Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus.
New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 μg (2.5 μM)/300 g/twice a week for DM2 and 7.18 μg (4.8 μM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.


Optical chiral metamaterials: a review of the fundamentals, fabrication methods and applications.
Optical chiral metamaterials have recently attracted considerable attention because they offer new and exciting opportunities for fundamental research and practical applications. Through pragmatic designs, the chiroptical response of chiral metamaterials can be several orders of magnitude higher than that of natural chiral materials. Meanwhile, the local chiral fields can be enhanced by plasmonic resonances to drive a wide range of physical and chemical processes in both linear and nonlinear regimes. In this review, we will discuss the fundamental principles of chiral metamaterials, various optical chiral metamaterials realized by different nanofabrication approaches, and the applications and future prospects of this emerging field.


Identifying Higher-Volume Antibiotic Outpatient Prescribers Using Publicly Available Medicare Part D Data - United States, 2019.
Antibiotic prescribing can lead to adverse drug events and antibiotic resistance, which pose ongoing urgent public health threats (1). Adults aged ≥65 years (older adults) are recipients of the highest rates of outpatient antibiotic prescribing and are at increased risk for antibiotic-related adverse events, including Clostridioides difficile and antibiotic-resistant infections and related deaths (1). Variation in antibiotic prescribing quality is primarily driven by prescribing patterns of individual health care providers, independent of patients' underlying comorbidities and diagnoses (2). Engaging higher-volume prescribers (the top 10% of prescribers by antibiotic volume) in antibiotic stewardship interventions, such as peer comparison audit and feedback in which health care providers receive data on their prescribing performance compared with that of other health care providers, has been effective in reducing antibiotic prescribing in outpatient settings and can be implemented on a large scale (3-5). This study analyzed data from the Centers for Medicare & Medicaid Services (CMS) Part D Prescriber Public Use Files (PUFs)* to describe higher-volume antibiotic prescribers in outpatient settings compared with lower-volume prescribers (the lower 90% of prescribers by antibiotic volume). Among the 59.4 million antibiotic prescriptions during 2019, 41% (24.4 million) were prescribed by the top 10% of prescribers (69,835). The antibiotic prescribing rate of these higher-volume prescribers (680 prescriptions per 1,000 beneficiaries) was 60% higher than that of lower-volume prescribers (426 prescriptions per 1,000 beneficiaries). Identifying health care providers responsible for a higher volume of antibiotic prescribing could provide a basis for additional assessment of appropriateness and outreach. Public health organizations and health care systems can use publicly available data to guide focused interventions to optimize antibiotic prescribing to limit the emergence of antibiotic resistance and improve patient outcomes.


Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations.
Five new AuIII -peptidodithiocarbamato complexes of the type [AuIII Br2 (dtc-AA1 -AA2 -OR] (in which AA1 =N-methylglycine (Sar), l/d-Pro; AA2 =l/d-Ala, α-aminoisobutyric acid (Aib); R=OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/or the chiral amino acid configuration, were designed to enhance tumor selectivity and bioavailability. The gold(III)-based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptide transporters (namely PEPT1 and PEPT2), which are upregulated in several tumor cells. The compounds were synthesized and fully characterized, mainly by means of elemental analysis, one- and two-dimensional NMR spectroscopy, FT-IR, and UV/Vis spectrophotometry. The crystal structures of three compounds were also solved by X-ray diffraction. In vitro cytotoxicity studies using a panel of human tumor cell lines (A549 [non-small-cell lung carcinoma], MCF-7 [breast cancer], A2780 [ovarian carcinoma], H1975 [non-small-cell lung carcinoma], H460 [large-cell lung carcinoma], and A431 [human epidermoid carcinoma]) showed the dtc-Pro-Aib-OtBu derivative to be very effective, with GI50 values much lower than those of cisplatin. This complex was thus selected for evaluating stability under physiological conditions and possible interactions with serum albumin, as well in PARP-1 enzyme inhibition assays and preliminary ex vivo toxicity experiments on healthy rat tissues.


Generation of Cascades of Care for Diabetes and Hypertension Care Continuum in Cambodia: Protocol for a Population-Based Survey Protocol.
Cardiovascular diseases (CVDs) were accountable for 24% of the total deaths in Cambodia, one of the low- and middle-income countries, where primary health care (PHC) settings generally do not perform well in the early detection, diagnosis, and monitoring of leading risk factors for CVDs, that is, type 2 diabetes (T2D) and hypertension (HT). Integrated care for T2D and HT in the Cambodian PHC system remains limited, with more than two-thirds of the population never having had their blood glucose measured and more than half of the population with T2D having not received treatment, with only few of them achieving recommended treatment targets. With regard to care for T2D and HT in the public health care system, 3 care models are being scaled up, including (1) a hospital-based model, (2) a health center-based model, and (3) a community-based model. These 3 care models are implemented in isolation with relatively little interaction between each other. The question arises as to what extent the 3 care models have performed in providing care to patients with T2D or HT or both in Cambodia. This protocol aims to show how to use primary data from a population-based survey to generate data for the cascades of care to assess the continuum of care for T2D and HT across different care models. We adapt the HIV test-treat-retain cascade of care to assess the continuum of care for patients living with T2D and HT. The cascade-of-care approach outlines the sequential steps in long-term care: testing, diagnosis, linkage with care, retention in care, adherence to treatment, and reaching treatment targets. Five operational districts (ODs) in different provinces will be purposefully selected out of 103 ODs across the country. The population-based survey will follow a multistage stratified random cluster sampling, with expected recruitment of 5280 eligible individuals aged 40 and over as the total sample size. Data collection process will follow the STEPS (STEPwise approach to NCD risk factor surveillance) survey approach, with modification of the sequence of the steps to adapt the data collection to the study context. Data collection involves 3 main steps: (1) structured interviews with questionnaires, (2) anthropometric measurements, and (3) biochemical measurements. As of December 2021, the recruitment process was completed, with 5072 eligible individuals participating in the data collection; however, data analysis is pending. Results are expected to be fully available in mid-2022. The cascade of care will allow us to identify leakages in the system as well as the unmet need for care. Identifying gaps in the health system is vital to improve efficiency and effectiveness of its performance. This study protocol and its expected results will help implementers and policy makers to assess scale-up and adapt strategies for T2D and HT care in Cambodia. International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN41932064; https://www.isrctn.com/ISRCTN41932064. DERR1-10.2196/36747.


Effect of Exogenous Abscisic Acid on Proline Dehydrogenase Activity in Maize (Zea mays L.).
Plant responses to drought stress include proline and abscisic acid (ABA) accumulation. Proline dehydrogenase (PDH) (EC 1.4.3) is the first enzyme in the proline oxidation pathway, and its activity has been shown to decline in response to water stress (PJ Rayapati, CR Stewart [1991] Plant Physiol 95: 787-791). In this investigation, we determined whether ABA treatment affects PDH activity in a manner similar to drought stress in maize (Zea mays L.) seedlings. Four exogenous ABA treatments (0, 11, 33, and 100 micromolar ABA) were applied to well-watered maize seedlings. Mitochondria were isolated and PDH was solubilized using Nonidet P-40. PDH activity was measured by the reduction of iodonitrotetrazolium violet under proline-dependent conditions. There was no effect of ABA on PDH activity at 33 and 100 micromolar ABA, but there was a 38% decline at 11 micromolar. This decline was less than the 69% reduction in activity under drought stress. Endogenous ABA determinations and plant growth rate showed that ABA entered the plant and was affecting metabolic processes. ABA treatments had a small effect on shoot and root proline concentration, whereas drought stress caused a 220% increase in root tissues. We conclude that ABA is not part of the pathway linking drought stress and decreased PDH activity.


Implementing best practices for the provision of long-acting reversible contraception: a survey of obstetrician-gynecologists.
To examine obstetrician-gynecologists' practices regarding provision of long-acting reversible contraceptive (LARC) methods same-day, immediately postpartum, or to women under age 21. Between August 2016 and March 2017, the American College of Obstetricians and Gynecologists (ACOG) sent 2500 of their members an electronic survey questionnaire regarding the provision of LARC methods. ACOG mailed nonresponders paper surveys. After exclusions, the final sample was 1280 respondents (52.2% response rate). Although 91% of obstetrician-gynecologists reported providing IUDs, only 29% (95% CI, 26-32%) offered same-day placement. Ninety-two percent (95% CI, 90-94%) offered IUDs to eligible patients under age 21. Nineteen percent (95% CI, 16.1-21.3%) offered immediate postpartum IUD placement and 21% (95% CI, 18-23%) offered immediate postpartum implant placement. Obstetrician-gynecologists practicing in states where Medicaid reimbursed for immediate postpartum LARC devices within the global fee for delivery (versus separate reimbursement) had lower odds of offering them. While most ob-gyns are offering IUDs to women under age 21, many are still not offering them same-day. A minority of ob-gyns offer either IUDs or implants immediately postpartum, and there are important geographic and practice setting disparities in this practice. Efforts to align LARC practices with published evidence and improve access to LARC methods for women desiring them will require a multipronged effort including continuing education of physicians, patient education and outreach, as well as advocacy to improve insurance coverage and reimbursement.


Pine Engravers Carry Bacterial Communities Whose Members Reduce Concentrations of Host Monoterpenes With Variable Degrees of Redundancy, Specificity, and Capability.
Bark beetles are eruptive forest insects that have the potential to cause landscape level mortality to conifer forests. The pine engraver, Ips pini (Say) (Coleoptera: Curculionidae), is the predominant pest of mature red pine (Pinus resinosa Aiton) plantations throughout the Great Lakes region of North America. Pine engraver attack elicits a localized response by host trees in which concentrations of terpenes rapidly exceed the tolerance levels of beetles and their fungal associates. We considered how bacterial associates degrade these toxins from the perspective of the symbiont communities of individual beetles. We demonstrate that 1) most pine engravers harbor bacterial communities that reduce monoterpene concentrations in vivo; 2) several individual bacterial isolates can reduce monoterpenes even at high concentrations; and 3) bacteria isolated from pine engravers are similar to those found in other bark beetles. Bacteria isolated from pine engravers decreased concentrations of (-)-α-pinene, myrcene, and 3-carene. Most beetles carried at least one bacterial isolate that reduced concentrations of at least one monoterpene. Different bacteria vary in the uppermost concentrations at which they can degrade monoterpenes. The community of bacteria associated with an individual beetle appears to have some manner of functional redundancy that could collectively increase the likelihood of successful host colonization.


Using a magnetic field to redirect an oncolytic adenovirus complexed with iron oxide augments gene therapy efficacy.
Adenovirus (Ad) is a widely used vector for cancer gene therapy but its therapeutic efficacy is limited by low coxsackievirus and adenovirus receptor (CAR) expression in tumors and non-specifically targeted infection. Ad infectivity and specificity can be markedly improved by creating Ad-magnetic nanoparticles cluster complexes and directing their migration with an external magnetic field (MGF). We electrostatically complexed GFP-expressing, replication-incompetent Ad (dAd) with PEGylated and cross-linked iron oxide nanoparticles (PCION), generating dAd-PCION complexes. The dAd-PCION showed increased transduction efficiency, independent of CAR expression, in the absence or presence of an MGF. Cancer cell killing and intracellular oncolytic Ad (HmT)-PCION replication significantly increased with MGF exposure. Site-directed, magnetically-targeted delivery of the HmT-PCION elicited significantly greater therapeutic efficacy versus treatment with naked HmT or HmT-PCION without MGF in CAR-negative MCF7 tumors. Immunohistochemical tumor analysis showed increased oncolytic Ad replication in tumors following infection by HmT-PCION using an MGF. Whole-body bioluminescence imaging of tumor-bearing mice showed a 450-fold increased tumor-to-liver ratio for HmT-PCION with, versus without, MGF. These results demonstrate the feasibility and potential of external MGF-responsive PCION-coated oncolytic Ads as smart hybrid vectors for cancer gene therapy.


ADAMTS13-binding IgG are present in patients with thrombotic thrombocytopenic purpura.
Functional assays are commonly used to measure the antibodies of ADAMTS13 found in patients of thrombotic thrombocytopenic purpura (TTP). In this study we used an enzyme-linked immunoassay to analyze the ADAMTS13-binding IgG levels in six groups of individuals: normal, random hospitalized patients, acute TTP, TTP after receiving plasma therapy, TTP in remission, and other types of thrombotic microangiopathy (TMA). The results showed that ADAMTS13-binding IgG levels were elevated in 100% of the acute TTP group, 75% of the TTP group after receiving plasma therapy, and 40% of the remission group. Overall, the ADAMTS13-binding IgG levels correlated with the inhibitory activity levels againstADAMTS13 (r = -0.69, P < 0.0001). The assay also detected elevated IgG binding levels in 5% - 15% of the normal, random, and other TMA control groups. Addition of purified ADAMTS13 protein to the plasma samples suppressed the IgG binding in each of the acute TTP patients, but in none of the non-TTP groups. Serial measurement in a patient that had two exacerbations of TTP within the first three weeks revealed that the ADAMTS13 activity levels remained <0.1 U/ml during this period, and the ADAMTS13-binding IgG remained elevated, suggesting that ADAMTS13 analysis may provide valuable insight to the disease status during the course of therapy. Analysis of ADAMTS13-binding IgG is helpful for the diagnosis and management of TTP.


A Role of Production on E-Commerce and Foreign Policy Influencing One Belt One Road: Mediating Effects of International Relations and International Trade.
One Road One Belt has made a drastic change not only to the lives of people but also to their minds and future prospective. This initiative has connected not only countries but has consolidated trading patterns. It has not only impacted physical trade but has also boosted the e-commerce of China. Therefore, this study has tried to find the major patterns of trading across the globe and digital commerce considering the factors of production. China, being the cheapest country for manufacturing, has excelled in the e-commerce as well. The targeted population for this study was contractors, marketers, logistic service providers, and engineers. The sample size in this study was 329. Data collection was done through a survey developed on the Likert scale. The software used for the data analysis was Smart-PLS for structural equation modeling. Findings of the study show that factors of production and international trade have an impact on e-commerce. Moreover, the foreign policy and international relations have also been found to have a significant role in e-commerce (digital entrepreneurship).


Using data to reduce hospital readmissions.
This article describes the importance and the development of data concerning hospital readmissions as an outcomes indicator. It emphasizes the need for consistent definition of readmissions according to time intervals and diagnostic categories. It describes the development of readmission information using computer abstract databases to ensure consistency of indicators. It also provides examples of data developed through this approach.


Intussusception: influence of age on reducibility.
Our experience of hydrostatic reduction of intussusception by barium enema over the last 7 years is reviewed. There were 115 attempted hydrostatic reductions out of a total of 129 patients diagnosed as having intussusception on barium enema or at surgery. Age at presentation varied from one month to nine years, 81% of patients presenting before one year of age. Of 115 attempted reductions, 63 were successful giving an overall success rate of 55%. Looking at the different age groups, it was found that hydrostatic reduction was much less successful in infants aged 3 months and younger; success rate 20% compared to a 60% success rate in the remainder. Conscious of recent reports in the literature of bowel perforation during attempted hydrostatic reduction in young infants, we suggest that there should be a reappraisal of the role of hydrostatic reduction in the three months and younger age group.


Increased levels of peroxisomal active oxygen-related enzymes in copper-tolerant pea plants.
The effect in vivo of high nutrient levels of copper (240 micromolar) on the activity of different metalloenzymes containing Cu, Mn, Fe, and Zn, distributed in chloroplasts, peroxisomes, and mitochondria, was studied in leaves of two varieties of Pisum sativum L. plants with different sensitivity to copper. The metalloenzymes studied were: cytochrome c oxidase, Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase I (Cu,Zn-SOD I), for mitochondria; catalase and Mn-SOD, for peroxisomes; and isozyme Cu,Zn-SOD II for chloroplasts. The activity of mitochondrial SOD isozymes (Mn-SOD and Cu,Zn-SOD I) was very similar in Cu-tolerant and Cu-sensitive plants, whereas cytochrome c oxidase was lower in Cu-sensitive plants. Chloroplastid Cu,Zn-SOD activity was the same in the two plant varieties. In contrast, the peroxisomal Mn-SOD activity was considerably higher in Cu-tolerant than in Cu-sensitive plants, and the activity of catalase was also increased in peroxisomes of Cu-tolerant plants. The higher activities of these peroxisomal active oxygen-related enzymes in Cu-tolerant plants suggest the involvement of reactive oxygen intermediates (O(2) (-), OH) in the mechanism of Cu lethality, and also imply a function for peroxisomal Mn-SOD in the molecular mechanisms of plant tolerance to Cu in Pisum sativum L.


The distribution of transcripts of neurogenic genes in neurogenic mutants of Drosophila melanogaster.
The neurogenic genes of Drosophila melanogaster are required for correct separation of neural and epidermal progenitor cells during early embryogenesis. Results from genetic analyses indicate that the neurogenic genes are functionally related. We have studied the spatial distribution of RNA from the neurogenic genes D1, neu, and m4, m5, m7 and E(spl) [four genes of the Enhancer of split complex] in various neurogenic mutant embryos by in situ hybridization. An abnormal distribution of RNA from certain of the genes is found in neurogenic mutants, suggesting that at least some of the functional interactions inferred from genetic data take place at the transcriptional level. We discuss these results in relation to the events of early neurogenesis.


Volatiles of French ferns and "fougère" scent in perfumery.
Six French ferns were investigated for volatile organic compounds (VOC) by GC-MS using organic solvent extraction. Seventy-seven VOC biosynthesized from the shikimic, lipidic and terpenic pathways, including isoprenoid derivatives, were identified from these putative natural resources. Asplenium trichomanes subsp. trichomanes contained mainly polyketides with an oily or waxy odor. (E)-2-Hexenal and (Z)-3-hexenol, responsible for the "green odor", were found in high contents in Polystichum setiferum, Dryopteris dilatata and Phegopteris connectilis. In the last, 7.4% of coumarin with a cut hay scent was highlighted from the volatile fraction. (E)-3-Hexenoic acid and (E)-2-hexenoic acid, both with herbal and fruity notes, were identified in Gymnocarpium dryopteris and Pteridium aquilinum. 1-Octen-3-ol, well-known for its mushroom-like odor, was abundant in all analyzed French ferns. While the "fougère" fragrance is claimed by the perfumers to be a fantasy scent, coumarin, (E)-2-hexenal, (Z)-3-hexenol and 1-octen-3-ol are the main odorous components of the perfumes belonging to the fougère accord family. This suggests that the fougère scent from the perfumers' imagination is a natural fragrance.


Distinctions of bipolar disorder symptoms in adolescence.
Bipolar disorder in adolescents is a serious mental illness with problematic diagnosis that adversely affects social, academic, emotional, and family functioning. The objective of this study was to analyze features of premorbid and clinical symptoms, comorbidity, and course of bipolar disorder in adolescence. Data for analysis were collected from all case histories (N=6) of 14-18-year-old patients, hospitalized with diagnosis of bipolar disorder in the Unit of Children's and Adolescents' Psychiatry, Department of Psychiatry, Hospital of Kaunas University of Medicine, during the period from 2000 to 2005. Analysis of bipolar disorder course showed that five patients previously had been diagnosed with an episode of depression. The most frequent symptoms typical to bipolar disorder were disobedience and impulsive behavior, rapid changes of mood. The most common premorbid features were frequent changes of mood, being active in communication, hyperactive behavior. Adolescence-onset bipolar disorder was frequently comorbid with emotionally instable personality disorder, borderline type. Findings of the study confirm the notion that oppositional or impulsive behavior, rapid changes of mood without any reason, dysphoric mood and euphoric mood episodes with increased energy were cardinal symptoms of bipolar disorder with mania in adolescents. Most frequent premorbid features of these patients were quite similar to attention-deficit/hyperactivity disorder making differential diagnosis problematic.


Physical and functional interaction of HIV-1 Tat with E2F-4, a transcriptional regulator of mammalian cell cycle.
Tat protein of the human immunodeficiency virus type-1 (HIV-1) plays a critical role in the regulation of viral transcription and replication. In addition, Tat regulates the expression of a variety of cellular genes and could account for AIDS-associated diseases including Kaposi's Sarcoma and non-Hodgkin's lymphoma by interfering with cellular processes such as proliferation, differentiation, and apoptosis. The molecular mechanisms underlying the pleiotropic activities of Tat may include the generation of functional heterodimers of Tat with cellular proteins. By screening a human B-lymphoblastoid cDNA library in the yeast two-hybrid system, we identified E2F-4, a member of E2F family of transcription factors, as a Tat-binding protein. The interaction between Tat and E2F-4 was confirmed by GST pull-down experiments performed with cellular extracts as well as with in vitro translated E2F-4. The physical association of Tat and E2F-4 was confirmed by in vivo binding experiments where Tat.E2F-4 heterodimers were recovered from Jurkat cells by immunoprecipitation and immunoblotting. By using plasmids expressing mutant forms of Tat and E2F-4, the domains involved in Tat.E2F-4 interaction were identified as the regions encompassing amino acids 1-49 of Tat and amino acids 1-184 of E2F-4. Tat x E2F-4 complexes were shown to bind to E2F cis-regions with increased efficiency compared with E2F-4 alone and to mediate the activity of E2F-dependent promoters including HIV-1 long terminal repeat and cyclin A. The data point to Tat as an adaptor protein that recruits cellular factors such as E2F-4 to exert its multiple biological activities.


Wireless capsule endoscopy in detecting small-intestinal polyps in familial adenomatous polyposis.
To detect the prevalence of small bowel polyps by wireless capsule endoscopy (WCE) in patients with familial adenomatous polyposis (FAP). We examined prospectively 14 patients with FAP to assess the location, size and number of small-intestinal polyps. Patients' age, sex, years of observation after surgery, type of surgery, duodenal polyps and colorectal cancer at surgery were analyzed. During WCE, polyps were detected in 9/14 (64.3%) patients. Duodenal adenomatous polyps were found in nine (64.3%) patients, and jejunal and ileal polyps in seven (50%) and eight (57.1%), respectively. The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps. Identification of the ampulla of Vater was not achieved with WCE. Importantly, the findings of WCE had no immediate impact on the further clinical management of FAP patients. No procedure-related complications were observed in the patients. WCE is a promising noninvasive new method for the detection of small-intestinal polyps. Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.


Impact of FODMAP Content Restrictions on the Quality of Diet for Patients with Celiac Disease on a Gluten-Free Diet.
Restrictive diets as gluten-free (GFD) or reduced in Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) are used to improve gastrointestinal (GI) symptoms in sensitive individuals. Aiming at comparing the nutritional quality and effects of a regular GFD regimen (R-GFD) and a low-FODMAP GFD (LF-GFD), in 46 celiac patients with persistent GI symptoms we conducted a randomized, double-blind intervention-controlled study. Patients received a personalized diet, either a strict GFD (n = 21) or a LF-GFD (n = 25) for 21 days. A validated food-frequency questionnaire before intervention and a 7-day weighed-food record after the intervention assessed the diets. Patients were 41.1 ± 10.1 years (mean ± SD), 94% women, with mean BMI 21.8 ± 2.9 kg/m2. On day 21, patients on R-GFD still showed poor nutritional adequacy compared to dietary recommendations, with decreased energy intake, even though an improvement in carbohydrates and folates was observed (all p < 0.025). In both groups, intake of iron, calcium, vitamin D, sodium and folates did not meet daily recommendations. As expected, consumption of legumes and grains was lower and that of fruits was higher in the LF-GFD group than in the R-GFD one (all p < 0.05). The nutritional quality of both diets was not different. When restrictive diets are useful to improve the persistent GI symptoms, careful nutritional surveillance and counseling is mandatory.


Importance of the E-46-D-160 polypeptide segment of the non-penicillin-binding module for the folding of the low-affinity, multimodular class B penicillin-binding protein 5 of Enterococus hirae.
Compared with the other class B multimodular penicillin- binding proteins (PBPs), the low-affinity PBP5 responsible for penicillin resistance in Enterococcus hirae R40, has an extended non-penicillin-binding module because of the presence of an approximately 110-amino-acid E-46(-)D-160 insert downstream from the membrane anchor. Expression of pbp5 genes lacking various parts of the insert-encoding region gives rise to proteins that are inert in terms of penicillin binding, showing that during folding of the PBP, the insert plays a role in the acquisition of a correct penicillin-binding configuration by the G-364(-)Q-678 carboxy-terminal module.


Stress fracture of the femoral neck as a complication of revision arthroplasty of the knee: a case report.
Stress fracture of the femoral neck is a rare complication of total knee arthroplasty. We report a case of femoral neck fracture following revision arthroplasty of the ipsilateral knee. Contributing factors may have been the patient's osteoporosis and a period of immobilisation before the revision arthroplasty. The patient was treated successfully with hemiarthroplasty of the hip. In patients who have undergone total knee arthroplasty, complaints of groin pain that radiates to the involved knee should alert to the possibility of a stress fracture of the femoral neck.


[Preadaption to nitrogen anesthesia and impairment of brain cortex structure in rats during hypoxia].
The attenuating effect of various variants of hypoxia on hyperbaric anesthesia in rats was studied. The most efficient turned out to be the daily 8-fold one-hour interval 6% hypoxia that decreased manifestations of the anesthesia by 60-67%. The immunocytochemical light optical microscopy showed that in the brain cortex after the 8th séance of such hypoxia the number of neurons with the strong and moderate reaction to heat shock proteins (HSP-70) increased essentially, whereas the number of neurons with the weak reaction to these proteins decreased significantly. After the first hypoxia séances the number of cells with no reaction for the nuclear protein NeuN increased, while after its 8th séance the areas of the absence of neurons appeared. It is believed that one of the main causes of an increase of resistance of the rat organism to nitrogen anesthesia after séances of the many-day interval 6% hypoxia is accumulation of HSP-70 in brain motor cortex cells. At the same time, taking into account a possible cell death and areas of deletion of neurons in cortex at use of the hypoxic action, it is better to use as a preadaptogen the more moderate or not too frequent hypoxia.


Recurrence of Pemphigus Vulgaris after Bilateral Breast Irradiation: A Case Report and Review of the Literature.
Pemphigus is a serious and rare chronic bullous autoimmune disease. It is characterized by mucocutaneous erosions secondary to autoantibodies directed against desmogleins 1 and 3, proteins involved in intercellular adhesion mechanisms. The occurrence of pemphigus is based on the triggering of genetic and external environmental factors such as drugs, infection, and more rarely radiotherapy. To date, only 16 cases of radiation-induced pemphigus are described in the context of breast cancer treatment. We present the case of a 76-year-old woman who had a recurrence of pemphigus vulgaris limited to the irradiation field after exposure to an adjuvant radiotherapy treatment for a bilateral triple-negative breast cancer. The onset was bilateral limited to the irradiation area and was treated effectively with local and systemic corticosteroids. After a rigorous review of the literature, only 16 cases of breast cancer radiation-induced pemphigus appeared. In contrast to several cases, the rash was limited to the irradiated area and improved with systemic corticosteroids. For more than three-quarters of the described cases in the literature, pemphigus occurs within 3 months following the end of treatment. After systemic immunosuppressive treatment, this disease disappears in the vast majority of the reported cases.


Role of mast cell and neutrophil proteases in airway secretion.
To investigate the hypothesis that mast cell and neutrophil proteases stimulate airway gland secretion, we studied the effects of two mast cell proteases (tryptase and chymase) and two neutrophil enzymes (human neutrophil elastase and cathepsin G) on secretion of 35S-labeled macro-molecules from cultured bovine airway gland serous cells. Tryptase had no effect, but the other three enzymes stimulated secretion. Threshold concentrations of the enzymes (greater than or equal to 10(-10) M) were lower by two orders of magnitude than other agonists (e.g., histamine, prostaglandins, beta-adrenergic agonists). Only proteases induced maximal secretory response (greater than or equal to 80% depletion of 35S-labeled macromolecules), and these responses were greater than 10-fold larger than those of other agonists. The active catalytic sites of the enzymes are required for their secretory activities. These findings suggest a role for these enzymes in the pathogenesis of inflammatory airway diseases associated with hypersecretion, and they suggest that the use of selective site-directed inhibitors of these enzymes may provide a novel strategy for intervention in inflammatory diseases of the airways associated with hypersecretion (e.g., cystic fibrosis, chronic bronchitis).


[Annular pancreas with high confluence of pancreaticobiliary ducts in an adult].
A man in his 80's was admitted complaining of epigastralgia, and acute pancreatitis was diagnosed. Abdominal CT and MRI showed enlargement of the pancreatic head encircling the descending part of the duodenum and a duodenal diverticulum. Endoscopic retrograde cholangio-pancreatography (ERCP) revealed annular pancreas and high confluence of pancreaticobiliary ducts. Annular pancreas had been reported to have associated with a broad spectrum of pancreatic anomalies, few cases of annular pancreas coexisting with high confluence of pancreaticobiliary ducts, or pancreaticobiliary maljunction have been reported. Combination of both anomalies was interesting from the view point of embryology. We report a rare case of annular pancreas with high confluence of pancreaticobiliary ducts.


Differential hypoxemia during venoarterial extracorporeal membrane oxygenation.
Venoarterial extracorporeal membrane oxygenation, indicated for severe cardio-respiratory failure, may result in anatomic regional differences in oxygen saturation. This depends on cannulation, hemodynamic state, and severity of respiratory failure. Differential hypoxemia, often discrete, may cause clinical problems in peripheral femoro-femoral venoarterial extracorporeal membrane oxygenation, when the upper body is perfused with low saturated blood from the heart and the lower body with well-oxygenated extracorporeal membrane oxygenation blood. The key is to diagnose and manage fulminant differential hypoxemia, that is, a state that may develop where the upper body is deprived of oxygen. We summarize physiology, assessment of diagnosis, and management of fulminant differential hypoxemia during venoarterial extracorporeal membrane oxygenation. A possible solution is implantation of an additional jugular venous return cannula. In this article, we propose an even better solution, to drain the venous blood from the superior vena cava. Drainage from the superior vena cava provides superiority to venovenoarterial configuration in terms of physiological rationale, efficiency, safety, and simplicity in clinical circuit design.


Aberrant allelic-switch of antisense lncRNA IRAIN may be an early diagnostic marker in laryngeal cancer.
Laryngeal carcinoma is a common head and neck malignancy, however, the molecular mechanism of the disease has not yet been elucidated. The present study aimed to investigate the role of IGF1R antisense imprinted non-protein coding RNA (IRAIN) long non-coding (lnc)RNA in laryngeal carcinoma. In total, specimens of healthy pharynx tissue from 6 healthy individuals, carcinoma tissue and paracancerous tissue from 37 patients with laryngeal carcinoma were used in this study. The single nucleotide polymorphism (SNP) rs8034564 was used to distinguish the two parental alleles of IRAIN. DNA and RNA were extracted from tissue specimens and the IRAIN allelic gene was sequenced. Reverse transcription-quantitative PCR was used to determine the expression levels of IRAIN and Insulin-like growth factor 1 receptor (IGF1R) in laryngeal carcinoma and paracancerous tissue. Bisulfite genomic sequencing was used to determine IRAIN promoter DNA methylation status in laryngeal carcinoma tissue. The expression of IRAIN was di-allelic in healthy pharynx tissue, laryngeal carcinoma tissue and paracancerous tissue. Moreover, IRAIN expression in laryngeal carcinoma tissue was lower compared with paracancerous tissue (P<0.05). IRAIN expression was not associated with age, histological type, tumor stage and grade and lymph node metastasis. IRAIN allelic expression imbalance was present in laryngeal carcinoma and paracancerous tissue, but not in healthy pharynx tissue. SNP analysis (rs8034564) indicated there was an allelic-switch of the two parental alleles. Furthermore, epigenetic analysis revealed no extensive DNA methylation of CpG islands in the IRAIN gene promoter of laryngeal carcinoma. Therefore, it was suggested that IRAIN allele was non-imprinted in laryngeal carcinoma and healthy pharynx tissue. It was also demonstrated that IRAIN may be a potential tumor suppressor in laryngeal carcinoma, and that DNA methylation is not involved in the regulation of IRAIN gene immobilization in laryngeal carcinoma tissue. Thus, detection of IRAIN allelic expression imbalance and aberrant allele-switch may serve as an early diagnostic marker of laryngeal carcinoma.


Evaluation of a Newly Developed Smartphone App for Risk Factor Management in Young Patients With Ischemic Stroke: A Pilot Study.
Background: Efficient treatment of modifiable vascular risk factors decreases reoccurrence of ischemic stroke, which is of uttermost importance in younger patients. In this longitudinal pilot study, we thus assessed the effect of a newly developed smartphone app for risk factor management in such a cohort. Methods: The app conveys key facts about stroke, provides motivational support for a healthy lifestyle, and a reminder function for medication intake and blood pressure measurement. Between January 2019 and February 2020, we consecutively invited patients with ischemic stroke aged between 18 and 55 years to participate. Patients in the intervention group used the app between hospital discharge and 3-month follow-up. The control group received standard clinical care. Modifiable risk factors (physical activity, nutrition, alcohol consumption, smoking behavior, obesity, and hypertension) were assessed during the initial hospital stay and at a dedicated stroke outpatient department three months post-stroke. Results: The study cohort comprised 21 patients in the app intervention group (62% male; age = 41 ± 11 years; education = 12 ± 3 years) and 21 sex-, age- and education-matched control patients with a comparable stroke risk factor profile. Baseline stroke severity was comparable between groups (intervention: median NIHSS = 3; control: median NIHSS = 4; p = 0.604). Three months post-stroke, patients in the intervention group reported to be physically almost twice as active (13 ± 9 h/week) compared to controls (7 ± 5 h/week; p = 0.022). More intense app usage was strongly associated with higher physical activity (r = 0.60, p = 0.005) and lower consumption of unhealthy food (r = -0.51, p = 0.023). Smoking behavior (p = 0.001) and hypertension (p = 0.003) improved in all patients. Patients in the intervention group described better self-reported health-related quality of life three months post-stroke (p = 0.003). Conclusions: Specifically designed app interventions can be an easily to implement and cost-efficient approach to promote a healthier lifestyle in younger patients with a stroke.


Systems analysis in health care: framework and example.
Due to the high complexity of structures and processes in health care, thorough systems analyses in health care run the risk of becoming very complex and difficult to handle. Therefore, we aimed to support systematic systems analysis in health care by developing a comprehensive framework that presents and describes potential areas of analysis. A framework for systems analysis in health care was developed and applied in a health care setting. To provide a clear structure, the framework describes the potential views and levels of systems analyses in a health care environment. The framework comprises five views (roles and responsibilities, information processing and tools, communication, business processes, teams structure and cooperation) and five levels of analysis (overall organization, organizational unit, staff member, role, task). The framework was successfully applied in an analysis of the structures and processes of the Department of Child and Adolescent Psychiatry of the University Medical Center Heidelberg. The proposed comprehensive framework aims to structure the views and levels of systems analysis in the complex health care environment. Our first experiences support the usefulness of such a framework.


An evaluation of a water purification system for use in animal facilities.
A commercially available water purification system was evaluated for its ability to minimize chemical and microbial contaminants. The reduction or removal of these impurities from the drinking water of experimental animals would reduce experimental variability. 3 strains of bacteria were collected from the processed water. An increase in the total number of bacteria was observed the longer the filters remained in use. Determinations of heavy metals in water samples before and after processing were made for lead, zinc, copper, nickel, manganese, iron, arsenic and mercury. Calcium and magnesium levels were also determined. The concentrations of these inorganic chemicals were reduced by the purification process except at 2 time points in which desorption of the chemical could have occurred. Bacterial colonization and desorption of these chemicals were controlled by installing new filter cartridges. Volatile halocarbon concentrations were determined for water samples before and after purification. All volatile halocarbons analyzed were less than 10 ppb before and after purification at all time points. Other organic chemicals were greatly reduced by the purification process. In a study of contaminants associated with installation of the unit, it was found that flushing the unit for 8 days reduced lead and methyl ethyl ketone concentrations to insignificant levels. The purification system was found to be effective in providing high quality drinking water as verified by a microbial and chemical testing program.


Q fever: current concepts.
Persons with Q fever usually present with severe retrobulbar headache, a fever to 104 degrees F or higher with shaking chills, general malaise, myalgia, chest pain, and sometimes pneumonia and hepatitis. Cattle, sheep, goats, and ticks are the primary reservoirs of the etiologic agent, Coxiella burnetii. Humans are usually infected by inhaling infectious aerosols. Because C. burnetii can survive for long periods in the environment, it poses a continuing health hazard once it is disseminated. Q fever usually occurs sporadically, but large outbreaks are frequently observed throughout the world, particularly among abattoir workers and personnel working in research centers. Q fever endocarditis follows a chronic course and is frequently fatal. Tests for antibodies to C. burnetii are required for confirmation of the diagnosis. Tetracyclines remain the mainstay of treatment for acute Q fever, and tetracyclines in combination with other antibiotics have been advocated for patients with Q fever endocarditis. Vaccines for Q fever have been proven effective in clinical trials.


Calix[4]phyrins. Effect of peripheral substituents on conformational mobility and structure within a series of related systems.
A new, stepwise synthesis of calix[4]phyrins is described. It relies on the condensation of a ketone with pyrrole to form a dipyrromethane containing a quaternary carbon center that is subsequently condensed with an aromatic aldehyde. This methodology, in contrast to the previous rational approach described by this group (involving formation of a trisubstituted dipyrromethane via the condensation of an aldehyde with pyrrole, followed by condensation of this dipyrromethane with acetone), allows for a variety of bulky, ketone-derived substituents to be incorporated into the meso-like positions. The resulting systems, while all containing the same central macrocyclic core, display conformational properties that reflect the nature of these meso-like substituents; these conformational features were independently assessed by X-ray diffraction analysis, NMR spectroscopy, and quantum chemical calculations.


[A role of cultured bovine lens epithelial cells in the fibrinolytic system].
The release of plasminogen activators (PAs) and plasminogen activator inhibitor (PAI) from cultured bovine lens epithelial cells was investigated, in an attempt to study the effect of lens epithelial cells on the fibrin deposit and fibrinolytic process on the surface of IOL. Cultured bovine lens epithelial cells released tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1). t-PA activity was completely inhibited by PAI-1. These findings suggest that lens epithelial cells cause suppression of fibrinolysis in the anterior chamber of the eye.


Play in Mexican-American mothers and toddlers is frequent, multimodal, and rich in symbolic content.
Play offers rich opportunities for toddlers to develop motor, social, cognitive, and language skills, particularly during interactions with adult caregivers who may scaffold toddlers to higher levels of play than toddlers achieve on their own. However, research on play has narrowly focused on children from White, middle-income backgrounds, leaving a dearth of knowledge about dyadic play in diverse cultural communities. We videorecorded 222 Mexican-American mothers playing with their 2-year-old toddlers with a standard set of toys. Play behaviors were coded as nonsymbolic or symbolic (play type) and as expressed through manual, verbal, or multiple channels (play modality). Play between toddlers and mothers was frequent, high in symbolic content, and toddler play closely corresponded with mother play in type and modality: Toddlers' nonsymbolic play related to mothers' nonsymbolic play; toddlers' symbolic play related to mothers' symbolic play; toddlers' manual play related to mothers' manual play; and toddlers' multimodal play related to mothers' multimodal play. Play in Mexican-American mothers and toddlers is frequent, multimodal, and symbolically rich, offering new directions for future research and practice.


Kinetics of inorganic phosphate release during the interaction of p21ras with the GTPase-activating proteins, p120-GAP and neurofibromin.
The rate of GTP hydrolysis on p21ras is accelerated by approximately 10(5) times by the catalytic domains of GTPase-activating proteins (GAPs), p120-GAP (GAP-344) or neurofibromin (NF1-334). The kinetic mechanism of this activation has been investigated by following the release of inorganic phosphate (Pi), using a fluorescent probe that is sensitive to Pi [Brune, M., Hunter, J., Corrie, J. E. T., & Webb, M. R. (1994) Biochemistry 33, 8262-8271]. Measurements were made in real time with a stopped-flow apparatus, in which the p21ras complex with the 2',3'-methanthraniloyl analogue of GTP (mantGTP) was mixed with the GAP in the presence of this Pi probe. The results show that Pi release is fast and that the overall hydrolysis is controlled by the cleavage itself or a conformational change preceding the cleavage. The time courses were single exponentials over a range of [GAP-344] and were modeled to show that a single step controlled Pi release. The maximum rate constant was 15 s-1 (all data at 30 degrees C, pH 7.6, low ionic strength) in experiments in which GAP-344 underwent a single turnover, compared with 5 s-1 for multiple-turnover experiments, and possible causes of this discrepancy were investigated and discussed. With NF1-334 the time courses were more complex, showing a lag prior to rapid release of Pi. The results were consistent with a Kd of 0.04 microM for NF1-344 affinity is some 3 orders of magnitude tighter than that of GAP-344.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunosenescence Study of T Cells: A Systematic Review.
Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence. To determine the best flow cytometry markers of circulating T cells associated with immunosenescence. We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18-44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity. A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias. Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.


[Initial and short-term results of percutaneous transluminal coronary angioplasty in patients over 70 years old: recent improvements in effectiveness].
Elderly patients have a higher incidence of procedure-related complications and recurrent angina after percutaneous transluminal coronary angioplasty (PTCA). However, early success rates seem to have improved. To determine whether outcome of PTCA in the elderly has changed recently, we compared initial results and short-term outcome in patients over 70 years old in two groups; 64 patients with 70 PTCA lesions who underwent first elective PTCA in 1982-1989 (early group) and 140 patients with 153 PTCA lesions in 1990-1993 (late group). The mean age of the late group was significantly older than that of the early group (74 +/- 3 vs 73 +/- 2 years, p < 0.01). The two groups had similar clinical characteristics including sex, prior myocardial infarction and multivessel disease. The overall success rate of PTCA was significantly higher in the late group than in the early group (92.8% vs 82.8%, p < 0.05). The rate of abrupt closure was similar in the two groups (2.9% vs 2.6%). Major complications (procedural myocardial infarction, emergency bypass surgery, hospital death) occurred in 4.7% of the early group and in 3.6% of the late group. Angiographic restenosis occurred in 41.5% of the early group and in 33.6% of the late group. Cardiac events (cardiac death and/or myocardial infarction) occurred in 6.6% of the early group and in 1.5% of the late group (p = 0.06). The initial success rate of PTCA has improved in the elderly as well as younger patients (< 70; 92.8% vs 91.6%). We conclude that PTCA can be performed with high initial success and satisfactory short-term outcome in patients over 70 years old.


Risk factors associated with acute pancreatitis in dogs: 101 cases (1985-1990).
The medical records of 101 dogs with acute pancreatitis, diagnosed on the basis of medical histories of acute vomiting, with serum lipase or amylase activity greater than the reference range, or with gross signs of pancreatitis at surgery or histopathologic evidence at necropsy, were evaluated to identify potential risk factors for the development of acute pancreatitis. Age, sex, and breed of dogs with acute pancreatitis were compared with those from a reference population of 100 dogs admitted for other medical emergencies during the same period. Analysis of multiple regression models indicated that dogs > 7 years old were at increased risk for acute pancreatitis. Spayed dogs and castrated male dogs had an increased risk, compared with that of sexually intact males. Similarly, terrier and nonsporting breeds appeared to be at higher risk of developing acute pancreatitis than were other breed types. Most dogs in this study (63/101) had intercurrent diseases, including diabetes mellitus (n = 14), hyperadrenocorticism (n = 12), chronic renal failure (n = 8), neoplasia (n = 17), congestive heart failure (n = 6), and autoimmune disorders (n = 5). Fourteen dogs had undergone anesthesia or surgery in the week before admission; only 3 had undergone abdominal procedures. Recent medication use was listed in 52 of 101 cases. Antibiotics (n = 18) and corticosteroids (n = 18) were most frequently described. Anticancer chemotherapeutic agents (n = 5) and organophosphate insecticides (n = 5) also were listed.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of thyroxine-binding globulin-San Diego in a family from Houston and its characterization by in vitro expression using Xenopus oocytes.
T4-binding globulin (TBG) is a liver glycoprotein that transports iodothyronines in serum. Several TBG variants with reduced T4 binding affinity have been described, all of which are also characterized by reduced serum TBG concentrations and reduced heat stability. Their loss of binding thus appears to be due to a general defect of the molecule. We now report the occurrence of a variant TBG, detected in a family from Houston, TX, with half the normal T4 binding affinity and heat stability but normal serum concentration and isoelectric focussing pattern. The propositus was identified by reduced total T4 and T3 serum levels. All family members were euthyroid, and inheritance followed an X-linked pattern. Sequence analysis of the TBG gene of the propositus and his heterozygous mother revealed two amino acid substitutions: serine 23 with threonine (S23T), and the known polymorphism leucine 283 with phenylalanine (L283F). These substitutions are identical to those of TBG-San Diego (TBG-SD), a variant with similar properties except for a reduced serum concentration. Expression of recombinant TBG-SD/H with the S23T substitution in Xenopus oocytes reproduced the binding defect and heat lability. The amount of TBG-SD/H synthesized and secreted by the oocytes was not different from that of normal TBG. The difference in serum TBG concentrations in affected members of the San Diego and Houston families thus does not appear to be due to an error in the measurement of TBG, but may be related to differences in the rates of degradation.


Children exposed to alcohol-related problems and DSM-5 alcohol use disorder in San Juan, Puerto Rico.
This article estimates the proportion of children (17 and younger) exposed to an adult with an alcohol problem or alcohol use disorder (AUD) in San Juan, Puerto Rico. Data are from a household random sample of 1,510 individuals 18-64 years of age. A total of 20.9% of children in sample households were exposed to an adult with an alcohol problem, and 5.7% were exposed to an adult with DSM-5 AUD. These considerable proportions suggest that alcohol treatment and family support programs should include help for adults in the family, and special support for exposed children in the household.


Prediction of the membrane-spanning beta-strands of the major outer membrane protein of Chlamydia.
There is preliminary experimental evidence indicating that the major outer-membrane protein (MOMP) of Chlamydia is a porin. We tested this hypothesis for the MOMP of the mouse pneumonitis serovar of Chlamydia trachomatis using two secondary structure prediction methods. First, an algorithm that calculates the mean hydrophobicity of one side of putative beta-strands predicted the positions of 16 transmembrane segments, a structure common to known porins. Second, outer loops typical of porins were assigned using an artificial neural network trained to predict the topology of bacterial outer-membrane proteins with a predominance of beta-strands. A topology model based on these results locates the four variable domains (VDs) of the MOMP on the outer loops and the five constant domains on beta-strands and the periplasmic turns. This model is consistent with genetic analysis and immunological and biochemical data that indicate the VDs are surface exposed. Furthermore, it shows significant homology with the consensus porin model of the program FORESST, which contrasts a proposed secondary structure against a data set of 349 proteins of known structure. Analysis of the MOMP of other chlamydial species corroborated our predicted model.


[Spinal multiple sclerosis mimicking a spinal cord tumor: a case report].
Since the advent of magnetic resonance imaging (MRI), to visualize lesions of multiple sclerosis has become easy to do. However, in some cases with primary spinal cord multiple sclerosis, it is not always easy to obtain a diagnosis in the first instance. We reported a case of primary spinal multiple sclerosis diagnosed through histological examination of a surgical specimen taken by an open biopsy. A 35-year-old woman was admitted with complaints of two-months duration of progressive weakness and sensory disturbance in the legs and buttocks. On radiological examinations including metrizamide CT myelography and MRI, enlargement of the conus medullaris was the only positive finding. Respective to her clinical course, intramedullary spinal cord tumor could not be ruled out, so an open biopsy was performed. Histological examination revealed that the cord lesion was acute demyelination with perivascular inflammation. Her neurological signs were almost completely cured with administration of corticosteroid, though new brainstem signs took place two months later and then a concrete diagnosis of her having multiple sclerosis was finally achieved. Since preoperative examinations can not differentiate spinal cord tumor from any other intramedullary cord lesions such as demyelinating foci of multiple sclerosis, surgical intervention would be approved in such atypical primary spinal cord multiple sclerosis.


Aniridia associated with lens coloboma and secondary glaucoma treated with transcorneal argon laser ciliary body photocoagulation: a case report.
The aim of this study is to describe the management of cataract and refractory glaucoma in a case of congenital aniridia (AN)-1. In an 18-year-old female patient affected by congenital AN, bilateral coloboma of the zonula and lens, cataract and glaucoma, pars plana vitrectomy, cataract extraction and subsequent transcorneal ciliary body argon laser photocoagulation were performed. Five years after laser treatment, the best-corrected visual acuity was 20/50 and the intraocular pressure was stable at 18 mm Hg with topical pharmacological management consisting of timolol 0.5% and latanoprost 0.005%. From our experience, transcorneal ciliary body photocoagulation after cataract extraction and vitrectomy could be a useful technique to manage high ocular pressure in eyes affected by congenital AN.


A novel serum extracellular vesicle protein signature to monitor glioblastoma tumor progression.
Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In our study, we evaluated the potential of serum-derived EVs from glioblastoma patients to serve as biomarker for tumor progression. EVs from serum of glioblastoma patients and healthy volunteers were separated by size exclusion chromatography and ultracentrifugation. EV markers were defined by using a proximity-extension assay and bead-based flow cytometry. Tumor progression was defined according to modified RANO criteria. EVs from the serum of glioblastoma patients (n = 67) showed an upregulation of CD29, CD44, CD81, CD146, C1QA and histone H3 as compared to serum EVs from healthy volunteers (P value range: <.0001 to .08). For two independent cohorts of glioblastoma patients, we noted upregulation of C1QA, CD44 and histone H3 upon tumor progression, but not in patients with stable disease. In a multivariable logistic regression analysis, a combination of CD29, CD44, CD81, C1QA and histone H3 correlated with RANO-defined tumor progression with an AUC of 0.76. Measurement of CD29, CD44, CD81, C1QA and histone H3 in serum-derived EVs of glioblastoma patients, along with standard MRI assessment, has the potential to improve detection of true tumor progression and thus could be a useful biomarker for clinical decision making.


Bleeding complications of thrombolytic treatment.
The mechanism and incidence of bleeding in patients undergoing fibrinolytic therapy are discussed, the role of laboratory findings in predicting the patient's clinical course is described, and guidelines concerning patient management are presented. Plasminogen activators have more similarities than differences in the mechanisms by which they dissolve thrombi and hemostatic plugs and, therefore, in their potential for vascular reperfusion or bleeding complications. The duration of an active lytic state in the blood varies according to the half-life of the activator; regardless of the agent chosen, however, plasma fibrinogen concentrations do not return to normal levels for one to two days following treatment. If plasminogen activator is still circulating, control of surgical bleeding after plasminogen activator treatment requires correction of the low plasma fibrinogen concentration with cryoprecipitate and administration of antifibrinolytic agents. Tests of coagulation and fibrinolysis can demonstrate a lytic state during therapy, but manipulation of drug therapy based on laboratory results is unlikely to control the patient's clinical course. Safe and effective therapy with plasminogen activators depends more on clinical judgment than on strict interpretation of laboratory test results.


[Mutation of NKX2-5 gene in patients with atrial septal defect].
The purpose of this investigation was to identify the novel genetic mutations in patients with a congenital atrial septal defect (ASD). Clinical data and blood specimens from a total of 12 unrelated ASD pedigrees and a cohort of 168 unrelated subjects with sporadic ASD were collected and evaluated in contrast to 200 healthy individuals. The whole exons and partial flanking introns of NKX2-5 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination approach. The acquired sequences were aligned with those publicized in GenBank by the aid of programme BLAST to identify the sequence variations. The software ClustalW was applied for analysis of the conservative of the altered amino acids. A novel heterozygous mutation of NKX2-5 gene, i.e., a substitution of thymine for cytosine at nucleotide 536, predicting the conversion of serine into phenylalanine at amino acid residue 179, was identified initially in a proband. The same missense mutation was thereafter detected in other 3 affected members of the identical family but neither in the healthy members of the kindred nor in the 200 normal controls. A cross-species alignment of the protein sequences encoded by NKX2-5 gene displayed that the mutated amino acid was highly conserved evolutionarily. No mutation of NKX2-5 gene was observed in the other 11 ASD pedigrees or in 168 patients with sporadic ASD. Additionally, a common synonymous single nucleotide polymorphism, a transition of adenine (A) into guanine (G) at nucleotide 63, was found in NKX2-5 gene. However, there were no significant differences in the prevalence of alleles A and G between ASD patients and healthy controls (chi(2) = 2.8641, P = 0.0906). A novel mutation of NKX2-5 gene identified in an ASD family suggests that mutated NKX2-5 gene is responsible for familial ASD.


Plasmodium sporozoite motility: an update.
Plasmodium, the causative agent of malaria, employs its own actin/myosin-based motor for forward locomotion, penetration of molecular and cellular barriers, and invasion of target cells. The sporozoite is unique amongst the extracellular Plasmodium developmental forms in that it has to cross considerable distances and different tissues inside the mosquito and vertebrate hosts to ultimately reach a parenchymal liver cell, the proper target cell where to transform and replicate. Throughout this dangerous journey, the parasite alternates between being passively transported by the body fluids and using its own active cellular motility to seamlessly glide through extracellular matrix and cell barriers. But irrespective of the chosen path, the sporozoite is compelled to keep on moving at a fairly fast pace to escape destruction by host defense mechanisms. Here, we highlight and discuss recent findings collected in Plasmodium sporozoites and related parasites that shed new light on the biological significance of apicomplexan motility and on the structure and regulation of the underlying motor machinery.


Endoscopic submucosal dissection for silent gastric Dieulafoy lesions mimicking gastrointestinal stromal tumors: Report of 7 cases-a case report series.
Dieulafoy lesion is a rare but serious cause of gastrointestinal hemorrhage. However, some cases can be occasionally found without bleeding during the endoscopic screening, and the management remains unclear. The aim of this article was to report the efficacy and safety of endoscopic submucosal dissection (ESD) for silent gastric Dieulafoy lesions, which presented as protrusion lesions mimicking gastrointestinal stromal tumors (GISTs). Data from the patients with gastric protrusion lesions who underwent ESD from September 2008 to April 2016 in General Hospital, Tianjin Medical University, China were recorded. Seven cases with pathological diagnosis of Dieulafoy lesion without bleeding were enrolled for further analysis. A total of 7 patients (2 males and 5 females) with mean age of 57.7 ± 4.15 years were pathologically diagnosed as Dieulafoy lesion. Four of the lesions were located in gastric antrum, 2 in the fundus, and 1 in the body of stomach, respectively. The mean sizes of the Dieulafoy lesions under white light endoscopy and endoscopic ultrasonography (EUS) were 1.06 ± 0.28 and 0.84 ± 0.29 cm. The origins of these lesions were submucosa (6/7, 85.7%) and muscularis propria (1/7, 14.3%). Three of them appeared with mixed echo under EUS, 3 with hypoechogenicity, and 1 with hyperechogenicity. En bloc complete resection was achieved in all the lesions by ESD with average time of 76.00 ± 16.86 minutes, and no intraoperative bleeding happened. In addition, all patients were followed up for 1 to 53 months, and no recurrence or long-term complications was observed. Therefore, ESD can be an effective and safe treatment for silent gastric Dieulafoy lesions with clinical presentations of submucosal protrusion lesions mimicking GISTs.


Endovascular treatment of scalp cirsoid aneurysms.
Scalp is the most common site of soft tissue arteriovenous fistulae and surgical excision has been the primary mode of treatment. Endovascular treatment has evolved as an alternative to the surgery. To evaluate the effectiveness of percutaneous direct-puncture embolization of cirsoid aneurysms. From January 1995 to December 2004, 15 patients underwent percutaneous direct-puncture embolization of cirsoid aneurysms. Plain X-ray, computerized tomography scan and complete selective cerebral angiogram were done in all. Seven patients had forehead lesions, four had temporal and the remaining four patients had occipital region cirsoid aneurysms. Lesions were punctured with 21-gauge needle and embolized with 20-50% cyanoacrylate-lipiodol mixture. Circumferential compression was applied during injection. Post-embolization angiogram showed complete obliteration in 11 patients. The remaining four patients required adjunctive transarterial embolization with polyvinyl alcohol particles for complete lesion devascularization. Two patients had post procedure surgery for removal of disfiguring and hard glue cast. There were no major procedure-related complications. No patients had any recurrence in the follow-up. Percutaneous direct puncture embolization of cirsoid aneurysms is a safe and effective procedure. It can be effectively used as an alternative to surgery. Sometimes adjunctive transarterial embolization is also required to deal with deeper feeders.


Effect of ethylene on the gibberellic Acid-enhanced synthesis and release of amylase by isolated barley aleurone layers.
Methods were developed and extended to enable the incubation of isolated barley (Hordeum vulgare cv. Himalaya) aleurone layers under carefully controlled conditions for studies on effects of ethylene on amylase synthesis and release. When layers in medium containing gibberellic acid were exposed to ethylene, the synthesis and release of amylase were altered relative to layers maintained in an ethylene-free environment. These ethylene effects were detected at the smallest concentration used, 0.041 nl/ml, indicating a very low threshold value. During the initial 24 h, ethylene accelerated both the appearance of total amylase activity, and the release of this activity from the aleurone layers. On the other hand, ethylene reduced the total amount of amylase activity that was recovered from samples after 48 and 72 h.Ethylene did not stimulate the release of amylase from membrane-bound structures within the aleurone layers, and did not interact with the enzyme directly.The isoelectric patterns of amylase activity and proteins released from control and ethylene-treated aleurone layers in 24 h were identical. Therefore, ethylene promoted only quantitative differences in amylase synthesis rather than qualitative differences.


Meeting the challenges of vascular dementia. Introduction.
Ongoing controversy over the challenges associated with the diagnosis and management of patients with vascular dementia (VaD) or Alzheimer's disease with cerebrovascular disease (CVD) has led to difficulties with establishing epidemiology and diagnostic guidelines, as well as deciding upon optimal management practices. In March 2001, an international group of physicians and researchers gathered to resolve some of these issues and provide clinicians with useful information relating to this large patient group. In addition to simple coexistence, VaD and Alzheimer's disease appear to share common pathophysiological mechanisms, such as neurotransmitter abnormalities. Treatments that target the common pathophysiology of the two conditions may prove useful. To date, no reports have been published of any agent demonstrating broad efficacy (on cognitive and noncognitive outcomes) in VaD and Alzheimer's disease with CVD in randomised, controlled trials. Recent developments in understanding the pathophysiology of the conditions, however, have taken researchers an important step closer to finding an effective treatment, not only for patients with Alzheimer's disease, but also for those with coexisting CVD and those with VaD.


Timolol and aceclidine. A clinical study of interaction in the eye.
In the Netherlands timolol maleate, probably the drug of first choice in antiglaucoma therapy, is often combined with other intraocular pressure lowering drugs. The efficacy of most combinations have been discussed in the literature several times, except the one with aceclidine, a parasympathetic drug, that has a reasonable popularity in Western Europe. Unlike pilocarpine, aceclidine does not seem to give a clinically significant additional pressure lowering effect in timolol pre-treated eyes. The decrease in IOP in aceclidine pre-treated eyes after single dose timolol seems to be an effect of timolol alone. Our results suggest that co-administration of timolol and aceclidine is not a rational action in antiglaucomatous therapy.


PEG ileus. A new cause of small bowel obstruction.
A case of small bowel obstruction due to a lodged percutaneous endoscopic gastrostomy tube inner bumper is described. Most probably inner bumper lodgement in the terminal ileum is related to its size. Laparotomy was required to remove the bumper and relieve the obstruction. We suggest that all percutaneous endoscopic gastrostomy bumpers be retrieved endoscopically when the PEG tube is removed or replaced unless a collapsible inner bumper is used.


Biodegradable block copolymer micelles with thiol-responsive sheddable coronas.
Novel sheddable micelles having hydrophilic coronas capable of being shed from biodegradable polylactide (PLA) cores by the cleavage of disulfide linkages in response to thiols were prepared by aqueous micellization of PLA-based amphiphilic block copolymers functionalized with disulfides at block junctions. These well-defined copolymers were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization in the presence of a new disulfide-functionalized double-head initiator having both terminal OH and Br groups. (1)H NMR and GPC results indicate that both polymerizations were well-controlled with molecular weight distribution as low as M(w)/M(n) < 1.2. Aqueous micellization to form core/shell micelles with disulfides at the interface of PLA cores and hydrophilic coronas and their thiol-responsive degradation were investigated. In the presence of water-soluble thiols, disulfide linkages in the micelles were cleaved and hydrophilic coronas were lost, causing PLA cores to precipitate due to the loss of colloidal stability. In a biomedical perspective, the new sheddable micelles were not cytotoxic and hence biocompatible.


Chemokines in transplant rejection.
Recent studies in transplant biology have demonstrated a role for chemokines in the migration of leukocytes into transplanted tissue. There is further evidence that modulation of the action of chemokines at their receptors can improve the outcome of acute rejection as well as long-term graft survival. A number of clinical therapies, based on both small molecules and biologicals, are currently under investigation with the potential for selective immunosupression. This article discusses the chemokines and receptors identified as the best characterized molecular targets, as well as the therapies under investigation for these targets.


Electrophysiological Properties of Human Cortical Organoids: Current State of the Art and Future Directions.
Human cortical development is an intricate process resulting in the generation of many interacting cell types and long-range connections to and from other brain regions. Human stem cell-derived cortical organoids are now becoming widely used to model human cortical development both in physiological and pathological conditions, as they offer the advantage of recapitulating human-specific aspects of corticogenesis that were previously inaccessible. Understanding the electrophysiological properties and functional maturation of neurons derived from human cortical organoids is key to ensure their physiological and pathological relevance. Here we review existing data on the electrophysiological properties of neurons in human cortical organoids, as well as recent advances in the complexity of cortical organoid modeling that have led to improvements in functional maturation at single neuron and neuronal network levels. Eventually, a more comprehensive and standardized electrophysiological characterization of these models will allow to better understand human neurophysiology, model diseases and test novel treatments.


Increased CXCL10 expression in nasal fibroblasts from patients with refractory chronic rhinosinusitis and asthma.
Chronic rhinosinusitis (CRS) is characterized by local inflammation of the sinonasal tissues. CRS patients with nasal polyps and asthma often develop acute exacerbation of sinonasal symptoms after upper respiratory tract infections. However, the influence of concomitant asthma on the nasal immune response to viral infection remains unclear. Specimens of nasal polyp and mucosal tissues were obtained from 3 groups of CRS patients (n = 14 per group): 1) patients without asthma (CRS group), 2) patients with aspirin-tolerant asthma (ATA group), and 3) patients with aspirin-intolerant asthma (AIA group). Nasal fibroblasts isolated from the specimens were stimulated with poly I:C. CXCL10 expression was analyzed by the quantitative real-time polymerase chain reaction and enzyme-linked immunoadsorbent assay. Biopsy specimens from CRS patients without asthma were subjected to immunohistochemistry for detection of T-bet and GATA-3 expression in CD3+ T cells by double labeling. Nasal fibroblasts from the ATA and AIA groups showed significantly enhanced expression of CXCL10 mRNA and protein after poly I:C stimulation compared with cells from the CRS group and the control group (normal nasal mucosa). In addition to T helper (Th)2 cells, there was more abundant infiltration of Th1 cells into tissues from the AIA and ATA groups. Our findings suggest that CRS associated with asthma may become intractable through the over-production of CXCL10 in response to viral infection.


Fluorescence in situ hybridization on human metaphase chromosomes detected by near-field scanning optical microscopy.
Fluorescence in situ hybridization on human metaphase chromosomes is detected by near-field scanning optical microscopy. This combination of cytochemical and scanning probe techniques enables the localization and identification of several fluorescently labelled genomic DNA fragments on a single chromosome with an unprecedented resolution. Three nucleic acid probes are used: pUC1.77, p1-79 and the plasmid probe alpha-spectrin. The hybridization signals are very well resolved in the near-field fluorescence images, while the exact location of the probes can be correlated accurately with the chromosome topography as afforded by the shear force image.


GmSYP24, a putative syntaxin gene, confers osmotic/drought, salt stress tolerances and ABA signal pathway.
As major environment factors, drought or high salinity affect crop growth, development and yield. Transgenic approach is an effective way to improve abiotic stress tolerance of crops. In this study, we comparatively analyzed gene structures, genome location, and the evolution of syntaxin proteins containing late embryogenesis abundant (LEA2) domain. GmSYP24 was identified as a dehydration-responsive gene. Our study showed that the GmSYP24 protein was located on the cell membrane. The overexpression of GmSYP24 (GmSYP24ox) in soybean and heteroexpression of GmSYP24 (GmSYP24hx) in Arabidopsis exhibited insensitivity to osmotic/drought and high salinity. However, wild type soybean, Arabidopsis, and the mutant of GmSYP24 homologous gene of Arabidopsis were sensitive to the stresses. Under the abiotic stresses, transgenic soybean plants had greater water content and higher activities of POD, SOD compared with non-transgenic controls. And the leaf stomatal density and opening were reduced in transgenic Arabidopsis. The sensitivity to ABA was decreased during seed germination of GmSYP24ox and GmSYP24hx. GmSYP24hx induced up-regulation of ABA-responsive genes. GmSYP24ox alters the expression of some aquaporins under osmotic/drought, salt, or ABA treatment. These results demonstrated that GmSYP24 played an important role in osmotic/drought or salt tolerance in ABA signal pathway.


Impaired development of a miltefosine-resistant Leishmania infantum strain in the sand fly vectors Phlebotomus perniciosus and Lutzomyia longipalpis.
To gain insight into the propagation of miltefosine (MIL) resistance in visceral leishmaniasis, this laboratory study explored development of resistant parasites with a defective miltefosine transporter (MT) in sand flies. Infectivity, colonization of stomodeal valve and metacyclogenesis of a MIL-resistant (MIL-R) Leishmania infantum LEM3323 line with a defective MT were assessed in the natural sand fly vectors Phlebotomus perniciosus and Lutzomyia longipalpis. Given our recent description of partial drug dependency of the MT-deficient line, the impact of MIL pre-exposure on sand fly infectivity was explored as well. A significant reduction in sand fly infection, stomodeal valve colonization and differentiation into metacyclics (determined by a lower flagellum/cell body length ratio) was observed in both vectors for MIL-R as compared to the isogenic parent MIL-susceptible line. Re-introduction of the wildtype MT gene into MIL-R tended to partially rescue the capacity to infect sand flies. Pre-exposure to MIL did not alter infectivity of the MIL-R line. The MIL resistant L. infantum LEM3323 line is significantly hampered in its development and transmissibility potential in two sand fly vector species. Additional studies are warranted to evaluate whether this applies to other visceral Leishmania parasites with acquired MIL-resistance.


Progression-Free Survival and Time to Progression as Potential Surrogate Endpoints for Overall Survival in Chemoradiotherapy Trials in Limited-Stage Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.
To investigate whether progression-free survival (PFS) or time to progression (TTP) could be a valid surrogate endpoint for overall survival (OS) in patients with limited-stage small-cell lung cancer (LS-SCLC) receiving combined chemoradiotherapy. Literature searching was performed in PubMed, Embase, and The Cochrane Library up to 2021. Prediction models were firstly established using data from phase III randomized controlled trials (RCTs) and then externally validated in phase II and retrospective studies. Correlation analysis was evaluated by a weighted linear regression model at both trial and arm levels. Cross-validation was performed to assess the consistency and robustness of the established models. 37 studies, including 15 phase III RCTs, 12 phase II studies, and 10 retrospective studies, were selected in the final analysis. In trial-level surrogacy, a very good correlation was observed between hazard ratios (HRs) of PFS/TTP and OS (R2 = 0.783, 95% CI 0.771-0.794). In arm-level surrogacy, very good correlations were also observed between 2-year (R2 = 0.823, 95% CI 0.814-0.832), 3-year (R2 = 0.843, 95% CI 0.833-0.850), 5-year (R2 = 0.852, 95% CI 0.843-0.859) PFS/TTP, and 5-year OS. An excellent correlation was observed between 4-year PFS/TTP and 5-year OS (R2 = 0.906, 95% CI 0.901-0.910). Cross-validation demonstrated reasonable overall consistency. External validation in phase II and retrospective studies showed good agreement (R2, 0.728-0.824). PFS/TTP was a valid surrogate endpoint for OS in patients with LS-SCLC receiving combined chemoradiotherapy. The finding provides high-level evidence to support PFS/TTP as the primary endpoint in clinical trials so as to speed up introducing novel agents to the treatment of LS-SCLC.


Change in Columellar-Philtral and Nasolabial Angles Over Time Following Rhinoplasty.
Preoperative analyses of the columellar-philtral and nasolabial angles (CPA and NLA) are important considerations for the rhinoplasty surgeon. This study aims to quantify and compare the degree of change in nasal tip rotation as measured by CPA and NLA over time following rhinoplasty and to identify surgical maneuvers or patient characteristics that may affect nasal tip rotation. Prospective analysis of CPA and NLA in 111 consecutive, consenting cosmetic, and/or functional rhinoplasty patients of the senior author over a 1-year time period was performed. Angles were analyzed before surgery, immediately after surgery, and at 1 week, 1 month, 6 months, and 1 year following surgery. Subgroup analyses based on surgical maneuvers and other covariates were performed. The greatest change to CPA and NLA in the upright position was 11.8 degrees (95% confidence interval [CI]: 9.8-13.7, p < 0.001) and 9.3 degrees (95% CI: 7.9-10.7, p < 0.001) of elevation 1 week after surgery, respectively. The mean CPA was not significantly different than preoperative measures 6 months after surgery; however, the NLA remained 4.94 degrees (95% CI: 2.1-8.4, p = 0.001) elevated. Females showed approximately 10 degrees more elevated CPA than males in pre- and postoperative time points; however, the NLA did not discriminate between sexes. Transfixion incisions appears to cause a significant decrease in postoperative NLA compared with patient who did not undergo transfixion incisions. Measurements for nasal tip rotation are variable and inconsistent throughout the literature. This study shows that rhinoplasty may have a greater effect on nasal tip rotation as measured by NLA and that the effects of NLA and CPA are independent, signifying that a standardized measurement for nasal tip rotation is warranted.


Penetration of aztreonam into pleural exudate following rapid intravenous bolus or constant infusion.
A study on the effects of the mode of administration on aztreonam (AZ) concentrations in pleural fluid was performed in human subjects. The same dose of AZ was given as an intravenous bolus injection to one group and as a drip infusion to another group of patients. Serum and pleural fluid samples were collected at different times after drug administration, and the antibiotic concentrations were measured by using a microbiological method. The highest serum and pleural exudate concentrations and area under the curve values were obtained after drip infusion. These results indicate that drip infusion gives higher concentrations of AZ in pleural effusion.


Cost-effectiveness of term induction of labour using inpatient prostaglandin gel versus outpatient Foley catheter.
Evaluating cost-effectiveness of induction of labour (IOL) using outpatient mechanical cervical ripening using a Foley catheter (OFC) compared to inpatient chemical ripening using prostin gel (IPG). Cost-effectiveness analysis from a hospital perspective alongside a RCT. Women in a metropolitan Australian maternity hospital with an unfavourable cervix requiring IOL at term were randomised to IPG (n = 51) or OFC (n = 50). Primary economic measures were mean patient costs, incremental cost per predelivery inpatient hour prevented, and incremental cost per vaginal delivery within 12 h of admission to the birthing unit. Bootstrapping estimates were used to construct 95% confidence intervals. Estimates of net monetary benefit were calculated to aid interpretation of the results. Mean hospital costs per woman were nonsignificantly higher ($6524 OFC vs $5876 IPG) and mean difference $643; 95% CI -$366 to $1652. OFC group experienced fewer predelivery inpatient hours, resulting in an incremental cost per inpatient hour prevented of $57 (95% CI -$79.44 to $190.65). However, OFC patients were less likely to deliver vaginally within 12 h of admission to birthing unit. Other cost influencing clinical outcomes, including caesarean section rates and total inpatient hours, were not statistically different. Results were not sensitive to changes in costs or the cost-effectiveness thresholds. OFC had fewer inpatient hours and costs prior to birth. However, OFC did not reduce overall inpatient hours and failed to achieve comparable rates of vaginal delivery within 12 h of birthing unit admission. Therefore, OFC is unlikely to be considered cost-effective compared to IPG in current hospital settings.


Recent advances in microflow photochemistry.
This review summarizes recent advances in microflow photochemical technologies and transformations. The portfolio of reactions comprises homogeneous and heterogeneous types, among them photoadditions, photorearrangements, photoreductions, photodecarboxylations, photooxygenations and photochlorinations. While microflow photochemistry is most commonly employed as a micro-scale synthesis tool, scale-up and technical production processes have already been developed.


Iced temperature injectate for thermodilution cardiac output determination causes minimal effects on cardiodynamics.
Controversy exists regarding the ideal injectate temperature for measuring cardiac output. Iced temperature injectate gives a higher signal/noise ratio and less variability in the measured cardiac output. Thus, less volume and fewer measurements are required. Advocates of room temperature injectate have suggested that iced temperature injectate may perturb cardiodynamics. This concern has remained largely untested. To help resolve this controversy, we examined the effects of 5 mL iced injectate (0 degrees to 4 degrees) infusions on cardiodynamics. Prospective, randomized, controlled study. A critical care research laboratory. Five domestic pigs, weighing between 20 to 25 kg. Under barbiturate anesthesia, pigs underwent placement of a) a thermodilution catheter in the right internal jugular vein; b) a right carotid artery catheter for mean arterial pressure; and c) sonomicrometry crystals for dynamic measurements of left ventricular dimensions. Calculations were made of end-systolic and end-diastolic left ventricular volume and ejection fraction. Six cardiac output measurements were performed in each pig. Data were obtained at baseline (just before iced temperature injectate infusion) and every 3 sec for 9 secs. The only significant effect seen with iced temperature injectate infusion was a small, transient decrease in heart rate (-5.9 +/- 1.1 beats/min from a baseline heart rate of 144.8 +/- 20.6 beats/min). Indices of preload, contractile function, and dynamic cardiac geometry were unaffected. Iced temperature injectate used in clinically relevant volumes causes transient negative chronotropic effects, but reservations regarding other perturbations of cardiodynamics are unfounded. Thus, the use of iced temperature injectate for cardiac output determination is still a viable alternative to room temperature injectate use, especially when a larger signal/noise ratio is required.


Difference in medical service use among Korean gastric cancer survivors according to regional healthcare vulnerabilities: a cohort study.
This study investigated the relationship between medical service use and healthcare vulnerability, pre- and post-gastric cancer diagnosis. Differences between healthcare-vulnerable and healthcare-nonvulnerable regions identified inequities that require intervention. This cohort study was done using the National Health Insurance claims data of patients diagnosed with gastric cancer between 2004 and 2013. The Position Value for Relative Comparison Index was used to determine whether the patients lived in a healthcare-vulnerable region. Medical service use was classified into annual outpatient treatment, hospitalization days, and emergency treatment. We used a generalized linear model to which the Poisson distribution was applied and compared regional differences in medical service use. A total of 1797 gastric cancer patients who had survived 5 years post-diagnosis were included in the study, of which 14.2% lived in healthcare-vulnerable regions. The patients in vulnerable regions surviving 5-7 years post-diagnosis had a higher number of outpatient visits than those in nonvulnerable regions. Furthermore, hospitalization days were lesser for patients in vulnerable regions who survived 6 years post-diagnosis than those in nonvulnerable regions; however, this number increased in the seventh year. Our results suggest that gastric cancer survivors living in healthcare-vulnerable regions have a higher probability of increased medical service use 5 years post-diagnosis compared with patients in nonvulnerable regions, which may significantly increase healthcare disparities over time. Therefore, in the future, additional research is needed to elucidate the causes of the disparities in healthcare use and the results of the differences in health outcomes.


Proton-pumping-ATPase-targeted antifungal activity of cinnamaldehyde based sulfonyl tetrazoles.
Azoles are generally fungistatic, and resistance to fluconazole is emerging in several fungal pathogens. We designed a series of cinnamaldehyde based sulfonyl tetrazole derivatives. To further explore the antifungal activity, in vitro studies were conducted against 60 clinical isolates and 6 standard laboratory strains of Candida. The rapid irreversible action of these compounds on fungal cells suggested a membrane-located target for their action. Results obtained indicate plasma membrane H(+)-ATPase as site of action of the synthesized compounds. Inhibition of H(+)-ATPase leads to intracellular acidification and cell death. Presence of chloro and nitro groups on the sulfonyl pendant has been demonstrated to be a key structural element of antifungal potency. SEM micrographs of treated Candida cells showed severe cell breakage and alterations in morphology.


Vertebral fracture assessment in supine position: comparison by using conventional semiquantitative radiography and visual radiography.
To retrospectively evaluate the accuracy of vertebral fracture assessment (VFA) performed with the patient in the supine position and conventional semiquantitative radiography of the spine by using conventional visual radiography of the spine as the reference standard. This retrospective study was approved by the institutional ethics review board; informed consent was obtained from the patients. A total of 250 consecutive patients (mean age, 62.0 years; range, 25-89 years) consisting of 190 women (mean age, 64 years; range, 25-89 years) and 60 men (mean age, 57.0 years; range, 27-83 years) who were suspected of having osteoporosis and who underwent VFA in the supine position and radiography of the spine were evaluated. VFA and semiquantitative radiography were analyzed by using a six-marker point method to describe the shape and deformity of each vertebra. Visual radiography of the lateral spine was performed by an experienced radiologist. The agreement between VFA, visual radiography, and semiquantitative radiography of semiquantitative graded fractures was assessed by using weighted kappa statistics. Visual radiography helped identify 92 (36.8%) patients with at least one vertebral fracture (mean, 1.8 per patient). Most fractures were present in T7, T12, and L1. Excellent agreement was found between VFA and visual radiography, with 97.5% concordance and kappa = 0.82; VFA and semiquantitative radiography were in agreement in 97.4% of patients, with kappa = 0.83; and visual radiography and semiquantitative radiography were in agreement in 98.1%, with kappa = 0.87. Sensitivity, specificity, and positive and negative predictive values calculated by lesion level for VFA compared with visual assessment were 83.6%, 99.1%, 84.1%, and 99.1%, respectively. VFA performed with patients in the supine position is an accurate method to help detect vertebral fractures when compared with conventional spine radiography. VFA permits combination of fracture assessment with bone mineral density measurement in a single session.


"Chemical transformers" from nanoparticle ensembles operated with logic.
The pH-responsive nanoparticles were coupled with information-processing enzyme-based systems to yield "smart" signal-responsive hybrid systems with built-in Boolean logic. The enzyme systems performed AND/OR logic operations, transducing biochemical input signals into reversible structural changes (signal-directed self-assembly) of the nanoparticle assemblies, thus resulting in the processing and amplification of the biochemical signals. The hybrid system mimics biological systems in effective processing of complex biochemical information, resulting in reversible changes of the self-assembled structures of the nanoparticles. The bioinspired approach to the nanostructured morphing materials could be used in future self-assembled molecular robotic systems.