Three-year follow-up of an outbreak of Serratia marcescens bacteriuria in a neurosurgical intensive care unit.
We report on the investigations and interventions conducted to contain an extended outbreak of Serratia marcescens bacteriuria that lasted for years in a neurosurgical intensive care unit (NSICU). A case-control study was performed to identify the risk factors for S. marcescens acquisition in urine. In case patients, urine sampling for tests and central venous catheterization were performed more frequently before the isolation of S. marcescens. Case patients were more frequently prescribed third-generation cephalosporins. Adherence to hand antisepsis was encouraged through in-service educational meetings and infection control measures, especially concerning the manipulation of indwelling urinary catheters, were intensified. The outbreak persisted despite the reinforcement of infection control measures. However, no patient has newly acquired the organism in the NSICU since December 2004. Multiple factors, including inadequate infection control practices and inappropriate antimicrobial usage, possibly contributed to the persistence of this S. marcescens outbreak. Healthcare workers should consistently follow infection control policies to ensure quality care.


The Regulation and Functions of Endogenous Retrovirus in Embryo Development and Stem Cell Differentiation.
Endogenous retroviruses (ERVs) are repetitive sequences in the genome, belonging to the retrotransposon family. During the course of life, ERVs are associated with multiple aspects of chromatin and transcriptional regulation in development and pathological conditions. In mammalian embryos, ERVs are extensively activated in early embryo development, but with a highly restricted spatial-temporal pattern; and they are drastically silenced during differentiation with exceptions in extraembryonic tissue and germlines. The dynamic activation pattern of ERVs raises questions about how ERVs are regulated in the life cycle and whether they are functionally important to cell fate decision during early embryo and somatic cell development. Therefore, in this review, we focus on the pieces of evidence demonstrating regulations and functions of ERVs during stem cell differentiation, which suggests that ERV activation is not a passive result of cell fate transition but the active epigenetic and transcriptional regulation during mammalian development and stem cell differentiation.


Capillary electrophoresis-tandem mass spectrometry as a highly selective tool for the compositional and site-specific assessment of multiple peptide-deamidation.
Site-specific mapping of multiple deamidations in peptides is a challenging analytical task. In this work, capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) is presented as a high-resolution tool for the detailed characterization of these subtle modifications in peptides. The 4.5-kDa peptide drug TRI-1144, which contains five closely-positioned potential deamidation sites, was selected as model compound. TRI-1144 was exposed to acidic conditions and/or elevated temperatures for 1-14 h. Stressed samples were analyzed using a background electrolyte (BGE) of 150 mM ammonium formate (pH 6.0) in combination with a capillary coated with a bilayer of Polybrene-dextran sulfate. Separation of deamidated and deacetylated TRI-1144 species, including several positional isomers, was greatly enhanced by adding up to 40 vol% of acetonitrile-isopropanol (87.5:12.5, v/v) to the BGE, allowing reliable determination of the number of deamidations/deacetylations per degradation product. Collision-induced dissociation MS/MS was conducted on the separated peptide components in order to reveal the exact position of deamidation on the peptide chain. Obtained fragment ions showed overlapping isotopic distributions in their MS/MS spectra resulting from the comigration of different isomeric deamidated species. Comparison of theoretical and measured isotope distributions for specific y ions of peptide fragments yielded the identity and relative abundance of isomeric deamidated products. The developed CE-MS/MS methodology was used for the highly selective evaluation of TRI-1144 stability under different stress conditions, providing detailed qualitative and semi-quantitative degradation maps of the peptide drug.


Subjects presented at ASHP Midyear Clinical Meetings, 1967-90.
The subject matter and trends of presentations made at ASHP Midyear Clinical Meetings (MCMs) were studied. A computerized database of information from MCM and Annual Meeting (AM) program and abstract books was created. The data were analyzed to determine the distribution of MCM presentations by subject and by author for the period 1967 to 1990, determine if there were differences in subjects covered between MCMs and AMs, explore the proposition that there has been duplication of material in MCM presentations, and evaluate the frequency with which MCM presentations have been published in ASHP journals. The total number of presentations made at MCMs from 1967 through 1990 was 8180, while the total for the AMs was 1547 for the two periods (1962-71 and 1985-90) studied. The most common keywords in titles were "pharmacy," "drug," "patient," "hospital," and "service." All International Pharmaceutical Abstracts subject categories and two other categories were represented; presentations in the institutional pharmacy practice category were the most frequent, while pharmacognosy-related presentations were least frequent. The overwhelming number of authors made only one presentation and were listed as the first author. The subjects of presentations were similar between AMs and MCMs. A tendency toward duplication of material was found. Of the 8180 MCM presentations, at least 1005 were published in an ASHP journal. Between 1967 and 1990, presentations at MCMs covered a wide range of subjects but were sometimes duplicative or not on the cutting edge.


Vagal integrity in vagal-sparing esophagectomy: a cadaveric study.
Esophagectomy is associated with a significant number of complications, some of them related to the concomitant vagotomy. The vagal-sparing esophagectomy is an attractive alternative to the conventional procedure; however, few clinical series have attested the integrity of the vagi nerves after esophagectomy. The surgical anatomy of the vagus in the mediastinum has received little interest as well. The anatomy of the vagus was studied in 30 fresh cadavers. Twenty cadavers were submitted to a vagal-sparing esophagectomy, and after the procedure, anatomical vagal integrity was evaluated. Concerning the anatomy of the vagus, one or more vagal trunks were present in all cases. Four patterns were identified: Type I, two distinct trunks without communicating branches, present in eight (26.7%) cases; Type II, two distinct trunks with communicating branches, present in 17 (56.7%) cases; Type III, one or more bifurcated trunks, present in four (13.3%) cases; and Type IV, crossing trunks, present in one (3.3%) case. Regarding the esophagectomy, operative accidents were not noticed; in five cases, there was incomplete removal of the muscular layer of the esophagus. In all cases vagi nerves were preserved. The vagus is preserved in a cadaveric model of the vagal sparing esophagectomy, irrespective of the anatomy of the vagus in the mediastinum.


Variants in DNA double-strand break repair genes and breast cancer susceptibility.
We performed genetic association studies in a population-based breast cancer case-control study analysing polymorphisms in genes involved in homologous recombination (NBS1, RAD52, RAD51, XRCC2 and XRCC3) and non-homologous end-joining (KU70/80 and LIG4). These DNA double-strand break repair genes are candidates for breast cancer susceptibility. Genotype results were available for up to 2205 cases and 1826 controls. In the homologous recombination (HR) pathway, genotype frequencies differed between cases and controls for two polymorphisms in XRCC3; T241M (P=0.015) and IVS5 A>G at nt 17893 (P=0.008). Homozygous carriers of M241 were associated with an increased risk [odds ratio (OR) MM versus TT=1.3 (95% confidence interval (CI) 1.1-1.6)], while the rare allele of IVS5A>G was associated with a dominant protective effect [OR AG versus AA=0.8 (0.7-0.9)]. The association of a rare variant in XRCC2 (R188H) was marginally significant [P=0.07; OR HH versus RR=2.6 (1.0-6.7)]. In the non-homologous end-joining (NHEJ) pathway, a polymorphism in LIG4 (T>C at nt 1977) was associated with a decrease in breast cancer risk [P=0.09; OR CC versus TT=0.7 (0.4-1.0)]. No significant association was found for 12 other polymorphisms in the other genes studied. For XRCC3, we found evidence for four common haplotypes and four rarer ones that appear to have arisen by recombination. Two haplotypes, AGC and GGC, were associated with non-significant reductions in breast cancer risk, and the rare GAT haplotype was associated with a significantly increased risk. These data provide some evidence that variants in XRCC2 and LIG4 alter breast cancer risk, together with stronger evidence that variants of XRCC3 are associated with risk. If these results can be confirmed, understanding the functional basis should improve our understanding of the role of DNA repair in breast carcinogenesis.


Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments.
Although amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer's disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by clinical dementia rating sum of boxes (CDR-SOB). Then, we compared the clinical and neuroimaging features among groups classified by cognitive trajectory. We retrospectively recruited 278 patients with aMCI who underwent three or more timepoints of neuropsychological testing. They also had magnetic resonance imaging (MRI) including structured three-dimensional volume images. Cortical thickness was measured using surface-based methods. We performed trajectory analyses to classify our aMCI patients according to their progression and investigate their cognitive trajectory using CDR-SOB. Trajectory analyses showed that patients with aMCI were divided into three groups: stable (61.8%), slow decliner (31.7%), and fast decliner (6.5%). Changes throughout a mean follow-up duration of 3.7 years in the CDR-SOB for the subgroups of stable/slow/fast decliners were 1.3-, 6.4-, and 12-point increases, respectively. Decliners were older and carried apolipoprotein E4 (APOE4) genotypes more frequently than stable patients. Compared with the stable group, decliners showed a higher frequency of aMCI patients with both visual and verbal memory dysfunction, late stage aMCI, and multiple domain dysfunction. In addition, compared with the stable group, the slow decliners showed cortical thinning predominantly in bilateral parietotemporal areas, while the fast decliners showed cortical thinning predominantly in bilateral frontotemporal areas. Both decliner groups showed worse cognitive function in attention, language, visuospatial, memory, and frontal/executive domains than the stable group. Our data-driven trajectory analysis provides new insights into heterogeneous cognitive trajectories of aMCI and further suggests that baseline clinical and neuroimaging profiles might predict aMCI patients with poor prognosis.


Monte Carlo Simulations Demonstrate Algorithmic Interventions Over Time Reduce Hospitalisation in Patients With Schizophrenia and Bipolar Disorder.
Non-adherence with pharmacologic treatment is associated with increased rates of relapse and rehospitalisation among patients with schizophrenia and bipolar disorder. To improve treatment response, remission, and recovery, research efforts are still needed to elucidate how to effectively map patient's response to medication treatment including both therapeutic and adverse effects, compliance, and satisfaction in the prodromal phase of illness (ie, the time period in between direct clinical consultation and relapse). The Actionable Intime Insights (AI2) application draws information from Australian Medicare administrative claims records in real time when compliance with treatment does not meet best practice guidelines for managing chronic severe mental illness. Subsequently, the AI2 application alerts clinicians and patients when patients do not adhere to guidelines for treatment. The aim of this study was to evaluate the impact of the AI2 application on the risk of hospitalisation among simulated patients with schizophrenia and bipolar disorder. Monte Carlo simulation methodology was used to estimate the impact of the AI2 intervention on the probability of hospitalisation over a 2-year period. Results indicated that when the AI2 algorithmic intervention had an efficacy level of (>0.6), over 80% of actioned alerts were contributing to reduced hospitalisation risk among the simulated patients. Such findings indicate the potential utility of the AI2 application should replication studies validate its methodologic and ecological rigour in real-world settings.


A case of adult intussusception with greyscale, contrast-enhanced ultrasound and computerised tomography correlation.
Intussusception is often misdiagnosed as a cause of bowel ischemia and obstruction among adults due to its relatively rare presentation outside of the paediatric population. Ultrasound is often the first-line investigation for non-specific abdominal pain and can identify the presence of intussusception. In the adult population, it is essential to evaluate for causes and consequences of intussusception; as a result, computerised tomography is often deemed necessary. However, contrast-enhanced ultrasound allows for evaluation of potential causes and complications, including a neoplastic lead point and ischaemia of the bowel, whilst avoiding ionising radiation or nephrotoxic iodinated contrast. We report a case of adult intussusception with a polyp lead point with ultrasound, contrast-enhanced ultrasound and computerised tomography correlation.


[Accuracy of three-step diagnosis in discriminating subtypes of acute ischemic stroke].
The aim of this study is to evaluate the accuracy of three-step diagnosis in discriminating subtypes of acute ischemic stroke. A total of 120 consecutive patients with first-ever ischemic stroke, admitted to one general hospital, were prospectively studied. In the first step (within 24 hours of clinical onset), the first diagnosis was made according to clinical symptoms and signs, and patients were subdivided into four groups according to the classification of Oxfordshire Community Stroke Project: lacunar infarcts (LACI), total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), and posterior circulation infarcts (POCI). In the second step (24 hours to 72 hours from the onset), neuroimaging diagnosis was performed by CT and/or MRI. Four lesion sites were classified: 1) small subcortical infarction < or = 1.5 cm in diameter in the perforating artery territory (SSI), 2) supratentorial cortical or striatocapsular infarction (CI), 3) low-flow infarction (LFI) which includes centrum semiovale infarct and internal junctional infarct, and 4) posterior circulation infarction other than SSI (PI). In the third step, etiological diagnosis was made by examination including trans-thoracic echocardiography and MRA (3-D, PC). In accordance with the TOAST Study, the presumed stroke mechanism was categorized as either small-vessel occlusion (lacune), cardioembolism (CE), large-artery atherosclerosis (LAA), or others. The majority of patients with TACI, PACI or POCI showed the corresponding lesions on CT or MRI, while only 69% of LACI patients demonstrated SSI. Seventy-five percent of patients with TACI were categorized as CE in the third diagnosis, while the etiology of the patients with PACI was either CE or LAA in equal numbers. Only 60% of LACI patients were classified as lacune and 21% of them as LAA. Patients with LACI but classified as LAA usually had atypical clinical symptoms (e.g. monoparesis) and lesions other than SSI. The positive predictive value (PPV) of lacune in the combination of LACI and SSI was 0.75. Eighty-two percent of patients with CE had atrial fibrillation (af), which was the most frequent cardioembolic source. When patients with TACI or PACI had af, the PPV of CE was 0.93, but when they did not, the PPV of LAA was only 0.68. The etiology of POCI was variable. In conclusion, the agreement of the three-step diagnosis is considerable, but more rigorous clinical examination is needed for some clinical groups (POCI and LACI) and the etiological diagnosis of LAA.


A transient tobacco expression system coupled to MALDI-TOF-MS allows validation of the impact of differential targeting on structure and activity of a recombinant therapeutic glycoprotein produced in plants.
Tobacco-based transient expression was employed to elucidate the impact of differential targeting to subcellular compartments on activity and quality of gastric lipase as a model for the production of recombinant glycoproteins in plants. Overall N-linked glycan structures of recombinant lipase were analyzed and for the first time sugar structures of its four individual N-glycosylation sites were determined in situ by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) on a trypsin digest without isolation or deglycosylation of the peptides. Three glycosylation sites contain both complex-type N-glycans and high-mannose-type structures, the fourth is exclusively linked to high-mannose glycans. Although the overall pattern of glycan structures is influenced by the targeting, our results show that the type of glycans found linked to a given Asn residue is largely influenced by the physico-chemical environment of the site. The transient tobacco system combined with MALDI-TOF-MS appears to be a useful tool for the evaluation of glycoprotein production in plants.


Parental survival, an independent predictor of longevity in middle-aged persons.
In a 25-year follow-up of 2370 middle-aged civil servants and spouses of civil servants, the authors studied the effect of the number of parents (none, one, or both) which a middle-aged person still has alive on this person's survival. Among men, no relationship was found with the number of parents alive after 15 years of follow-up and a weak gradient was found after 25 years. Among women, there was a clear gradient of mortality according to the number of parents alive, both after 15 and after 25 years. In a logistic regression analysis of mortality, after 25 years, the age-adjusted effect of having both parents alive relative to none was significant in men and women (for men: odds ratio = 0.63, 95% confidence interval = 0.42-0.97; for women: odds ratio = 0.36, 95% confidence interval = 0.19-0.69). These estimates did not change materially upon inclusion of other determinants for chronic disease and death into the model (smoking, blood pressure, serum cholesterol, and body mass index). The authors concluded that the parental effect was independent of these risk factors.


Radiation damage to DNA in aqueous solution: effects of radiosensitizers.
Systems are described for examining the molecular mode of action of anoxic radiosensitisers with DNA-OH radicals. Pulse radiolysis showed that NPPN reacts with these radicals even in the presence of 0.5 mM oxygen. Analysis of low molecular weight products liberated from DNA by irradiation showed that NPPN does not act in an oxygen-like way but that misonidazole does. Thus a molecular rationale exists for the use of combinations of radiosensitizers.


Quartz microbalance device for transfer into ultrahigh vacuum systems.
An uncomplicated quartz microbalance device has been developed which is transferable into ultrahigh vacuum (UHV) systems. The device is extremely useful for flux calibration of different kinds of material evaporators. Mounted on a commercial specimen holder, the device allows fast quartz microbalance transfer into the UHV and subsequent positioning exactly to the sample location where subsequent thin film deposition experiments shall be carried out. After backtransfer into an UHV sample stage, the manipulator may be loaded in situ with the specimen suited for the experiment. The microbalance device capability is demonstrated for monolayer and submonolayer vanadium depositions with an achieved calibration sensitivity of less the 0.001 ML coverage.


Electrospinning-thermal treatment synthesis: a general strategy to decorate highly porous nanotubes on both internal and external side-walls with metal oxide/noble metal nanoparticles.
The hybrid structure of nanoparticle-decorated highly porous nanotubes combines the advantages of large specific surface areas of nanoparticles and anisotropic properties of highly porous nanotubes, which is desirable for many applications, including batteries, photoelectrochemical water splitting, and catalysis. Here, we report a novel emulsion electrospinning-thermal treatment method to synthesize the nanoparticles deposited on both side walls of nanotubes with two unique characteristics: (1) large loading amount of nanoparticles per highly porous nanotubes (with the morphology of nanoparticles); (2) intimate contact between nanoparticles and highly porous nanotubes. Both features are advantageous for the above applications that involve both surface reactions and charge transportation processes. Moreover, the emulsion electrospinning-thermal treatment method is simple and straightforward, with which we have successfully decorated various highly porous metal oxide nanotubes with metal oxide or noble metal nanoparticles. The new method will have an impact on diverse technologies such as lithium ion batteries, catalysts, and photoelectrochemical devices.


[RESEARCH ON THE LEVEL, COMPONENTS AND THE TYPE OF COOPERATIVITY IN THE PATIENTS WITH ASTHMA].
The patient's cooperativity is the major factor which determines the patient's adherence to doctor's prescriptions and, consequently, the achievement of disease control. We proposed the "Evaluation of the cooperativity in asthma" questionnaire to evaluate the level, components and types of cooperativity in 141 patients with the mixed or atopic form of asthma (94.3 and 5.7%, respectively) at admission to hospital who were aware about their disease. The analysis of investigated parameters depending on the level of patients' awareness of their condition (according to the "Awareness of patients about asthma" test), severity and duration of the disease, presence of alexithymia and social and economic index was done. It was found out that patients with asthma exaggerate the degree of their compliance. The general indices of cooperativity (GIC=58.1±7.3%) and understanding of danger (35.8±3.3%) in the patients who were aware about their disease were low. Qualitative characteristics of individual cooperativity components in examined patients are presented. Nearly 76% of the patients showed negative cooperativity inversely correlating with the severity of asthma and the duration of the disease. Positive cooperativity appeared to be directly related with the higher educational level, occupation and higher income level of the patients. Generally speaking, low average GIC ratings and low patients' adherence to asthma treatment suggest their low cooperativity.


Draft Genome Sequences of Tersicoccus phoenicis DSM 30849T, Isolated from a Cleanroom for Spacecraft Assembly, and Tersicoccus sp. Strain Bi-70, Isolated from a Freshwater Lake.
Here, we report the draft genome sequences of Tersicoccus phoenicis DSM 30849T, isolated from a spacecraft assembly cleanroom at the National Aeronautics and Space Administration (NASA), and Tersicoccus sp. strain Bi-70, isolated from Lake Biwa, the largest lake in Japan. These genome sequences facilitate our understanding of the adaptation of these closely related strains to different habitats.


Knowledge about adverse drug reactions reporting among healthcare professionals in Nepal.
To investigate the knowledge about ADRs and ADR reporting among healthcare professionals working at four regional pharmacovigilance centers (RPCs) of Nepal. It was a cross sectional study, done by a survey using a validated self-administered structured questionnaire. The questionnaire was distributed to 450 healthcare professionals working at four RPCs. The overall response rate was 74%. Only 53% and 38% of respondents knew about the existence of National Pharmacovigilance Centre (NPC) and RPC, respectively. Among the respondents, 29% and 33% did not know what a Type A and Type B ADR was. Similarly, 30% and 45% were not aware of the common types of ADRs or the thalidomide tragedy. Only, 9% knew about Uppsala Monitoring Centre (UMC) and only 10% answered correctly about the Naranjo algorithm as a causality assessment tool for ADRs. Of the respondents, only 19% knew about spontaneous reporting system and only 18% were aware about its drawbacks. The overall mean score on knowledge about ADR among healthcare professionals was 7.64 ± 2.38 out of the maximum possible score of 12. Whereas, the overall mean score of knowledge about ADR reporting was 3.95 ± 1.78 out of maximum possible score of 11. Healthcare professionals working at four RPCs of Nepal have some knowledge about ADRs themselves but limited knowledge about ADR reporting. There is an urgent need of action to be taken by RPCs at the regional level and NPC at the national level to improve knowledge and ADR reporting by healthcare professionals.


Critical incident stress debriefing after adverse patient safety events.
Adverse events (AEs) are common, estimated to occur in around 10% internationally. Although preventable harm can be minimized, when AEs occur it is important that they be managed appropriately. AEs can be traumatic not only for patients, their friends, and relatives, but also for the involved clinicians, who have been referred to as "second victims" in a growing body of international research. Despite the frequency with which AEs occur, organizational mechanisms for supporting staff in these circumstances are not routinely embedded in healthcare settings. Critical Incident Stress Debriefing (CISD) has long been provided for professionals, such as disaster workers, who are exposed to traumatic and high-stress events. CISD is considered an effective strategy to promote resilience and recovery. We explore the potential value of providing CISD for health professionals involved in patient safety-related AEs and discuss the instances in which this could be routinely implemented.


[Capsulorhexis technique in pediatric cataract. Presented in the rabbit model].
Continuous curvilinear capsulorhexis (CCC) has become a standard procedure in cataract surgery. In pediatric cataracts, however, this technique is difficult to perform. Because of the elasticity and tension of the pediatric anterior lens capsule the danger of radial tears is high. Similar conditions are found in the rabbit model. The anterior lens capsule of young albino rabbits is very elastic. We have developed a CCC technique in rabbits that allows a controlled round capsular opening. This technique was used in an experimental study with 16 rabbits (32 eyes). The mean capsulorhexis diameter was 4.9 +/- 0.9 mm. A radial tear occurred in only 2/32 cases. The technique permits a controlled circular anterior capsulectomy for capsules with high surface tension and elastic properties. This can readily be applied to human pediatric cases.


Repellent Effects of Selected Organic Leaf Extracts of Tithonia diversifolia (Hemsl.) A. Gray and Vernonia lasiopus (O. Hoffman) against Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae).
Sitophilus zeamais infestation is among the major setbacks to sustainable maize farming and availability. It causes an estimated annual loss of 5-10% and 20-30% of the total maize grains loss in the temperate and tropical zones, respectively. Although synthetic pesticides are quick and effective in managing crop pests, their overuse and misuse is discouraged due to their detrimental effects on human and environment. Natural pesticidal products that are extracted from plants are particularly gaining importance as an alternative to synthetic pesticides. They are available, easily biodegraded and have low toxicity to nontarget organisms. Most botanical pesticides act on insects by repelling them away from the crops in the field or in the stores. Therefore, this study aimed to determine repellency potential of organic leaf extracts of Tithonia diversifolia and Vernonia lasiopus on S. zeamais. Materials and methods. The phytochemical profile of T. diversifolia and V. lasiopus was determined using GC-MS. Laboratory-based experiments were carried out using area preference method to assess the efficacy of the extracts against weevils for a test period of 5 h. Six groups of experiments were set up with ten S. zeamais in each test: positive control (Actellic), negative control (solvent only), and four different experimental extract concentrations (25, 50, 75, and 100%). The results indicated that T. diversifolia and V. lasiopus leaf extracts possess potent repellency effect on weevils. All the extracts simply discouraged S. zeamais from the treated areas recording significantly good levels of repellent activities between 26 and 96%. Furthermore, the GC-MS analysis manifested the presence of bioactive compound in the extracts which are associated with the repellency effects. The study scientifically confirms the traditional use of the T. diversifolia and V. lasiopus and provides important platform for further study on the extracts as bioresource of botanical repellent.


Incorporation of dietary fibre-rich oyster mushroom (Pleurotus sajor-caju) powder improves postprandial glycaemic response by interfering with starch granule structure and starch digestibility of biscuit.
The purpose of this study was to determine the effects of Pleurotus sajor-caju (PSC) powder addition at 0, 4, 8 and 12% levels on the nutritional values, pasting properties, thermal characteristics, microstructure, in vitro starch digestibility, in vivo glycaemic index (GI) and sensorial properties of biscuits. Elevated incorporation levels of PSC powder increased the dietary fibre (DF) content and reduced the pasting viscosities and starch gelatinisation enthalpy value of biscuits. The addition of DF-rich PSC powder also interfered with the integrity of the starch granules by reducing the sizes and inducing the uneven spherical shapes of the starch granules, which, in turn, resulted in reduced starch susceptibility to digestive enzymes. The restriction starch hydrolysis rate markedly reduced the GI of biscuits. The incorporation of 8% PSC powder in biscuits (GI=49) could be an effective way of developing a nutritious and low-GI biscuit without jeopardizing its desirable sensorial properties.


Pharmacological interactions and menopausal hormone therapy: a review.
Menopausal hormone therapy (HT) is widely used, and there are several statements of international scientific societies to guide prescribers; however, a summary of existing literature about possible drug interactions with HT does not exist, although many midlife women take medications for other conditions. Therefore, our objective was to create a document that presents and synthesizes the most relevant interactions. The impact of the interaction itself and the number of candidates for HT who are likely to use other treatments are considered based on the best available evidence. A systematic review was performed to determine the best evidence of interaction effects on relevant outcomes of interest for decision making. A working framework was developed to formulate explicit and reasoned recommendations according to four predefined categories for coadministration: (1) can be used without expected risks, (2) acceptable use (no evidence of negative interaction), (3) alternative treatment should be considered, and (4) nonuse without express justification. The project protocol was registered in the Open Science Framework platform (doi: 10.17605/OSF.IO/J6WBC ) and in PROSPERO (registration number CRD42020166658). Studies targeting our objective are scarce, but 23 pharmacological groups were assigned to one of the predefined categories of recommendation for concomitant use of HT. Vaginal HT was assigned to category 1 for 21 of the analyzed pharmacological groups. For oral and transdermal HT (estrogen-only or combined) and tibolone, there were 12 pharmacological groups assigned to category 1, 12 to category 2, 5 to category 3, and 4 to category 4. Results are shown in crossed-tables that are useful for counseling and prescription. Available evidence of HT interactions with other drugs is scarce and mainly indirect. It comes from biological plausibility, knowledge of extensive concomitant use without reported incidents, and/or extrapolation from hormonal contraception, but there are pharmacological groups in all categories showing that information is useful. These eligibility criteria summarize it and can help in the decision process of HT coadministration with other drugs. Decisions should be taken based on these recommendations but also individualized risk/benefit evaluation, according to underlying pathology, patient's clinical requirements, and the existence or nonexistence of alternatives.


An experimental comparative study of the efficiency of twisted and flat flapping wings during hovering flight.
This work presents a parametric study to find a proper wing configuration for achieving economical flight using unsteady blade element theory, which is based on the 3D kinematics of a flapping wing. Power loading was first considered as a performance parameter for the study. The power loadings at each wing section along the wingspan were obtained for various geometric angles of attack (AoAs) by calculating the ratios of the vertical forces generated and the power consumed by that particular wing section. The results revealed that the power loading of a negatively twisted wing could be higher than the power loading that a flat wing can have; the power loading of the negatively twisted wing was approximately 5.9% higher. Given the relatively low average geometric AoA (α A,root ≈ 44° and α A,tip ≈ 25°), the vertical force produced by the twisted wing for the highest power loading was approximately 24.4% less than that produced by the twisted wing for the strongest vertical force. Therefore, for a given wing geometry and flapping amplitude, a flapping-wing micro air vehicle required a 13.5% increase in flapping frequency to generate the same strongest cycle-average vertical force while saving about 24.3% power. However, when force3/power2 and force2/power ratios were considered as performance indices, the twisted wings for the highest force3/power2 (α A,root ≈ 43° and α A,tip ≈ 30°) and force2/power (α A,root ≈ 43° and α A,tip ≈ 36°) required only 6.5% and 4% increases in flapping frequency and consumed 26.2% and 25.3% less power, respectively. Thus, it is preferable to use a flapping wing operating at a high frequency using the geometric AoAs for the highest power loading, force3/power2 ratio, and force2/power ratio over a flapping wing operating at a low frequency using a high geometric AoA with the strongest vertical force. Additionally, by considering both aerodynamic and inertial forces, this study obtained average geometric AoAs in the range of 30° to 40°, which are similar to those of a typical hovering insect's wings. Therefore, the operation of an aerodynamically uneconomical, high AoA in a hovering insect's wings during flight is explainable.


Overview of hospitalizations by ambulatory care sensitive conditions in the municipality of Cotia, Brazil.
Objective To describe the profile of Hospitalizations by Amulatory Care Sensitive Conditions (HACSC), in the Municipality of Cotia, from 2008 to 2012. Method ecological, exploratory, longitudinal study with a quantitative approach. Data on HACSC, by age group and sex, were obtained from the Department of the Unified Health System. For data analysis descriptive statistics were used. Results During the period, there were 46,676 admissions, excluding deliveries, 7,753 (16.61%) by HACSC. The main causes were cerebrovascular diseases, 16.96%, heart failure, 15.50%, hypertension, 10.80% and infection of the kidney and urinary tract, 10.51%. Regarding gender, HACSC occurred predominantly in males. There was a greater number of HACSC at extreme age ranges, especially in the elderly. Conclusion Chronic diseases predominate among the leading causes of HACSC and there was no significant difference between sex.


[Survival of patients with diabetic nephropathy on continuous ambulatory peritoneal dialysis. Own experiences].
We analyzed 5 years survival on CAPD diabetics with respect to the type of diabetes (D). There were 24 pts with type 1 D, 13 pts with type 2 D and 29 non diabetic CAPD pts (for comparison of long-term survival). In the D groups we analyzed adequacy of dialysis, nutritional status (albumin level), frequency of peritonitis (PN) as well as character and progression of cardiovascular complications. Patients with type 2 D were older (58.46 +/- 8.54 yrs), had lower initial level of albumin's in serum (3.3 +/- 1.0 g/dl), more cardiovascular complications at the start of CAPD. Survival of 1st 3rd, and 5th year of CAPD was achieved respectively in 89%, 70.8% and 58.3% of type 1 D; in 100%, 69% i 38.5% of type 2 D; and in 96.5%, 72.4% i 65.5% of the control group of non diabetics. Despite similar adequacy of CAPD (Kt/V 2.14 +/- 0.62 vs 2.08 +/- 0.36; weekly CrCI 64.15 +/- 16.1 vs 62.08 +/- 12.72 ml/min/1.73 sq.m) and low ratio of PN (1:30.6 vs 1:32.7 ptsmnths) cardiovascular complications progressed in both groups of D, especially in type 2, being responsible for death of 3/24 pts with type 1 D and 8/13 pts with type 2 up to 5th year of observation. Because of progressive character of cardiovascular complications and high ratio of death especially in diabetes type 2 despite adequate dialysis, we recommend early referral of predialysis diabetics to nephrologist as well as earlier start of CAPD with simultaneous application for kidney or kidney and pancreas transplantation.


Low molecular weight urinary peptides in ceroid-lipofuscinoses: potential biochemical markers for the juvenile subtype.
Urine from patients with classical and atypical forms of juvenile ceroid-lipofuscinosis (CL) was analyzed for the presence of disease-specific peptides. Two distinct peptide patterns were recognized on lithium dodecyl sulfate polyacrylamide gel electrophoresis in classical juvenile CL patients. Pattern 1 consisted of a single, intensely staining peptide of apparent Mr 2,000, and up to 4 heterogeneous, weakly staining peptides between 2,500 and 6,300 Mr. This peptide pattern was not seen in over 30 samples from patients with other neurodegenerative disorders, nor in normal control individuals. Reduced amounts of the 2,000 Mr peptide were seen in 2 of 3 female heterozygotes whose children had the peptide pattern 1. The presence of large amounts of the 2,000 Mr peptide in urine extracts made patient identification unequivocal. Pattern 2 had 2 to 3 intensely staining peptides of 3,800, 5,000 and 7,000 Mr, a variable number of minor bands, and diffuse staining above 7,000 and below 3,800 Mr. Parents had 2 to 3 weakly staining peptides with molecular weights similar to the major bands seen in the patients. No consistent peptide pattern was seen in 8 patients with atypical CL. Late infantile CL patients had no or very small amounts of low Mr urinary peptides. The urinary components stained well with silver, poorly with Coomassie Blue, and were digested by a nuclease-free protease, as expected for protein. They were distinctly different from the peptides isolated from ovine CL tissues. Amino acid composition analysis showed a predominantly normal spectrum of amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)


Helping students to understand that outward currents depolarize cells.
The physiology of excitable membranes is a fundamental topic in neuroscience and physiology courses at graduate and undergraduate levels. From the building blocks of ionic gradients and membrane channels whose permeability is selective and variable, we build the concepts of resting potential, action potential, and propagation in neurons and muscle fibers. Many students have an intuitive understanding of the movements of ions and the associated changes in membrane potential. For example, potassium ions leaving a cell through potassium-selective channels become unbalanced positive charges on the outside of the cell (and leave unbalanced negative charges on the inside), thus producing a potential across the membrane with the inside negative with respect to the outside. Later, when we discuss the local circuit currents that underlie propagation or the basis for extracellular stimulation, we make the general statement that "outward currents depolarize cells." Students respond with utter disbelief. Two simple additions to a discussion of membranes are suggested that permit the formulation of a consistent set of rules that apply to everything from the resting and action potentials of nerve and muscle through synaptic potentials and stimulation techniques.


Sorption of sulfonamide pharmaceutical antibiotics on whole soils and particle-size fractions.
Residues of pharmaceutical antibiotics are found in the environment, whose fate and effects are governed by sorption. Thus, the extent and mechanisms of the soil sorption of p-aminobenzoic acid and five sulfonamide antibiotics (sulfanilamide, sulfadimidine, sulfadiazine, sulfadimethoxine, and sulfapyridine) were investigated using topsoils of fertilized and unfertilized Chernozem and their organic-mineral particle-size fractions. Freundlich adsorption coefficients (K(f)) ranged from 0.5 to 6.5. Adsorption increased with aromaticity and electronegativity of functional groups attached to the sulfonyl-phenylamine core. Adsorption to soil and particle-size fractions increased in the sequence: coarse silt < whole soil < medium silt < sand < clay < fine silt and was influenced by pH. Sorption nonlinearity (1/n </= 0.76) indicated specific interactions with functional groups of soil organic matter (SOM). Phenolic and carboxylic groups, N-heterocyclic compounds, and lignin decomposition products were tentatively assigned as preferred binding sites using statistical analysis of pyrolysis-mass spectra and adsorption coefficients. Adsorption of sulfonamides to mineral soil colloids was weaker and resulted in a stronger desorption from clay-size fractions. Moreover, steric accessibility of organic-mineral complexes in clay-size fractions was significantly reduced. With a quantitative structure-property relationship (QSPR) model, combining the organic carbon concentration, the sulfonamides' chromatographic capacity factor (k'), and nondissociated species concentration (CF(a)), distribution coefficients (K(d)) were estimated with a cross-validated regression coefficient Q(2) = 0.71. Modeling and molecular mechanics calculations of antibiotic-SOM complexes showed preferred site-specific sorption via hydrogen bonds and van der Waals interactions. Distinct chemical structural properties, such as aromaticity and van der Waals volumes, correlated with the sorption data.


Radiologically guided percutaneous fine-needle aspiration biopsy of the liver: retrospective study of 119 cases evaluating diagnostic effectiveness and clinical complications.
We reviewed 119 percutaneous, radiologically guided fine-needle aspirations (FNA) from 114 patients with liver masses to evaluate diagnostic effectiveness and complications of this procedure. Satisfactory material was obtained in 118 cases (99%), of which 78 were diagnosed as positive (66%), three suspicious (2%), five atypical (4%), and 32 (27%) as negative for malignancy. Compared to surgical biopsy (48 cases) and clinical data, the sensitivity and specificity of FNA for malignancy was 95.1% and 100%, respectively, yielding a positive predictive value of 100% and a negative predictive value of 88.8%. Four cytology cases (3.4%) were false-negatives (FN); all were interpretive errors. Four FN surgical biopsies (8.3%) were sampling errors. Minor complications occurred in three cases (2.5%). We conclude that FNA is safe and effective for determining the malignant potential of liver masses and should be the procedure of choice. Our experience suggests that having a pathologist present in the radiology suite provides optimal patient care.


Testing evidence routine practice: Using an implementation framework to embed a clinically proven asthma service in Australian community pharmacy.
Community pharmacists are well placed and evidence clearly demonstrates that they can be suitably trained to deliver professional services that improve the management of asthma patients in clinical, economic and humanistic terms. However the gap between this evidence and practice reality remains wide. In this study we measure the implementation process as well as the service benefits of an asthma service model. Using an effectiveness-implementation hybrid design, a defined implementation process (progression from Exploration through Preparation and Testing to Operation stages) supporting an asthma service (promoting asthma control and inhaler technique) was tested in 17 community pharmacies across metropolitan Sydney. Seven pharmacies reached the Operation stage of implementation. Eight pharmacies reached the Testing stage of implementation and two pharmacies did not progress beyond the Preparation stage of implementation. A total of 128 patients were enrolled in the asthma service with 110 patients remaining enrolled at the close of the study. Asthma control showed a positive trend throughout the service with the overall proportion of patients with 'poor' asthma control at baseline decreasing from 72% to 57% at study close. There was a statistically significant increase in the proportion of patients with correct inhaler technique from 12% at Baseline (Visit 1) to 33% at Visit 2 and 57% at study close. Implementation of the asthma service varied across pharmacies. Different strategies specific to practice sites at different stages of the implementation model may result in greater uptake of professional services. The asthma service led to improved patient outcomes overall with a positive trend in asthma control and significant change in inhaler technique.


Relationship between serum ferritin level and transient elastography findings among patients with nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is raising prevalence among children, and adolescence population in developed and developing countries as a major public health concern. The present study aims to determine the relationship between serum ferritin level and transient elastography findings in patients suffering from NAFLD. The demographic and biochemical profile of included individuals such as body mass index, age, level of serum transaminases, fasting blood sugar, lipid profile, and serum ferritin level were determined and a transient elastography was performed for all of them. The mean serum ferritin level among men with mild and advanced liver stiffness was 154 ± 97 and 244 ± 214, respectively (P < 0.001), which showed a meaningful relationship. These figures among female patients with mild and advanced liver stiffness included 79 ± 91 and 161 ± 103, respectively (P = 0.003) and again revealed a significant relationship. The cutoff values of ferritin with 90% accuracy for differentiation of mild from advanced liver stiffness among male and female patients were determined as 255 ng/ml and 135 ng/ml, respectively. These cutoff values for ruling out of advanced liver stiffness with 90% accuracy among both sexes were 72.5 ng/ml and 65.5 ng/ml, respectively. The finding of this study revealed a significant relationship between serum ferritin level and liver stiffness among NAFLD patients, and if these results repeated in further investigations, it could be advisable to measure serum ferritin level for predicting possibility of advanced liver fibrosis.


Passive immunization with a multicomponent vaccine against conserved domains of apical membrane antigen 1 and 235-kilodalton rhoptry proteins protects mice against Plasmodium yoelii blood-stage challenge infection.
During malaria parasite invasion of red blood cells, merozoite proteins bind receptors on the surface of the erythrocyte. Two candidate Plasmodium yoelii adhesion proteins are apical membrane antigen 1 (AMA1) and the 235-kDa rhoptry proteins (P235). Previously, we have demonstrated that passive immunization with monoclonal antibodies (MAbs) 45B1 and 25.77 against AMA1 and P235, respectively, protects against a lethal challenge infection with P. yoelii YM. We show that MAb 45B1 recognizes an epitope located on a conserved surface of PyAMA1, as determined by phage display and analysis of the three-dimensional structure of AMA1, in a region similar to that bound by the P. falciparum AMA1-specific inhibitory antibody 4G2. The epitope recognized by 25.77 could not be assigned. We report here that MAbs 45B1 and 25.77 also protect against challenge with the nonlethal parasite line 17X, in which PyAMA1 has a significantly different amino acid sequence from that in YM. When administered together, the two MAbs acted at least additively in providing protection against challenge with the virulent YM parasite. These results support the concept of developing a multicomponent blood-stage vaccine and the inclusion of polymorphic targets such as AMA1, which these results suggest contain conserved domains recognized by inhibitory antibodies.


Well-Being: Its Relationship with Work-to-Family Conflict and Burnout among Males and Females.
The present study aims to apply gender-specific analyses to examine how work-to-family conflict (WFC) and burnout are related to well-being among the workers in Taiwan. A cross-sectional research design was adopted. A questionnaire was distributed to obtain information pertaining to demographic characteristics, WFC, burnout, and well-being. In total, 4259 full-time workers in the manufacturing industry were recruited. Gender-specific statistical analyses were used. The results showed that no significant gender difference occurred on WFC; however, females had higher scores on burnout compared to males. In the correlation analyses, WFC as well as burnout were negatively associated with well-being in both genders. In the regression analyses when demographic factors were controlled, burnout explained larger variances of well-being in both genders compared with WFC. WFC made a smaller contribution to the models predicting well-being in males in contrast to females. Moreover, the significant association between WFC and well-being for males disappeared when burnout was taken into account. The conclusion reached was that to improve workers' well-being, organizations should develop relevant policies to decrease the extent of burnout for different genders. The policies that the organization adopted should consider females' needs beyond work-related burden. Moreover, merely decreasing the extent of WFC is insufficient to enhance males' well-being.


Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.
This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually.


Dietary glycemic index and load, measures of glucose metabolism, and body fat distribution in older adults.
Recent evidence suggests that the rate of carbohydrate digestion and absorption may influence the development of type 2 diabetes. The aim of this study was to examine associations of dietary glycemic index and glycemic load with predictors of type 2 diabetes in older adults. This study evaluated cross-sectional relations of dietary glycemic index and glycemic load with measures of glucose metabolism and body fat distribution in participants of the Health, Aging and Body Composition Study, a prospective cohort study of adults aged 70-80 y (n = 2248). In men, dietary glycemic index was positively associated with 2-h glucose (P for trend = 0.04) and fasting insulin (P for trend = 0.004), inversely associated with thigh intramuscular fat (P for trend = 0.02), and not significantly associated with fasting glucose, glycated hemoglobin, or visceral abdominal fat. Dietary glycemic load was inversely associated in men with visceral abdominal fat (P for trend = 0.02) and not significantly associated with fasting glucose, 2-h glucose, glycated hemoglobin, fasting insulin, or thigh intramuscular fat. In women, although dietary glycemic index and load were not significantly related to any measures of glucose metabolism or body fat distribution, the association between dietary glycemic index and 2-h glucose was nearly significant (P for trend = 0.06). The findings of this cross-sectional study indicate an association between dietary glycemic index and selected predictors of type 2 diabetes in older adults, particularly in men.


Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.


Ursolic acid attenuates cigarette smoke-induced emphysema in rats by regulating PERK and Nrf2 pathways.
Ursolic acid (UA) is widely distributed in natural plants to against oxidation, virus, inflammation, tumor, and has been widely used in the pharmaceutical and cosmetics. However, its effect on emphysema of chronic obstructive pulmonary disease (COPD) is unknown. Unfolded protein response is involved in pathogenesis of COPD through PERK pathway. Nuclear erythroid-related factor 2 (Nrf2) regulates antioxidant defensive mechanism in COPD. This study was to explore effect and mechanism of UA on cigarette smoke (CS)-induced rat emphysema. 50 Wistar rats were divided into 5 groups (n = 10 each): rats were exposed to CS for 12 weeks in absence (CS group) or presence of UA at different doses. Control group was treated with UA vehicle only. Histopathology, apoptosis, key protein expression of PERK and Nrf2 pathway were determined in lung tissues. Oxidative stress levels in lung were represented by 8-OHdG, MDA and GSH levels. Emphysema-related pathology, based on inter-alveolar wall distance and alveolar density, was less severe in UA groups than in CS group. Compared with CS group, UA treatment down-regulated PERK pathway protein expression, up-regulated expression of Bcl-2 and down-regulated expression of Bax, Cleaved-Caspase3 and Cleaved-Caspase12. Moreover, UA decreased number of apoptotic cells in rat lungs. UA also up-regulated protein expression of Nrf2/ARE pathway and GSH level, decreased expression of oxidant stress factor 8-OHdG and MDA. These improvements were in accordance with attenuation of severity of emphysema. UA attenuates CS-induced rat emphysema by down-regulating PERK pathway to alleviate CS-induced apoptosis in lung, and up-regulating Nrf2 pathway to improve cigarette smoke-induced oxidant stress in rat lungs.


Crassulacean acid metabolism in the Basellaceae (Caryophyllales).
C4 and crassulacean acid metabolism (CAM) have evolved in the order Caryophyllales many times but neither C4 nor CAM have been recorded for the Basellaceae, a small family in the CAM-rich sub-order Portulacineae. 24 h gas exchange and day-night changes in titratable acidity were measured in leaves of Anredera baselloides exposed to wet-dry-wet cycles. While net CO2 uptake was restricted to the light period in well-watered plants, net CO2 fixation in the dark, accompanied by significant nocturnal increases in leaf acidity, developed in droughted plants. Plants reverted to solely C3 photosynthesis upon rewatering. The reversible induction of nocturnal net CO2 uptake by drought stress indicates that this species is able to exhibit CAM in a facultative manner. This is the first report of CAM in a member of the Basellaceae.


Moderate Intensity Exercise in Pre-manifest Huntington's Disease: Results of a 6 months Trial.
While it has been shown that aerobic exercise interventions are well tolerated in participants with the Huntington disease (HD) gene mutation, no study to date has tested whether an aerobic exercise intervention benefits brain structure and function in pre-manifest HD. In this study we utilized magnetic resonance (MR) imaging techniques to assess the efficacy of moderate-to-vigorous exercise treatment relative to active stretching and toning control. Forty pre-manifest participants with confirmed HD gene expansion were recruited into a two-arm intervention study that included a moderate-to-vigorous intensity home-based walking exercise intervention (N=34) and an active stretching and toning control intervention (N=6). Participants were assessed at baseline and after 26 weeks in one of the two study arms. 25 of the 34 (74%) participants assigned to the moderate-to-vigorous intensity group completed the intervention while 4 of the 6 (67%) participants in the stretching and toning intervention completed the study. The primary analyses compared the two arms of the study and found no statistical differences between the groups. Both groups were found to have improved their cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2max). A secondary analysis combined the two arms of the study and there was a significant relationship (p<0.05) between change in VO2max and change in brain structure. Though this study did not show efficacy for the exercise intervention, secondary results suggest that aerobic exercise interventions increasing cardiorespiratory fitness may be a potential way to slow progression in pre-manifest HD.


Alpha 1-adrenoceptors mediate the responses to BHT-920 and rauwolscine in dog mesenteric artery after partial depolarization by KCl.
In normal (5 mM KCl) HEPES buffer solution, BHT-920 and rauwloscine did not produce any contractile responses in dog mesenteric artery strips. However, when the preparation was bathed in 20 mM KCl HEPES buffer solution, BHT-920 and rauwloscine evoked significant contractile responses. These effects were markedly inhibited by parazosin which caused a parallel shift to the right of the concentration-response curve to BHT-920. In 45Ca uptake experiments carried out in the 20 mM KCl HEPES buffer solution BHT-920 and rauwolscine significantly increased 45Ca influxes which were reduced by prazosin. These results suggest that postsynaptic alpha 1-adrenoceptors in dog mesenteric artery mediate the contractile responses and the 45Ca influxes induced by BHT-920 and rauwloscine after partial depolarization by 20 mM KCl.


Preparation of benznidazole pellets for immediate drug delivery using the extrusion spheronization technique.
Recent advances in the treatment of Chagas disease have followed combinations of drugs that act synergistically against infection, predominantly including benznidazole (BNZ) and azoles derivatives. Possible incompatibilities between these drugs, slow dissolution of BNZ and dose adjustment difficulties are technological obstacles to the development of multidrug formulations. Thus, in the present study, BNZ pellets were developed using extrusion spheronization for immediate drug delivery. Preformulation studies were then performed using thermal analysis and infrared spectroscopy and compatibility between the drug and selected excipients (polyethylene glycol 6000, sodium starch glycolate, microcrystalline cellulose and sodium croscarmellose) was investigated. No chemical decomposition of BNZ was observed, even in samples submitted to wet granulation and thermal stress. Subsequently, formulations were elaborated according to a simplex lattice experimental design using polyethylene glycol, sodium starch glycolate and sodium croscarmellose as disintegrating agents. In these experiments, BNZ pellets showed appropriate physicochemical characteristics, including high drug load capacity and excellent flow properties. The mixture experimental design allowed identification of adequate compositions of disintegrating agents and achieved rapid disintegration and dissolution of pellets. Optimum performance was achieved using polyethylene glycol and sodium croscarmellose at 5.0% w/w each. The present BNZ pellets are versatile alternatives to treat Chagas disease and provide insights into the preparation of multidrug systems.


Vaccinations against respiratory infections in Arabian Gulf countries: Barriers and motivators.
To study the uptake, barriers and motivators of influenza, pneumococcal, meningococcal and pertussis vaccines among members of public in Arabian Gulf countries. A cross-sectional survey among the Gulf Cooperation Council (GCC) countries' residents. Data collected electronically through a smartphone app. The survey variables aimed to investigate the respondents' awareness about vaccines against influenza, pneumococcal, meningococcal and pertussis infections. Collected data concerning the respondents' socio-demographic characteristics, their perception toward vaccine uptake and the factors that motivate or demotivate them from taking influenza vaccine. The data were analysed statistically using the SPSS v.23.0. Differences in the characteristics of users from different countries were quantified through bivariate analysis. Other important variables and controlling factors were studied using logistic regression. A total of 1812 respondents participated in the study. Their mean age was 27 years, 82% were male and 24% had ≥ 1 chronic diseases. The overall uptake of influenza vaccine was 17% (21% among "at risk" people) and ranged from 15% in Saudi Arabia to 24% in Qatar. Doctor's advice (23%) and a perception of having low body immunity (21%) were the main cited reasons for being vaccinated, whereas unawareness about the vaccine (43%) was the main barrier. The overall uptake of pneumococcal vaccine in the preceding three years was 22% (25% among "at risk" individuals) and ranged from 0% in Bahrain to 79% in Kuwait. The overall uptake of pertussis vaccine was 16% (31% among "vulnerable" people), and ranged from 7% in Saudi Arabia to 75% in Oman. The overall uptake of meningococcal vaccine was 20% (29% among the "at risk" people) and ranged from 3% in Oman to 50% in Bahrain. The vaccination uptake across GCC countries is suboptimal and varies widely across the countries. Further research is needed to unearth the reasons and formulate action plan.


Betaxolol attenuates retinal ischemia/reperfusion damage in the rat.
This study was performed to elucidate the protection afforded by post-treatment with Betoptic (0.25% betaxolol) against neuronal cell damage after ischemia/reperfusion insult in rats. Betaxolol was applied topically after the start of reperfusion and its effect was evaluated by morphometry and choline acetyltransferase immunoreactivity of retinas at 7 days after reperfusion. In non-treated eyes, the thickness of the inner plexiform layer decreased markedly after a reperfusion period of both 3 and 7 days. However, when eyes were treated with betaxolol after ischemia/reperfusion injury, both the reduction of the inner plexiform layer thickness and the retinal choline acetyltransferase immunoreactivity were significantly attenuated. These findings suggest that betaxolol is an efficient neuroprotective agent and prevents the retinal cell damage induced by ischemic injury in rats.


Rapport building with adolescents to enhance reporting and disclosure.
Adolescents comprise a vulnerable population that is exposed to crime and also may be reluctant to disclose full details of their experiences. Little research has addressed effective ways of increasing their willingness to disclose and provide complete reports. Strategies that improve honesty and report completeness in other age groups have not been evaluated to determine whether they are similarly effective at increasing adolescents' reporting. In the current study, we tested whether rapport building techniques, modified from those commonly used with children and adults to address reasons why adolescents are likely reluctant, enhance the amount of detail adolescents provide about prior experiences. The participants, 14- to 19-year-olds (N = 125), completed an online questionnaire regarding significant events (e.g., big argument with family member) they experienced during the last 12 months. After a delay, they completed a remote interview asking them to recount details of one of the events. The interview began with either standard rapport building composed of largely yes/no questions about the adolescents' background or one of two expanded rapport building phases: open-ended (questions about the adolescents' backgrounds that required narrative answers) or enhanced (open-ended questions paired with the interviewer also sharing personal information). Although only adolescents in the standard condition showed age-related increases in information disclosed, overall adolescents in the enhanced condition provided significantly longer and more detailed narratives than adolescents in the other conditions. This effect was largest for the youngest adolescents, suggesting that mutual self-disclosure may be especially beneficial for eliciting honest complete reports from adolescents about salient prior experiences.


Topical glucocorticosteroid (fluticasone propionate) inhibits cells expressing cytokine mRNA for interleukin-4 in the nasal mucosa in allergen-induced rhinitis.
Allergen-induced late nasal responses are associated with recruitment and activation of T lymphocytes and eosinophils and preferential mRNA expression for T-helper type 2 (Th2) cytokines. We tested the hypothesis that topical corticosteroids may inhibit late responses by inhibiting cells expressing mRNA for Th2 cytokines. A randomized double-blind placebo-controlled trial of topical corticosteroid (fluticasone propionate) was performed in 48 adult grass pollen-sensitive patients. Nasal biopsies were taken at baseline and repeated 24 hr after local nasal allergen provocation following 6 weeks treatment with either fluticasone propionate 200 micrograms or placebo nasal spray twice daily. Baseline mRNA expression for interleukin-4 (IL-4) (P = 0.01) and IL-5 (P = 0.002) was higher in the patients than in normal controls. Topical corticosteroid treatment significantly inhibited immediate nasal symptoms, with almost complete inhibition of the late response following allergen challenge. This was associated with a marked decrease in the allergen-induced increases in cells expressing mRNA for IL-4 (P = 0.002) but not for IL-5. Inhibition of the late response was also accompanied by decreases in CD25+ cells, presumed T lymphocytes and eosinophils. A significant correlation was observed between the decreases in IL-4 mRNA+ cells and in eosinophils after treatment (r = 0.46, P < 0.05). These results suggest that prolonged treatment with topical corticosteroid inhibits allergen-induced early and late nasal responses and the associated tissue eosinophilia, and that, at least in part, this may result from inhibition of cells expressing mRNA for IL-4.


Internal stress distribution in cervical intervertebral discs: the influence of an artificial cervical joint and simulated anterior interbody fusion.
There is concern that cervical interbody fusion can result in accelerated degenerative changes occurring at adjacent spinal levels. The cervical spine clearly evolved to be mobile. It would seem to be desirable for spinal surgeons to have an alternative to fusion, and spinal arthroplasty is an appealing concept. The Bristol Disc is a mechanical device comprising two articulating components that result in motion with 6 df. It has been shown to have favorable kinematics when compared with intact and fused cadaveric spines. The current study attempts to record changes in the distribution of stresses within cervical intervertebral discs adjacent to the artificial disc or a simulated fusion. The technique used to measure intradiscal stress distributions is based on earlier work by McNally and Adams on lumbar intervertebral discs. The study generated stress profiles through cervical intervertebral discs statically loaded in four different postures in addition to recording changes in intradiscal pressure within both the nucleus and the annulus during flexion. Similar stress profiles were recorded from intact specimens and those with the artificial joint inserted. The artificial joint resulted in reduced stresses in the annulus compared with spines with a simulated fusion. The study demonstrates how different testing conditions can result in researchers being confronted with paradoxical data, and the simulation of muscle forces is recommended.


Ethnic differences in mental health and lifestyle issues: results from multi-item general practice screening.
To determine ethnic differences in response, acceptance and desire to address problems identified by the multi-item screening tool (MIST). Patients were assessed using the MIST in urban Auckland. Fifty consecutive adult patients from 20 randomly selected practices completed the MIST and evaluation sheet before their consultation. All patients and general practitioners (GPs) completed feedback forms. Analysis adjusted for the clustered nature of the data. Participants were 1000 patients and 20 urban GPs. The participation rate was 87% of GPs and 97.75% of patients. Compared with New Zealand Europeans, Pacific Island people were significantly more likely to be concerned about abuse and anger control. Maori were significantly more likely to want help with cutting down their alcohol use. The screening tool was accepted by all patients (<1% objection rate) regardless of ethnicity. This is the first study to examine possible ethnic differences between primary care patients' response to screening on lifestyle behaviours and mental health issues.


Substance use, self-esteem, and depression among Asian American adolescents.
The relationship of self-esteem and depression with alcohol, tobacco, and other drug (ATOD) use was tested in a California statewide sample of more than 4,300 Asian American high school students comprising five subgroups: Chinese, Japanese, Korean, Filipino, and Vietnamese. Estimated prevalence rates of alcohol, tobacco, and marijuana use among males and females from these Asian American subgroups are presented. Correlations revealed that cigarette, alcohol, and marijuana use were generally more related to high depression and low self-esteem in females than in males. Logistic regression analysis with only the female subjects investigated whether the relationship between the psychological variables and ATOD use was maintained even after controlling for traditionally important constructs in ATOD use (grade level in school, born in the United States, ethnicity, and ATOD use by friends). These results indicated that for females, depression was significantly related to alcohol and tobacco use, but self-esteem was not. Neither self-esteem nor depression was a significant contributor to marijuana use. Issues related to the application of these results are discussed.


The impact of changing methods of data collection on the reliability of self-reported drug use of adolescents.
The purpose of this study is to determine the impact of different modes of data collection on the reliability of self-reported drug use of adolescents in a panel study. Adolescents were assigned to four groups based upon the ways they chose to respond to the survey instruments: 1) mailed questionnaires in both years, 2) survey interview in one year and mailed questionnaire in the next year, 3) mailed questionnaire in one year and survey interview in the following year, and 4) survey interview in both years. The quality of the self-reported data was examined in terms of return rates, missing data, internal consistency, and consistency of reported information over time. No significant differences were found between groups, suggesting that the mode of data collection does not affect the reliability of adolescents' self-reports of substance use.


Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation.
Gene transcription is required for long-term memory (LTM) formation. LTM formation is impaired in a male-specific manner in mice lacking either of the two Ca(2+)/calmodulin-dependent kinase kinase (Camkk) genes. Since altered transcription was suggested to cause these impairments in LTM formation, we used microarrays to screen for CaMKKbeta-dependent gene expression changes. Here we show that the hippocampal mRNA expression of two splicing factors, splicing factor arginine/serine-rich 3 (Sfrs3/Srp20) and polypyrimidine tract-binding protein-associated splicing factor (Psf), is altered in CaMKKbeta-deficient males. In wild-type (WT) mice, the basal expression level in the hippocampus is higher in males than in females, and the sex difference in Srp20 expression is detectable before puberty. Training in two hippocampus-dependent learning tasks, the spatial version of the Morris water maze (MWM) and background contextual fear conditioning, increases the hippocampal mRNA expression of both splicing factors in WT males. However, the increase in Srp20 mRNA expression occurs only in males and not in females, whereas the up-regulation of Psf expression occurs in both sexes. Importantly, control experiments demonstrate that the up-regulation of both splicing factors is specific for the learned associations after contextual fear conditioning. In summary, we provide the first evidence for a regulation of splicing factors during LTM formation and we suggest that alternative splicing contributes to sex differences in LTM formation.


[Stable tachycardia as a cause of heart failure].
The authors described a patient in whom the right vagus had been cut during removal of hormonally inactive chemodectoma in the bifurcation of the external and internal carotid arteries. Stable sinus and then atrial tachycardia (140-180 strokes per min.) developed on the operating table. Congestive cardiac insufficiency developed in 3 yrs. Treatment with diuretics cardiac glycosides was ineffective. Clinical and x-ray signs of cardiac insufficiency disappeared after atrial tachycardia was converted into atrial fibrillation with ventricular contractions up to 80 per min. A conclusion has been made that stable tachycardia causes the development of cardiac insufficiency.


Migration inhibitory factor and macrophage bactericidal function.
A homogeneous population of immunologically active lymphocytes was obtained from peritoneal exudates of guinea pigs with delayed hypersensitivity to bovine gamma globulin (BGG). The lymphocytes were cultured with and without BGG for 24 hr, and cell-free supernatant fluids were then assayed simultaneously for their ability to influence two in vitro parameters of macrophage function: migration from capillary tubes and bactericidal capacity. In four consecutive experiments, supernatants from antigenically stimulated lymphocytes exhibited substantial migration-inhibitory-factor activity without enhancing the ability of macrophages to kill Listeria monocytogenes. Lymphocyte lysates were inactive in both assays. Possible mechanisms of lymphocyte-macrophage interactions are discussed.


Platycodonis Radix Alleviates LPS-Induced Lung Inflammation through Modulation of TRPA1 Channels.
Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the lungs. The aim of this study was to determine the TRPA1-targeted effects of PR against pulmonary inflammation and to investigate the affinity of PR constituents for TRPA1 and their potential mechanisms of action. Using a C57BL/6J mouse lipopolysaccharides (LPS) intratracheal instillation pneumonia model and advanced analytical techniques (UPLC-Q-TOF-MS/MS, molecular docking, immuno-fluorescence), five platycodins were isolated from PR, and the interaction between these platycodins and hTRPA1 was verified. Additionally, we analyzed the impact of platycodins on LPS-induced TRPA1 expression and calcium influx in BEAS-2B cells. The results indicated that PR treatment significantly reduced the severity of LPS-triggered inflammation in the mouse model. Interestingly, there was a mild increase in the expression of TRPA1 caused by PR in healthy mice. Among five isolated platycodins identified in the PR extract, Platycodin D3 (PD3) showed the highest affinity for hTRPA1. The interaction between platycodins and TRPA1 was verified through molecular docking methods, highlighting the significance of the S5-S6 pore-forming loop in TRPA1 and the unique structural attributes of platycodins. Furthermore, PD3 significantly reduced LPS-induced TRPA1 expression and calcium ion influx in BEAS-2B cells, substantiating its own role as an effective TRPA1 modulator. In conclusion, PR and platycodins, especially PD3, show promise as potential lung inflammation therapeutics. Further research should explore the precise mechanisms by which platycodins modulate TRPA1 and their broader therapeutic potential.


Educational disparities in mortality among patients with type 2 diabetes in The Netherlands (ZODIAC-23).
Relative mortality differences between educational level in mortality have been reported among diabetic as well as among non-diabetic subjects in Europe, but data on absolute differences are lacking. We studied the effect of educational disparities on mortality in a Dutch prospective cohort of type 2 diabetes mellitus (T2DM) patients. This study was part of the ZODIAC study, a prospective observational study of patients with T2DM. Data on educational level were first collected on 19 May 1998, and from this date on, 858 patients were included in 1998; educational level was known for 656 patients. Vital status was assessed in 2009. The relationship between mortality and educational level was studied using a Cox proportional hazard model, the relative index of inequality (RII), slope index of inequality (SII) and the population attributable risk (PAR). Educational level was divided into four categories; the highest educational level was used as reference. After a median follow-up time of 9.7 years, 365 out of 858 patients had died. The hazard ratio of primary education for total mortality was 3.02 (95% CI 1.44-6.34). The RII was 2.85 (95% CI 1.21-6.67), the absolute difference in the risk for mortality (SII) was 384 deaths (95% CI 49-719) per 10,000 follow-up years. PAR for patients with the lowest level of education was 51.4%. A low educational level had a higher impact on mortality than having a macrovascular complication. Given the substantial differences in mortality between educational levels in T2DM, more understanding of underlying (modifiable) mechanisms is necessary.


Method for Analyzing the Molecular and Carbon Isotope Composition of Volatile Hydrocarbons (C1-C9) in Natural Gas.
Solid-phase microextraction (SPME) coupled with gas chromatography-isotope ratio mass spectrometry (GC-IRMS) has already been applied to collect and identify volatile light hydrocarbons in oil and source rocks. However, this technology has not yet been used to analyze volatile light hydrocarbons in dry gas (natural gas with C1/C2+ > 95%). In this study, we developed a method to measure the molecular and carbon isotope composition of natural gas using divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber. This fiber proved to be suitable for extracting C1-C9 hydrocarbons from natural gas without inducing carbon isotopic fractionation. Notably, the extraction coefficients of the analytes were not the same but rather increased with the increasing carbon number of the hydrocarbons. Nevertheless, we successfully identified 24 hydrocarbons from the in-lab standard natural gas, while also obtaining the carbon isotope composition of C1 to C9 hydrocarbons with satisfying repeatability. The relative standard deviation (RSD) of the molecular composition data was in the range of 0.06-0.74%, with the RSDs of the carbon isotope composition data not exceeding 1‰. Finally, seven natural gas samples, collected from different sedimentary basins, were successfully analyzed and the stable carbon isotope compositions of C1-C9 hydrocarbons present in these were determined through this method. Overall, the new approach provides a simple but useful technique to obtain more geochemical information about the source and evolution of natural gas.


Enhanced small group instruction using choral responding and student interaction for children with autism and developmental disabilities.
The use of effective instructional strategies in small groups was investigated to determine learning effects for 24 elementary age students with autism and developmental disabilities. Effective strategies included (a) the use of choral responding; (b) the use of student-to-student responding; (c) the rotation of materials every 5 minutes during the 30-minute group while teaching 2 to 3 concepts; and (d) the use of random, unpredictable trials for student responding. Thirty-minute language groups were targeted to teach receptive and expressive skills using pictures and common objects across five categories (e.g., household items, foods). Results showed increased opportunities to respond, increased levels of responding and academic engagement, higher gains on weekly criterion-referenced pre- and posttests, and decreased passive and inappropriate student behavior during interventions.


Prevalence of Brucella spp in humans.
to determine the seroprevalence of Brucella spp in humans. this is an observational study, developed with 455 individuals between 18 and 64 years old, who use the Estratégia de Saúde da Família (Brazil's family health strategy). The serum samples of volunteers underwent buffered acid antigen tests, such as screening, agar gel immunodiffusion and slow seroagglutination test in tubes and 2-Mercaptoethanol. among the samples, 1.98% has responded to buffered-acid antigen, 2.85% to agar gel immunodiffusion test and 1.54% to the slow seroagglutination tests on tubes/2-Mercaptoethanol. The prevalence of Brucella spp was 4.4%, represented by the last two tests. the results of this research suggest that the studied population is exposed to Brucella spp infection.


The emergence and transmission dynamics of HIV-1 CRF07_BC in Mainland China.
A total of 1155 partial pol gene sequences of human immunodeficiency virus (HIV)-1 CRF07_BC were sampled between 1997 and 2015, spanning 13 provinces in Mainland China and risk groups [heterosexual, injecting drug users (IDU), and men who have sex with men (MSM)] to investigate the evolution, adaptation, spatiotemporal and risk group dynamics, migration patterns, and protein structure of HIV-1 CRF07_BC. Due to the unequal distribution of sequences across time, location, and risk group in the complete dataset ('full1155'), subsampling methods were used. Maximum-likelihood and Bayesian phylogenetic analysis as well as discrete trait analysis of geographical location and risk group were carried out. To study mutations of a cluster of HIV-1 CRF07_BC (CRF07-1), we performed a comparative analysis of this cluster to the other CRF07_BC sequences ('backbone_295') and mapped the mutations observed in the respective protein structure. Our findings showed that HIV-1 CRF07_BC most likely originated among IDU in Yunnan Province between October 1992 to July 1993 [95 per cent hightest posterior density (HPD): May 1989-August 1995] and that IDU in Yunnan Province and MSM in Guangdong Province likely served as the viral sources during the early and more recent spread in Mainland China. We also revealed that HIV-1 CRF07-1 has been spreading for roughly 20 years and continues to cause local transmission in Mainland China and worldwide. Overall, our study sheds light on the dynamics of HIV-1 CRF07_BC distribution patterns in Mainland China. Our research may also be useful in formulating public health policies aimed at controlling acquired immune deficiency syndrome in Mainland China and globally.


Silent Migration of a Left Common Iliac Venous Stent to the Right Atrium: A Case Report and Review of Literature.
In the past decade, percutaneous endovenous stenting has emerged as the primary procedure for treating symptomatic venous outflow obstruction. Stent migration is a rare but serious and well-recognized complication of venous stenting. Cardiopulmonary complications following stent migration can manifest in a number of ways, including damage to the valves, arrhythmias, endocarditis, tamponade, and acute heart failure. Both extracardiac and intracardiac dislodgement of stents may be treated with catheter-directed extraction, stent redeployment, or surgical extraction. The decision on the type of procedure depends on multiple factors including the location of the stent, the size and accessibility of the stent, the symptoms, the extent of damage to the vital structures, and the overall health of the patient. We present the case of a 68-year-old male who presented with tachycardia. On further evaluation and workup, he was found to have an iliac venous stent that had migrated to the right atrium.


Injection site radioactivity of (99m)Tc-labeled mannosylated dextran for sentinel lymph node mapping.
The high and persistent radioactivity at the injection site hinders the accuracy and expansion of sentinel lymph node (SLN) mapping. We investigated the mechanism underlying the undesirable radioactivity after subcutaneous injection of (99m)Tc-labeled mannosylated dextran ((99m)Tc(CO)3-DCM20), a SLN mapping agent targeting mannose receptors on macrophages and dendritic cells, in a mouse model. Biodistribution studies were performed 1 h after subcutaneous injection of (99m)Tc(CO)3-DCM20 from the rear footpad of mice in the presence of varying molar amounts of DCM20 or DC15, a modified dextran without mannose. Biodistribution studies were also conducted after subcutaneous injection of [(125)I]radioiodinated mannosyl-neoglycoalbumin ((125)I-NMA) from the rear footpad. The distribution of fluorescence-labeled DCM20 and DC15 at the injection site was also compared 1 h after subcutaneous injection by immunofluorescent histochemistry. The radioactivity levels of (99m)Tc(CO)3-DCM20 at the injection site and popliteal lymph node, a SLN in this model, decreased with an increase in the molar amounts of DCM20, whereas no significant changes in biodistribution were observed after injection of (99m)Tc(CO)3-DCM20 with varying molar amounts of DC15. (125)I-NMA exhibited rapid elimination of radioactivity from both the popliteal lymph node and the injection site. The fluorescence-labeled DCM20 colocalized well with CD68-positive cells such as macrophages and dendritic cells at the injection site. While partial colocalization was observed between DC15 and CD68-positive cells, the signal intensity was very weak. These findings suggest that specific binding of (99m)Tc(CO)3-DCM20 to the mannose receptor on macrophages and dendritic cells would be responsible for the sustained radioactivity levels at the injection site. These results also imply that discriminated blockage of (99m)Tc(CO)3-DCM20 binding to mannose receptors at the injection sites would reduce the radioactivity at the injection site.


Myristoyl's dual role in allosterically regulating and localizing Abl kinase.
c-Abl kinase, a key signaling hub in many biological processes ranging from cell development to proliferation, is tightly regulated by two inhibitory Src homology domains. An N-terminal myristoyl modification can bind to a hydrophobic pocket in the kinase C-lobe, which stabilizes the autoinhibitory assembly. Activation is triggered by myristoyl release. We used molecular dynamics simulations to show how both myristoyl and the Src homology domains are required to impose the full inhibitory effect on the kinase domain and reveal the allosteric transmission pathway at residue-level resolution. Importantly, we find myristoyl insertion into a membrane to thermodynamically compete with binding to c-Abl. Myristoyl thus not only localizes the protein to the cellular membrane, but membrane attachment at the same time enhances activation of c-Abl by stabilizing its preactivated state. Our data put forward a model in which lipidation tightly couples kinase localization and regulation, a scheme that currently appears to be unique for this non-receptor tyrosine kinase.


Circumstances that promote social connectedness in older adults participating in intergenerational programmes with adolescents: a realist review.
Limited social connectedness in older adults is a risk factor for poor physical and mental health. Older adults who are socially isolated, lonely and disconnected have a higher risk of chronic illness, depression and premature death. Current literature suggests that improved social connectedness reduces these risks. Intergenerational programmes are an effective way to improve health outcomes. Despite this, there is yet to be a review using realist review methods that seeks to identify the circumstances that promote social connectedness in older adults participating in intergenerational programmes with adolescents. A realist review methodology was chosen to account for the complexity of intergenerational interventions. Nine studies were included. In line with realist review methodology, iterative data extraction and analysis was conducted to identify the specific contexts, mechanisms and outcomes of the programmes. Specific circumstances were identified to develop theories relating to improved social connectedness in older adults. MEDLINE, PsycINFO, CINAHL were searched using English language limitation. Included participants were aged 65 and over (older adults) and between 13 and 19 years (adolescents) participating in intergenerational programmes from non-familial generations. Studies had to be published in English between 2000 and 2020 and could be quantitative, qualitative or mixed-methods primary research studies. Two independent reviewers used a bespoke data extraction form. All authors were involved in the synthesis process which used the extracted data to illuminate the contexts, mechanisms and outcomes that underpinned reviewed programmes. The nine included studies were set in different contexts, including community organisations, schools and aged care facilities. They used an array of interventions including reminiscence therapy, craft or space for conversation. Despite study heterogeneity, the parallels in psychosocial development between older adults and adolescents were shown to be a likely driver for improved social health outcomes. Programmes most likely to improve social health outcomes were those that acknowledged psychosocial development, were delivered in community settings, leveraged pedagogical frameworks, used trained facilitators and supported participants to build relationships through shared purpose. This review contributes a logic model to support the design and development of intergenerational programmes involving adolescents to improve social connectedness in older adults. Future research to test the logic model in practice is needed.


Can microRNAs improve the management of lung cancer patients? A clinician's perspective.
The treatment of patients with lung cancer is increasingly individualised. Rather than treating lung cancer as a single disease, clinicians are often called upon to consider the precise histology and molecular biology of each tumour in addition to the individual characteristics of each patient. Paralleling advances in lung cancer management, advances in the detection of lung cancer are changing practice. Lung cancer screening promises to find disease at a curable stage; however, the high false positive rate in screening trials has clinical and fiscal ramifications which demand attention. Biomarkers able to stratify for the risk of cancer, prognosticate the course of disease, or predict the response to treatment are in increasing demand. This paper summarizes some of the clinical problems faced by those treating lung cancer patients, and examines how knowledge about the role of microRNAs in lung cancer biology may change patient management.


Effect of topical levocabastine on allergic and non-allergic perennial rhinitis. A double-blind study, levocabastine vs. placebo, followed by an open, prospective, single-blind study on beclomethasone.
Forty-four patients, with symptoms of nasal obstruction, sneezing, itching and/or rhinorrhea, were entered into a placebo-controlled, double-blind study to evaluate the clinical efficacy of a topical antihistamine drug, levocabastine, applied 4 times a day for 14 days. At the end of the treatment the placebo patients were treated with levocabastine and the levocabastine patients were treated with beclomethasone dipropionate in a single-blind design for another 14 days. This study showed that levocabastine is significantly more active than placebo with reference to nasal discharge and sneezing. Placebo application improved the symptom score. Levocabastine could not be proved to be more effective against nasal obstruction than placebo in the double-blind trial. In the single-blind set-up, levocabastine resulted in an additional improvement in the score for obstruction, after the placebo period. Although the allergic group tended to respond better, no statistically significant difference could be detected between allergic and non-allergic patients. After treatment with levocabastine, beclomethasone dipropionate administration could not improve the results for nasal discharge and sneezing. For nasal congestion, beclomethasone dipropionate proved to be superior to levocabastine.


Will Angiosocopy Replace Operative Arteriography in the 1990s?
Vascular surgeons have always been concerned with the intra-operative assessment of their reconstructions. Failure of vascular reconstructions in the early post-operative period is most commonly a result of a technical error at the time of surgery. Hence, any technique which aids the vascular surgeon in evaluating his reconstruction and in preventing technical errors will be beneficial to both the surgeon and their patient. Traditionally, intra-operative arteriography has been the 'gold standard' for evaluating vascular surgical procedures.