The health consequences of teenage fertility.
A review of the literature on the health consequences of teenage pregnancy and childbirth shows remarkable similarity in findings from studies conducted in the United States, Canada, Britain, France and Sweden. In particular, results of studies conducted since 1970 have tended to indicate that the increased risk of maternal complications from pregnancy and delivery among teenagers--especially those older than 15--is associated more with socioeconomic factors than with the biological effects of age. Smaller differences in maternal mortality between teenagers and older women exist in England and Wales than in the United States and France; this finding suggests that England and Wales may have minimized the age or socioeconomic factors contributing to a difference in rates. Inadequate prenatal care may be a major cause of pregnancy-related complications for mothers, since teenagers in all countries are more likely than older mothers to seek care late in the pregnancy or not all. There is a very marked association between young age of mother and low birth weight in all countries. Sweden has the lowest rate of low birth weight at all maternal ages, and the United States generally has the highest. Some of the apparent effect of young maternal age on birth weight may be because the birth is likely to be the mother's first, and first births have a higher incidence of prematurity. As in the case of maternal health, inadequate prenatal care has been singled out as an important determinant of both prematurity and low birth weight. Late fetal death rates in the United States, England and Wales, and France are slightly higher among teenagers than among women in their 20s. In Canada and Sweden, however, no substantially increased risk for young women is found. Perinatal death rates, which one might expect to be influenced more by environmental factors than are late fetal deaths, show a more marked increase among infants of teenagers than do rates of late fetal deaths. Again, Sweden does not fit the pattern. Studies that separate data for young teens and older teenage mothers also indicate that increased perinatal and late fetal mortality rates may occur only among very young teenage mothers. There is no evidence of an overall increase in congenital malformations among babies born to teenagers. When individual birth defects are examined, some studies have shown increased rates of cardiovascular and central nervous system malformations among the children of teenage mothers.(ABSTRACT TRUNCATED AT 400 WORDS)


Kaposi's sarcoma-associated herpesvirus seropositivity is associated with parasite infections in Ugandan fishing communities on Lake Victoria islands.
We investigated the impact of helminths and malaria infection on Kaposi's sarcoma associated herpesvirus (KSHV) seropositivity, using samples and data collected from a cluster-randomised trial of intensive versus standard anthelminthic treatment. The trial was carried out in 2012 to 2016 among fishing communities on Lake Victoria islands in Uganda. Plasma samples from 2881 participants from two household surveys, the baseline (1310 participants) and the final (1571 participants) surveys were tested for KSHV IgG antibody responses to K8.1 and ORF73 recombinant proteins using ELISA. The baseline survey was carried out before the trial intervention while the final survey was carried out after three years of the trial intervention. Additionally, a subset sample of 372 participants from the final survey was tested for IgE, IgG and IgG4 antibody concentrations to S. mansoni adults worm antigen (SWA) and S. mansoni egg antigen (SEA) using ELISA. Infection by helminths (S. mansoni, N. americanus, T. trichiura and S. stercoralis) was diagnosed using real-time PCR, urine circulating cathodic antigen (CCA) and stool microscopy (Kato-Katz method) while malaria infection was diagnosed using microscopy. We analysed the relationship between helminth and malaria infections and KSHV seropositivity using regression modelling, allowing for survey design. At baseline, 56% of the participants were male while 48% of the participants were male in the final survey. The most prevalent helminth infection was S. mansoni (at baseline 52% and 34% in the final survey by microscopy, 86% by CCA and 50% by PCR in the final survey). KSHV seropositivity was 66% (baseline) and 56% (final survey) among those 1-12 years and >80% in those 13+ years in both surveys; malaria parasitaemia prevalence was 7% (baseline) and 4% (final survey). At baseline, individuals infected with S. mansoni (detected by microscopy) were more likely to be KSHV seropositive (aOR = 1.86 (1.16, 2.99) p = 0.012) and had higher anti-K8.1 antibody levels (acoefficient = 0.03 (0.01, 0.06) p = 0.02). In the final survey, S. mansoni (by microscopy, adjusted Odds Ratio (aOR = 1.43 (1.04-1.95), p = 0.028) and malaria parasitaemia (aOR = 3.49 (1.08-11.28), p = 0.038) were positively associated with KSHV seropositivity. Additionally, KSHV seropositive participants had higher S. mansoni-specific IgE and IgG antibody concentrations in plasma. Furthermore, HIV infected individuals on cART were less likely to be KSHV seropositive compared to HIV negative individuals (aOR = 0.46 (0.30, 0.71) p = 0.002). Schistosoma species skew the immune response towards Th2 and regulatory responses, which could impact on KSHV reactivation if co-infected with both organisms.


The Effects of Intravenous Lipid Emulsion Therapy in the Prevention of Depressive Effects of Propofol on Cardiovascular and Respiratory Systems: An Experimental Animal Study.
Background and objectives: Although there are several hypotheses about the mechanism of action, intravenous lipid emulsion (ILE) therapy has been shown to be effective in the treatment of toxicities due to local anaesthetics and many lipophilic drugs. In this study, we had hypothesized that ILE therapy might also be effective in preventing mortality and cardiorespiratory depressant effects due to propofol intoxication. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into four groups. Saline was administered to the subjects in the control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth group was administered propofol and ILE therapy together (ILE+PP group). Systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), heart rate (HR), and mortality were recorded at 10 time-points during a period of 60 min. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group; SBP, DBP, RR, and HR levels declined steadily; and all rats in this group died after the 60-min period. In the ILE+PP group, the initially reduced SBP, DBP, RR, and HR scores increased close to the levels observed in the control group. The SBP, DBP, RR, and HR values in the PP group were significantly lower compared to the other groups (p < 0.01). The mortality rate was 100% (with survival duration of 60 min) for the PP group; however, it was 0% for the remaining three groups. Conclusions: Our results suggest that the untoward effects of propofol including hypotension, bradycardia, and respiratory depression might be prevented with ILE therapy.


The effect of two surgical modalities for the treatment of subtrochanteric fractures of the femur on postoperative wound complications in patients: A meta-analysis.
Currently, there are two methods of treating subtrochanteric femur fractures: intramedullary nailing and extramedullary plate fixation. However, it remains to be seen whether internal or external fixation is the primary treatment for subrotator femur fractures in adults. In this meta-analysis, we reviewed the effects of internal and external fixation on the treatment of subrotator and subrotator fractures. Until July 2023, the researchers have been researching the Cochrane Library, Embase, Web of Science and PubMed, with English as their only language. The aims of the study are as follows: (1) to assess the efficacy of internal and external fixation for the treatment of postoperative wound infections in adult patients with subrotator femur fractures; (2) to assess the efficacy of various types of internal fixation for the treatment of adult patients with subrotator femur fractures, including postoperative complications, infections, and operative time. Meta-analysis showed that there was no significant difference in the treatment of subrotator fracture with internal versus external fixation in terms of wound infections, intra-operative bleeding, length of incision, and operative time were not significantly different. Therefore, more research is needed to support these findings with a number of large, high-quality randomized studies.


A retroperitoneal approach for transureteroureterostomy: a neglected and forgotten procedure.
Transureteroureterostomy in 17 consecutive cases is reviewed. Our technique of the operation (with retroperitoneal approach) is described. Stenosis of the recipient ureter or other complications did not develop in any of our cases. Based on our experience we continue to regard this procedure as an excellent means of urinary diversion for patients with unilateral lower ureteral lesions.


A non-tight junction function of claudin-7-Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment.
Claudins are a family of tight junction (TJ) membrane proteins involved in a broad spectrum of human diseases including cancer. Claudin-7 is a unique TJ membrane protein in that it has a strong basolateral membrane distribution in epithelial cells and in tissues. Therefore, this study aims to investigate the functional significance of this non-TJ localization of claudin-7 in human lung cancer cells. Claudin-7 expression was suppressed or deleted by lentivirus shRNA or by targeted-gene deletion. Cell cycle analysis and antibody blocking methods were employed to assay cell proliferation and cell attachment, respectively. Electron microscopy and transepthelial electrical resistance measurement were performed to examine the TJ ultrastructure and barrier function. Co-immunolocalization and co-immunoprecipitation was used to study claudin-7 interaction with integrin β1. Tumor growth in vivo were analyzed using athymic nude mice. Claudin-7 co-localizes and forms a stable complex with integrin β1. Both suppressing claudin-7 expression by lentivirus shRNA in human lung cancer cells (KD cells) and deletion of claudin-7 in mouse lungs lead to the reduction in integrin β1 and phospho-FAK levels. Suppressing claudin-7 expression increases cell growth and cell cycle progression. More significantly, claudin-7 KD cells have severe defects in cell-matrix interactions and adhere poorly to culture plates with a remarkably reduced integrin β1 expression. When cultured on uncoated glass coverslips, claudin-7 KD cells grow on top of each other and form spheroids while the control cells adhere well and grow as a monolayer. Reintroducing claudin-7 reduces cell proliferation, upregulates integrin β1 expression and increases cell-matrix adhesion. Integrin β1 transfection partially rescues the cell attachment defect. When inoculated into nude mice, claudin-7 KD cells produced significantly larger tumors than control cells. In this study, we identified a previously unrecognized function of claudin-7 in regulating cell proliferation and maintaining epithelial cell attachment through engaging integrin β1.


Combating drug-resistant bacteria: small molecule mimics of plasmid incompatibility as antiplasmid compounds.
A major mechanism for bacterial resistance to antibiotics is through the acquisition of a plasmid coding for resistance-mediating proteins. Described herein is a strategy to eliminate these plasmids from bacteria, thus resensitizing the bacteria to antibiotics. This approach involves mimicking a natural mechanism for plasmid elimination, known as plasmid incompatibility. The compound apramycin was identified as a tight binder to SLI RNA (Kd = 93 nM), the in vivo target of the plasmid incompatibility determinate RNA I, and footprinting/mutagenesis studies indicate apramycin binds SLI in the important regulatory region that dictates plasmid replication control and incompatibility. In vivo studies demonstrate that this compound causes significant plasmid loss and resensitizes bacteria to conventional antibiotics. The demonstration that a small molecule can mimic incompatibility, cause plasmid elimination, and resensitize bacteria to antibiotics opens up new targets for antibacterial research.


Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol.
A large segment of the population is modifying its dietary cholesterol intake to achieve a healthier life-style. However, all individuals do not respond equally. We have investigated the effects that that two physiologically important polymorphisms in the apolipoprotein (apo) E and B genes have on the responses of plasma lipid, lipoprotein, and apolipoprotein levels to a high-cholesterol diet. Over a 6-wk period, individuals were prescribed two diets, one consisting of 300 mg dietary cholesterol/d for 3 wk and one consisting of 1,700 mg dietary cholesterol/d for 3 wk. Total cholesterol, low-density-lipoprotein cholesterol (LDL-C), and apo B levels were significantly increased on the high-cholesterol diet. Average total cholesterol (numbers in parentheses are SDs) went from 167.6 (23.4) mg/dl on the low-cholesterol diet to 190.8 (36.2) mg/dl on the high-cholesterol diet; LDL-C went from 99.9 (24.8) mg/dl to 119.2 (33.4) mg/dl, and apo B went from 74.9 (24.5) mg/dl to 86.8 (29.5) mg/dl. In 71 individuals, the frequencies of the apo epsilon 2, epsilon 3, and epsilon 4 alleles were .09, .84, and .07, respectively. The frequency of the longer, apo B signal peptide allele (5'beta SP27) was .68. Apo epsilon 2/3 individuals had significantly lower LDL-C levels than did epsilon 3/3 homozygotes, on both the low-cholesterol diet (LDL-C lower by 21 mg/dl) and the high-cholesterol diet (LDL-C lower by 27 mg/dl). Average triglyceride levels were significantly different among apo B signal peptide genotypes, with the 5'beta SP27/37 homozygotes having the lowest levels (70 mg/dl). When individuals were switched from the low-cholesterol diet to the high-cholesterol diet, in no case were the average responses in lipid levels significantly different among apo E or B genotypes. Therefore, these gene loci do not have a major effect on the response of lipid levels to increased dietary cholesterol.


40-Hz oscillations underlying perceptual binding in young and older adults.
Auditory object perception requires binding of elementary features of complex stimuli. Synchronization of high-frequency oscillation in neural networks has been proposed as an effective alternative to binding via hard-wired connections because binding in an oscillatory network can be dynamically adjusted to the ever-changing sensory environment. Previously, we demonstrated in young adults that gamma oscillations are critical for sensory integration and found that they were affected by concurrent noise. Here, we aimed to support the hypothesis that stimulus evoked auditory 40-Hz responses are a component of thalamocortical gamma oscillations and examined whether this oscillatory system may become less effective in aging. In young and older adults, we recorded neuromagnetic 40-Hz oscillations, elicited by monaural amplitude-modulated sound. Comparing responses in quiet and under contralateral masking with multitalker babble noise revealed two functionally distinct components of auditory 40-Hz responses. The first component followed changes in the auditory input with high fidelity and was of similar amplitude in young and older adults. The second, significantly smaller in older adults, showed a 200-ms interval of amplitude and phase rebound and was strongly attenuated by contralateral noise. The amplitude of the second component was correlated with behavioral speech-in-noise performance. Concurrent noise also reduced the P2 wave of auditory evoked responses at 200-ms latency, but not the earlier N1 wave. P2 modulation was reduced in older adults. The results support the model of sensory binding through thalamocortical gamma oscillations. Limitation of neural resources for this process in older adults may contribute to their speech-in-noise understanding deficits.


An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems.
Bacterial DNA and immunostimulatory CpG oligodeoxynucleotides (ODNs) activate the innate immune system to produce proinflammatory cytokines. Shown to be potent Th1-like adjuvants, stimulatory CpG motifs are currently used as effective therapeutic vaccines for various animal models of infectious diseases, tumors, allergies, and autoimmune diseases. In this study, we show that the application of an immunomodulatory GpG ODN, with a single base switch from CpG to GpG, can effectively inhibit the activation of Th1 T cells associated with autoimmune disease. Moreover, this immunomodulatory GpG ODN suppresses the severity of experimental autoimmune encephalomyelitis in mice, a prototypic Th1-mediated animal disease model for multiple sclerosis.


Rapid and Efficient Arsenic Removal by Iron Electrocoagulation Enabled with in Situ Generation of Hydrogen Peroxide.
Millions of people are exposed to toxic levels of dissolved arsenic in groundwater used for drinking. Iron electrocoagulation (FeEC) has been demonstrated as an effective technology to remove arsenic at an affordable price. However, FeEC requires long operating times (∼hours) to remove dissolved arsenic due to inherent kinetics limitations. Air cathode Assisted Iron Electrocoagulation (ACAIE) overcomes this limitation by cathodically generating H2O2 in situ. In ACAIE operation, rapid oxidation of Fe(II) and complete oxidation and removal of As(III) are achieved. We compare FeEC and ACAIE for removing As(III) from an initial concentration of 1464 μg/L, aiming for a final concentration of less than 4 μg/L. We demonstrate that at short electrolysis times (0.5 min), i.e., high charge dosage rates (1200 C/L/min), ACAIE consistently outperformed FeEC in bringing arsenic levels to less than WHO-MCL of 10 μg/L. Using XRD and XAS data, we conclusively show that poor arsenic removal in FeEC arises from incomplete As(III) oxidation, ineffective Fe(II) oxidation and the formation of Fe(II-III) (hydr)oxides at short electrolysis times (<20 min). Finally, we report successful ACAIE performance (retention time 19 s) in removing dissolved arsenic from contaminated groundwater in rural California.


Facilitating translational team science: The project leader model.
Project management expertise is employed across many professional sectors, including clinical research organizations, to ensure that efforts undertaken by the organization are completed on time and according to specifications and are capable of achieving the needed impact. Increasingly, project leaders (PLs) who possess this expertise are being employed in academic settings to support clinical and preclinical translational research team science. Duke University's clinical and translational science enterprise has been an early adopter of project management to support clinical and preclinical programs. We review the history and evolution of project management and the PL role at Duke, examine case studies that illustrate their growing value to our academic research environment, and address challenges and solutions to employing project management in academia. Furthermore, we describe the critical role project leadership plays in accelerating and increasing the success of translational team science and team approaches frequently required for systems biology and "big data" scientific studies. Finally, we discuss perspectives from Duke project leadership professionals regarding the training needs and requirements for PLs working in academic clinical and translational science research settings.


Modeling patient response to acute myocardial infarction: implications for a tailored technology-based program to reduce patient delay.
We are examining ways in which a clinical information system can favorably influence the appropriateness and rapidity of decision-making in patients suffering from symptoms of acute myocardial infarction. In order to do so, we have developed a theoretically based cognitive model for patient decision making. Our model includes somatic and emotional awareness, perceived threat (vulnerability and susceptibility), expectations of symptoms, self-efficacy and response efficacy to explain the response of an individual their symptoms. Variables are explained within a framework that details how they are interrelated in the context of other moderating variables. With an understanding of the decision process, we are able to collect, maintain and access patient specific data to tailor technology-based interventions unique to the requirements of each individual at various phases of the decision process. Existing clinical information systems at Columbia-Presbyterian Medical Center already address issues related to patient relevant on-line data. Other patient specific information will be collected through on-line questionnaires. By basing our approach on the use of a cognitive model, we can assess the capacity of our interventions to modify variables important to the decision-making process, allowing us to pinpoint which interventions are effective and the reasons why they are ineffective.


Light-Dependent Aerobic Methane Oxidation Reduces Methane Emissions from Seasonally Stratified Lakes.
Lakes are a natural source of methane to the atmosphere and contribute significantly to total emissions compared to the oceans. Controls on methane emissions from lake surfaces, particularly biotic processes within anoxic hypolimnia, are only partially understood. Here we investigated biological methane oxidation in the water column of the seasonally stratified Lake Rotsee. A zone of methane oxidation extending from the oxic/anoxic interface into anoxic waters was identified by chemical profiling of oxygen, methane and δ13C of methane. Incubation experiments with 13C-methane yielded highest oxidation rates within the oxycline, and comparable rates were measured in anoxic waters. Despite predominantly anoxic conditions within the zone of methane oxidation, known groups of anaerobic methanotrophic archaea were conspicuously absent. Instead, aerobic gammaproteobacterial methanotrophs were identified as the active methane oxidizers. In addition, continuous oxidation and maximum rates always occurred under light conditions. These findings, along with the detection of chlorophyll a, suggest that aerobic methane oxidation is tightly coupled to light-dependent photosynthetic oxygen production both at the oxycline and in the anoxic bottom layer. It is likely that this interaction between oxygenic phototrophs and aerobic methanotrophs represents a widespread mechanism by which methane is oxidized in lake water, thus diminishing its release into the atmosphere.


The structure of ICD-11 post traumatic stress disorder in a clinical sample of refugees based on the International Trauma Interview.
The ICD-11 proposes fundamental changes to the PTSD diagnostic criteria, prompting thorough validation. While this is ideally carried out based on diagnostic interviews, most-and in the case of transcultural psychiatry all-studies have relied on self-reported measures. In this study, we used the International Trauma Interview (ITI) to assess the factor structure of ICD-11 PTSD symptoms in a sample of trauma-affected refugees. The ITI was administered with a sample of refugees (n = 198), originating mainly from the Greater Middle East. The symptom ratings were subjected to a confirmatory factor analysis (CFA), comparing the ICD-11 concordant three-factor model with alternative two- and one-factor models. The overall fit was adequate for both the two- and three-factor models, but favored the two-factor model. Results for both models indicated local misspecifications and that item 5, hypervigilance, displayed a suboptimal loading. The results generally support the use of the ITI in a severely trauma-affected refugee population, albeit with particular attention needed in the administration of item 5. The superior fit of a two-factor model warrants further testing across populations.


Severity of patellar luxation and frequency of concomitant cranial cruciate ligament rupture in dogs: 162 cases (2004-2007).
To evaluate severity of medial patellar luxation (MPL) and frequency of concomitant cranial cruciate ligament rupture (CCLR) in dogs. Retrospective case series. 162 dogs (266 stifle joints). Medical records of 162 small-breed dogs with MPL were reviewed. Signalment, body weight, luxation grade, bilateral or unilateral MPL, CCLR, and difference in luxation grades between stifle joints were evaluated. Association between severity of MPL and CCLR was investigated. 58 dogs had unilateral MPL, and 104 dogs had bilateral MPL. Dogs ranged from 8.4 months to 16.7 years of age (mean, 5.7 years), and mean body weight was 5.45 kg (12 lb). Forty-one percent of all dogs had concomitant CCLR. Mean age for dogs with MPL alone was 3.0 years, which differed significantly from mean age of dogs with MPL and concomitant CCLR (7.8 years). Dogs with grade IV MPL were significantly more likely to have concomitant CCLR than were dogs with any other grade of MPL. In dogs with bilateral MPL and unilateral CCLR, there was a significantly higher grade of luxation in the stifle joint with CCLR. Small-breed dogs with MPL and concomitant CCLR were older than were dogs with only MPL. Dogs with grade IV MPL were more likely to have CCLR than were dogs with other grades of MPL. Most dogs with concomitant CCLR had a higher MPL grade in the affected stifle joint than in the intact joint. These findings should be beneficial in client education and clinical diagnosis.


LDL apheresis reduces the susceptibility of LDL to in vitro oxidation in a diabetic patient with hemodialysis treatment.
We studied whether LDL apheresis would alter the susceptibility of LDL to in vitro oxidative modification induced by copper ion in a diabetic patient undergoing hemodialysis treatment. Isolated LDL was dialyzed against phosphate-buffered saline and resuspended at a concentration of 0.3 mg cholesterol mass/ml buffer LDL oxidation was then initiated by addition of 1.66 mumol/l CuSO4, and the formation of conjugated dienes was continuously monitored spectrophotometrically at 234 nm. The duration of the lag phase of LDL obtained after LDL apheresis was markedly longer than that of LDL obtained before LDL apheresis. The propagation rate and the maximum conjugated diene formation of LDL oxidation were not changed after LDL apheresis. A LDL subfraction that was susceptible to oxidation was removed by LDL apheresis, resulting in reduction of susceptibility of LDL to in vitro oxidation remaining in plasma. LDL apheresis may be of clinical importance for preventing atherosclerotic disease in diabetic patients undergoing hemodialysis.


High-resolution FTIR spectroscopy of trisulfane HSSSH: a candidate for detecting parity violation in chiral molecules.
We report the first successful high-resolution analyses of the Fourier transform infrared (FTIR) spectrum of trisulfane. A band centered at 861.0292 cm-1 can be assigned unambiguously to the chiral trans conformer by means of ground state combination differences in comparison with known rotational spectra. A second band near 864.698 cm-1 is tentatively assigned to the cis conformer by comparison with theory. The results are discussed in relation to their importance for experimental attempts to measure the parity violating energy difference ΔpvE between the ground states of enantiomers of chiral molecules.


The use of serial human chorionic gonadotropin levels to establish a viable or a nonviable pregnancy.
Measurement of serial human chorionic gonadotropin (hCG) concentrations facilitates the diagnosis of normal or abnormal early gestation, as deviations from expected rates of rise or decline prompt intervention and/or treatment of abnormal pregnancies. Recently, the expected rise in hCG levels for normal intrauterine pregnancies (IUPs) was well characterized, and based on a 95% confidence interval, it was determined that the slowest rise in a normal IUP was 53% in 2 days. When the hCG level is decreasing, it is clear that the pregnancy is not viable. The management of such cases consists of observation or intervention. The rate of decline associated with nonviable pregnancies that resolved with expectant management has been described, with a faster decline observed with higher hCG levels at presentation. A rate of decline that is slower than 21 to 35% in 48 hours suggests the presence of retained trophoblastic tissue or an ectopic pregnancy and indicates the need for intervention to achieve a definitive diagnosis. While there is no consistent pattern of serial hCG levels characterizing ectopic pregnancies, the majority of patients ultimately diagnosed with ectopic pregnancy will exhibit rates of rise or decline that are outside the "normal" range as defined by the established curves.


A postal intervention for dependent cannabis users.
INTRODUCTION AND AIMS. In Australia, many would-be treatment seekers for problematic cannabis use live in rural and remote areas, thereby limiting their access to face-to-face treatments. In order to address this gap in treatment availability, the present study aimed to assess the feasibility of a mail-based intervention for regular cannabis users. Treatment was based upon cognitive-behavioural and motivational interviewing principles, and consisted of six treatment modules posted fortnightly to participants. In addition to the standardised modules, participants received personalised feedback at four points, based upon their mailed-in responses to the modules. Participants were recruited via advertisements in rural newspapers and a Google advertisement. A total of 268 people expressed interest in this study and 36 participants went on to complete treatment. Treatment completers demonstrated a significant reduction in cannabis use at the 1 month follow-up. Transposing face-to-face treatments into a mailed format has shown some promise and future research is warranted to determine the efficacy of such treatments in a controlled study.


Interleukin-6, TNF-alpha and interleukin-1 beta levels in blood and tissue in severely burned rats.
Previous studies have demonstrated the early appearance of inflammatory cytokines in the systemic circulation after thermal injury both in humans and animals. The aim of this study was to evaluate the time course of several cytokines, IL-6, TNF-alpha and IL-1beta in serum, lung, liver and brain of severely burned rats during the first week after thermal injury. Cytokine measurements were performed by enzyme-linked immunosorbent assay (ELISA). The comparison between the sham-burned animals and animals with third-degree burns on 20% or 40% of their total body surface area allowed for the study of the inflammatory process relative to the size of the injury. Serum IL-6 levels, which were undetectable in sham-treated animals, peaked during the first hours after injury and were proportionate to the size of the area burned. After a few days, IL-6 increased once more, but only in the most severely burned rats. In lung, liver and brain, low but measurable basal levels of TNF-alpha and IL-1 were detected in sham-burned animals. Strikingly, IL-1beta levels remained significantly elevated in the lung after injury in animals having 20% and 40% burned skin area. Unexpectedly, both TNF-alpha and IL-1beta production decreased gradually in liver and brain after burn injury. Also, the inflammatory response after a burn injury appeared to be biphasic. The first period corresponded to the early release of IL-6 into the circulation, proportional to the severity of the injury. After a few days, a second period was marked by the extension of the inflammatory processes from the injured area to the rest of the body, particularly to lung, which could be considered as at potential risk of involvement in severely burned patients.


Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton.
Growth factors such as insulin regulate phosphatidylinositol 3-kinase-dependent actin cytoskeleton rearrangement in many types of cells. However, the mechanism by which the insulin signal is transmitted to the actin cytoskeleton remains largely unknown. Yeast two-hybrid screening revealed that the phosphatidylinositol 3-kinase downstream effector phosphoinositide-dependent protein kinase-1 (PDK1) interacted with protein kinase N (PKN), a Rho-binding Ser/Thr protein kinase potentially implicated in a variety of cellular events, including phosphorylation of cytoskeletal components. PDK1 and PKN interacted in vitro and in intact cells, and this interaction was mediated by the kinase domain of PDK1 and the carboxyl terminus of PKN. In addition to a direct interaction, PDK1 also phosphorylated Thr(774) in the activation loop and activated PKN. Insulin treatment or ectopic expression of the wild-type PDK1 or PKN, but not protein kinase Czeta, induced actin cytoskeleton reorganization and membrane ruffling in 3T3-L1 fibroblasts and Rat1 cells that stably express the insulin receptor (Rat1-IR). However, the insulin-stimulated actin cytoskeleton reorganization in Rat1-IR cells was prevented by expression of kinase-defective PDK1 or PDK1-phosphorylation site-mutated PKN. Thus, phosphorylation by PDK1 appears to be necessary for PKN to transduce signals from the insulin receptor to the actin cytoskeleton.


First in Human Subjects Testing of the UroMonitor: A Catheter-free Wireless Ambulatory Bladder Pressure Monitor.
Urodynamics is the standard method of diagnosing bladder dysfunction, but involves catheters and retrograde bladder filling. With these artificial conditions, urodynamics cannot always reproduce patient complaints. We have developed a wireless, catheter-free intravesical pressure sensor, the UroMonitor, which enables catheter-free telemetric ambulatory bladder monitoring. The purpose of this study was twofold: to evaluate accuracy of UroMonitor pressure data, and assess safety and feasibility of use in humans. Eleven adult female patients undergoing urodynamics for overactive bladder symptoms were enrolled. After baseline urodynamics, the UroMonitor was transurethrally inserted into the bladder and position was confirmed cystoscopically. A second urodynamics was then performed with the UroMonitor simultaneously transmitting bladder pressure. Following removal of urodynamics catheters, the UroMonitor transmitted bladder pressure during ambulation and voiding in private. Visual analogue pain scales (0-5) were used to assess patient discomfort. The UroMonitor did not significantly alter capacity, sensation, or flow during urodynamics. The UroMonitor was also easily inserted and removed in all subjects. The UroMonitor reproduced bladder pressure, capturing 98% (85/87) of voiding and nonvoiding urodynamic events. All subjects voided with only the UroMonitor in place with low post-void residual volume. Median ambulatory pain score with the UroMonitor was rated 0 (0-2). There were no post-procedural infections or changes to voiding behavior. The UroMonitor is the first device to enable catheter-free telemetric ambulatory bladder pressure monitoring in humans. The UroMonitor appears safe and well tolerated, does not impede lower urinary tract function, and can reliably identify bladder events compared to urodynamics.


Implementation of health care quality indicators for out-of-hospital emergencies: a systematic review.
Although many health care quality indicators have been defined for establishing a common, homogeneous, and reliable system for assessing emergency department care, less information is available on the use of indicators of quality in attending emergencies outside the hospital. We aimed to identify and analyze quality indicators that have appeared in the literature on out-of-hospital emergencies. This systematic review of the literature followed the ations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We developed protocols for searching 5 databases to locate studies using quality indicators to evaluate care in out-of-hospital emergencies. Studies were published between July 2017 and July 2018 in either English or Spanish. We identified 22 studies naming 333 quality indicators in out-of-hospital emergencies. The indicators were classified as clinical or nonclinical; within each of these 2 sets, we also identified domains, or subcategories. As nonclinical quality identifiers were more numerous in the literature, it seems that they are the ones most often used to assess out-of-hospital emergency care at this time. This finding leaves the door open to designing and implementing new indicators able to measure quality of care in this clinical setting.


The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer's Disease-like Pathogenesis.
This work aims to clarify the effect of dietary polyunsaturated fatty acid (PUFA) intake on the adult brain affected by amyloid pathology. McGill-R-Thy1-APP transgenic (Tg) rat and 5xFAD Tg mouse models that represent earlier or later disease stages were employed. The animals were exposed to a control diet (CD) or an HFD based on corn oil, from young (rats) or adult (mice) ages for 24 or 10 weeks, respectively. In rats and mice, the HFD impaired reference memory in wild-type (WT) animals but did not worsen it in Tg, did not cause obesity, and did not increase triglycerides or glucose levels. Conversely, the HFD promoted stronger microglial activation in Tg vs. WT rats but had no effect on cerebral amyloid deposition. IFN-γ, IL-1β, and IL-6 plasma levels were increased in Tg rats, regardless of diet, while CXCL1 chemokine levels were increased in HFD-fed mice, regardless of genotype. Hippocampal 3-nitrotyrosine levels tended to increase in HFD-fed Tg rats but not in mice. Overall, an HFD with an elevated omega-6-to-omega-3 ratio as compared to the CD (25:1 vs. 8.4:1) did not aggravate the outcome of AD regardless of the stage of amyloid pathology, suggesting that many neurobiological processes relevant to AD are not directly dependent on PUFA intake.


Peroxisome proliferator activated receptors alpha and gamma require zinc for their anti-inflammatory properties in porcine vascular endothelial cells.
Zinc is an essential structural component of various proteins and is crucial for the integrity of the vascular endothelium. The present study focused on the effect of zinc deficiency on the anti-inflammatory properties of peroxisome proliferator activated receptor (PPAR) alpha and gamma agonists. Porcine pulmonary-arterial endothelial cells were deprived from zinc by chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylene diamine. Cells were exposed to TNF-alpha for 2 h following pretreament with the PPARalpha agonists fenofibrate or ciprofibrate or the PPARgamma agonists thiazolidinedione or troglitazone. The inflammatory response was tested by measuring nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) binding activities as well as by measuring mRNA expression levels of inflammatory genes, such as vascular cell adhesion molecule-1 (VCAM-1) and IL-6. All PPAR agonists tested lost their potency to downregulate the TNF-alpha-induced inflammatory response in zinc-deficient cells. However, if zinc was added back, all PPAR agonists significantly downregulated the TNF-alpha-mediated induction of inflammatory transcription factors NF-kappaB and AP-1 and significantly reduced the expression of their target genes, VCAM-1 and IL-6. We therefore hypothesize that zinc is required for the PPARalpha and -gamma DNA binding activity. Indeed, zinc deficiency significantly reduced the agonist-induced binding activity of PPARalpha and -gamma to the PPAR response element. Our data demonstrate the importance of zinc in PPAR signaling and the requirement of zinc for the anti-inflammatory properties of PPARalpha and -gamma agonists.


Genomic characterization of a rotavirus G8P[1] detected in a child with diarrhea reveal direct animal-to-human transmission.
Group A rotavirus is a major cause of severe gastroenteritis in children and young animals. During a retrospective analysis of samples collected from Paraguayan children under 5 years old with diarrhea, and previously negative for rotavirus and norovirus, we detected the presence of bovine rotavirus sequences by viral metagenomics. Nucleic acid was extracted direct from stool sample and determined to be G8P[1]. The genomic analyzes revealed that the strain presents an Artiodactyl-like genome (G8-P[1]-I2-R2-C2-M1-Ax-N2-T6-E12-H3) suggesting a direct animal-to-human transmission.


Insulin restores UCP3 activity and decreases energy surfeit to alleviate lipotoxicity in skeletal muscle.
An early insulin regimen ameliorates glucotoxicity but also lipotoxicity in type 2 diabetes; however, the underlying mechanism remains elusive. In the present study, we investigated the role of mitochondria in lipid regulation following early insulin administration in insulin-resistant skeletal muscle cells. Male C57BL/6 mice, fed a high-fat diet (HFD) for 8 weeks, were treated with insulin for 3 weeks, and L6 myotubes cultured with palmitate (PA) for 24 h were incubated with insulin for another 12 h. The results showed that insulin facilitated systemic glucose disposal and attenuated muscular triglyceride accumulation in vivo. Recovery of AMP-activated protein kinase (AMPK) phosphorylation, inhibition of sterol-regulated element binding protein-1c (SREBP-1c) and increased carnitine palmitoyltransferase‑1B (CPT1B) expression were observed after insulin administration. Moreover, increased ATP concentration and cellular energy charge elicited by over-nutrition were suppressed by insulin. Despite maintaining respiratory complex activities, insulin restored muscular uncoupling protein 3 (UCP3) protein expression in vitro and in vivo. By contrast, knockdown of UCP3 abrogated insulin-induced restoration of AMPK phosphorylation in vitro. Importantly, the PA-induced decrease in UCP3 was blocked by the proteasome inhibitor MG132, and insulin reduced UCP3 ubiquitination, thereby prohibiting its degradation. Our findings, focusing on energy balance, provide a mechanistic understanding of the promising effect of early insulin initiation on lipotoxicity. Insulin, by recovering UCP3 activity, alleviated energy surfeit and potentiated AMPK-mediated lipid homeostasis in skeletal muscle cells following exposure to PA and in gastrocnemius of mice fed HFD.


Rare Post-Tonsillectomy Internal Carotid Artery Pseudoaneurysm: Management by Parent Artery Occlusion Using Detachable Balloons.
Iatrogenic cervical internal carotid artery pseudoaneurysm is a rare and potentially lethal complication following tonsillectomy. It can be complicated by thromboembolism, mass effect and eventually may rupture leading to death. Various endovascular treatment options are available for the management of these pseudoaneurysms, including coil embolization, detachable balloon occlusion, or stent graft placement. Parent artery occlusion using detachable balloons can be a therapeutic option in a subset of patients. However, evaluation of cross circulation with preprocedure balloon test occlusion is imperative in such cases.


Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human vagina.
The transient receptor potential cationic channel type A1 (TRPA1), belonging to a superfamily of cationic membrane channels, has been suggested to act as mechano- and pain sensor and, thus, to play a role in neurotransmission in the human body, including the urogenital tract. While the expression of TRPA1 has been investigated in a variety of tissues, up until today, no study has addressed the expression and distribution in the female genital tract. The present study aimed to investigate the expression and distribution of TRPA1 protein in human vaginal tissue. Reverse transcriptase PCR (RT-PCR) was applied in order to identify messenger ribonuleic acid specifically encoding for TRPA/A1. The distribution of TRPA1 in relation to the neuronal nitric oxide synthase (nNOS) and the signaling peptide calcitonin gene-related peptide (CGRP) was examined by means of immunohistochemical methods (double-antibody technique, laser fluorescence microscopy). RT-PCR analysis revealed the expression of mRNA encoding sequences specific for TRPA in the vaginal wall and epithelium. Immunostaining related to TRPA1 was observed in the basal epithelium and in slender varicose nerve fibers transversing the subepithelial and stromal space of the vaginal sections. In addition, these fibers presented immunoreactivity specific for nNOS or CGRP. The smooth musculature of the vaginal wall and small vessels interspersing the tissue did not present signals related to TRPA1. The findings indicate that TRPA1 might be involved in afferent neurotransmission in the vagina and work synergistically together with the nitric oxide/cyclic guanosine monophosphate pathway.


Morphological basis of long-term habituation and sensitization in Aplysia.
The morphological basis of the persistent synaptic plasticity that underlies long-term habituation and sensitization of the gill withdrawal reflex in Aplysia californica was explored by examining the fine structure of sensory neuron presynaptic terminals (the critical site of plasticity for the short-term forms of both types of learning) in control animals and in animals whose behavior had been modified by training. The number, size, and vesicle complement of sensory neuron active zones were larger in animals showing long-term sensitization than in control animals and smaller in animals showing long-term habituation. These changes are likely to represent an anatomical substrate for the memory consolidation of these tasks.


Antipsychotic use in children and adolescents: a 1-year follow-up study.
The objective of this study was to analyze the initial treatment with antipsychotics (APs) and its changes during the first year of treatment in patients visited in specialized child and adolescent psychiatry departments. Participants were 265 patients, aged 4 to 17 years, who attended consecutively at 4 different centers and were naive of AP or quasi-naive (less than 30 days since the beginning of AP treatment). Type of AP, dosage, and concomitant medication were registered at baseline, 1, 3, 6, and 12 months after beginning the treatment with AP. At baseline, the patients' mean age was 14.4 (2.9) years, and 145 (54.7%) patients were males. Antipsychotics were more prescribed in the following: schizophrenia spectrum disorders (30.2%), disruptive behavior disorders (DBDs) (18.9%), bipolar disorders (14.3%), depressive disorders (12.8%), and eating disorders (11.7%). A total of 93.2% of the patients were on an off-label indication of AP. Risperidone was the AP most prescribed in all the assessments, but differences were observed in the type of AP according to diagnosis. Thus, risperidone was significantly most prescribed in patients with DBD and olanzapine was most prescribed in patients with eating disorders. Olanzapine and quetiapine were the second-generation APs (SGAs) most prescribed after risperidone, and haloperidol was the most prescribed first-generation AP. Up to 8.3% of patients during the follow-up were on AP polypharmacy. Almost 16% patients had a change in its AP treatment during the follow-up, and the main switch was from one SGA to another. Second-generation APs were the APs most prescribed in our sample and approximately 93% of the patients used AP off-label. Risperidone was the most common AP used above all in patients with DBD, whereas olanzapine was most prescribed in patients with eating disorders. Antipsychotic polypharmacy and switch rates were low during the follow-up.


Systematic review of the evidence relating FEV1 decline to giving up smoking.
The rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta. Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors. Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex. The available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV1 decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.


Institutional distrust among gay, bisexual, and other men who have sex with men as a barrier to accessing pre-exposure prophylaxis (PrEP).
Populations at highest risk for acquiring HIV are more likely to pass through criminal justice (CJ) settings, and CJ-involved individuals are often at the intersection of multiple overlapping risk factors. The present study explored interest in, knowledge of, and barriers to PrEP uptake among gay, bisexual, and other men who have sex with men involved in the criminal justice system. Using semi-structured interviews, 26 participants who identified as MSM were asked about PrEP knowledge and interest, HIV risk, and incarceration experience. One theme that emerged across interviews was how institutional distrust in CJ settings may instill lack of trust in medical care after perceived mistreatment. Participants explained how lack of privacy fostered feelings that medical care was not confidential, care received was tied to status as an incarcerated person, and feelings of dehumanization led to distrust. Findings explore how distrust may hinder PrEP uptake and other HIV prevention efforts in CJ settings as well as after release. They highlight the need for greater privacy efforts and cultural humility, and explore how medical settings may function as spaces for people who are incarcerated to disclose HIV risk status. Few studies to our knowledge have examined the role of institutional distrust on men who have sex with men (MSM) in the context of pre-exposure prophylaxis (PrEP) interventions. The present study has implications for creating best practices to structure HIV prevention interventions in CJ settings.


'I saved a life': a heroin addict's reflections on managing an overdose using 'take home naloxone'.
Research shows that most heroin addicts, at some point in their drug using careers, accidentally overdose and that accidental overdose is the most common cause of death in this group. As most such overdoses are witnessed by other drug users or their carers, it is argued that providing 'take home naloxone' (a fast-acting opiate antagonist) to them (as potential witnesses to an overdose) can save lives. Despite the robust evidence base to support the feasibility and effectiveness of this strategy, its integration into clinical practice in the UK is still very limited. Here, we report the case of a heroin addict who used his take home naloxone to manage an overdose and thereby saved a life. Through this account, we hope to raise clinicians' awareness of this simple yet life-saving intervention. We will also briefly discuss the evidence base for take home naloxone with particular reference to the UK and will also give some practical guidance to clinicians on prescribing take home naloxone.


Opinions and preferences in flexor tendon surgery.
Responses to 378 questionnaires that were completed by members of the American Society for Surgery of the Hand are tabulated. The questionnaire was distributed in January 1984 in an attempt to determine the opinions and preferences of surgeons performing flexor surgery throughout the country. Those polled were asked to answer philosophical questions regarding their approach to flexor tendon repair, grafting, reconstruction, and lysis.


Uvulopalatoplasty and obstructive sleep apnea.
We present results of uvulopalatoplasty (UPP) in 22 patients with obstructive sleep apnea who had preoperative and postoperative polysomnograms. Symptomatic improvement in daytime somnolence, snoring, and quality of sleep was reported by 20 patients. After operation, ten of 22 patients had more than a 50% improvement in the apnea index and apnea/sleep percentage, and the number of apneas, apnea index, apnea/sleep percentage, apneic duration, lowest oxygen saturation and longest apneas were significantly better (P less than .05). In the remaining 12 patients there was significant improvement in only the lowest oxygen saturation and longest apneic duration categories. We conclude that UPP is an effective alternative to tracheostomy in the treatment of obstructive sleep apnea; we observed symptomatic improvement in 91%, objective improvement in 46%, and cure in 36% of the patients. Because of the discordance in subjective improvement and objective assessment, we believe all patients should have follow-up polysomnograms after UPP.


Generation and transformation of a hemi-iminal-based metal-organic Fe(ii) structure obtained via subcomponent self-assembly in water.
We report the synthesis and characterization of a coordination architecture with a Fe(ii) center obtained by subcomponent self-assembly in water. The complex is based on very rare hemi-iminal ligands spontaneously generated from commercially available materials. The complex can be further transformed into another species by oxidation reaction of both the metal center and organic ligand.


CLIMATE CHANGE: Enhanced: The Greenland Ice Sheet Reacts.
The Greenland Ice Sheet holds a substantial part of Earth's fresh water, and melting of the sheet contributes to sea level rise. Dahl-Jensen discusses the reports by Krabill et al. and Thomas et al., which shed light on short- and long-term surface elevation changes of the ice sheet. Low-altitude areas are melting, but high-altitude areas show no net reduction over both the short and the long term.


Modeling RNA tertiary structure motifs by graph-grammars.
A new approach, graph-grammars, to encode RNA tertiary structure patterns is introduced and exemplified with the classical sarcin-ricin motif. The sarcin-ricin motif is found in the stem of the crucial ribosomal loop E (also referred to as the sarcin-ricin loop), which is sensitive to the alpha-sarcin and ricin toxins. Here, we generate a graph-grammar for the sarcin-ricin motif and apply it to derive putative sequences that would fold in this motif. The biological relevance of the derived sequences is confirmed by a comparison with those found in known sarcin-ricin sites in an alignment of over 800 bacterial 23S ribosomal RNAs. The comparison raised alternative alignments in few sarcin-ricin sites, which were assessed using tertiary structure predictions and 3D modeling. The sarcin-ricin motif graph-grammar was built with indivisible nucleotide interaction cycles that were recently observed in structured RNAs. A comparison of the sequences and 3D structures of each cycle that constitute the sarcin-ricin motif gave us additional insights about RNA sequence-structure relationships. In particular, this analysis revealed the sequence space of an RNA motif depends on a structural context that goes beyond the single base pairing and base-stacking interactions.


The effect of enterovirus 71 immunization on neuropathogenesis and protein expression profiles in the thalamus of infected rhesus neonates.
Enterovirus 71 (EV71) is a major pathogen that causes hand-foot-mouth disease (HFMD). Our previous studies have demonstrated that the complete process of pathogenesis, which may include tissue damage induced by host inflammatory responses and direct tissue damage caused by viral infection, can be observed in the central nervous system (CNS) of animals infected in the laboratory with EV71. Based on these observations, the neuropathogenesis and protein expression profiles in the thalamic tissues of EV71-infected animals were further analyzed in the present study. Changes in protein expression profiles following immunization with the inactivated EV71 vaccine followed by virus challenge were observed and evaluated, and their physiological roles in viral pathogenesis are discussed. Taken together, the results of these experiments provide evidence regarding the neuropathogenesis and molecular mechanisms associated with EV71 infection and identify several protein indicators of pathogenic changes during viral infection.


Impact of Ophthalmic Surgeon Experience on Early Postoperative Central Corneal Thickness After Cataract Surgery.
To assess the impact of surgeon experience on early postoperative central corneal thickness (CCT) in eyes that have undergone phacoemulsification-based cataract surgery. One hundred sixty eyes underwent phacoemulsification-based cataract surgery performed by an experienced surgeon (n = 110; senior group) or a surgically less experienced ophthalmic assistant (n = 50; junior group), using the divide-and-conquer or tilt-and-tumble technique for cataractous lens extraction. The primary endpoint was postoperative corneal edema 2 hours after surgery, determined by pachymetry-based CCT. Mean age of patients was 71.5 ± 9.1 years. Mean CCT at postoperative hour 2 was 622.8 ± 69.3 μm: an increase of 14.3% ± 10.8 from 545.3 ± 33.7 μm preoperatively (P = 0.0028). Mean CCT at postoperative hour 2 and postoperative corneal edema were significantly higher for the junior group than the senior group, with mean respective increases of 105.8 ± 81.4 μm (19.3% ± 14.2%) and 66.4 ± 3.7 μm (12.3% ± 8.3%), P = 0.0001. After adjustment for confounding factors, surgical experience was the only factor significantly associated with corneal edema: β = 39.58; SD = 11.05; P = 0.0005. Other intergroup differences observed included significantly longer mean operating and mean ultrasound times in the junior group than in the senior group. A final corneal suture was used more frequently in the senior than in the junior group, at rates of 32.7% and 2.0%, respectively, P < 0.0001. Greater surgical experience was found to be associated with reduced early postoperative corneal edema, shorter operative time, and shorter ultrasound time. This suggests that beyond mastering the initial learning curve of phacoemulsification, surgical experience enables faster and safer surgery.


[Abortion and physicians in training: the opinion of medical students in Mexico City]
This research project explores doctors' views regarding induced abortion. Abortion's penalization in Mexico greatly conditions its relevance as a social and public health problem. Physicians constitute a professional sector that can play an important role in reforming current laws on abortion. As a professional group, they have taken a conservative stance towards abortion. Their attitudes are to a great extent influenced by the medical training they receive. In this article we present results from a survey of 96 medical students from the Universidad Autónoma Metropolitana Xochimilco, in Mexico City. Data were processed with the SPSS program. Simple frequencies show that students have limited knowledge concerning the legal status of abortion and that they tolerate it with restrictions and in limited situations. Women students apparently take a more conservative stance, but statistical analysis with the c-square test did not show significant differences by gender. The article poses the need to modify doctors' training in the reproductive health field, allowing future doctors to acquire a broader view of health problems related to sexuality and reproduction. In the long run, this should also promote a kind of comprehensive health care practice in medical services, thus responding more satisfactorily to women's needs.


A pharmacometric model describing the relationship between warfarin dose and INR response with respect to variations in CYP2C9, VKORC1, and age.
The objective of the study was to update a previous NONMEM model to describe the relationship between warfarin dose and international normalized ratio (INR) response, to decrease the dependence of the model on pharmacokinetic (PK) data, and to improve the characterization of rare genotype combinations. The effects of age and CYP2C9 genotype on S-warfarin clearance were estimated from high-quality PK data. Thereafter, a temporal dose-response (K-PD) model was developed from information on dose, INR, age, and CYP2C9 and VKORC1 genotype, with drug clearance as a covariate. Two transit compartment chains accounted for the delay between exposure and response. CYP2C9 genotype was identified as the single most important predictor of required dose, causing a difference of up to 4.2-fold in the maintenance dose. VKORC1 accounted for a difference of up to 2.1-fold in dose, and age reduced the dose requirement by ~6% per decade. This reformulated K-PD model decreases dependence on PK data and enables robust assessment of INR response and dose predictions, even in individuals with rare genotype combinations.


Erythromelalgia and vascular complications in polycythemia vera.
The vascular complications in patients with polycythemia vera are microvascular circulatory disturbances typical of thrombocythemia including erythromelalgia, peripheral ischemia, atypical cerebral ischemic attacks, and major arterial and venous thrombotic events. These are positively related to hematocrits due to the increased red cell mass and its concomitant increased whole blood viscosity. Phlebotomy does not prevent the aspirin-responsive microcirculatory circulation disturbances in polycythemia vera because thrombocythemia (platelet count > 400 x 10(9)/L) persists. The risk of major vascular ischemic episodes in poorly controlled polycythemia vera at hematocrits between 0.45 and 0.50 is rather high. The risk of vascular complications in polycythemia vera is best controlled by maintaining the hematocrit at less than 0.45 and the platelet count below 400 x 10(9)/L. The microvascular syndrome associated with thrombocythemia in early stage polycythemia vera in remission by phlebotomy is easily and best controlled by low-dose aspirin (50 to 100 mg) or by selective reduction of platelet count to normal with low-dose myelosuppressive agents. The potential leukemogenic myelosuppressive agents busulfan and hydroxyurea and the nonleukemogenic cytosine interferon-alpha have proven to be effective in the control of the proliferative phase of polycythemia vera. However, data on the natural history of polycythemia vera and the best treatment modality of the various stages of myeloproliferative disease are still lacking.


Adenosine deaminase activity in lymphoid subpopulations and leukemias.
Adenosine deaminase has been measured by the indirect spectrophotometric method in lymphoblasts from adult and pediatric lymphoblastic leukemias, peripheral T- and B-cells, mature T-cell leukemia (Sézary cell), and mitogen-stimulated peripheral control T- and B-cells. It was found that, if the specific activity of the enzyme is expressed in terms of cell cytoplasmic protein concentration rather than cell number, null-cell leukemia has enzyme levels markedly higher than T-cell lymphoblastic leukemic or Sézary cells. The range in values is far less than those reported by other authors using the direct spectrophotometric assay and cell number prior to lysis. Non-leukemic T- and B-cells from control individuals show minor differences as do T gamma-enriched cells. Lymphocytes from female oriental control populations were significantly lower. Both mitogen-stimulated lymphoblasts and control lymphocytes show similar elevations in adenosine deaminase activity so that no effect per se can be ascribed to lymphoblastic transformation.


NEMO-binding domain peptide inhibits constitutive NF-κB activity and reduces tumor burden in a canine model of relapsed, refractory diffuse large B-cell lymphoma.
Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive, poorly chemoresponsive lymphoid malignancy characterized by constitutive canonical NF-κB activity that promotes lymphomagenesis and chemotherapy resistance via overexpression of antiapoptotic NF-κB target genes. Inhibition of the canonical NF-κB pathway may therefore have therapeutic relevance in ABC-DLBCL. Here, we set out to determine whether dogs with spontaneous DLBCL have comparative aberrant constitutive NF-κB activity and to determine the therapeutic relevance of NF-κB inhibition in dogs with relapsed, resistant DLBCL. Canonical NF-κB activity was evaluated by electrophoretic mobility shift assays and immunoblot analyses, and NF-κB target gene expression was measured by quantitative real time PCR. Primary malignant canine B lymphocytes were treated with the selective IKK complex inhibitor NF-κB essential modulator-binding domain (NBD) peptide and evaluated for NF-κB activity and apoptosis. NBD peptide was administered intranodally to dogs with relapsed B-cell lymphoma and NF-κB target gene expression and tumor burden were evaluated pre- and post-treatment. Constitutive canonical NF-κB activity and increased NF-κB target gene expression were detected in primary DLBCL tissue. NBD peptide inhibited this activity and induced apoptosis of primary malignant B cells in vitro. Intratumoral injections of NBD peptide to dogs with relapsed DLBCL inhibited NF-κB target gene expression and reduced tumor burden. This work shows that dogs with spontaneous DLBCL represent a clinically relevant, spontaneous, large animal model for human ABC-DLBCL and shows the therapeutic relevance of NF-κB inhibition in the treatment of ABC-DLBCL. These results have important translational relevance for ABC-DLBCL treatment in human patients.


[College education for medical technologists of the next generation].
Medical Technologists (MTs) of the next generation will be expected to: 1) perform clinical tests in clinical laboratories as so-called Clinical Laboratory Scientists(CLS), 2)research and develop highly advanced reagents, devices, or procedures for clinical laboratories, and 3) educate MTs and research in the college or university. CLS are required to develop and maintain highly advanced medical skills as follows: (1) explaining medical tests and those results to patients, (2) evaluating and explaining test results to medical doctors, (3) advising medical doctors of laboratory diagnoses, (4) analyzing the patients' pathophysiology based on samples with aberrant results, (5) evaluating newly developed reagents, devices, or procedures, and (6) promoting the total medical cure of patients with specialized skills. In the MT course at Shinshu University, to develop the skills necessary to become a CLS before graduation, students participate in a number of programs, i.e., freshman seminars, observing the clinical laboratory, and basic training for medical tests (first grade), special lectures from MTs working in the clinical laboratory (second and third grades), examination for clinical practice, 12-week clinical practice, and 15-week laboratory research (fourth grade). Several academic members working in a clinical laboratory and collaboration with the Department of Clinical Laboratory at Shinshu University Hospital are essential to realize the above-mentioned course.


[Early melanoma as opposed to a benign nevus, nevus-associated melanoma, or halo nevus with regression?].
A 43-year-old woman, in whom a melanoma associated with a melanocytic nevus had been removed 2 years previously, came for a follow-up examination presenting with two light brown to medium brown maculae measuring approximately 7x5 mm with a flat papular center. One of the lesions was surrounded by a large white halo about 2 mm in size. The differential diagnosis on clinical grounds included a halo nevus with a second common nevus, a nevus with regression, and a melanoma associated with a nevus. Under the dermatoscope, an unremarkable homogeneous/reticular pattern could be seen and in one portion hallmarks of regression, namely gray tones and distinct gray-black dots. The diagnosis based on histopathological analysis was that of an atypical congenital nevus with regression.


[Etiological diagnosis and treatment of central airway obstruction: report of 40 cases and review of the literature].
To explore the etiology, clinical features, diagnosis and treatment of central airway obstruction (CAO), and therefore to raise awareness of this disease. Forty patients with central airway obstruction were analyzed retrospectively and their clinical characteristics were described. Among these 40 cases of CAO, the diagnoses included squamous cell carcinoma (n = 13), adenoid cysts (n = 5), esophageal squamous cell carcinoma (n = 4), and benign tumor (n = 6). The presenting symptoms included cough (n = 36), shortness of breath or difficulty breathing (n = 21), and hemoptysis or bloody sputum which was more common in cases with airway squamous cell carcinoma (n = 11). All the patients underwent chest CT examination, and the lesions were evident in all the cases. Twenty-one cases underwent three-dimensional reconstruction of the airway. Six patients underwent pulmonary function test, and ventilatory abnormalities were revealed, and showed the characteristic blunting of the flow-volume loop. Thirty-nine cases underwent bronchoscopy and correct clinical diagnosis was made. Eleven patients received interventional therapy with argon plasma coagulation (APC), and their symptoms were all relieved within 2 days. CAO may be caused by variety of diseases, but the most common cause is malignancy. The common symptoms of CAO are cough and dyspnea. Chest CT with airway reconstruction, bronchoscopy and pathological examination can provide accurate information for diagnosis. The choice of treatment modalities depends on the size, location and the pathology of the lesions. APC is a safe and effective therapy for short-term management of malignant lesions.


Airway microbial culture and susceptibility patterns in dogs and cats with respiratory disease of varying severity.
To compare airway microbiological culture and susceptibility results in 2 groups of dogs and cats: 1 with respiratory failure requiring positive pressure ventilation (PPV) and 1 with respiratory disease. Retrospective study. University teaching hospital. Fifty-two dogs and cats requiring PPV that had an airway microbiologic culture submitted from October 1, 2003 to October 31, 2008 were included. One hundred and four airway microbiologic cultures from dogs and cats with respiratory disease not requiring PPV were randomly sampled for comparison. None. Patients with respiratory failure were more likely to have a gram-negative enteric isolate identified (P<0.001), while patients with respiratory disease were more likely to have a gram-negative nonenteric isolate (P<0.001) or anaerobic isolate (P<0.001) identified. Aerobic bacterial isolates from patients with respiratory failure were less likely to be susceptible to ampicillin (P=0.006), amoxicillin/clavulonate (P<0.001), chloramphenicol (P=0.004), enrofloxacin (P<0.001), ticarcillin/clavulonate (P=0.004), and the combination of ampicillin with enrofloxacin (P<0.001) than were aerobic bacterial isolates from patients with respiratory disease. Canine and feline patients with respiratory failure severe enough to require PPV exhibit a different pattern of bacterial isolates cultured from their airways when compared with isolates from patients with respiratory disease that has not resulted in ventilator dependence. These isolates are more likely to be resistant to commonly used antimicrobials/antimicrobial combinations than patients in the respiratory disease group. These findings suggest that in canine and feline patients with infectious lower respiratory tract disease, consideration of the severity of the pulmonary insult may allow for better prediction of likely isolates and their antimicrobial susceptibilities. Further prospective studies with a standardized collection technique are warranted.


Nimbolide B and nimbic acid B, phytotoxic substances in neem leaves with allelopathic activity.
Neem (Azadirachta indica) has been widely used as a traditional medicine and several bioactive compounds have been isolated from this species, but to date no potent allelopathic active substance has been reported. Therefore, we investigated possible allelopathic property and phytotoxic substances with allelopathic activity in neem. An aqueous methanol extract of neem leaves inhibited the growth of roots and shoots of cress, lettuce, alfalfa, timothy, crabgrass, ryegrass, barnyard grass and jungle rice. The extracts were then purified by several chromatographic runs while monitoring the inhibitory activity and two phytotoxic substances were isolated. The chemical structures of the two substances were determined by spectral data to correspond to novel compounds, nimbolide B (1) and nimbic acid B (2). Nimbolide B inhibited the growth of cress and barnyard grass at concentrations greater than 0.1‒3.0 μM. Nimbic acid B inhibited the growth of cress and barnyard grass at concentrations greater than 0.3-1.0 μM. These results suggest that nimbolide B and nimbic acid B may contribute to the allelopathic effects caused by neem leaves.


Consequences of In Utero Zika Virus Exposure and Adverse Pregnancy and Early Childhood Outcomes: A Prospective Cohort Study.
We aimed to describe adverse pregnancy outcomes among women who had symptomatic, RT-PCR-confirmed ZIKV infection and early childhood outcomes among their infants. We enrolled pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection in a prospective cohort study, and their infants in a prospective pediatric cohort study. We defined adverse pregnancy and early childhood outcomes based on selected neurologic, ophthalmologic, auditory, musculoskeletal, and anthropometric abnormalities. We used RT-PCR and serologic tests to determine the ZIKV infection status of the child. Between 10 March and 24 November 2016, we enrolled 546 pregnant women with RT-PCR-confirmed ZIKV infection. The overall risk of adverse pregnancy and early childhood outcomes possibly related to in utero ZIKV exposure was 15.7% (95% CI: 12.8-19.0), distributed as follows: 3.6% (95% CI: 2.3-5.6) severe sequelae or fatality; 2.7% (95% CI: 1.6-4.5) major abnormalities; 9.4% (95% CI:7.1-12.2) mild abnormalities. The risk of severe sequelae or fatality was higher when ZIKV infection occurred during the first trimester (7.0%), compared to the second (2.7%) or third trimester (1.4%) (p = 0.02). Among the infants for whom ZIKV infection status could be determined, the vertical transmission rate was 3.0% (5/167) (95% CI: 1.1-7.2). Among pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection, severe or major pregnancy or early childhood outcomes were present in 6.3% of fetuses and infants. Severe outcomes occurred more frequently in fetuses and infants whose mothers had been infected in the first trimester.


A review on phosphate based, solid state, protonic conductors for intermediate temperature fuel cells.
The electrolytes currently used for proton exchange membrane fuel cells are mainly based on polymers such as Nafion which limits the operation regime of the cell to ∼80 °C. Solid oxide fuel cells operate at much elevated temperatures compared to proton exchange membrane fuel cells (∼1000 °C) and employ oxide electrolytes such as yttrium stabilized zirconia and gadolinium doped ceria. So far an intermediate temperature operation regime (300 °C) has not been widely explored which would open new pathways for novel fuel cell systems. In this review we summarize the potential use of phosphate compounds as electrolytes for intermediate temperature fuel cells. Various examples on ammonium polyphosphate, pyrophosphate, cesium phosphate and other phosphate based electrolytes are presented and their preparation methods, conduction mechanism and conductivity values are demonstrated.


Occupational therapy: what does this look like practised in very remote Indigenous areas?
Occupational therapy in very remote, predominantly Indigenous, settings requires therapists to modify traditional models of practice to make practice applicable, culturally relevant and culturally safe. This article describes some of the author's observations of similarities and differences in what occupational therapy 'does' and 'is' in four different, but in many ways similar, very remote contexts. A Churchill Fellowship allowed the author to travel to visit teams in three very remote regions of Canada and the USA, allowing comparison to practice in the Top End of the Northern Territory in Australia. These very remote settings are unable to support onsite therapy services resulting in fly/drive-in visits from hub towns, influencing service models and extending professional tasks and roles. In many of these remote contexts populations are predominantly Indigenous, which requires therapists to work cross-culturally. This requires occupational therapists to adapt therapy assessments and interventions to make these appropriate to the contexts. Therapists perceived a range of therapeutic adaptations and resources as useful in their practice and some barriers to implementing these. These included supports to practice such as cultural liaisons or interpreters; being open and respectful to differences in beliefs around health, wellbeing, desired occupational pursuits and function; using a client/family-directed approach in care planning, goal setting and development of therapeutic strategies; being selective around use of standardised assessment tools; and taking time and developing relationships with family and clients. Therapists in these areas also reported their scope of practice as being broader in remote settings, requiring skills in a greater range of areas. Therapists also reported the increased use of technology to supplement and support remote practice.


Angiomyolipoma with minimal fat and non-clear cell renal cell carcinoma: differentiation on MDCT using classification and regression tree analysis-based algorithm.
Differentiation between angiomyolipoma with minimal fat (AMLmf) and non-clear cell renal cell carcinoma (nccRCC) may be difficult owing to lack of macroscopic fat in AMLmf. However, the differential points between AMLmf and nccRCC has not been well established in the literature. To evaluate quantitative triphasic multidetector computed tomography (MDCT) features that differentiate between small AMLmf and nccRCC, and to integrate them to develop a simple and easy diagnostic algorithm. This study was approved by the Institutional Review Board; informed consent was waived. Triphasic MDCT images of pathologically-proven AMLmfs (n = 24) and nccRCCs (n = 55) of 79 patients were retrospectively evaluated. Age, sex, size, long-to-short axis ratio (LSR), attenuation and enhancement degree in all phases, unenhanced tumor-kidney attenuation difference (UTKAD) in Hounsfield units (HU) were compared with Chi-square analysis, independent-samples t-test, and receiver-operating characteristic (ROC) curves. A criterion was formulated with classification and regression tree analysis (CART). Thereafter, CART-based algorithm was tested with additional interpretations from two radiologists. Intra- and inter-observer variability was analyzed with Bland-Altman analysis. LSR was greater in AMLmf than nccRCC (P < 0.001). AMLmf showed higher attenuation (all phases), CMP enhancement, and wash-out than nccRCC (P ≤ 0.001). UTKAD was greater in AMLmf than nccRCC (P < 0.001). ROC curve analysis yielded area under the curves of 0.936, 0.888, and 0.853 using UTKAD, unenhanced attenuation, and LSR. CART-based algorithm (UTKAD > 7.5 HU, LSR > 1.23) predicted AMLmf with sensitivity, specificity, PPV, and NPV of 87.5%, 96.4%, 91.3%, and 94.6%. Mean intra- and inter-observer difference was -0.1/0.03 HU and -1.0/0.09 HU for UTKAD/LSR, respectively. These interpretations changed the final diagnosis in 1.3% (1/79) and 5.1% (4/79) patients for radiologists 1 and 2. Triphasic MDCT was useful for differentiating AMLmf and nccRCC. CART-based algorithm using UTKAD > 7.5 and LSR > 1.23 was simple and accurate in predicting AMLmf.


In vitro susceptibilities of human and wild-type isolates of Basidiobolus and Conidiobolus species.
The in vitro activities of amphotericin B, miconazole, ketoconazole, 5-fluorocytosine, and potassium iodide (KI) were studied on human and wild-type isolates of Basidiobolus and Conidiobolus species. Of the antifungal agents tested, the imidazole derivatives, especially ketoconazole, were the most active against the agents of entomophthoromycosis. Transmission electron microscopy showed severe morphological alteration of Basidiobolus sp. exposed to 0.78 micrograms of ketoconazole per ml. The MIC and minimal fungicidal concentration of ketoconazole was often lowered in the presence of 10% fetal calf serum or antibiotic medium no. 3. Half of the Basidiobolus isolates and all Conidiobolus isolates were inhibited by amphotericin B at 0.39 micrograms/ml. None of the strains tested were inhibited or killed at maximum concentrations of 5-fluorocytosine and KI. The in vitro resistance of these fungi to KI at high concentrations suggests that the reported favorable treatment with KI may not be due to its direct effect on these fungi but rather to other, undefined factors in combination with KI. These data suggest that ketoconazole may be of use in the treatment of entomophthoromycosis, particularly in cases which are not responsive to KI.


Minimal effects of reduced teaching hours on undergraduate medical student learning outcomes and course evaluations.
Introduction: Various pressures exist for curricular change, including economic forces, burgeoning knowledge, broadening learning outcomes, and improving quality and outcomes of learning experiences. In an Australian 5-year undergraduate medical course, staff were asked to reduce teaching hours by 20% to alleviate perceived overcrowded preclinical curriculum, achieve operating efficiencies and liberate time for students' self-directed learning.Methods: A case study design with mixed methods was used to evaluate outcomes.Results: Teaching hours were reduced by 198 hours (14%) overall, lectures by 153 hours (19%) and other learning activities by 45 hours (7%). Summative assessment scores did not change significantly after the reductions: 0.4% increase, 1.5% decrease and 1.7% increase in Years 1, 2 and 3, respectively. The percentage of students successfully completing their academic year did not change significantly: 94.4% before and 93.3% after the reductions. Student evaluations from eVALUate surveys changed little, except workload was perceived to be more reasonable.Conclusions: Teaching hours, particularly lectures, can be moderately reduced with little impact on student learning outcomes or satisfaction with an undergraduate medical course.


The effect of pregnancy and the oestrus cycle on purinergic and cholinergic responses of the rat urinary bladder.
The urinary bladder undergoes plastic changes during physiological alterations such as pregnancy. This study has shown that bladders from pregnant rats weighed three times more than bladders from virgin rats. Each milligram of detrusor muscle from pregnant rats contracted more strongly to nerve stimulation (150% greater) and agonists (50% greater or more) compared to detrusor from virgin rats at any stage during the oestrus cycle. The purinergic component of nerve-mediated responses altered during the oestrus cycle, being greatest during oestrus (oestrogen and progesterone fall rapidly) and dioestrus (low oestrogen and progesterone), smaller during pregnancy and even smaller during pro-oestrus (high oestrogen and progesterone); in contrast the cholinergic component remained relatively unchanged. In conclusion, during pregnancy the detrusor muscle generates larger contractions compared to virgin detrusor muscle, probably due to hormonal influences on smooth muscle contraction mechanisms. As agonist responses were unchanged during the oestrus cycle, changes in the purinergic component of nerve stimulation was not due to altered P2 receptor expression but possibly to an increase in ATP release or a reduction in breakdown. The hormonal effect may have implications for the treatment of bladder disorders due to alterations in hormones, such as stress incontinence in post-menopausal women.


Management of Metastatic Spine and Hip Alveolar Soft Part Sarcoma: Case Report and Review of Literature.
Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor. Primary or metastatic involvement of the spine is unusual in ASPS. In most case, it is refractory to chemotherapy and radiation. Surgical resection is the most effective intervention. We report the case of a 38-year-old female having ASPS along with metastatic spine and hip involvement treated surgically as a single-stage operation, which is the first of its kind approach to our knowledge. We present the case of a 38-year-old female with simultaneous L4 pathological fracture with symptomatic lumbar canal stenosis without focal neurology and pathological fracture of neck of femur of left hip, secondary to metastatic ASPS. Since both conditions were contributing equally to her disability and demanded early intervention, they were treated simultaneously with intralesional excision of the tumor and posterior stabilization of the spine and left hip proximal femur resection and replaced it with proximal femur endoprosthesis as a single-stage operation. Postoperatively, she had significant relief of radiculopathy and left hip pain. She was mobilized out of bed on the postoperative day 1 and was discharged from hospital on the postoperative day 6. She was given chemotherapy drug sunitib postoperative. At her last follow-up, 20 months' postoperative, she was asymptomatic and was independent in terms of activities of daily living. Metastatic ASPS of the spine and hip is a rare clinical entity. Simultaneous surgical treatment of the spine and hip pathology is technically demanding. If the conditions demands, as in our case, both of them can be managed safely in a single-stage with good midterm outcome.


Multilamellar Vesicle Formation Probed by Rheo-NMR and Rheo-SALS under Large Amplitude Oscillatory Shear.
The formation of multilamellar vesicles (MLVs) in the lyotropic lamellar phase of the system triethylene glycol mono n-decyl ether (C10E3)/water is investigated under large amplitude oscillatory shear (LAOS) using spatially resolved rheo-NMR spectroscopy and a combination of rheo-small angle light scattering (rheo-SALS) and conventional rheology. Recent advances in rheo-NMR hardware development facilitated the application of LAOS deformations in high-field NMR magnets. For the range of investigated strain amplitudes (10-50) and frequencies (1 and 2 rad s-1), MLV formation is observed in all NMR and most SALS experiments. It is found that the MLV size depends on the applied frequency in contrast to previous steady shear experiments where the shear rate is the controlling parameter. The onset of MLV formation, however, is found to vary with the shear amplitude. The LAOS measurements bear no indication of the intermediate structures resembling aligned multilamellar cylinders observed in steady shear experiments. Lissajous curves of stress vs strain reveal a transition from a viscoelastic solid material to a pseudoplastic material.


Evaluation of the Mycoplasma genitalium Resistance Plus kit for the detection of M. genitalium and mutations associated with macrolide resistance.
To compare performance of the ResistancePlus kit (SpeeDx, Australia) with in-house methods for the detection of Mycoplasma genitalium-specific DNA and mutations associated with resistance to macrolide antimicrobials, directly from clinical specimens. Assay specificity and sensitivity was analysed using DNA from 46 non-M. genitalium organisms and standard curve analysis, respectively. A panel of archived DNA extracted from 97 M. genitalium-positive clinical specimens, for which the macrolide susceptibility genotype had been previously determined, were tested on the assay and results compared. Final analytical specificity was 100%. Sensitivity was detected to at least 140 genome copies/µL. The assay detected M. genitalium in 92/97 (94.9%, 95% CI 88.4% to 98.3%) previously positive specimens. The genetic macrolide susceptibility assigned was concordant with previous results in 85/92 (92.4%, 95% CI 85.0% to 96.9%) specimens or 85/97 (87.6%, 95% CI: 79.4% to 93.4%) when the false-negative specimens were included. On seven (7/92, 7.6%) occasions, resistant specimens were called susceptible. Further testing resolved discrepancies for all but five (5.2%) specimens. The ResistancePlus assay generally performed well in comparison to methods currently employed at the reference laboratory. It detected a range of different mutations; however, a small number of specimens that were genotyped as macrolide resistant by Sanger sequencing were either not detected by the assay or were genotyped as susceptible. This could impact on treatment outcomes if assay results were used for patient management.


Growth Performance, Carcass Characteristics and Meat Yield of Boer Goats Fed Diets Containing Leaves or Whole Parts of Andrographis paniculata.
The study was conducted to determine the effect of feeding diets containing Andrographis paniculata leaves (APL), whole Andrographis paniculata plant (APWP) and a control without Andrographis paniculata (AP0), on growth performance, carcass characteristics and meat yield of 24 intact Boer bucks. The results obtained indicated that inclusion of Andrographis paniculata significantly improved feed intake, weight gain, feed efficiency and live weight. The ratios of carcass to fat, lean to bone, lean to fat, and composition of meat were also improved. In addition, there were significant differences (p<0.05) between the dietary treatments in dressing percentage and chilling loss. Goats fed on AP0 (control) had significantly higher proportions of fat and bone, as well as thicker back fat than the supplemented animals (APL and APWP). Higher gut fill in animals fed Andrographis paniculata suggested slow rate of digestion, which could have improved utilization and absorption of nutrients by the animals. Goats fed Andrographis paniculata also produced higher meat yield and relatively lower fat contents (p<0.05).


Effect of size variation on microbubble mass transfer coefficient in flotation and aeration processes.
Microbubble technology dramatically raises the efficiency of the flotation and aeration processes of water treatment plants (WTPs), which see extensive use in developed countries. A local institution, Indonesia Water Institute, has tried to investigate microbubble technology intended for lab-scale WTP. However, the current reactor system does not yet meet the microbubble criteria, especially as it has had few investigations of its abilities in flotation and aeration. This study aims to analyze the effect of size variations that affect the rising velocity and mass transfer coefficient (kLa) of aeration contact time. Three local spargers were used to produce microbubbles. Bubble diameters were measured optically and analyzed using ImageJ software. The dissolved oxygen (DO) concentration was measured every minute using an automated sensor so that the kLa could be determined. Of the three spargers, the smallest bubble size was produced by the vortex type with an average bubble diameter of 89 μm and the slowest rising velocity of 17.67 m/h. It also yielded the highest kLa of 0.297/min, which gave an aeration contact time of 3.64 minutes. The experimental uses of three local spargers revealed that the smaller the microbubble diameter, the higher the mass transfer coefficient in flotation and aeration processes. This research can be the basis for developing microbubble technology for WTP in Indonesia.


Reactive oxygen species mediate ERK activation through different Raf-1-dependent signaling pathways following cerebral ischemia.
Production of reactive oxygen species (ROS) results in up-regulation of the extracellular signal-regulated kinase (ERK) cascade in response to numerous stimuli. Cerebral ischemia induces calcium-dependent kinase activation followed by ROS production. Here, we examined how ROS mediates the activation of ERK following cerebral ischemia in the rat hippocampus. We found that alpha-tocopherol, a free radical scavenger, attenuated the initial, robust activation of ERK by inhibiting Raf-1 dephosphorylation at Ser259. Alpha-tocopherol also down-regulated the second and mild activation of ERK through inhibition of Src-dependent phosphorylation of Raf-1 at Tyr340/341. Our results suggest that ROS production mediates the biphasic activation of ERK through different signaling cascades following post-ischemic reperfusion. Mediation of these signaling pathways involves changes in Raf-1 phosphorylation at different sites.


Impact of nonintrusive clinical decision support systems on laboratory test utilization in a large academic centre.
The near-universal prevalence of electronic health records (EHRs) has made the utilization of clinical decision support systems (CDSS) an integral strategy for improving the value of laboratory ordering. Few studies have examined the effectiveness of nonintrusive CDSS on inpatient laboratory utilization in large academic centres. Red blood cell folate, hepatitis C virus viral loads and genotypes, and type and screens were selected for study. We incorporated the appropriate indications for these labs into text that accompanied the laboratory orders in our hospital's EHR. Providers could proceed with the order without additional clicks. An interrupted time-series analysis was performed, and the primary outcome was the rate of tests ordered on all inpatient medicine floors. The rate of folate tests ordered per monthly admissions showed no significant level change at the time of the intervention with only a slight decrease in rate of 0.0109 (P = .07). There was a 43% decrease in the rate of hepatitis C virus tests per monthly admissions immediately after the intervention with a decrease of 0.0135 tests per monthly admissions (P = .02). The rate of type and screens orders per patient days each month had a significant downward trend by 0.114 before the intervention (P = .04) but no significant level change at the time of the intervention or significant change in rate after the intervention. Our study suggests that nonintrusive CDSS should be evaluated for individual laboratory tests to ensure only effective alerts continue to be used so as to avoid increasing EHR fatigue.


G proteins regulate dihydropyridine binding to moss plasma membranes.
The role of calcium as an activator and regulator of many biological processes is linked to the ability of the cell to rapidly change its cytoplasmic calcium levels. Calcium acts as an intracellular messenger in hormone-induced bud formation during the development of the moss Physcomitrella patens. Calcium transport and ligand binding studies have implicated plasma membrane-localized 1, 4-dihydropyridine (DHP)-sensitive calcium channels in this increase in cellular calcium. To understand the regulation of the moss calcium channel, we investigated the involvement of GTP binding regulatory proteins (G proteins). Guanosine 5'-(gamma-thio)triphosphate (GTPgammaS), a nonhydrolyzable GTP analog that locks G proteins into their active state, stimulated DHP binding to high affinity receptors in the moss plasma membrane. DHP binding was measured as the ability of the DHP agonist Bay K8644 or the DHP antagonist nifedipine to compete with the DHP arylazide [3H]azidopine for binding to moss plasma membranes. G protein stimulation of binding was seen when competition was carried out with either nifedipine or Bay K8644. G proteins regulated the rates of association and dissociation of bound [3H]azidopine, and stimulation was dependent on GTPgammaS concentration. Guanosine 5'-(beta-thio)diphosphate, a GDP analog that locks G proteins into their inactivated state, did not affect the dose dependence of either the agonist or the antagonist. These results suggest that G proteins may act via a membrane-delimited pathway to regulate calcium channels in the moss plasma membrane.