichen planus (OLP) is an autoimmune inflammatory disease mediated by T cells, in whose pathogenesis CD4+ T helper cells are supposed to play vital roles. MiR-29b has recently been recognized as a crucial regulator in immune response and inflammation. The current research focuses on exploring how miR-29b functions in the immunopathogenesis of OLP. Our findings showed that miR-29b expression in CD4+ T cells was upregulated in OLP, especially in its erosive form. MiR-29b in CD4+ T cells repressed IFN-γ mRNA and IFN-γ secretion, but not T-bet and EOMES; in turn, IFN-γ increased the expression of STAT1 and miR-29b in CD4+ T cells. Moreover, miR-29b in CD4+ T cells suppressed DNMT1 expression and induced global DNA hypomethylation. In conclusion, elevated miR-29b interacts with IFN-γ via a regulatory feedback loop and induces global DNA hypomethylation in CD4+ T cells, which consequently modulates Type 1 T helper immune response, thus contributing to the immune dysregulation of OLP.


On the existence of MH(n) species with M = Al, Ga and n = 4, 5, 6. Computational study of structures, stabilities and bonding.
Based on second-order perturbation theory (MP2) predictions with large 6-311 + + G(3df, 3pd) basis set we have reviewed the possible structures and stabilities of a series of neutral MH(n)(M = Al, Ga; n = 4, 5, 6) species. For AlH4 and AlH5, our results confirm the previous theoretical findings, which indicate the dihydrogen C(s) complexes (2A') AlH2(H2) and (1A') AlH3(H2), respectively, as the lowest energy isomers. We found, similarly, C(s) (2A') GaH2(H2) and (1A') GaH3(H2) van der Waals complexes as the most stable species of the gallium analogues GaH4 and GaH5. The calculated H2 dissociation energies (D(e)) for AlH2(H2) and AlH3(H2) are of the order 1.8-2.5 kcalmol(-1), whereas this range of values for GaH2(H2) and GaH3(H2) is 1.4-1.8 kcalmol(-1) . Symmetry-adapted perturbation theory (SAPT) was used to analyze the interaction energies of these dihydrogen complexes (for n = 5) to determine why the Ga species show a smaller binding energy than the Al species. The SAPT partitioning of the interaction energy showed significant differences between AlH3(H2) and GaH3(H2), resulting from the much stronger "hydride" character of the aluminum species. The experimental observation of AlH2(H2) and AlH3(H2), and likely GaH3(H2), via low-temperature matrix isolation has been reported recently by Pullumbi et al. and Andrews et al., supporting the theoretical predictions. For n = 6, we found the degenerate C2(2A) and C(s)(2A') MH2(H2)2 "double H2" type van der Waals complexes as the lowest energy species for both M = Al and Ga.


Non Uniqueness of Power-Law Flows.
We apply the technique of convex integration to obtain non-uniqueness and existence results for power-law fluids, in dimension d ≥ 3 . For the power index q below the compactness threshold, i.e. q ∈ ( 1 , 2 d d + 2 ) , we show ill-posedness of Leray-Hopf solutions. For a wider class of indices q ∈ ( 1 , 3 d + 2 d + 2 ) we show ill-posedness of distributional (non-Leray-Hopf) solutions, extending the seminal paper of Buckmaster & Vicol [10]. In this wider class we also construct non-unique solutions for every datum in L 2 .


Fabrication of soy protein isolate/κ-carrageenan hydrogels for release control of hydrophilic compounds: Flax lignans.
A suitable carrier for flax lignans using Soybean protein isolated (SPI) - κ-carrageenan (KC) hydrogels was developed. The effects of KC concentration on the stability of hydrogels were investigated, as well as water holding capacity (WHC), syneresis and morphological changes. A solid-like gel network and viscoelasticity of composite hydrogels were confirmed by rheological behavior test. Scanning electron microscopy (SEM) displayed a dense and uniform structure for hydrogels with the optimum KC concentration (0.6 %). Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) curves suggested lignan might interact with SPI and KC by hydrogen bonding or hydrophobic effects. The release of flax lignans in hydrogels was followed with Fick diffusion in simulated gastric fluids (SGF) and non-Fickian diffusion in simulated intestinal fluids (SIF), respectively. The cumulative release rate of flax lignan in complex gels (46.00 %) was lower than that of pure SPI hydrogels (77.43 %) at the end of digestion. The results indicated that KC protected the protein by hindering the accession of digestive enzymes into the hydrogels, thus resulting in a reduction of gel matrix erosion and lignan release during digestion. These findings shield a light on SPI-KC hydrogels as carriers for water-soluble bioactive compounds in food and pharmaceutical industries.


Modulation of tumor endothelial cell marker 7 expression during endothelial cell capillary morphogenesis.
Angiogenesis, the process of new blood vessel formation from preexisting capillaries, is a multistep process. The principle cell type in this process is endothelial cells which are required to undergo proliferation, migration, differentiation, and coalescence into cord-like structures with a central lumen. However, the molecular and cellular mechanisms that regulate this process require further investigation. In this study, we have used the fibrin/fibrinogen-based three-dimensional culture to enrich for primary cultured mouse aortic endothelial cells, and to induce endothelial cell capillary morphogenesis. We found among all the cell surface markers examined that only TEM7 expression was up-regulated upon endothelial cells capillary morphogenesis. In addition, inhibition of capillary morphogenesis by serum stimulation completely blocked TEM7 expression. In contrast, stimulation of endothelial cell capillary morphogenesis with PMA enhanced TEM7 expression. Furthermore, incubation of endothelial cells with a recombinant extracellular domain of TEM7 blocked capillary morphogenesis in three-dimensional cultures. These results suggest that TEM7 is a novel protein whose cell surface expression is essential during endothelial cell capillary morphogenesis.


Strategies to prevent neurologic deficit based on motor-evoked potentials in type I and II thoracoabdominal aortic aneurysm repair.
Motor-evoked potentials (MEPs) were monitored during thoracoabdominal aortic aneurysm (TAAA) repair to assess spinal cord ischemia and evaluate the subsequent protective strategies to prevent neurologic deficit. Between January 1996 and December 1997, 52 consecutive patients with type I (n = 24) and type II (n = 28) TAAA underwent surgery (mean patient age, 60 years; range, 21-78 years). The surgical protocol included left heart bypass, cerebrospinal fluid drainage, and monitoring transcranial myogenic MEPs. When spinal cord ischemia was detected, distal aortic pressure and mean arterial pressure were increased. By means of sequential crossclamping, MEPs were used to identify critical intercostal or lumbar arteries. Reproducible MEPs could be recorded in all patients, and spinal cord ischemia was detected within 2 minutes. During distal aortic perfusion, 14 patients (27%) showed rapid decrease in the amplitude of MEPs to less than 25% of baseline, indicating spinal cord ischemia, which could be corrected by increasing distal aortic pressure. The mean distal aortic pressure to maintain adequate cord perfusion was 66 mm Hg; however, it varied among individuals between 48 and 110 mm Hg. In 24 patients (46%), MEPs disappeared after segmental clamping and returned after reattachment of intercostal arteries. In 9 patients (17%), MEPs disappeared completely, but no intercostal arteries were found. After aortic endarterectomy, 6 or 8 mm Dacron grafts were anastomosed to intercostal arteries, and MEPs returned after reperfusion. Using this aggressive surgical approach based on MEPs, no early or late paraplegia occurred in this series. Monitoring of MEPs is an effective technique to assess spinal cord ischemia. Operative strategies based on MEPs prevented neurologic deficits in patients treated for type I and II TAAA.


Auditory neuroscience: neuronal sensitivity in humans.
Microelectrode recordings from the human auditory cortex suggest that the tuning of individual neurons can account for sound frequency discrimination thresholds and that this tuning varies in a context-dependent fashion with the type of sound used to measure it.


Validation of a polymerase chain reaction/restriction enzyme analysis method for species identification of thermophilic campylobacters isolated from domestic and wild animals.
To compare and evaluate a polymerase chain reaction/restriction enzyme analysis (PCR/REA) method with standard phenotypic tests for the identification and differentiation of the thermophilic campylobacters Campylobacter jejuni, C. coli, C. lari and C. upsaliensis. One hundred and eighty-two presumptive thermophilic campylobacters from 12 different animal species were tested by a recently published PCR/REA and standard phenotypic tests. By PCR/REA, 95% of the isolates were clearly identified as either one of the four thermophilic Campylobacter species or as not belonging to this group of organisms at all. By standard phenotyping, 174 of the 182 isolates were initially identified as either C. jejuni, C. coli, C. lari or C. upsaliensis. Additional genotypic tests and phenotyping showed that 52 of these identifications were either incorrect or unreliable. Of the C. jejuni isolates, 19% were identified as C. coli by initial phenotyping and 27 sheep isolates phenotyped as C. coli or C. lari were, in fact, arcobacters. The PCR/REA was more reliable than standard phenotyping for the identification of thermophilic campylobacters from different animals. Routinely used phenotypic tests often resulted in unreliable identifications, requiring additional testing. The PCR/REA, however, gave unequivocal results and was considered useful for the routine identification of thermophilic campylobacters from different animals.


Hemophagocytic lymphohistiocytosis associated with hepatocellular carcinoma.
A man in his 60s was admitted because of abdominal pain and fatigue. Contrast enhanced computed tomography (CECT) showed a hypovascular tumor, 7 cm in size, in the left lobe of liver. He had no history of alcohol consumption. HBs antigen and HCV antibody were negative. For definitive diagnosis, biopsy of the hepatic tumor was performed. After the biopsy, the patient suddenly got high fever, and blood tests showed WBC 22,000/L, Hb 8.9 g/dL, Plts 11.6 × 104/L, AST 140 IU/L, ALT 93 IU/L, LDH 635 U/L. He died on the following day despite of supportive therapy. Autopsy revealed that the hepatic tumor was poorly differentiated hepatocellular carcinoma (HCC) and that hemophagocytic macrophages were found in the bone marrow and spleen. Based on the pathological findings of autopsy, he was finally diagnosed with hemophagocytic lymphohistiocytosis (HLH) associated with HCC. HLH is a rare and life-threaded disorder of immune overactivation. Malignancy-associated HLH is well-known; however, it is usually associated with malignant lymphoma. To our knowledge, this is the first reported case of HLH associated with HCC, which was diagnosed by autopsy. Although extremely rare, our case highlights that HLH should be considered as a differential diagnosis of unknown high fever and bicytopenia in patients with solid tumors, including HCC.


Transperineal 125iodine seed implantation in prostatic cancer guided by transrectal ultrasonography.
A new method is described for precise transperineal insertion of radioactive 125iodine seeds in patients with prostatic cancer. The procedure is done under transrectal ultrasonography guidance using a special multichannel puncture attachment and a simple, efficient insertion technique. The advantages of the method are 1) the patients are spared the inconvenience and risk of an operation, 2) improved dose calculations are possible, and 3) seed application is easy and more precise than by the conventional operative free-hand technique.


Effects of a polysaccharide-rich extract derived from Irish-sourced Laminaria digitata on the composition and metabolic activity of the human gut microbiota using an in vitro colonic model.
Brown seaweeds are known to be a rich source of fiber with the presence of several non-digestible polysaccharides including laminarin, fucoidan and alginate. These individual polysaccharides have previously been shown to favorably alter the gut microbiota composition and activity albeit the effect of the collective brown seaweed fiber component on the microbiota remains to be determined. This study investigated the effect of a crude polysaccharide-rich extract obtained from Laminaria digitata (CE) and a depolymerized CE extract (DE) on the gut microbiota composition and metabolism using an in vitro fecal batch culture model though metagenomic compositional analysis using 16S rRNA FLX amplicon pyrosequencing and short-chain fatty acid (SCFA) analysis using GC-FID. Selective culture analysis showed no significant changes in cultured lactobacilli or bifidobacteria between the CE or DE and the cellulose-negative control at any time point measured (0, 5, 10, 24, 36, 48 h). Following metagenomic analysis, the CE and DE significantly altered the relative abundance of several families including Lachnospiraceae and genera including Streptococcus, Ruminococcus and Parabacteroides of human fecal bacterial populations in comparison to cellulose after 24 h. The concentrations of acetic acid, propionic acid, butyric acid and total SCFA were significantly higher for both the CE and DE compared to cellulose after 10, 24, 36 and 48 h fermentation (p < 0.05). Furthermore, the acetate:propionate ratio was significantly reduced (p < 0.05) for both CD and DE following 24, 36 and 48 h fermentation. The microbiota-associated metabolic and compositional changes noted provide initial indication of putative beneficial health benefits of L. digitata in vitro; however, research is needed to clarify if L. digitata-derived fiber can favorably alter the gut microbiota and confer health benefits in vivo.


Heart rate variability during auricular acupressure at the left sympathetic point on healthy volunteers: a pilot study.
This research is a pilot, single-blinded study investigating heart rate variability (HRV) during auricular acupressure at the left sympathetic point (AH7) in healthy volunteers. There were 120 healthy volunteers with hemodynamic indexes (heart rate, blood pressure) within normal ranges, randomly divided into two groups AG and SG (in each group having a gender ratio 1:1, aged 20-29), to receive either auricular acupressure using ear seed (AG) or sham method using adhesive patches without seed (SG) at the left sympathetic point while lying in a supine position. Acupressure intervention lasted 25 min, and HRV was recorded by a photoplethysmography device-namely, Kyto HRM-2511B and Elite appliance. Auricular acupressure at the left Sympathetic point (AG) led to a significant reduction in heart rate (HR) (p < 0.05) and a considerable increase in HRV parameters demonstrated by HF (High-frequency power) (p < 0.05), compared to sham auricular acupressure (SG). However, no significant changes in LF (Low-frequency power) and RR (Respiratory rate) (p > 0.05) were observed in both groups during the process. These findings suggest that auricular acupressure at the left sympathetic point may activate the parasympathetic nervous system while a healthy person is lying relaxed.


The effects of maternal drug dependence on neonatal mortality.
Addiction in pregnancy has become an important health problem owing to the tendency of drug-dependent women to neglect general health care and to avoid seeking prenatal care. In addition, continued heroin administration during pregnancy carries additional risks for the maternal-fetal unit. Thus, there is an increased incidence of obstetrical and medical complications in these mothers, resulting in high incidences of prematurity, low birth weight and mortality in their infants. Therefore, there is a high neonatal mortality rate due to clinical conditions most commonly seen among premature infants. Data from three groups of drug-dependent women and their infants and one control group demonstrate that the high mortality rate, as well as the incidence of low birth weight, can be reduced to a rate similar to the control group in infants of mothers who receive comprehensive services that include prenatal care in conjunction with methadone maintenance.


Spontaneous rupture of splenic vein in a pregnant woman during a religious ritual.
The treatment of retroperitoneal hemorrhage can be by surgical or a conservative approach but the main problems about these cases are difficulty in diagnosis due to negative results after abdominal lavage and the difficulties in accessing the retroperitoneal area surgically. Retroperitoneal hemorrhage during pregnancy, occurring as a result of spontaneous rupture, is very rare event. Such cases require urgent operation and if not, result in high mortality. A twenty-eight year old pregnant woman was admitted to the hospital dead after collapsing at home during a religious ritual. No systemic or gynecological pathology had been diagnosed. No traumatic injury on her body was found at early postmortem examination. The pathologic findings found at the autopsy are; approximately 2.5 L of coagulated blood in the retroperitoneal region and 10-12 cm of haematoma at the hilum of spleen; dissection revealed a tear of 0.5 cm on lienal vein at a point 3 cm from the hilum. Surgical approach is the most important procedure for diagnosis and therapy of the bleeding. Autopsy may be only diagnostic technique in the case of retroperitoneal hemorrhage death when the death is so rapid that there is no time to intervene surgically.


AdpA, a developmental regulator, promotes ε-poly-L-lysine biosynthesis in Streptomyces albulus.
AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-L-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors in Streptomyces. In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation in Streptomyces albulus NK660 by heterologously expressing adpA from S. neyagawaensis NRRLB-3092 (adpASn). First, we identified a novel AdpA homolog named AdpASa in S. albulus NK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles in S. albulus, and AdpASn was demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield of S. albulus heterologously expressing adpASn was approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpASn in enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF-MS. AdpASn was purified, and its seven direct targets, zwf, tal, pyk2, pta, ack, pepc and a transketolase gene (DC74_2409), were identified, suggesting that AdpASn may cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis in S. albulus. Here, we characterized the positive regulatory roles of Streptomyces AdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpASn promotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of the Streptomyces AdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpASn may be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites in Streptomyces.


Cajal-type cells from human mammary gland stroma: phenotype characteristics in cell culture.
We report here the in vitro isolation of Cajal-like interstitial cells from human inactive mammary-gland stroma. Primary cell cultures examined in phase-contrast microscopy or after vital methylene-blue staining revealed a cell population with characteristic morphological phenotype: fusiform, triangular or polygonal cell body and the corresponding (very) long, slender, moniliform cytoplasmic processes. Giemsa staining pointed out the typical knobbed aspect of cell prolongations. Immunofluorescence (IF) showed, like in situ immunohistochemistry, that Cajal-type cells in vitro (primary cultures), expressed c-kit/CD117 and vimentin. In conclusion, the images presented here reinforce our previous hypothesis that human mammary glands have a distinct population of Cajal-like cells in non-epithelial tissue compartments.


The role of the middle ear and tonsil in the etiology of febrile convulsions.
The middle ear and tonsil are thought to be important sources of infection in children with febrile seizures. However, these patients are rarely examined by an otolaryngologist in the acute phase and we are unaware of any previous studies where otolaryngologists have documented the presence of acute suppurative otitis media (ASOM) and tonsillitis in a series of children with febrile convulsions. We carried out a prospective study on 47 children admitted to two Dublin hospitals with a diagnosis of simple febrile convulsion. All children were examined by an otolaryngology resident within 6 h of admission. Nine children were noted to have ASOM and 18 had acute tonsillitis. The otolaryngology resident's opinion of the condition of the ears and throat often differed from that of the admitting pediatric resident, as documented in the clinical records. We review the recent literature on febrile convulsions and discuss the possible role of the otolaryngologist in the prevention of seizure recurrence.


Impact of Covid-19 on rates of gestational diabetes in a North American pandemic epicenter.
We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada. We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition. Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age. Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population.


Pain management, controlled substances, and state medical board policy: a decade of change.
Physicians' concerns about regulatory scrutiny and the possibility of unwarranted investigation by regulatory agencies negatively affect their prescribing of opioid analgesics to treat pain. Indeed, some state medical boards have rejected prescribing practices that are considered acceptable by today's standards. This article describes a ten-year program of research, education, and policy development implemented by the Pain & Policy Studies Group aimed at updating and clarifying state medical board policies on the use of opioid analgesics to treat pain, including cancer and chronic noncancer pain. Following surveys of medical board members and educational workshops, state medical board policies began an initial period of change, drawing on guidelines from other states, particularly in California. The next phase of policy development was marked by the introduction of Model Guidelines by the Federation of State Medical Boards of the U.S. The Model Guidelines address professional standards for the appropriate prescribing of opioid analgesics for pain management, as well as physicians' fears of regulatory scrutiny. Although most state medical boards have adopted regulations, guidelines, or policy statements relating to controlled substances and pain management, to date ten boards have adopted the Model Guidelines, while ten more have adopted the Model Guidelines in part. Further actions are recommended so that state medical boards can address inadequate pain management and physician concerns about regulatory scrutiny.


DNA nucleotide excision-repair synthesis is independent of perturbations of deoxynucleoside triphosphate pool size.
We have investigated the effects of fluctuations in deoxynucleoside triphosphate (dNTP) pool size on DNA repair and, conversely, the effect of DNA repair on dNTP pool size. In confluent normal human skin fibroblasts, dNTP pool size was quantitated by the formation of [3H]TTP from [3H]thymidine; DNA repair was examined by repair replication in cultures irradiated with UV light. As defined by HPLC analysis, the [3H]TTP pool was formed within 30 min of the addition of [3H]thymidine and remained relatively constant for the next 6 h. Addition of 2-10 mM hydroxyurea (HU) caused a gradual 2-4-fold increase in the [3H]TTP pool as HU inhibited DNA synthesis but not TTP production. No difference was seen between the [3H]TTP pool size in cells exposed to 20 J/m2 and unirradiated controls, although DNA-repair synthesis was readily quantitated in the former. This result was observed even though the repair replication protocol caused an 8-10-fold reduction in the size of the [3H]TTP pool relative to the initial studies. In the UV excision-repair studies the presence of hydroxyurea did not alter the specific activity of [3H] thymidine 5'-monophosphate incorporated into parental DNA due to repair replication. These results suggest that fluctuations in the deoxynucleoside triphosphate pools do not limit the extent of excision-repair synthesis in human cells and demonstrate that DNA nucleotide excision-repair synthesis does not significantly diminish the size of the [3H]TTP pool.


Development of tools for quantitative intracellular metabolomics of Aspergillus niger chemostat cultures.
In view of the high citric acid production capacity of Aspergillus niger, it should be well suited as a cell factory for the production of other relevant acids as succinic, fumaric, itaconic and malic. Quantitative metabolomics is an important omics tool in a synthetic biology approach to develop A. niger for the production of these acids. Such studies require well defined and tightly controlled cultivation conditions and proper rapid sampling, sample processing and analysis methods. In this study we present the development of a chemostat for homogeneous steady state cultivation of A. niger, equipped with a new dedicated rapid sampling device. A quenching method for quantitative metabolomics in A. niger based on cold methanol was evaluated using balances and optimized with the aim of avoiding metabolite leakage during sample processing. The optimization was based on measurements of the intermediates of the glycolysis, TCA and PPP pathways and amino acids, using a balance approach. Leakage was found to be absent at -20 °C for a 40 % (v/v) methanol concentration in water. Under these conditions the average metabolite recovery was close to 100 %. When comparing A. niger and Penicillium chrysogenum metabolomes, under the same cultivation conditions, similar metabolite fingerprints were found in both fungi, except for the intracellular citrate level which is higher for A. niger.


The complete nucleotide sequence of a variant of Coxsackievirus A24, an agent causing acute hemorrhagic conjunctivitis.
The complete nucleotide sequence was determined for the cDNAs that represent the RNA genome of the standard strain of a variant of coxsackievirus A24, the EH24/70, one of the agents causing acute hemorrhagic conjunctivitis. The genome is 7461 nucleotide long and is polyadenylated at the 3'-end terminus. Following a 750-nucleotide 5'-noncoding region, there was a long open reading frame of 6642 nucleotides, which serve to encode a viral polyprotein consisting of 2214 amino acids. Comparison of the deduced amino acid sequence of the polyprotein with those of known enteroviruses allowed us to predict the possible cleavage sites. The overall structure and the organization of the RNA genome is typical for an enterovirus. Based on the similarity of the nucleotide sequence of the 5' and 3' noncoding regions, together with the amino-acid sequence of the encoded proteins, EH24/70 appeared to be closely related to polioviruses and coxsackievirus A21.


Observations on the neuromuscular blocking action of alcuronium in the dog and its reversal by neostigmine.
The action of alcuronium chloride on neuromuscular transmission in the dogs was investigated by electrical and mechanical methods. The mean duration of action was 70 min. Reversal of its action was produced with atropine and neostigmine.


Incidental paranasal sinus imaging abnormalities and the normal Lund score in children.
Our goal was to determine the incidental Lund score for pediatric patients without chronic rhinosinusitis (CRS). Pediatric patients with computed tomography scans of the orbit or brain were identified. Patients with a clinical history of sinonasal disorders or skeletal facial trauma were excluded. The remaining scans were scored according to the Lund-MacKay system. Pneumatization of the frontal and sphenoid sinuses was also recorded. A scaled Lund score was computed, and the mean Lund score for this normal population was determined. One hundred ninety-two computed tomography scans were examined (mean age, 9.0 years). The frontal sinuses and sphenoid sinuses were absent in 40.1% and 1.6% of cases, respectively. The mean scaled Lund score in this pediatric population without CRS was 2.81 (95% confidence interval, 2.40 to 3.22). This result differed statistically from a score of 0 (P < 0.001). Only 37 (19.3%) patients had completely radiographically normal sinuses. The mean incidental Lund score in the absence of CRS approaches 3, and this should be considered when determining the diagnostic likelihood of CRS in pediatric patients.


Concomitant crystallization of two polymorphs-a ring and a helix: concentration effect on supramolecular isomerism.
For the first time in Ag coordination chemistry, two supramolecular isomers, a ring and a helix, are isolated from the same mother liquor as a result of concentration effects.


The effect of a whole-system approach in an antimicrobial stewardship programme at the Singapore General Hospital.
Inappropriate antibiotic use contributes to antimicrobial resistance. Multi-faceted antimicrobial stewardship programmes (ASPs) are recommended for sustainable changes in prescribing practices. A multi-disciplinary ASP was established in October 2008 and piloted in the Departments of General Surgery, Renal Medicine and Endocrinology sequentially. To improve the quality of patient care via optimising the (1) choice, (2) dose, (3) route and (4) duration of antibiotics, a "whole-system" approach incorporating prospective review with immediate concurrent feedback (ICF), prescriber education (public or individualised), de-escalation of therapy, dose optimisation and parenteral-to-oral conversion, while recognising the autonomy of primary prescribers, was adopted. The audited department received a quarterly outcomes report and any common unaccepted practices would be addressed. Outcomes were analysed for 12 months post-ASP implementation. A total of 1,535 antibiotic prescriptions were reviewed. Antimicrobial use in 376 (24.5%) prescriptions was inappropriate. Of 596 interventions made, 70.2% were accepted. A reduction in audited antibiotics consumption resulted in acquisition cost savings of S$198,575 for the hospital. Patients' cost-savings attributable to ASP-initiated interventions were $91,194. The overall all-cause mortality rate and median monthly inpatient-days pre- and post-intervention remained stable. A "whole-system" ASP was effective in optimising antibiotic use in our hospital, without compromising clinical outcomes.


Complementary and Integrative Approaches to Prevention and Treatment of Child and Adolescent Obesity.
Childhood obesity is a significant global challenge with increasing prevalence. It is associated with long-term health risks. Interventions especially early on can be effective in the prevention and reducing the impact on health in children. In children, dysbiosis and inflammation are associated with obesity. Studies demonstrate that intensive lifestyle interventions in form of parent education, motivational interviewing to improve diet and exercise as well as mindfulness, and sleep improvement can help alleviate the risk. The article outlines the current research describing complementary and integrative approaches to the prevention and treatment of obesity in children.


Spatial evolution of global petrochemical risk and the influence by industrialization.
The petrochemical industry is an integral contributor to the global economy and plays a critical role in improving the lives of people worldwide. However, its development has also led to frequent accidents, and the evolution and global impact of these risks have not been adequately assessed. This study is aimed at quantitatively analyzing the current state of petrochemical risk and its impact on industrial development in 58 coastal countries (regions) worldwide by identifying petrochemical risk impact indicators and constructing threshold regression models. We showed that the global petrochemical risk has been unevenly decreasing in recent years. In some countries (regions), the petrochemical risk remains unchanged or is increasing; in particular, coastal provinces of China need to address this issue. Moreover, when industrialization and economic development levels are < 53.6 and 34,918.4 USD/person, respectively, petrochemical accidents negatively affect industrial development; however, above these thresholds, they do not impact industrial development. Coastal areas of China and some developing countries are far below these thresholds. Therefore, the risk from petrochemicals remains a critical factor affecting industrial development in countries with low industrialization levels.


Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes.
Liraglutide (NN2211) is a long-acting GLP-1 analogue, with a pharmacokinetic profile suitable for once-daily administration. This multicentre, double-blind, parallel-group, double-dummy study explored the dose-response relationship of liraglutide effects on bodyweight and glycaemic control in subjects with Type 2 diabetes. Subjects (BMI 27-42 kg/m(2)) with Type 2 diabetes who were previously treated with an OAD (oral anti-diabetic drug) monotherapy (69% with metformin), and had HbA(1c) < or = 10% were enrolled. After a 4-week metformin run-in period, 210 subjects (27-73 years, 60% female) were randomised to receive liraglutide (0.045-0.75 mg) once daily or continued on metformin 1000 mg b.d. for 12 weeks. Mean baseline values for the six treatment groups ranged from 6.8 to 7.5% for HbA(1c), and 8.06-9.44 mmol/l (145-170 mg/dl) for fasting plasma glucose. After 12-week treatment, a weight change of -0.05 to -1.9% was observed for the six treatment groups. Mean HbA(1c) changes from baseline for 0.045, 0.225, 0.45, 0.6, 0.75 mg liraglutide and metformin were +1.28%, +0.86%, +0.22%, +0.16%, +0.30% and +0.09%, respectively. No significant differences in HbA(1c) were observed between liraglutide and metformin groups at the three highest liraglutide dose levels (0.45, 0.6 and 0.75 mg). The lowest two liraglutide doses (0.045 mg and 0.225 mg) were not sufficient to maintain the fasting plasma glucose values achieved by metformin. No major hypoglycaemic episodes were reported. Episodes of nausea and/or vomiting were reported by 11 patients (6.3%) receiving liraglutide and three (8.8%) receiving metformin. Once-daily liraglutide improved glycaemic control and weight, in a comparable degree to metformin. Liraglutide appeared to be safe and generally well tolerated. Higher doses of liraglutide merit study in future clinical trials.


Health-related quality of life measured with the EQ-5D-5L in critical care survivors: A cross-sectional study.
The aim of this study was to investigate health-related quality of life (HRQOL) and related factors in intensive care unit survivors one-12 months after discharge. This cross-sectional survey included survivors who had been admitted to an intensive care unit for ≥48 hours. HRQOL was measured using the EQ-5D-5L profile, which evaluates five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) on five levels (no, slight, moderate, severe, and extreme problems), EQ-VAS (score range 0-100, 100 indicating best health) and EQ values (score range -0.066-1, 1 indicating best health). The factors influencing HRQOL were analyzed by Tobit regression. Survivors treated in an intensive care unit at six institutions in Korea. Only 7.9% of the 534 participants had self-reported profiles of no health problems in all five dimensions. The proportion of participants with slight problems was highest in pain/discomfort with 85.0%. The proportion with severe problems was highest in usual activities with 21.7%, followed by mobility with 21.0%. The median and interquartile range of the EQ-VAS and EQ values were 60.00 (45.00 to 75.00) and 0.72 (0.52 to 0.80), respectively. Negative impact factors on HRQOL included older age, women, residing in a long term care facility, unemployment, emergency intensive care admission, and intensive care stay ≥ 7 days. HRQOL among Korean intensive care survivors is low. The level of problems in physical dimensions is more severe than that in mental health dimensions. Early rehabilitation in the intensive care unit should be provided to facilitate long-term recovery.


Longitudinal changes in MoCA performances in patients with mild cognitive impairment and small vessel disease. Results from the VMCI-Tuscany Study.
The Montreal Cognitive Assessment (MoCA) is a cognitive screening test largely employed in vascular cognitive impairment, but there are no data about MoCA longitudinal changes in patients with cerebral small vessel disease (SVD). We aimed to describe changes in MoCA performance in patients with mild cognitive impairment (MCI) and SVD during a 2-year follow-up, and to evaluate their association with transition to major neurocognitive disorder (NCD). Within the prospective observational VMCI-Tuscany Study, patients with MCI and SVD underwent a comprehensive clinical, neuropsychological, and functional evaluation at baseline, and after 1 and 2 years. Among the 138 patients (mean age 74.4 ± 6.9 years; males: 57%) who completed the study follow-up, 44 (32%) received a major NCD diagnosis. Baseline MoCA scores (mean±SD) were lower in major NCD patients (20.5 ± 5) than in reverter/stable MCI (22.2 ± 4.3), and the difference approached the statistical threshold of significance (p=.051). The total cohort presented a decrease in MoCA score (mean±SD) of -1.3 ± 4.2 points (-2.6 ± 4.7 in major NCD patients, -0.7 ± 3.9 in reverter/stable MCI). A multivariate logistic model on the predictors of transition from MCI to major NCD, showed MoCA approaching the statistical significance (OR=1.09, 95% CI=1.00-1.19, p=.049). In our sample of MCI patients with SVD, longitudinal changes in MoCA performances were consistent with an expected more pronounced deterioration in patients who received a diagnosis of major NCD. MoCA sensitivity to change and predictive utility need to be further explored in VCI studies based on larger samples and longer follow-up periods.


Hydrogeochemical, isotopic and geophysical characterization of saline lake systems in semiarid regions: The Salada de Chiprana Lake, Northeastern Spain.
Most of the athalassic saline and hypersaline lakes are located in arid and semiarid regions where water availability drives the hydrological dynamics of the lake itself and the associated ecosystems. This is the case of the Salada de Chiprana Lake, in the Ebro River basin (Spain). It is the only athalassic permanent hypersaline lake in Western Europe, and where rare and endangered bacterial mats exist. This work presents a robust hydrogeological conceptual model for the lake system. The model evaluates the contribution of groundwater discharge to the whole water budget and explains the hydrological behaviour of the lake system. The lake behaves as a flow-through system rather than a closed basin. About 40% of total water outflow from the lake occurs as groundwater, whereas evaporation accounts for the remaining 60%. The surface water inflows are variable, but the groundwater contribution seems almost constant, amounting to 13% of the average total water inflow and contributing 1.9% of salt income. The high water salinity of the lake is controlled by evaporation, by saline water inflows from irrigation return flows, and the by groundwater outflows. The role of groundwater should be taken into account when drafting the water and land planning, once the conditions for the conservation of the algal mats are defined. A major contribution of this study is the water balance in the Salada de Chiprana Lake, which is consistent with a robust hydrogeological conceptual model defined upon scarce hydrogeological, hydrochemical and isotopic data in the local context as conditioned by the regional behaviour. The water balance is a key tool to help to correctly manage this unique athalassic saline lake, and the approach used here can be extrapolated to other similar ecosystems around the world.


A sensitive test for tactile extinction: results in patients with parietal and frontal lobe disease.
A simple test for detecting tactile extinction is described. In a population of parietal-damaged patients it yielded fewer false negatives than the classical clinical procedure. Contrary to expectations, lesions confined to the right frontal lobe produced no extinction, while those in right-handed, left frontal cases revealed ipsilateral extinction with the new test.