The effects of postexercise consumption of high-molecular-weight versus low-molecular-weight carbohydrate solutions on subsequent high-intensity interval-running capacity.
The aim of this study was to determine the effects of postexercise ingestion of different-molecular-weight glucose polymer solutions on subsequent high-intensity interval-running capacity. In a repeated-measures design, 6 men ran for 60 min in the morning at 70% VO2max. Immediately post- and at 1 and 2 hr postexercise, participants consumed a 15% low-molecular-weight (LMW) or high-molecular-weight (HMW) carbohydrate solution, at a rate of 1.2 g of carbohydrate/kg body mass, or an equivalent volume of flavored water (WAT). After recovery, participants performed repeated 1-min intervals at 90% VO2max interspersed with 1 min active recovery (walking) until volitional exhaustion. Throughout the 3-hr recovery period, plasma glucose concentrations were higher (p=.002) during the HMW and LMW conditions than with WAT (M 7.0±0.8, 7.5±1.0, and 5.6±0.2 mmol/L, respectively), although there was no difference (p=.723) between HMW and LMW conditions. Exercise capacity was 13 (43±10 min; 95% CI for differences: 8-18; p=.001) and 11 min (41±9 min; 95% CI for differences; 2-18: p=.016) longer with HMW and LMW solutions, respectively, than with WAT (30±9 min). There was no substantial difference (2 min; 95% CI for differences: -5 to 10; p=.709) in exercise capacity between LMW and HMW solutions. Although this magnitude of difference is most likely trivial in nature, the uncertainty allows for a possible small substantial enhancement of physiological significance, and further research is required to clarify the true nature of the effect.


Mixed-metal uranium(VI) iodates: hydrothermal syntheses, structures, and reactivity of Rb[UO(2)(CrO(4))(IO(3))(H(2)O)], A(2)[UO(2)(CrO(4))(IO(3))(2)] (A = K, Rb, Cs), and K(2)[UO(2)(MoO(4))(IO(3))(2)].
The reactions of the molecular transition metal iodates A[CrO(3)(IO(3))] (A = K, Rb, Cs) with UO(3) under mild hydrothermal conditions provide access to four new, one-dimensional, uranyl chromatoiodates, Rb[UO(2)(CrO(4))(IO(3))(H(2)O)] (1) and A(2)[UO(2)(CrO(4))(IO(3))(2)] (A = K (2), Rb (3), Cs (4)). Under basic conditions, MoO(3), UO(3), and KIO(4) can be reacted to form K(2)[UO(2)(MoO(4))(IO(3))(2)] (5), which is isostructural with 2 and 3. The structure of 1 consists of one-dimensional[UO(2)(CrO(4))(IO(3))(H(2)O)](-) ribbons that contain uranyl moieties bound by bridging chromate and iodate anions as well as a terminal water molecule to create [UO(7)] pentagonal bipyramidal environments around the U(VI) centers. These ribbons are separated from one another by Rb(+) cations. When the iodate content is increased in the hydrothermal reactions, the terminal water molecule is replaced by a monodentate iodate anion to yield 2-4. These ribbons can be further modified by replacing tetrahedral chromate anions with MoO(4)(2)(-) anions to yield isostructural, one-dimensional [UO(2)(MoO(4))(IO(3))(2)](2)(-) ribbons. Crystallographic data: 1, triclinic, space group P(-)1, a = 7.3133(5) A, b = 8.0561(6) A, c = 8.4870(6) A, alpha = 88.740(1) degrees, beta = 87.075(1) degrees, gamma = 71.672(1) degrees, Z = 2; 2, monoclinic, space group P2(1)/c, a = 11.1337(5) A, b = 7.2884(4) A, c = 15.5661(7) A, beta = 107.977(1) degrees, Z = 4; 3, monoclinic, space group P2(1)/c, a = 11.3463(6) A, b = 7.3263(4) A, c = 15.9332(8) A, beta = 108.173(1) degrees, Z = 4; 4, monoclinic, space group P2(1)/n, a = 7.3929(5) A, b = 8.1346(6) A, c = 22.126(2) A, beta = 90.647(1) degrees, Z = 4; 5, monoclinic, space group P2(1)/c, a = 11.3717(6) A, b = 7.2903(4) A, c = 15.7122(8) A, beta = 108.167(1) degrees, Z = 4.


Clinical expression of Best's vitelliform macular dystrophy in Swedish families with mutations in the bestrophin gene.
To examine the clinical phenotype of three Swedish families with Best's vitelliform macular dystrophy (BMD) and three different mutations in the recently identified bestrophin gene. Three families, including 13 patients, were examined clinically using visual acuity testing, electro-oculography, fundus inspection, and fundus photography. The mutations were previously determined by direct sequence analysis of the individual exons in the bestrophin gene. The largest family (SL76), with the Y85K (T357C) mutation in the bestrophin gene, demonstrated a clinical phenotype characterized by a variable degree of visual acuity reduction and a marked intrafamilial variability in macular pathology. The electro-oculograms, however, demonstrated similar results in all patients regardless of the severity of the macular dysfunction. The smallest family (SL3), with the mutation V9A (T130C) in the bestrophin gene, and the family (SL2) with the mutation D104E (C416A) demonstrated a similar clinical phenotype. The majority of patients (11/13 examined subjects) had a binocular visual acuity of 20/63 or better at a late stage of the disease course, indicating a relatively good prognosis for visual acuity in this specific phenotype. The ophthalmoscopic changes were followed in one of the patients for 38 years and in three of the patients for 19 years and showed that the macular appearance seems to be stable after adolescence. Patients with BMD and mutations in the bestrophin gene have a similar clinical phenotype characterized by a variable, but relatively moderate visual acuity reduction, atrophic changes in the macula, and pathological results of the electro-oculograms. The macular appearance remains essentially unchanged through the atrophic stage (stage IV) in the majority of patients, indicating a stationary disease course associated with this specific genotype.


TRIM Proteins in Host Defense and Viral Pathogenesis.
Tripartite motif (TRIM) proteins are a large group of E3 ubiquitin ligases involved in different cellular functions. Of special interest are their roles in innate immunity, inflammation, and virus replication. We discuss novel roles of TRIM proteins during virus infections that lead to increased pathogenicity. TRIM proteins regulate different antiviral and inflammatory signaling pathways, mostly by promoting ubiquitination of important factors including pattern recognition receptors, adaptor proteins, kinases, and transcription factors that are involved in type I interferon and NF-κB pathways. Therefore, viruses have developed mechanisms to target TRIMs for immune evasion. New evidence is emerging indicating that viruses have the ability to directly use TRIMs and the ubiquitination process to enhance the viral replication cycle and cause increased pathogenesis. A new report on TRIM7 also highlights the potential pro-viral role of TRIMs via ubiquitination of viral proteins and suggests a novel mechanism by which ubiquitination of virus envelope protein may provide determinants of tissue and species tropism. TRIM proteins have important functions in promoting host defense against virus infection; however, viruses have adapted to evade TRIM-mediated immune responses and can hijack TRIMs to ultimately increase virus pathogenesis. Only by understanding specific TRIM-virus interactions and by using more in vivo approaches can we learn how to harness TRIM function to develop therapeutic approaches to reduce virus pathogenesis.


[Surgical treatment of submacular hemorrhage combined with tissue plasminogen activator (a case report)].
Authors present the possibilities of extensive submacular hemorrhage surgery in a patient after serious eye injury with bleeding into the vitreous and underneath the retina. The combination of vitrectomy with tissue plasminogen activator application into the subretinal space allows better to dissolve the coagulated blood and facilitates its removal. This procedure with correct operation technique decreases the damage of the retinal tissue and consequently preserves the photoreceptors' function. In this report, a result of surgical treatment in a 22-year-old man is presented. In the presence of intravitreal bleeding and submacular hemorrhage, during the vitrectomy the tissue plasminogen activator was used, which during few minutes dissolved the already coagulated hemorrhage and facilitated its whole removal from the subretinal space.


Products Released from Structurally Different Dextrans by Bacterial and Fungal Dextranases.
Dextran hydrolysis by dextranases is applied in the sugar industry and the medical sector, but it also has a high potential for use in structural analysis of dextrans. However, dextranases are produced by several organisms and thus differ in their properties. The aim of this study was to comparatively investigate the product patterns obtained from the incubation of linear as well as O3- and O4-branched dextrans with different dextranases. For this purpose, genes encoding for dextranases from Bacteroides thetaiotaomicron and Streptococcus salivarius were cloned and heterologously expressed in Escherichia coli. The two recombinant enzymes as well as two commercial dextranases from Chaetomium sp. and Penicillium sp. were subsequently used to hydrolyze structurally different dextrans. The hydrolysis products were investigated in detail by HPAEC-PAD. For dextranases from Chaetomium sp., Penicillium sp., and Bacteroides thetaiotaomicron, isomaltose was the end product of the hydrolysis from linear dextrans, whereas Penicillium sp. dextranase led to isomaltose and isomaltotetraose. In addition, the latter enzyme also catalyzed a disproportionation reaction when incubated with isomaltotriose. For O3- and O4-branched dextrans, the fungal dextranases yielded significantly different oligosaccharide patterns than the bacterial enzymes. Overall, the product patterns can be adjusted by choosing the correct enzyme as well as a defined enzyme activity.


Measuring the attitudes of dental students towards social accountability following dental education - Qualitative findings.
The term social accountability has gained increased interest in medical education, but is relatively unexplored in dentistry. The aim of this study is to explore dental students' attitudes towards social accountability. A qualitative study utilizing focus groups with University of Otago final year (5th year) Bachelor of Dental Surgery (BDS) students was carried out. A questionnaire designed to measure medical students' attitudes towards social responsibility was used as a guide. Following data collection, framework analysis was used to analyze each of the three focus groups, and repeating themes were noted. Analysis of the focus groups discovered recurring themes, such that participants believed that dentists should be accountable to society in a professional context and that they are responsible for patients who present at their clinic but that there is no professional obligation to help reduce oral health inequalities by working with populations facing inequalities. There was strong agreement that there needs to be change to the dental health care system from a structural and political level to address oral health inequalities, rather than individual dentists assuming greater responsibility. Our findings show that dental education may not be accountable to society in the sense that it is not producing graduates who believe that they have an obligation to address the priority oral health concerns of society.


Two-Point versus Three-Point Fixation in the Management of Zygomaticomaxillary Complex Fractures: A Comparative Study.
The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore, zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements that require a protocol for management and long-term follow-up. The objectives of this study were to compare the efficacy of zygomatic bone after treatment with open reduction internal fixation (ORIF) using two-point fixation and ORIF using three-point fixation and compare the outcome of two procedures. Twenty patients were randomly divided equally into two groups. In Group A, ten patients were treated by ORIF using two-point fixation by miniplates and in Group B, ten patients were treated by ORIF using three-point fixation by miniplates. They were evaluated with their advantages and disadvantages and the difference between the two groups was observed. We found that postoperative facial and neurological complications are minimum in two-point fixation group. Based on this study, open reduction and internal fixation using two-point fixation by miniplates is sufficient and the best available treatment of choice for the management of zygomaticomaxillary complex fractures. Alignment of the fracture at three points and fixation at two stable points provide the most accurate and satisfactory postoperative results. Two-point interosseous fixation at the "buttress" fracture and the frontozygomatic (FZ) fracture is suitable for routine surgery. The results of these studies confirm with the present study that two-point fixation provided better stability in patients with clinical and radiological evidence of fracture in FZ and zygomaticomaxillary buttress area.


Single nucleotide polymorphism and FMR1 CGG repeat instability in two Basque valleys.
Fragile X Syndrome (FXS, MIM 309550) is mainly due to the expansion of a CGG trinucleotide repeat sequence, found in the 5' untranslated region of the FMR1 gene. Some studies suggest that stable markers, such as single nucleotide polymorphisms (SNPs) and the study of populations with genetic identity, could provide a distinct advance to investigate the origin of CGG repeat instability. In this study, seven SNPs (WEX28 rs17312728:G>T, WEX70 rs45631657:C>T, WEX1 rs10521868:A>C, ATL1 rs4949:A>G, FMRb rs25707:A>G, WEX17 rs12010481:C>T and WEX10 ss71651741:C>T) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28-T, WEX70-C, WEX1-C, ATL1-G, and WEX10-C are preferably associated with cis-acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of "susceptible" alleles and (2) association between "susceptible" alleles and STR and SNP haplotypes. These results may indicate that, in Arratia, SNP status does not identify a pool of susceptible alleles, as it does in Markina. In Arratia valley, the SNP haplotype association reveals also a potential new "protective" factor.


[Advances in fecal microbiota transplantation for treatment of Parkinson's disease].
Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.


Anticonvulsants in bipolar disorder.
To review the literature on the effectiveness of anticonvulsant drugs in the management of bipolar disorder. A selective review of the literature. Valproate is an effective drug, alone or in combination, for mania, but has limited benefit in bipolar depression. Although valproate is widely used in maintenance therapy of bipolar disorder, and secondary analyses suggest benefit, in the largest randomised maintenance trial there was only a trend favouring valproate. Lamotrigine has benefit in bipolar depression and maintenance, but not in mania. Carbamazepine is effective in mania. Other anticonvulsant drugs have been tried in mania, but with mixed results. Valproate, lamotrigine and carbamazepine have a valuable place in the management of bipolar disorder.


Attitudes toward COVID-19 vaccination in the nursing profession: validation of the Italian version of the VAX scale and descriptive study.
Nurses' attitudes towards COVID-19 vaccination is a relevant issue, for the protection of the vulnerable people they care for, and the key role they play in promoting health behaviors that encourage trust and adherence to vaccination among population. This study aimed to validate the Italian version of the Vaccination Attitudes Examination (VAX) scale and to describe nurses' attitudes towards COVID-19 vaccination. A cross-sectional study was carried out from May to June 2021. Descriptive statistics, Explorative and Confirmatory Factor Analyses have been performed. An online survey was carried out in Italy. The VAX scale referring to the COVID-19 vaccine was used. 430 nurses participated in the study, mainly female (73.2%). Mean age was 40.2 years. VAX scale revealed an optimal reliability; Exploratory Factor Analysis and Confirmatory Analysis supported a 4-factors model. VAX scale mean scores showed low mistrust about vaccine's benefit (2.03±1.07), concerns about commercial profiteering (2.33±1.39) and preference for natural immunity (2.90±1.37). More worries concerning unexpected future effects were found (4.46±1.36). Gender, taking care of a frail person in family, having children or working in a COVID-19 setting are no significantly related to vaccination attitude. Participants from northern Italy expressed greater confidence in vaccine's benefits, the younger had significant lower scores about commercial profiteering. The Italian version of the VAX scale resulted a reliable tool to assess the nurses' attitudes towards COVID-19 vaccination. An overall positive nurses' attitude towards the COVID-19 vaccination was highlighted. The concern about unforeseen future effects suggested the need to increase the information on this issue. The results provided a valid and reliable tool to measure vaccination attitudes in the Italian context. This study could strengthen the health policies with educational interventions of healthcare workers through specific vaccination pathways. The healthcare professionals' vaccination attitudes play the key role also in promoting vaccination uptake in the population.


5-Item Modified Frailty Index Predicts Outcomes After Below-Knee Amputation in the Vascular Quality Initiative Amputation Registry.
Patient frailty indices are increasingly being utilized to anticipate post-operative complications. This study explores whether a 5-factor modified frailty index (mFI-5) is associated with outcomes following below-knee amputation (BKA). All BKAs in the vascular quality initiative (VQI) amputation registry from 2012-2017 were reviewed. Preoperative frailty status was determined with the mFI-5 which assigns one point each for history of diabetes, chronic obstructive pulmonary disease or active pneumonia, congestive heart failure, hypertension, and nonindependent functional status. Outcomes included 30-day mortality, unplanned return to odds ratio (OR), post-op myocardial infarction (MI), post-op SSI, all-cause complication, revision to higher level amputation, disposition status, and prosthetic use. 2040 BKAs were performed. Logistic regression showed an increasing mFI-5 score that was associated with higher risk of combined complications (OR 1.22, confidence interval [CI] 1.07-1.38, P < .05), 30-day mortality (OR 1.60, CI 1.19-2.16, P < .05), post-op MI (OR 1.79, CI 1.30-2.45, P < .05), and failure of long-term prosthetic use (OR 1.17, CI 1.03-1.32, P < .05). In the VQI, every one-point increase in mFI-5 is associated with an increased risk of 22% for combined complications, 60% for 30-day mortality, nearly 80% for post-op MI, and 17% for failure of prosthetic use in BKA patients. The mFI-5 frailty index should be incorporated into preoperative planning and risk stratification.


A Preliminary Study Comparing Pre-service and In-service School Principals' Self-Perception of Distributed Leadership Competencies in Relation to Teaching and Managerial Experience.
So far little are the studies that have focussed on exploring school principals' self-conception of their distributed leadership competencies in relation to their managerial and teaching experience. To do so, an exploratory research was carried out with a sample of 163 pre-service and in-service school principals studying a Master's programme in School Management, Innovation and Leadership at a Spanish University. Data were obtained by using an Ad hoc questionnaire of 7 units of competence and 5 proficiency levels for each unit, based on an existing rubric to analyse students' self-conception of their development of leadership competencies. The findings of this preliminary study show statistically significant differences in the self-perception in all dimensions associated to Managerial Experience (ME) and Teaching Experience (TE) in schools. Study participants with ME showed statistically higher levels than those who had non-ME in four of seven dimensions: lead the school organisation, address the needs of the students, manage the organisation of the school organisation, and manage administrative work. Similar results were obtained in relation to TE versus non-TE were statistically significant differences are found in six dimensions: manage pedagogical and didactic resources, attend to the needs of students, manage didactic strategies, manage the organisation of the school organisation, manage the link between the school organisation and the community, and lead the school organisation. This study shows the importance of teaching and professional experience to acquire leadership competencies in education, therefore the school principal should also be a teacher. This preliminary study provides insights into the relevance of providing pre-service or in-service school principals with training and professional development programmes on sustainability distributed leadership that enable them to genuinely engage the school community, develop innovative pedagogies and lead the process of change toward building more sustainable schools.


Dual motor response to l-dopa and nociceptin/orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxical inhibition is relieved by D(2)/D(3) receptor blockade.
Motor activity of mice acutely treated with the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was monitored for 6 days using behavioral tests which provide complementary information on motor function: the bar, reaction time, drag, stair climbing, grip, rotarod and footprinting tests. These tests consistently disclosed a prolonged motor impairment characterized by akinesia, bradykinesia, speed reduction, loss of coordination and gait patterns. This impairment was associated with approximately 60% loss of striatal dopamine terminals, as revealed by tyrosine hydroxylase immunohistochemistry, and was attenuated by dopaminergic drugs. Indeed, the dopamine precursor, l-dopa (1-10 mg/kg), and the D(3)/D(2) receptor agonist pramipexole (0.0001-0.001 mg/kg) promoted stepping activity in the drag test (a test for akinesia/bradykinesia). The novel nociceptin/orphanin FQ receptor (NOP) antagonist 1-[1-(cyclooctylmethyl)-1,2,3,6-tetrahydro-5-(hydroxymethyl)-4-pyridinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (Trap-101, 0.001-0.1 mg/kg), an analogue of 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397), also promoted stepping and synergistically or additively (depending on test) attenuated parkinsonism when combined to dopamine agonists. High doses of l-dopa (100 mg/kg), pramipexole (0.1 mg/kg), Trap-101 and J-113397 (1 mg/kg), however, failed to modulate stepping, worsening immobility time and/or rotarod performance. Low doses of amisulpride (0.1 mg/kg) reversed motor inhibition induced by l-dopa and J-113397, suggesting involvement of D(2)/D(3) receptors. This study brings further evidence for a dopamine-dependent motor phenotype in MPTP-treated mice reinforcing the view that this model can be predictive of symptomatic antiparkinsonian activity provided the appropriate test is used. Moreover, it offers mechanistic interpretation to clinical reports of paradoxical worsening of parkinsonism following l-dopa. Finally, it confirms that NOP receptor antagonists may be proven effective in reversing parkinsonism when administered alone or in combination with dopamine agonists.


A new variant in the human Kv1.3 gene is associated with low insulin sensitivity and impaired glucose tolerance.
The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed in a variety of tissues including liver and skeletal muscle. In animal models, knockout of Kv1.3 has been found to improve insulin sensitivity and glucose tolerance. We examined whether mutations in the Kv1.3 gene exist in humans and whether they are associated with alterations of glucose homeostasis. We conducted a genotype-phenotype association study at a university hospital. In 50 nondiabetic subjects, we screened approximately 4.5 kb of chromosome 1 comprising the single exon, the promoter/5'-untranslated region, and the 3'-untranslated region of the human Kv1.3 gene for mutations by direct sequencing. Subsequently, all identified single-nucleotide polymorphisms were analyzed in 552 nondiabetic subjects who underwent an oral glucose tolerance test (OGTT). Of these, 304 had undergone an additional hyperinsulinemic euglycemic clamp. We assessed postprandial blood glucose during OGTT and insulin sensitivity measured by hyperinsulinemic euglycemic clamp. We identified five single-nucleotide polymorphisms in the promoter region (T-548C, G-697T, A-845G, T-1645C, and G-2069A) with allelic frequencies of the minor allele of 26, 23, 9, 41, and 16%, respectively. The -1645C allele was associated with higher plasma glucose concentrations in the 2-h OGTT (P = 0.03) even after adjustment for sex, age, and body mass index (P = 0.002). In addition, it was associated with lower insulin sensitivity (P = 0.01, adjusted for sex, age, and body mass index). Functional in vitro analysis using EMSA showed differential transcription factor binding to the T-1645C polymorphism. We show that a variant in the promoter of the Kv1.3 gene is associated with impaired glucose tolerance and lower insulin sensitivity. Therefore, the Kv1.3 channel represents a candidate gene for type 2 diabetes.


Computational observers and visualization methods for stereoscopic medical imaging.
As stereoscopic display devices become common, their image quality assessment evaluation becomes increasingly important. Most studies conducted on 3D displays are based on psychophysics experiments with humans rating their experience based on detection tasks. The physical measurements do not map to effects on signal detection performance. Additionally, human observer study results are often subjective and difficult to generalize. We designed a computational stereoscopic observer approach inspired by the mechanisms of stereopsis in human vision for task-based image assessment that makes binary decisions based on a set of image pairs. The stereo-observer is constrained to a left and a right image generated using a visualization operator to render voxel datasets. We analyze white noise and lumpy backgrounds using volume rendering techniques. Our simulation framework generalizes many different types of model observers including existing 2D and 3D observers as well as providing flexibility to formulate a stereo model observer approach following the principles of stereoscopic viewing. This methodology has the potential to replace human observer studies when exploring issues with stereo display devices to be used in medical imaging. We show results quantifying the changes in performance when varying stereo angle as measured by an ideal linear stereoscopic observer. Our findings indicate that there is an increase in performance of about 13-18% for white noise and 20-46% for lumpy backgrounds, where the stereo angle is varied from 0 to 30. The applicability of this observer extends to stereoscopic displays used for in the areas of medical and entertainment imaging applications.


Oxygen radicals and renal diseases.
Reactive oxygen metabolites (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorous acid) are important mediators of renal damage in acute renal failure and glomerular and tubulointerstitial diseases. The role of these oxygen metabolites in the above entities is discussed, and the effects of antioxidants and scavengers of O2 radicals are considered. The role of oxygen radicals in the regulation of gene transcription is also considered.


Increased perivascular norepinephrine following intracerebroventricular infusion of NGF into adult rats.
In the present study, we used high performance liquid chromatography coupled with electrochemical detection to examine perivascular catecholamines associated with the intradural segment of the internal carotid artery following a 2-week in vivo intracerebroventricular infusion of the neurotrophin nerve growth factor (NGF). Following administration of NGF, a significant increase (87.3%) in perivascular norepinephrine (NE; microgram/g) was observed when compared with vehicle-infused controls, suggesting that increased sympathetic neurotransmitter accompanies the NGF-induced sprouting response by sympathetic perivascular axons previously observed using electron microscopy (13, 15). The biochemical quantification of perivascular NE in the present study taken together with our previous morphological quantification of perivascular sprouts at the ultrastructural level reveal that the increase in NE is not proportional to the increase in the number of axons. Thus, when compared with controls, the relative amount of norepinephrine per axon apparently is reduced following NGF infusion. The apparent decrease in NE per axon following NGF infusion suggests that, during the 2-week infusion period, exogenous NGF did not stimulate the biosynthesis of perivascular NE beyond that necessary to accommodate the newly sprouted axons. These results extend our morphological findings and provide evidence for plasticity of neurotransmitter expression by adult sympathetic perivascular axons in vivo. In addition, we provide evidence that the increased perivascular catecholamine histofluorescence previously observed following NGF infusion results from an increase in the number of perivascular axons associated with the vessel rather than from an increase in the amount of NE within individual axons.


Chronic cocaine use and its association with myocardial steatosis evaluated by 1H magnetic resonance spectroscopy in African Americans.
Cardiac steatosis is a manifestation of ectopic fat deposition and is associated with obesity. The impact of chronic cocaine use on obesity measures and on the relationship between obesity measures and cardiac steatosis is not well-characterized. The objectives of this study were to compare obesity measures in chronic cocaine users and nonusers, and to explore which factors, in addition to obesity measures, are associated with myocardial triglyceride in African Americans, using noninvasive magnetic resonance spectroscopy. Between June 2004 and January 2014, 180 healthy African American adults without HIV infection, hypertension, and diabetes were enrolled in an observational proton magnetic resonance spectroscopy and imaging study investigating factors associated with cardiac steatosis. Among these 180 participants, 80 were chronic cocaine users and 100 were nonusers. The median age was 42 (interquartile range, 34-47) years. Obesity measures trended higher in cocaine users than in nonusers. The median myocardial triglyceride was 0.6% (interquartile range, 0.4%-1.1%). Among the factors investigated, years of cocaine use, leptin, and visceral fat were independently associated with myocardial triglyceride. Body mass index and visceral fat, which were significantly associated with myocardial triglyceride in noncocaine users, were not associated with myocardial triglyceride content in cocaine users. This study shows (1) cocaine users may have more fat than nonusers and (2) myocardial triglyceride is independently associated with duration of cocaine use, leptin, and visceral fat in all subjects, whereas leptin and high-density lipoprotein cholesterol, but not visceral fat or body mass index, in cocaine users, suggesting that chronic cocaine use may modify the relationships between obesity measures and myocardial triglyceride.


The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial.
Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/- physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (-13.1% and -5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (-5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724).


[Dehabituation in drug-addicts and chronic pain].
In a sample of patients under treatment for dependence disorder, the fear-avoidance model of pain was used as a theoretical framework to investigate differences between patients who developed chronic pain after the abstinence period and those who did not. In line with the model, a set of variables involved in the chronification process were considered: anxiety sensitivity, experiential avoidance, fear of pain, coping styles, anxiety, depression, and quality of life. Differences in clinical and dependence-related variables were analyzed: diagnosis of dual pathology, polyconsumption, prescribed medication, and methadone dose. A group of chronic pain patients (n=63) and a pain-free group (n=58) were compared. MANOVA and chi2 results indicated that the chronic pain patients had been diagnosed with dual pathology significantly more often than the pain-free group, they presented higher polyconsumption, and had been prescribed higher doses of methadone and more medications. The chronic pain group had poorer quality of life and significantly higher scores in anxiety sensitivity, experiential avoidance, and depression. No significant differences were found in coping strategies, fear of pain and anxiety.


Ser16 prevails over Thr17 phospholamban phosphorylation in the beta-adrenergic regulation of cardiac relaxation.
Phospholamban is a critical regulator of sarcoplasmic reticulum Ca2+-ATPase and myocardial contractility. To determine the extent of cross signaling between Ca2+ and cAMP pathways, we have investigated the beta-adrenergic-induced phosphorylation of Ser16 and Thr17 of phospholamban in perfused rat hearts using antibodies recognizing phospholamban phosphorylated at either position. Isoproterenol caused the dose-dependent phosphorylation of Ser16 and Thr17 with strikingly different half-maximal values (EC50 = 4.5 +/- 1.6 and 28. 2 +/- 1.4 nmol/l, respectively). The phosphorylation of Ser16 induced by isoproterenol, forskolin, or 3-isobutyl-1-methylxanthine correlated to increased cardiac relaxation (r = 0.96), whereas phosphorylation of Thr17 did not. Elevation of extracellular Ca2+ did not induce phosphorylation at Thr17; only in the presence of a submaximal dose of isoproterenol, phosphorylation at Thr17 increased eightfold without additional effects on relaxation rate. Thr17 phosphorylation was partially affected by ryanodine and was completely abolished in the presence of 1 micromol/l verapamil or nifedipine. The data indicate that 1) phosphorylation of phospholamban at Ser16 by cAMP-dependent protein kinase is the main regulator of beta-adrenergic-induced cardiac relaxation definitely preceding Thr17 phosphorylation and 2) the beta-adrenergic-mediated phosphorylation of Thr17 by Ca2+-calmodulin-dependent protein kinase required influx of Ca2+ through the L-type Ca2+ channel.


Transcriptome-Based Identification of a Functional Fasciola hepatica Carboxylesterase B.
Bioinformatics analysis of the complete transcriptome of Fasciola hepatica, identified a total of ten putative carboxylesterase transcripts, including a 3146 bp mRNA transcript coding a 2205 bp open reading frame that translates into a protein of 735 amino acids, resulting in a predicted protein mass of 83.5 kDa and a putative carboxylesterase B enzyme. The gene coding for this enzyme was found in two reported F. hepatica complete genomes stretching 23,230 bp, containing two exons of 1282 and 1864 bp, respectively, as well as a 20,084 bp intron between the exons. The enzymatic activity was experimentally assayed on F. hepatica protein extracts by SDS-PAGE zymograms using synthetic chromogenic substrates, confirming both the theoretical molecular weight and carboxylesterase enzymatic activity. Further bioinformatics predicted that this enzyme is an integral component of the cellular membrane that should be active as a 167 kDa homodimer complex and polyacrylamide gel electrophoresis (PAGE) zymograms experiments confirmed the analysis. Additional bioinformatics analysis showed that DNA sequences that code for this particular enzyme are highly conserved in other parasitic trematodes, although they are labeled hypothetical proteins.


Enzyme-assisted synthesis and structure characterization of glucuronide conjugates of methyltestosterone (17 alpha-methylandrost-4-en-17 beta-ol-3-one) and nandrolone (estr-4-en-17 beta-ol-3-one) metabolites.
A new and useful method based on enzyme-assisted synthesis was developed for producing 3 alpha-O-beta-D-glucuronide conjugates from synthetic phase I metabolites of methyltestosterone and nandrolone. The formed glucuronide conjugates of 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol (I), 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (II), 5 alpha-estran-3 alpha-ol-17-one (III), and 5 beta-estran-3 alpha-ol-17-one (IV) are urinary metabolites, indicating the human misuse of the above-mentioned anabolic androgenic steroids (AAS). The common lack of reference material precludes the use and validation of these biomarkers in human doping control. Liver microsomes from Aroclor 1254-induced rats were used as a highly active source of mammalian UDP-glucuronosyltransferases (UGT, EC 220.127.116.11). After purification by protein precipitation, liquid-liquid extraction (dichloromethane), C-18 solid-phase extraction, and lyophilization, the steroid glucuronide structures were characterized by (1)H and (13)C NMR spectroscopy and tandem mass spectrometry. The enzymatic method was highly stereoselective, producing a single major conjugate from the parent steroids I-IV. The stereochemically pure steroid glucuronide conjugates were recovered in milligram amounts (1.0-2.8 mg, yield 12-29%), which is sufficient for veterinary and human doping control analyses; for pharmaco-, toxico-, and enzyme kinetic studies in the pharmaceutical industry; for clinical laboratories; and for forensic medicine. A new sensitive LC-MS method was developed for controlling the product purity in syntheses, as well as for enzyme kinetic characterization of AAS-metabolizing UGT activities in rat liver toward the aglycones I-IV. In this study, the UGT enzymes responsible for the formation of 3 alpha-O-linked glucuronides from the substrates I, II, III, and IV exhibited the specific enzyme activity values: 25, 124, 48, and 212 nmol/mg microsomal protein in a 2-h incubation, respectively.


Collective Excitations at Filling Factor 5/2: The View from Superspace.
We present a microscopic theory of the neutral collective modes supported by the non-Abelian fractional quantum Hall states at filling factor 5/2. The theory is formulated in terms of the trial states describing the Girvin-MacDonald-Platzman mode and its fermionic counterpart. These modes are superpartners of each other in a concrete sense, which we elucidate.


Identification and prevention of genotyping errors caused by G-quadruplex- and i-motif-like sequences.
Reliable PCR amplification of DNA fragments is the prerequisite for most genetic assays. We investigated the impact of G-quadruplex- or i-motif-like sequences on the reliability of PCR-based genetic analyses. We found the sequence context of a common intronic polymorphism in the MEN1 gene (multiple endocrine neoplasia I) to be the cause of systematic genotyping errors by inducing preferential amplification of one allelic variant [allele dropout (ADO)]. Bioinformatic analyses and pyrosequencing-based allele quantification enabled the identification of the underlying DNA structures. We showed that G-quadruplex- or i-motif-like sequences can reproducibly cause ADO. In these cases, amplification efficiency strongly depends on the PCR enzyme and buffer conditions, the magnesium concentration in particular. In a randomly chosen subset of candidate single-nucleotide polymorphisms (SNPs) defined by properties deduced from 2 originally identified ADO cases, we confirmed preferential PCR amplification in up to 50% of the SNPs. We subsequently identified G-quadruplex and i-motifs harboring a SNP that alters the typical motif as the cause of this phenomenon, and a genomewide search based on the respective motifs predicted 0.5% of all SNPs listed by dbSNP and Online Mendelian Inheritance in Man to be potentially affected. Undetected, the described phenomenon produces systematic errors in genetic analyses that may lead to misdiagnoses in clinical settings. PCR products should be checked for G-quadruplex and i-motifs to avoid the formation of ADO-causing secondary structures. Truly affected assays can then be identified by a simple experimental procedure, which simultaneously provides the solution to the problem.


Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.
What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P < 0.001) reduced total neopterin production from the mixed cell culture, whereas cold water immersion significantly (P < 0.05) attenuated urinary neopterin and total neopterin during the training camp without having any effect on physical performance parameters. Soreness and fatigue showed little variation between the groups, whereas training session performance was significantly (P < 0.05) elevated in the cold water immersion group. The data suggest that acute and repetitive cryotherapy attenuates in vitro T-cell and monocyte activation. This may explain the disparity in in vivo neopterin and total neopterin between cold water immersion and passive recovery following repetitive exposure during a high-intensity physical impact sport that remains independent of physical performance.


Impulsivity moderates the effects of movie alcohol portrayals on adolescents' willingness to drink.
This study examined impulsivity as a moderator of adolescents' reactions to positive versus negative portrayals of drinking in American movie clips. Impulsivity, along with willingness and intentions to drink in the future, were assessed in a pretest session. In the experimental sessions, adolescents viewed a series of clips that showed drinking associated with either positive outcomes (e.g., social facilitation) or negative outcomes (fights, arguments). A third group viewed clips with similar positive or negative outcomes, but no alcohol consumption. All participants then responded to an implicit measure of attentional bias regarding alcohol (a dot probe), followed by explicit alcohol measures (self-reports of willingness and intentions to drink). Hypotheses, based on dual-processing theories, were: (a) high-impulsive adolescents would respond more favorably than low-impulsive adolescents to the positive clips, but not the negative clips; and (b) this difference in reactions to the positive clips would be larger on the willingness than the intention measures. Results supported the hypotheses: Adolescents high in impulsivity reported the highest willingness to drink in the positive-clip condition, but were slightly less willing than others in the negative-clip condition. In addition, results on the dot probe task indicated that RTs to alcohol words were negatively correlated with changes in alcohol willingness, but not intention; that is, the faster their response to the alcohol words, the more their willingness increased. The results highlight the utility of a dual-processing perspective on media influence. (PsycINFO Database Record


An Exploratory Study of the Differences in Attitudes and Motives Regarding COVID-19 Plasma Donation.
Understanding the attitude and motives and differences between voluntary and replacement blood donation is the key to the sustainable availability of this precious resource. This study aimed to assess the attitude and motives for convalescent plasma (CP) donation in the recovered COVID-19 plasma donors and further understand the differences between voluntary and replacement donation. This prospective cross-sectional survey-based study was conducted among500 COVID-19 recovered blood donors who visited for CP donation at a tertiary care super-speciality centre in northern India. Data were collected using a structured questionnaire based on donor attitude, motives, and belief, which was validated by the experts of Psychiatry, Transfusion Medicine, and Epidemiology and was administered by the online medium. The study's findings depicted that voluntary plasma donors were previously regular blood donors (36.8%) compared to replacement plasma donors (26.4%). Almost all voluntary donors (99.5%) showed altruistic reasons to donate plasma and expressed that donating plasma is a good way to save a life, and it was more than for replacement plasma donors (p=0.004). The motives of most voluntary plasma donors were to contribute to society, and they believed that donating plasma is a good way, while it was not the case for most replacement plasma donors (p=0.02). Voluntary donors were more eagerly willing to donate plasma to help COVID sufferers (40.9%) when compared to replacement donors (33.2%) (p=0.037). Most voluntary plasma donors were regular whole blood donors and were keen to contribute to society. Convalescent plasma donation during this time of grief and loss was considered a moral responsibility by voluntary donors. The impact of media was more highly perceived in voluntary plasma donors when compared to replacement donors.


Psychiatrists' compliance with nonpsychiatric consultations: does compliance affect concordance?
Utilizing a systematic methodology (The Consultation-Liaison Outcome Evaluation System), the compliance of nonpsychiatric consultations within a general hospital psychiatric unit staffed by private practitioners was assessed. Thirty-one percent of the patients received such consultations and these patients had a longer length of stay than those without a consultation. Psychiatrists were generally compliant with both medication and diagnostic recommendations; but in only half the discharge summaries was the consultant's primary medical diagnosis fully reflected. The implications of these data are discussed.


Effectiveness of Educational Physical Activity Intervention for Preventive of Musculoskeletal Disorders in Bus Drivers.
Driving is a challenging job. Drivers always face the high risk of musculoskeletal disorders (MSDs). Educational interventions could be effective in preventing and controlling these disorders. The present study aims to assess the effectiveness of an educational physical activity intervention in preventing MSDs among bus drivers in Isfahan, Iran. This quasi-experimental study was conducted on 60 urban bus drivers, who were selected using multistage sampling. They were evaluated at two time points, namely before and three months after the intervention. The intervention was conducted in three 90-minute sessions. The HBM-based educational content was delivered through lectures, PowerPoint presentations, videos, practical demonstrations of corrective exercises, and educational pamphlets. Data were analysed using the SPSS program, version 20, the paired t-test, and the independent t-test. Before the intervention, there was no significant difference between the two groups with respect to the mean scores of the HBM constructs. However, later on, the mean scores of perceived susceptibility, perceived severity, perceived benefits, perceived barriers, self-efficacy, and behaviour increased significantly in the intervention group, compared with those in the control group. (P < 0.001). The results showed that the physical activity as an HBM-based educational intervention had a positive effect on the prevention of MSDs in urban bus drivers.


Comparison of analytic performances of Cellsearch and iFISH approach in detecting circulating tumor cells.
Circulating tumor cells (CTCs) have been widely used to predict the prognosis of breast cancer patients. The aim of the present study was to compare the performances of Cellsearch and immunostaining-fluorescence in situ hybridization (iFISH) in detecting CTCs in breast cancer patients. Forty-five newly diagnosed breast cancer patients and 14 healthy donors were recruited and their CTCs were detected by both Cellsearch and iFISH. Correlation between clinicopathological features and CTCs was investigated. We found that the positive rate of CTC detected by iFISH was significantly higher than by Cellsearch system (91% vs 38%). The CTC count, detected either by iFISH or Cellsearch, was not significantly associated with clinical pictures of patients with breast cancer. Therefore, we concluded that, compared to conventional Cellsearch CTC detection, in situ karyotypic identification performed by iFISH had higher detection rate. Therefore, iFISH may be more clinically useful than Cellsearch system.


Role of solid lipid nanoparticle for the delivery of Lipophilic Drugs and Herbal Medicines in the treatment of pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is an uncommon condition marked by elevated pulmonary artery pressure that leads to right ventricular failure. The majority of drugs are now been approved by FDA for PAH, however, several biopharmaceutical hindrances lead to failure of the therapy. Various novel drug delivery systems are available in the literature from which lipid-based nanoparticles i.e. solid lipid nanoparticle is widely investigated for improving the solubility and bioavailability of drugs. In this paper, the prototype phytoconstituents used in pulmonary arterial hypertension have limited solubility and bioavailability. We highlighted the novel concepts of SLN for lipophilic phytoconstituents with their potential applications. This paper also reviews the present state of the art regarding production techniques for SLN like High-Pressure Homogenization, Micro-emulsion Technique, and Phase Inversion Temperature Method, etc. Furthermore, toxicity aspects and in vivo fate of SLN are also highlighted in this review. In a nutshell, safer delivery of phytoconstituents by SLN added a novel feather to the cap of successful drug delivery technologies.


Development of a deep learning network for Alzheimer's disease classification with evaluation of imaging modality and longitudinal data.
Objective. Neuroimaging uncovers important information about disease in the brain. Yet in Alzheimer's disease (AD), there remains a clear clinical need for reliable tools to extract diagnoses from neuroimages. Significant work has been done to develop deep learning (DL) networks using neuroimaging for AD diagnosis. However, no particular model has emerged as optimal. Due to a lack of direct comparisons and evaluations on independent data, there is no consensus on which modality is best for diagnostic models or whether longitudinal information enhances performance. The purpose of this work was (1) to develop a generalizable DL model to distinguish neuroimaging scans of AD patients from controls and (2) to evaluate the influence of imaging modality and longitudinal data on performance.Approach. We trained a 2-class convolutional neural network (CNN) with and without a cascaded recurrent neural network (RNN). We used datasets of 772 (NAD = 364,Ncontrol= 408) 3D18F-FDG PET scans and 780 (NAD = 280,Ncontrol= 500) T1-weighted volumetric-3D MR images (containing 131 and 144 patients with multiple timepoints) from the Alzheimer's Disease Neuroimaging Initiative, plus an independent set of 104 (NAD = 63,NNC = 41)18F-FDG PET scans (one per patient) for validation.Main Results. ROC analysis showed that PET-trained models outperformed MRI-trained, achieving maximum AUC with the CNN + RNN model of 0.93 ± 0.08, with accuracy 82.5 ± 8.9%. Adding longitudinal information offered significant improvement to performance on18F-FDG PET, but not on T1-MRI. CNN model validation with an independent18F-FDG PET dataset achieved AUC of 0.99. Layer-wise relevance propagation heatmaps added CNN interpretability.Significance. The development of a high-performing tool for AD diagnosis, with the direct evaluation of key influences, reveals the advantage of using18F-FDG PET and longitudinal data over MRI and single timepoint analysis. This has significant implications for the potential of neuroimaging for future research on AD diagnosis and clinical management of suspected AD patients.


Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion.
Neurotrophins play a crucial role in the development of the peripheral nervous system and their mRNAs are often regulated after several types of tissue injury. This study has investigated the regulation of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) mRNAs 30 min after myocardial ischaemia followed by reperfusion, by northern blotting, and in situ hybridization in a rat model. Between 2 and 120 h of reperfusion, Ngf mRNA levels showed two- to four-fold up-regulation compared with sham-operated hearts. Scattered Ngf-expressing cells, probably pericytes, were detected in the viable border zone of the myocardium in close association with capillaries, venules, and arterioles. In addition, diffuse Ngf expression was seen in the infarct area after 120 h of reperfusion. Bdnf mRNA showed transient up-regulation after 2 and 5 h of reperfusion and remained at control levels thereafter. Bdnf was expressed in the myocytes of the viable border zone. Nt-3 expression showed no significant changes compared with sham-operated hearts. These results suggest a role for NGF and/or BDNF in the pathogenesis of reperfusion injury or in the alterations of cardiac sensory and sympathetic neuronal function after myocardial ischaemia and reperfusion.


Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987.
The admissions to Vancouver General Hospital from its Surgical Day Care Centre were reviewed for the period 1977 to 1987. The overall mean rate of admission for the period was 0.28 per cent, for surgically-related admissions 0.22 per cent and for anaesthesia-related admissions 0.07 per cent. The principal reasons for surgery-related admissions were postoperative bleeding, complications, the need for further surgery, the requirement for prolonged postoperative care, and pain. Urology had a particularly high percentage of admissions compared with its workload, because of the diagnostic nature of much of the work. Anaesthesia-related admissions included "syncope," lack of an accompanying adult, aspiration pneumonitis and coincident acute disease. Twelve of the 14 patients admitted with syncope had surgery in the afternoon and had received less than ideal amounts of intravenous fluid. Seven of the 12 ASA physical status II patients admitted had an admission diagnosis related to the coincident disease.


Engaging perioperative students in online learning: Human factors.
The aim of this article is to reflect on how a specific approach to teaching and learning - role-play and in particular the 'radio play' format - can overcome some of the alienation and barriers to student engagement that the necessity for online teaching can engender. The example used is a post-registration module in perioperative nursing delivered in a London University. Authors reflect on experiences of developing and implementing an activity designed to increase student engagement in an online session focussing on human factors in the perioperative setting. The aim of the session was to highlight the factors that potentially lead to clinical error in a way that engaged students and enabled them to relate learning to their own experiences. The challenge was how best to do this in an online setting. This article describes the use of an approach devised by AdvanceHE. Two student participants contribute their reflections to this article and focus on the extent to which the session facilitated a new understanding of the impact of human factors in a perioperative setting. These reflections suggest that the approach to the teaching employed was useful to participants and that it has promise as an online approach. The authors recommend evaluation of this approach.


High-Performance Giant Dielectric Properties of Cr3+/Ta5+ Co-Doped TiO2 Ceramics.
The effects of the sintering temperature on microstructures, electrical properties, and dielectric response of 1%Cr3+/Ta5+ co-doped TiO2 (CrTTO) ceramics prepared using a solid-state reaction method were studied. The mean grain size increased with an increasing sintering temperature range of 1300-1500 °C. The dielectric permittivity of CrTTO ceramics sintered at 1300 °C was very low (ε' ∼198). Interestingly, a low loss tangent (tanδ ∼0.03-0.06) and high ε' (∼1.61-1.9 × 104) with a temperature coefficient less than ≤ ±15% in a temperature range of -60 to 150 °C were obtained. The results demonstrated a higher performance property of the acceptor Cr3+/donor Ta5+ co-doped TiO2 ceramics compared to the Ta5+-doped TiO2 and Cr3+-doped TiO2 ceramics. According to a first-principles study, high-performance giant dielectric properties (HPDPs) did not originate from electron-pinned defect dipoles. By impedance spectroscopy (IS), it was suggested that the giant dielectric response was induced by interfacial polarization at the internal interfaces rather than by the formation of complex defect dipoles. X-ray photoelectron spectroscopy (XPS) results confirmed the existence of Ti3+, resulting in the formation of semiconducting parts in the bulk ceramics. Low tanδ and excellent temperature stability were due to the high resistance of the insulating layers with a very high potential barrier of ∼2.0 eV.


Axillary versus rectal temperatures in preterm infants under radiant warmers.
Twenty-five preterm neonates were studied to determine whether monitoring of body temperature may be accomplished by taking axillary instead of rectal temperatures. Both axillary and rectal temperatures were taken simultaneously 12 times over a two-day period. Temperatures were recorded at three, five, eight, and ten minutes. The researchers concluded that an axillary measurement of temperature may be adequately substituted for rectal measurement of temperature.


[The impact of surgical treatment on the life quality of patients with locally advanced hypopharyngeal carcinoma].
Objective: To explore the impact of surgical treatment on the life quality of patients with locally advanced hypopharyngeal carcinoma. Methods: A retrospective analysis of the clinical data of 21 patients with advanced hypopharyngeal carcinoma who underwent surgery at the Shenzhen Hospital of Chinese Academy of Medical Sciences Cancer Hospital from January 1, 2017 to December 31, 2019 was conducted. There were 3 patients with recurrence after radiotherapy and chemotherapy, 4 cases of postoperative recurrence, 3 cases of postoperative recurrence after radiotherapy and chemotherapy. Three cases were hypopharyngeal carcinoma with esophageal carcinoma and 8 cases were stage Ⅳ hypopharyngeal carcinoma. Among them, 3 cases were repaired by stomach, 4 cases by free jejunum, 2 case by great saphenous vein for internal carotid artery, 1 case by artificial blood vessel for internal carotid artery, 5 cases by transfer of pectoralis major musculocutaneous flap and 2 cases by transfer of submental island flap. The 21 patients were scored using the European Cancer Research and Treatment Organization's Quality of Life Head and Neck Tumor Special Scale (EORTC QLQ-H&N35) on the 3 months before and after surgery, and the changes in postoperative life quality were compared. Results: The preoperative life quality score of 21 patients was (56.86±7.95) points and life quality score of 3 months after operation was (50.93±7.91) points. The postoperative life quality was significantly improved (P<0.05). The improvement of the postoperative life quality of the patients mainly included the improvements of the head and neck pain, swallowing function, diet, taking analgesics and indwelling nasal feeding tubes. The preoperative scores were (7.58±1.56) points, (8.46±1.63) points, (7.94±0.43) points, (1.76±0.12) points and (1.86±0.28) points, respectively, while the scores of 3 months after operation were (5.02±1.23) points, (6.28±1.58) points, (6.34±0.36) points , (1.12±0.08) points and (1.24±0.18) points, the differences were statistically significant (all P<0.05). Conclusion: The flexible selection of flap repair for locally advanced hypopharyngeal carcinoma is still feasible, and surgery can improve the life quality of patients.


APC/C(Cdh1)-dependent degradation of Cdc20 requires a phosphorylation on CRY-box by Polo-like kinase-1 during somatic cell cycle.
Cdc20 is an activator of the anaphase-promoting complex (APC/C), and APC/C(Cdc20) is essential for metaphase-anaphase transition. To allow progression beyond mitosis, Cdc20 is degraded through KEN-box-dependent APC/C(Cdh1) activity. Mammalian Cdc20 contains the CRY box, a second APC/C(Cdh1)-dependent degron, but the molecular mechanism in degradation process remains undefined. Polo-like kinase-1 (Plk1) is an essential mitotic kinase regulating various targets in kinetochore, centrosome, and midbody for proper mitotic progression. Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase. The phosphorylation on serine-170 by Plk1 was important for ubiquitination and Cdh1-dependent proteolysis. However, this modification by Plk1 on CRY box had no effect on the subcellular localization of Cdc20 and the formation of APC/C-inhibitory checkpoint complexes under spindle assembly checkpoint. This mechanism will be the first finding of inhibitory phosphorylation related to Cdc20 instability.


Clozapine impact on FosB/ΔFosB expression in stress preconditioned rats: response to a novel stressor.
Prolonged treatment with neuroleptics has been shown to induce FosB/ΔFosB expression in several brain regions including the medial prefrontal cortex, dorsomedial and dorsolateral striatum, ventrolateral and dorsolateral septum, nucleus accumbens shell and core, and the hypothalamic paraventricular nucleus (PVN). Some of these regions are known to be also stress responsive. This study was designed to determine whether repeated clozapine (CLZ) administration for 7 consecutive days to Wistar rats may modify FosB/ΔFosB expression in the above-mentioned brain areas induced by acute stress or novel stressor that followed 13-day chronic mild stress preconditioning. Following experimental groups were used: unstressed animals treated with vehicle/ CLZ for 7 days; 7-day vehicle/CLZ-treated animals on the last day exposed to acute stress - forced swimming (FSW); and animals preconditioned with stress for 13 days treated from the 8th day with vehicle/CLZ and on the 14th day exposed to novel stress - FSW. In the unstressed animals CLZ markedly increased FosB/ΔFosB immunoreactivity in the ventrolateral septum and PVN. FSW elevated FosB/ΔFosB expression in the medial prefrontal cortex, striatum, and septum. CLZ markedly potentiated the effect of the FSW on FosB/ΔFosB expression in the PVN, but suppressed it in the dorsomedial striatum. Novel stress with stress preconditioning increased FosB/ΔFosB immunoreactivity in the prefrontal cortex, striatum, ventrolateral septum, and the PVN. In the nucleus accumbens the effect of the novel stressor was potentiated by CLZ. Our data indicate that CLZ may modulate the acute as well as novel stress effects on FosB/ΔFosB expression but its effect differs within the individual brain regions.


Paving the way: training the influentials in population education.
A number of countries in Far East Asia are in the process of launching national population education programs. To get them off the ground and to keep them working needs the support of key personnel in the program. This means that basic training in population education should be given to key personnel to enable them to promote and efficiently run the population education programs. The Sub-Regional Group Training Course in Population Education organized by the Mobile Team of the Unesco Regional Office for Education in Asia and Oceania to be held in Bangkok from 18 August to 5 September is a response to this need. Training will be given to key personnel from Afghanistan, India, Nepal, and Pakistan. The specific objectives of the course are to provide the participants with: 1) opportunities for exchanges of information and experience; exposure to and involvement in developing population education curricula, teaching units and sample instructional materials; 2) an understanding of various strategies for curriculum development and methodologies used for designing and implementing programs; and 3) preparation as teams from each Member State able to contribute to the promotion of population education in school and out of school in their countries. The training course has 5 main thrusts, namely: 1) sharing of experiences and clarification of the concepts of population education; 2) development of population education curriculum; 3) development of teaching units; 4) development of sample alternative instructional materials; and 5) field visit to ongoing population education programs in Thailand. The content will cover: 1) the knowledge base which includes concepts, nature, issues and status of population education; demographic concepts, population and development; and 2) strategies and approaches such as those used in curriculum development and teaching units, methods of teaching, and instructional materials development. The training methodologies will include lecture and panel discussions, film shows, and practicum.


A new multiphasic buffer system for sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins and peptides with molecular masses 100,000-1000, and their detection with picomolar sensitivity.
A novel multiphasic buffer system for high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis of dansylated and nondansylated proteins/peptides in the relative molecular mass (Mr) range of 100,000-1000 is described. The system, based on Jovin's theory of multiphasic zone electrophoresis, allows complete stacking and destacking of proteins/peptides within the above Mr range. The buffer system uses Bicine and sulfate as trailing and leading ion, respectively, and Bistris and Tris as counter ions in the stacking and separating phase, respectively. Through selection of two different counter ions--the characteristic feature of the present ionic system--the stacking limits of a multiphasic buffer system can be further widened, thus making it applicable to gel electrophoresis of a larger spectrum of rapidly migrating species, such as sodium dodecyl sulfate-proteins/peptides and nucleic acids, than has been possible previously. Highly sensitive detection methods for proteins as well as for polypeptides down to approximately Mr 1000 are described. Dansylated proteins/peptides were detected by their fluorescence either directly within the gel or following electroblotting into anion-exchange or polyvinylidene difluoride membranes. The latter procedure resulted in detection sensitivities of approximately 1 ng. Nondansylated proteins/peptides were either detected within the gel by colloidal Coomassie staining or by electroblotting into polyvinylidene difluoride membranes, followed by colloidal gold staining. Prior to both staining procedures the proteins/peptides were pretreated with glutardialdehyde in the presence of borate at near neutral pH values to generate protein/peptide polymers of poor solubility. For a given pH the efficiency of the latter procedure was significantly influenced by the nature of the buffer ion used in the fixation buffer. In contrast to conventional fixation procedures even small polypeptides (Mr 1000) were immobilized and approximately 15 ng and 0.75 ng could be detected after colloidal Coomassie and colloidal gold staining, respectively.


Inhibition of P-glycoprotein-dependent multidrug resistance by an isoquinolinesulfonamide compound H-87 in rat ascites hepatoma AH66 cells.
The effects of an isoquinolinesulfonamide compound, H-87, on naturally acquired multidrug-resistance (MDR) in rat hepatoma AH66 cells were examined. AH66 cells were highly resistant to vinblastine, SN-38, an active camptothecin analog, adriamycin, and etoposide, compared with the sensitive variant AH66F cells. Although H-87 hardly affected the sensitivities to antitumor agents of AH66F cells, this compound completely inhibited the resistance to vinblastine, moderately inhibited the resistance to SN-38 and adriamycin and had little effect on etoposide, mitomycin C, cisplatin, and 5-fluorouracil. H-87 significantly decreased the efflux of vinblastine from the resistant cells and increased the drug accumulation. SN-38 and adriamycin also exhibited a weak but significant increase in vinblastine accumulation in AH66 cells. H-87 inhibited [3H]azidopine-photolabeling to 160 kDa P-glycoprotein in the plasma membrane of AH66 cells, as reported in acquired MDR leukemic cells. Consequently, the MDR-overcoming effect of H-87 seems to be due to its direct inhibition of the binding of antitumor agents on P-glycoprotein in the plasma membrane.


[Changes in the conceptual system of the censuses of population relating to family and household].
The author reviews Hungarian census methods concerning measurement of families and households, and the different definitions the government has used to define these terms since World War II. "The changes in the concepts of the household and family make [it] necessary to analyse how the conceptual systems used in different periods can be adapted to the concepts of our days. Moreover, the study makes an attempt to estimate, if possible, the number and structure of households and families for the years when such data collection (or processing) has not been carried out." (SUMMARY IN ENG AND RUS)


Pharmacokinetic Drug-Drug Interactions Involving Antiretroviral Agents: An Update.
Antiretroviral therapy is the recognized treatment for human immunodeficiency virus (HIV) infection involving several antiviral agents. Even though highly active antiretroviral therapy has been proven to be very effective in suppressing HIV replication, the antiretroviral drugs, belonging to different pharmacological classes, present quite complex pharmacokinetic properties such as extensive drug metabolism and transport by membrane-associated drug carriers. Moreover, due to uncomplications or complications in HIV-infected populations, an antiretroviralbased multiple-drug coadministration therapy strategy is usually applied for treatment effect, thus raising the possibility of drug-drug interactions between antiretroviral drugs and common drugs such as opioids, stains, and hormonal contraceptives. Herein, thirteen classical antiretroviral drugs approved by US Food and Drug Administration were summarized. Besides, relative drug metabolism enzymes and transporters known to interact with those antiretroviral drugs were detailed and described. Furthermore, one after the summarized antiretroviral drugs, the drug-drug interactions between two antiretroviral drugs or antiretroviral drug - conventional medical drugs of the past decade were discussed and summarized. This review is intended to deepen the pharmacological understanding of antiretroviral drugs and promote more secure clinical applications for antiretroviral drugs to treat HIV.


Taste responses of neurons in the hamster solitary nucleus are modulated by the central nucleus of the amygdala.
Previous studies have shown a modulatory influence of forebrain gustatory areas, such as the gustatory cortex and lateral hypothalamus, on the activity of taste-responsive cells in the nucleus of the solitary tract (NST). The central nucleus of the amygdala (CeA), which receives gustatory afferent information, also exerts descending control over taste neurons in the parabrachial nuclei (PbN) of the pons. The present studies were designed to investigate the role of descending amgydaloid projections to the NST in the modulation of gustatory activity. Extracellular action potentials were recorded from 109 taste-responsive cells in the NST of urethan-anesthetized hamsters and analyzed for a change in excitability following electrical and chemical stimulation of the CeA. Electrical stimulation of the CeA orthodromically modulated 36 of 109 (33.0%) taste-responsive NST cells. An excitatory response was observed in 33 (30.28%) cells. An initial decrease in excitability to electrical stimulation of the CeA, suggestive of postsynaptic inhibition, was observed in three (2.75%) NST taste cells. NST cells modulated by the CeA were significantly less responsive to taste stimuli than cells that were not. Many of these cells were under the modulatory influence of the contralateral CeA (28/36 = 77.8%) as well as the ipsilateral (22/36 = 61.1%); 14 (38.9%) were excited bilaterally. Latencies for excitation were longer after ipsilateral than after contralateral CeA stimulation. Microinjection of DL-homocysteic acid (DLH) into the CeA mimicked the effect of electrical stimulation on each of the nine cells tested: DLH excited eight and inhibited one of these electrically activated NST cells. Application of subthreshold electrical stimulation to the CeA during taste trials increased the taste responses of every CeA-responsive NST cell (n = 7) tested with this protocol. These effects would enhance taste discriminability by increasing the signal-to-noise ratio of taste-evoked activity.


Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts.
Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor β. The present study investigated famitinib's activity against human gastric cancer cells in vitro and in vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol -2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacy in vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growth in vivo via inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (>85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancer in vitro and in vivo, which may lay the foundations for future clinical trials.


Multiple Spinal CSF Leaks in Spontaneous Intracranial Hypotension: Do They Exist?
To determine the frequency of multiple spinal CSF leaks in a recent group of patients with spontaneous intracranial hypotension (SIH) who were investigated with digital subtraction myelography (DSM). This observational study was conducted using data from a prospectively maintained data base of patients who meet the International Classification of Headache Disorders, third edition, criteria for SIH. The patient population consisted of a consecutive group of 745 patients with SIH who underwent DSM between March 2009 and February 2020. Based on the results of DSM, participants were classified according to the type and number of spinal CSF leaks. Among 398 patients with SIH and extradural CSF on spinal imaging, multiplicity of CSF leaks was observed in none of 291 patients with type 1a ventral leaks and in 4 (6.2%) of 65 patients with type 1b (postero-) lateral leaks. Among 97 patients with SIH from spinal CSF-venous fistulas (type 3 leaks) who did not have extradural CSF on spinal imaging, 9 patients (9.3%) had multiple fistulas (p < 0.0001 for comparison between groups). Type 3 and type 1a or 1b CSF leaks coexisted in an additional 5 patients. Among patients with SIH, multiplicity of CSF leaks was observed radiographically in none of the patients with ventral leaks, in 6% of patients with lateral leaks, and in 9% of patients with CSF-venous fistulas. These results suggest that patients with SIH can be reassured that the occurrence of multiple CSF leaks is negligible to uncommon at most, depending on the type of CSF leak.


Optimization of Scatter Correction Method in Samarium-153 Single-photon Emission Computed Tomography using Triple-Energy Window: A Monte Carlo Simulation Study.
In single-photon emission computed tomography imaging, the presence of scatter degrades image quality. The goal of this study is to optimize the main- and sub-energy windows for triple-energy window (TEW) method using Monte Carlo SImulating Medical Imaging Nuclear Detectors (SIMIND) code for samarium-153 (Sm-153) imaging. The comparison is based on the Monte Carlo simulation data with the results estimated using TEW method. Siemens Symbia gamma-camera equipped with low-energy high-resolution collimator was simulated for Sm-153 point source located in seven positions in water cylindrical phantom. Three different main-energy window widths (10%, 15%, and 20%) and three different sub-energy window widths (2, 4, and 6 keV) were evaluated. We compared the true scatter fraction determined by SIMIND and scatter fraction estimated using TEW scatter correction method at each position. In order to evaluate the image quality, we used the full width at half maximum (FWHM) computed on the PSF and image contrast using Jaszczak phantom. The scatter fraction using TEW method is similar to the true scatter fraction for 20% of the main-energy window and 6 keV sub-energy windows. For these windows, the results show that the resolution and contrast were improved. TEW method could be a useful scatter correction method to remove the scatter event in the image for Sm-153 imaging.


Lack of tumor uptake of 131-I labeled rituximab in a patient with a CD20 positive lymphoma lesion.
Radioimmunotherapy has emerged as a treatment modality for patients with CD20 positive B-cell non-Hodgkin's lymphoma (NHL). Prior to administration of a therapeutic dose, confirmation of uptake of the radiolabeled compound in tumor locations and calculation of an appropriate dose can be performed using a diagnostic dose and subsequent imaging. We report the case of a 69-year-old male with a relapsed mantle cell lymphoma scheduled for radioimmunotherapy, where diagnostic imaging with 131-I labeled rituximab revealed unexpected new insights with implications for treatment. Persistence of the mantle cell lymphoma in a lymph node in the left arm was demonstrated by an 18-F fluorodeoxyglucose scan. However, a scan after a diagnostic dose of 131-I labeled rituximab did not show any uptake of the tracer, even though subsequent cytological analysis unequivocally confirmed a CD20 positive B-cell population in the lesion. The administration of a therapeutic dose of 131-I labeled rituximab was therefore cancelled. We here discuss the mechanisms that may explain lack of targeting in a proven CD20-positive lymphoma and provide recommendations for further studies.


Homozygous protein C deficiency in two siblings.
Homozygous protein C (PC) deficiency is reported in two siblings (girl and boy) who received their proper diagnoses at the ages of 7 4/12 and 1 3/12 years respectively. The girl had perinatal asphyxia without bleeding. At 1 year of age she developed purpura fulminans. Treatment with heparin and plasma was successful. At 7 4/12 years she developed tender, bluish nonnecrotic skin changes after an orthopedic operation. The PC level was 0.08 U/ml. The boy had had a large intraventricular hemorrhage neonatally and developed severe brain damage. At 1 3/12 years he manifested the same skin changes as his sister and was treated similarly. The PC level was 0.05 U/ml. Both children now receive warfarin continuously and are essentially free of symptoms. The cases represent homozygous phenotypes in a family with a recessive trait of PC deficiency without thrombotic disease. The cases also show that severe PC deficiency may be compatible with life beyond infancy without any specific therapy.


Electronic structure of simple phosphorus containing molecules [C,xH,O,P] candidate for astrobiology (x=1, 3, 5).
The present report is a prospective study aimed at finding phosphorus containing compounds for astrobiology. Since PN, PC and HCP are the only species detected so far, it was deemed reasonable to enlarge the quest for phosphorus compounds to mixed carbon oxygen containing compounds [C,xH,O,P] analogue to the CHON family. Ab initio Møller-Plesset (MP2), Coupled Cluster (CCSD(T)) and Density Functional Theory (DFT) were used. State of the art level of theory, CCSD(T)/cc-pVQZ, was necessary to show that CH3-PH2=O is the most stable isomer, with CH3-PH-OH close by in the [C,5H,O,P] sub-family. This structure has the same C-P-O connectivity as the most stable compound of the [C,3H,O,P] sub-family, CH3-P=O but differs from the simplest [C,H,O,P] system HP=C=O. Rotational constants B=7.1377 and C=6.0636 GHz associated with a dipole moment of 4.2 Debye together with an IR spectrum with very strong bands at 1214, 2282, 2264 and 1039 cm(-1) have been calculated for CH3-PH2=O. For CH3-P=O, one has B=7.9881 and C=6.4659 GHz, a dipole moment of 2.9 Debye and four IR bands at 1198, 623, 835, 1256 cm(-1) of medium intensity. The simplest HPCO system with B=5.5206 and 5.3952 GHz and a dipole moment of 0.8 Debye has only one very strong IR frequency at 2037 cm(-1). The above values should be precise enough to encourage laboratory experiments on these prototype molecules.


Application of Transmission Raman Spectroscopy in Combination with Partial Least-Squares (PLS) for the Fast Quantification of Paracetamol.
In recent years, transmission Raman spectroscopy (TRS) has emerged as a potent new tool for rapid, nondestructive quantitation in pharmaceutical manufacturing. In order to expand the applicability of TRS and enhance its use in product quality monitoring during drug production, we aimed, in the present study, to apply partial least-squares (PLS) approaches to build a model consisting of 150 handmade tablets and covering 15 levels through the use of a multifactor orthogonal design of experiment (DOE), which was used to predict concentrations of validation tablets made by hand. The difference between results according to HPLC and TRS were negligible. The model was used to predict the active pharmaceutical ingredient (API) content in four random commercial paracetamol tablets, and corrected with the spectra of the commercial tablets to obtain four corresponding models. The results show that the content relative error in the model's predictions after correction with commercially available tablets was significantly lower than that before correction. The corrected model was used to make predictions for 20 tablets from the brand Panadol. Compared with the HPLC results, the prediction relative error was basically less than 4.00%, and the relative standard deviation (RSD) of the content was 0.86%.


[Lyre and lancet: doctors as writers].
Many medical doctors have become famous writers or poets. The two professions do have similarities: both have a professional preference for people in a crisis situation, both need to come close to their subject while maintaining a certain distance, the relationship between the individual and the general plays a central role in the practice of medicine and writing, writing and healing are similar in many ways and stories play an important role for both doctors and writers. We discuss these similarities in this article.


Associations of Adherence to the DASH Diet and the Mediterranean Diet With All-Cause Mortality in Subjects With Various Glucose Regulation States.
A dietary pattern concordant with either the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean diet has been associated with a lower risk of all-cause mortality in general population. We investigated the associations of adherence to the DASH diet and the Mediterranean diet with all-cause mortality across three glucose regulation states (normal glucose tolerance, prediabetes, and diabetes) using data from the National Health and Nutrition Examination Survey (NHANES). Data from the NHANES participants from 1999 to 2010, including their vital status linked to the National Death Index through the end of 2011, were analyzed. Adherence to the DASH diet and the Mediterranean diet was assessed using the DASH score and the alternative Mediterranean Diet Index (aMED), respectively. Weighted Cox proportional hazards regression models were used to compare the hazard ratios for the associations of adherence (diet score >median vs. ≤ median) to the DASH diet and the Mediterranean diet with all-cause mortality. A total of 28,905 participants were analyzed, and 2,598 of them had died after a median follow-up of 6.3 years. The median DASH score and aMED were 2 and 3, respectively. Adherence to the Mediterranean diet (aMED >3 vs. ≤ 3), but not the DASH diet, was associated with a lower risk of all-cause mortality (adjusted HR 0.74, 95% CI 0.66-0.83, p < 0.001) in the overall population. The findings were consistent across the three glucose regulation states. A joint effect of aMED >3 and DASH score >2 (adjusted HR 0.71, 95% CI 0.52-0.99, p = 0.042) was noted in participants with diabetes. Adherence to the Mediterranean diet (aMED >median) was associated with reduced all-cause mortality in a general population. For people with diabetes, a dietary pattern concordant with both the DASH diet and the Mediterranean diet (DASH score >median and aMED >median) was associated with a lower risk of mortality.


Quantifying the Counterion-Specific Effect on Surfactant Adsorption Using Modeling, Simulation, and Experiments.
Ionic surfactants behave differently in the presence of various counterions, which plays an important role in many scientific and engineering processes. Previous work has shown that the counterion-specific surface tension can be reproduced with classical adsorption models, but the underlying origin of this effect has not been explained. In this paper, we extend our previously developed adsorption model to account for the specific counterion adsorption. This model can accurately predict the surface tension of surfactant solutions like sodium dodecyl sulfate (SDS) in the presence of the monovalent salts LiCl, NaCl, KCl, and CsCl. The predicted surface excess and surface potential are validated by corresponding sum-frequency generation (SFG) spectroscopy experiments. We also used molecular dynamic (MD) simulation to explain the origin of the counterion-specific effect for surfactant behavior. Our study shows that for SDS, binding of the counterion to both the headgroup and a few CH2 fragments close to the surfactant head contributes to the counterion-specific effect. In general, SDS behaves like a large ion, and it prefers to bind with large counterions such as Cs+, which is consistent with Collins's law of matching water affinity. Therefore, large counterions enhance the surface adsorption and lower the surface tension the most.


Is there an association between variants in candidate insulin pathway genes IGF-I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population?
Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.


Gonadal Steroids and Sperm Quality in a Cohort of Relapsing Remitting Multiple Sclerosis: A Case-Control Study.
Introduction: Evaluation of the hypothalamic-pituitary-testicular axis and sperm analyses are not a standard examination of patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Methods: This is a prospective-case-controlled study. Patients, aged 18-55, with a confirmed diagnosis of RRMS, naïve to any DMT were enrolled. Controls were men with normal evaluation who acceded to the Andrology Center of Catania in a contemporary matched randomized fashion to the group of RRMS patients. The aim of the study is to evaluate gonadal steroids and sperm quality in men at the time of RRMS diagnosis and 12 months following the first disease modifying treatment (DMT). Results: Out of 41 patients with RRMS, 38 were included in the study (age 40.3 ± 12.3) to be compared with matched controls. Patients with RRMS showed no differences in gonadal steroids or sperm parameters, except for free testosterone (fT) plasma levels, which were lower in RRMS patients than controls (median 0.09 vs. 1.4, p < 0.0001). The correlation analyses, corrected for age and Body Mass Index, did not reveal any correlation between hormonal/sperm parameters and level of disability or disease activity at onset. Additionally, 12 months following the start of DMT, there were no differences in gonadal steroids and sperm quality compared to baseline. Conclusions: Results suggest that RRMS may not have an impact on fertility status but prospective long-term studies are needed.


Not All Play Equipment Is Created Equal: Associations Between Equipment at Home and Children's Physical Activity.
Play equipment at home could be targeted in interventions to increase children's physical activity (PA), but evidence is mixed, potentially because current methods do not reflect children's lived experience. This study investigated associations between combinations of equipment and PA. Data were from the Mothers and their Children's Health study and the Australian Longitudinal Study on Women's Health. Mothers (n = 2409) indicated the types of fixed active (eg, trampolines), portable active (eg, bicycles), and electronic (eg, computers) equipment at home, and the number of days children (n = 4092, aged 5-12 y, 51% boys) met PA guidelines. Latent class analysis was used to identify combinations of equipment, and linear regressions were used to investigate associations with PA. Compared with children with high active (fixed and portable) and medium electronic equipment, children with portable active and medium (B = -0.53; 95% confidence interval, -0.72 to -0.34) or high (B = -0.58; 95% confidence interval, -0.83 to -0.33) electronic equipment met the guidelines on fewer days. Children with similar active equipment (but more electronic equipment) met the PA guidelines on fewer days (mean difference = -0.51, SE = 0.14, P = .002). Having the right combination of play equipment at home may be important for children's PA.


The role of carbon dioxide insufflation in colonoscopy: a systematic review and meta-analysis.
Insufflation of the intestinal tract, usually with room air, is necessary to improve visualization during colonoscopy. However, most patients complain of bowel distension and abdominal pain afterwards. Recently, carbon dioxide (CO2) rather than air insufflation has been used. We aimed to evaluate the efficiency, safety, and comfort of colonoscopy CO2 insufflation, with systematic review and meta-analysis of published randomized controlled trials (RCTs). Databases including PubMed, EMBASE, the Cochrane Library, the Science Citation Index, and important meeting abstracts were searched and evaluated by two reviewers independently. Nine RCT studies involving 1577 patients were analyzed. There was significant heterogeneity for some major results; we analyzed these using a random-effects model. Meta-analysis showed fewer patients with abdominal pain in the CO2 group during the procedure (relative risk [RR] 0.77, 95% confidence intervals [CI] 0.62-0.96), and post procedure at 1 hour (0.26, 0.16-0.43), 6 hours (0.36, 0.20-0.64), and 24 hours (0.53, 0.31-0.91). The number needed to treat (NNT) during the procedure was 7; post procedure, the NNT at 1 hour was 2, at 6 hours it was 3, and at 24 hours it was 12. Compared with air, CO2 insufflation was associated with less passage of flatus post procedurally, at 1 hour (RR 0.09, 95%CI 0.03-0.24) and 6 hours (0.30, 0.14-0.62). There were no significant differences between the two groups regarding safety, gas volume, and cecal intubation rate. Insufflation with CO2 in colonoscopy could decrease abdominal discomfort during and following the procedure, without any additional adverse reactions, warranting routine clinical use.


Fabrication and characterization of infrared hollow fiber with multi- SiO(2) and AgI inner-coating layers.
We report the transmission characteristics of infrared hollow fiber with multi- AgI and SiO(2) inner-coating layers in the mid-infrared region. A three-dielectric-layer hollow glass fiber with a SiO(2)-AgI-SiO(2)-Ag structure was fabricated and low-loss property was obtained in the mid-infrared region. The SiO(2) films were coated by use of the liquid-phase coating method and a semi-inorganic polymer was used as the coating material. For deposition of the AgI film between the two SiO(2) films, a silver film was first plated by use of the silver mirror reaction method. Then the iodination process was conducted to turn the silver layer into silver iodide. A calculation method was also developed to estimate the film thickness of dielectric layers in each fabrication step according to the position of loss peaks in the measured loss spectra. Good agreement between calculated and measured loss spectra was demonstrated by taking into consideration material dispersion and surface roughness of inner-coating films.