Inhibition of human telomerase by a retrovirus expressing telomeric antisense RNA.
Human telomerase, the RNA-dependent DNA polymerase that adds TTAGGG repeats to chromosome ends, is selectively expressed in immortalised cells and most tumours, suggesting a potential role for telomerase inhibitors in cancer therapy. Replication-deficient retroviruses were used to determine whether mRNA containing UUAGGG, the complementary sequence to the template region of the hTR telomerase RNA, is sufficient to inhibit telomerase activity. Telomerase activities measured by the telomeric repeat amplification protocol (TRAP) assay in extracts prepared from immortalised mouse fibroblasts, human HeLa cells and human kidney carcinoma cells were inhibited by 75% or greater in 26 of 56 cell clones expressing UUAGGG. Telomerase activity was not inhibited by expression of mRNA containing a transposed sequence, GGGAUU. Telomerase activities in vivo were inferred from changes in cellular morphology, proliferation capacity, growth rate and measurement of the content of telomere DNA. Giant senescent-like cells emerged shortly after cloning mouse PA317 and human HeLa cells expressing UUAGGG. The fraction of giant cells varied from 100% at the fifth population doubling (PD) in one culture to 2-6% at 50 PD in several other cultures. Giant cells were absent in all parental cells and clones expressing GGGAUU. The average cellular content of telomere DNA was independent of telomerase activity over 50 PD. The results indicate that expression of RNA complementary to the template region of hTR is sufficient to inhibit telomerase in vitro and in vivo, but that the effect of inhibition on individual cells is highly variable.


Trends in cystic fibrosis survival over 40 years in South Africa: An observational cohort study.
Temporal trends in cystic fibrosis (CF) survival from low-middle-income settings is poorly reported. We describe changes in CF survival after diagnosis over 40 years from a South African (SA) CF center. An observational cohort study of people diagnosed with CF from 1974 to 2019. Changes in age-specific mortality rates from 2000 (vs. before 2000) were estimated using multivariable Poisson regression. Data were stratified by current age < or ≥10 years and models controlled for diagnosis age, sex, ethnicity, genotype, and Pseudomonas aeruginosa (PA) infection. A second analysis explored the association of mortality with weight and forced expiratory volume in 1 s reported as z-scores (FEV1z-scores) at age 5-8 years. A total of 288 people (52% male; 57% Caucasian; 44% p.Phe508del homozygous) were included (median diagnosis age 0.5 years: Q1, Q3: 0.2, 2.5); 100 (35%) died and 30 (10%) lost to follow-up. Among age >10 years, age-specific mortality from 2000 was significantly lower (adjusted hazard ratio [aHR]: 0.14; 95% confidence interval [CI]: 0.06, 0.29; p < 0.001), but not among age <10 years (aHR: 0.67; 95% CI: 0.28, 1.64; p = 0.383). In children <10 years, Caucasian ethnicity was associated with lower mortality (aHR 0.17; 95% CI: 0.05, 0.63), and longer times since first PA infection with higher mortality (aHR: 1.31; 95% CI: 1.01, 1.68). Mortality was sevenfold higher if FEV1z was <-2.0 at age 5-8 years (aHR: 7.64; 95% CI: 2.58, 22.59). Overall, CF survival has significantly improved in SA from 2000 in people older than 10 years. However, increased risk of mortality persists in young non-Caucasian children, and with FEV1z <-2.0 at age 5-8 years.


Relationship quality for mothers of very preterm infants.
There is a paucity of information on couple relationship quality in mothers of preterm infants during the first year of life. To determine couple relationship quality in mothers of very preterm infants in comparison to mothers of term infants and to examine maternal and infant factors associated with impaired couple relationship for the preterm mothers. At 4 and 12 months (corrected for prematurity for the preterm cohort), the mothers completed the Dyadic Adjustment Scale, the Edinburgh Postnatal Depression Scale, the Parenting Stress Index and the Short Temperament Scale. At 12 months, the infants had a neurodevelopmental assessment. 86 mothers of preterm infants and 97 term mothers participated at 4 months, with 101 mothers of the preterm infants and 98 term mothers participating at 12 months. Comparisons of the two groups revealed no differences in Dyadic Adjustment or for any of the subscales. For the preterm mothers at 4 months, the independent variables associated with poor dyadic adjustment were ethnicity and higher levels of parenting stress. At 12 months, parenting stress was also an independent variable associated with impaired couple relationship. No differences in the incidence of poor quality couple relationship was found between mothers of very preterm and term infants. For preterm mothers, impaired couple relationship was associated with parenting stress.


Clusters of ventricular tachycardias signify impaired survival in patients with idiopathic dilated cardiomyopathy and implantable cardioverter defibrillators.
This retrospective study was undertaken to provide data on occurrence, significance and therapy of ventricular tachyarrhythmia (VT) clusters (VTCs) in patients with dilated cardiomyopathy (DCM) and implantable cardioverter defibrillators (ICDs). Data on the clinical significance of VTCs are lacking in patients with DCM and ICDs. Baseline characteristics of 106 consecutive patients with DCM and ICDs were prospectively collected, and chart reviews and episode data retrospectively analyzed. A VTC was defined as > or =3 sustained VTs/24 h. During a mean follow-up of 33+/-23 months, 73 patients (68.9%) had recurrent VT or ventricular fibrillation (VF), 43 patients (40.6%) suffered only single VTs and 30 patients (28.3%) experienced 52 clusters of VTs. Actuarial survival free of VT or VF was 44.6%, 33.0% and 26.5%, and survival free of VTC was 77.3%, 72.2% and 67.1% after one, two and three years, respectively. Independent predictors of VT clusters were heart failure before ICD implantation (p = 0.033), presenting monomorphic VT (p = 0.044), EF <0.40 (p = 0.014) and inducible mVT, especially with right bundle branch block and superior axis configuration (p<0.001). Survival free of recurrent VTCs was 50.8%, 38.1% and 19.0% after one, two and three years, respectively. Once a VTC had occurred, only 56.7%, 46.4%, 30.9% and 15.5% of patients survived and were not transplanted after one, two, three and four years, respectively. Survival was even more reduced if a VTC was associated with cardiac decompensation: 65.6% and 21.9% after one and two years, respectively. Despite antiarrhythmic intervention, clusters of VTs occur and recur frequently in patients with DCM. They signify impaired survival, especially if they are associated with cardiac decompensation, and may be a harbinger of progressive myocardial deterioration rather than a primarily arrhythmic problem. The benefit of ICD therapy may therefore be low in these patients.


Quantitative volcanic susceptibility analysis of Lanzarote and Chinijo Islands based on kernel density estimation via a linear diffusion process.
Risk management stakeholders in high-populated volcanic islands should be provided with the latest high-quality volcanic information. We present here the first volcanic susceptibility map of Lanzarote and Chinijo Islands and their submarine flanks based on updated chronostratigraphical and volcano structural data, as well as on the geomorphological analysis of the bathymetric data of the submarine flanks. The role of the structural elements in the volcanic susceptibility analysis has been reviewed: vents have been considered since they indicate where previous eruptions took place; eruptive fissures provide information about the stress field as they are the superficial expression of the dyke conduit; eroded dykes have been discarded since they are single non-feeder dykes intruded in deep parts of Miocene-Pliocene volcanic edifices; main faults have been taken into account only in those cases where they could modified the superficial movement of magma. The application of kernel density estimation via a linear diffusion process for the volcanic susceptibility assessment has been applied successfully to Lanzarote and could be applied to other fissure volcanic fields worldwide since the results provide information about the probable area where an eruption could take place but also about the main direction of the probable volcanic fissures.


Beyond the therapeutic: A Habermasian view of self-help groups' place in the public sphere.
Self-help groups in the United Kingdom continue to grow in number and address virtually every conceivable health condition, but they remain the subject of very little theoretical analysis. The literature to date has predominantly focused on their therapeutic effects on individual members. And yet they are widely presumed to fulfil a broader civic role and to encourage democratic citizenship. The article uses Habermas' model of the public sphere as an analytical tool with which to reconsider the literature on self-help groups in order to increase our knowledge of their civic functions. In doing this it also aims to illustrate the continuing relevance of Habermas' work to our understanding of issues in health and social care. We consider, within the context of current health policies and practices, the extent to which self-help groups with a range of different forms and functions operate according to the principles of communicative rationality that Habermas deemed key to democratic legitimacy. We conclude that self-help groups' civic role is more complex than is usually presumed and that various factors including groups' leadership, organisational structure and links with public agencies can affect their efficacy within the public sphere.


Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson's Disease: Past, Present, and Future.
Monoamine oxidase-B (MAO-B) inhibitors are commonly used for the symptomatic treatment of Parkinson's disease (PD). MAO-B inhibitor monotherapy has been shown to be effective and safe for the treatment of early-stage PD, while MAO-B inhibitors as adjuvant drugs have been widely applied for the treatment of the advanced stages of the illness. MAO-B inhibitors can effectively improve patients' motor and non-motor symptoms, reduce "OFF" time, and may potentially prevent/delay disease progression. In this review, we discuss the effects of MAO-B inhibitors on motor and non-motor symptoms in PD patients, their mechanism of action, and the future development of MAO-B inhibitor therapy.


Midwifery and Nursing Strategies to protect against COVID-19 During the Third Trimester of Pregnancy.
The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents significant challenges to midwives and nurses. This study aimed to explore midwifery and nursing interventions to limit the transmission of COVID-19 among women in their third trimester of pregnancy, to reduce the incidence of nosocomial infection and promote safety of care for women and their infants. We completed a retrospective review of medical records from 35 women in their third trimester of pregnancy with SARS-CoV-2, admitted to one hospital in Wuhan, China in January and February 2020. We investigated the clinical characteristics of the COVID-19 infection in pregnancy, and the individualized midwifery and nursing care offered, including environmental protection, prevention of nosocomial infection, maternal observations, monitoring of signs and symptoms of COVID-19, and psychological care. Thirty-one women had a caesarean section, and four had vaginal births. Retrospective analysis of midwifery and nursing strategies implemented to care for these women showed no maternal complications or nosocomial infections. The care strategies we implemented could prevent complications and nosocomial infection in the third trimester of pregnancy, thus ensuring the safety of women and their infants. Further research needs to determine treatment priorities for women infected with COVID-19 during pregnancy and the postnatal period.


Impact of post-emergent imazethapyr on morpho-physiological and biochemical responses in lentil (Lens culinaris Medik.).
Yield reduction in lentil crop due to weed infestation is a key hindrance to its growth due to poor weed-crop competition. Imazethapyr (IM), a selective herbicide, target acetolactate synthase (ALS) which catalyzes the first reaction in biosynthesis of branched chain amino acids, required for plant growth and development. The objective of the present study was to investigate the impact of IM treatment on weeds, ALS enzyme activity, antioxidant capacity, osmolyte accumulation, growth and yield related parameters in lentil genotypes. Two IM tolerant (LL1397 and LL1612) and two susceptible (FLIP2004-7L and PL07) lentil genotypes were cultivated under weed free, weedy check and IM treatments. Weed control efficiency reached its peak at 21 days after spray (DAS). Imazethapyr treatment decreased chlorophyll and carotenoid content up to 28 DAS with higher reduction in susceptible genotypes. FLIP2004-7L and PL07 had reduced plant height and lower number of pods under IM treatment which resulted in decreased seed yield. Higher ALS activity in LL1397 and LL1612 at 21 DAS, higher antioxidant capacity and glycine betaine content both at 21 and 28 DAS and lower decrease in relative leaf water content might be mediating herbicide tolerance in these genotypes that led to higher seed yield. The identified IM tolerance mechanism can be used to impart herbicide resistance in lentil. The online version contains supplementary material available at 10.1007/s12298-022-01244-x.


The autopsy in modern undergraduate medical education: a qualitative study of uses and curriculum considerations.
Medical education has undergone dramatic changes over the past decade. In the UK, the General Medical Council (GMC), the driving force behind curriculum reform, now requires curricula to be founded on a base of educational theory and research. This qualitative study investigated the roles of the autopsy within the context of the modern medical curriculum. Using a phenomenological methodology, a non-representative 'theoretical sample' was selected to include medical educators with a wide range of teaching experience and responsibilities and disparate views both for and against the autopsy. Semistructured, tape-recorded interviews were undertaken to investigate the roles of the autopsy within the medical curriculum. Anonymised interview transcripts were subjected to a themed content analysis. Theoretical saturation was reached after 9 interviews. No new themes were added by a further 5 interviews. All the interviews were polythematic. In all, 43 themes were identified. In addition to confirming overt uses of the autopsy reported in previous studies, educators identified issues of curriculum design and development, the impact on the hidden curriculum, and a range of disadvantages and alternatives to the autopsy. Educators continue to perceive the autopsy as having a multifactorial role in providing the doctors of tomorrow with the appropriate knowledge and attitudes needed for the practice of medicine in the 21st century.


A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice.
Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice. Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 μg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ɣ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture. HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks. We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.


A new clinico-tomographic classification and management algorithm for Descemet's membrane detachment.
To propose a new clinico-tomographic classification of Descemet's detachment (DD). Interventional case series of 35 eyes with DD were clinico-tomographically classified as: (1)Rhegmatogenous DD (RDD)-lax, free floating DM secondary to DM tear/hole/dialysis; ASOCT showing undulating linear signal with total length equalling overlying stromal arc length. (2) Tractional DD (TDD)-foreshortened, taut DM with tractional/fibrotic component; ASOCT showing detached DM chord length less than overlying stromal arc length. (3) Bullous DD (BDD)-bulge of DM into AC in absence of DM break or needle puncture break too small to allow egress of contents; ASOCT showing convex signal. (4) Complex DD (CDD)-Complex variants and combinations seen clinically and on ASOCT. RDD was most common (n=23), 19 were RDD with tear (post-surgical) treated by observation(n=3)/pneumodescemetopexy(n=16), 2 were RDD with hole due to inadvertent DM perforation in deep anterior lamellar keratoplasty treated by pneumodescemetopexy and fibrin glue, 2 were RDD with dialysis post-Descemetorhexis in Descemet's Membrane Endothelial Keratoplasty, not requiring treatment. TDD (n=4) was treated by relaxing Descemetotomy (n=3) or EK (n=1, poor endothelium); BDD (n=3) with two improving spontaneously; CDD (n=5) treated by refloatation with air (n=3)/EK (n=1)/penetrating keratoplasty (n=1). Treatment and prognosis of DD varies based on etio-morphology. This classification allows systematic approach for diagnosis, management and prognostication.


Marked improvement in clinical pregnancy rates following in vitro fertilization-embryo transfer seen when transfer technique and catheter were changed.
To compare in vitro fertilization (IVF) outcome with two different embryo transfer (ET) catheters: the Frydman and Wallace catheters. Retrospective review of outcome of IVF cycles where there was at least one embryo that had assisted hatching prior to transfer at 72 hours according to which catheter was used. Pregnancy rate 17.6% per transfer with Frydman (FET-SET) vs 44.2% for fresh ETs and 15.4% and 43.2% for frozen ETs. The implantation rates for fresh ETs were 7.6% vs 20.0% for fresh and 5.7 vs 21.1% for frozen ETs. The soft Wallace catheter is superior to the stiffer Frydman catheter when transferring embryos subjected to assisted embryo hatching.


The effect of insulin deficiency on tau and neurofilament in the insulin knockout mouse.
Complications of diabetes mellitus within the nervous system are peripheral and central neuropathy. In peripheral neuropathy, defects in neurofilament and microtubules have been demonstrated. In this study, we examined the effects of insulin deficiency within the brain in insulin knockout mice (I-/-). The I-/- exhibited hyperphosphorylation of tau, at threonine 231, and neurofilament. In addition, we showed hyperphosphorylation of c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 beta (GSK-3 beta) at serine 9. Extracellular signal-regulated kinase 1 (ERK 1) showed decrease in phosphorylation, whereas ERK 2 showed no changes. Ultrastructural examination demonstrated swollen mitochondria, endoplasmic reticulum, and Golgi apparatus, and dispersion of the nuclear chromatin. Microtubules showed decrease in the number of intermicrotubule bridges and neurofilament presented as bunches. Thus, lack of insulin brain stimulation induces JNK hyperphosphorylation followed by hyperphosphorylation of tau and neurofilament, and ultrastructural cellular damage, that over time may induce decrease in cognition and learning disabilities.


Capital & candor. To meet the needs of obese patients, hospitals change processes, equipment and attitudes.
To meet the needs of obese patients, hospitals are investing in new equipment and renovations, reconsidering processes to avert injuries to staff, and retraining staff to treat those patients with sensitivity. Innovative hospitals are even developing new service lines.


Dosimetry studies on prototype 241Am sources for brachytherapy.
Sealed sources of 241Am emit primarily 60 keV photons which, because of multiple Compton scattering, produce dose distributions in water that are comparable to those from 226Ra or 137Cs. However, americium gamma rays can be shielded by thin layers of high atomic number materials since the half value layer thickness is only 1/8th of a mm of lead for americium gamma rays as compared to a value of 12 mm for 226Ra gamma rays. This may allow effective in vivo shielding of critical organs, for example; the bladder can be partially shielded by hypaque solution, and the rectum and sigmoid colon by barium sulfate. In addition, the exposure to medical personnel involved in intracavitary application and patient care may be reduced substantially by the use of relatively thin lead aprons and light weight, portable shields. To investigate the feasibility of 241Am sources for intracavitary irradiation, dosimetry studies on prototype 241Am sources have been performed and a computer model for the determination of dose distributions around encapsulated cylindrical sources of 241Am has been developed and tested. Results of dosimetry measurements using ionization chambers, lithium fluoride thermoluminescent dosimeters, a scanning scintillation probe, and film dosimetry, confirm theoretical predictions that these sources can deliver dose rates adequate for intracavitary irradiation. Further dosimetry measurements in simulated clinical situations using lead foils and test tubes filled with hypaque or barium sulfate, confirm the predicted effectiveness of in vivo shielding which can be readily achieved with 241Am sources.


[Bone in hepatic cirrhosis: morphometric and biological study (author's transl)].
Quantitative bone histomorphometry and evaluation of blood parameters have been performed in 24 patients with hepatic cirrhosis. 13 patients show osteoporosis which, in 8 of them, is associated with osteoclastic hyperactivity but without elevation of blood parathormon. All patients have hypocalcemia and 14 of them hyperosteidosis. These results are compared with data of the literature on bone morphometry and phosphocalcic metabolism during hepatic cirrhosis.


Structural Switching of a Distorted Trigonal Metal-Organic Cage to a Tetragonal Cage and Singlet Oxygen Mediated Oxidations.
Construction of metal-organic cages with unique architecture and guest binding abilities is highly desirable. Herein, we report the synthesis of a distorted trigonal cage (1) from a twisted tetratopic ligand (L) and a PdII acceptor. Surprisingly, 1 exhibited a complete structural reorganization of its building units in the presence of C70 and C60 to form guest-encapsulated tetragonal cages, (C70 )2 @2 and (C60 )2 @2, respectively. These guest-bound cages were found to be potential 1 O2 generators, with the former effectively catalyzing two different varieties of 1 O2 -mediated oxidation reactions.


The Role of Early and Later Response on Overall Outcomes in School-Based Obesity Intervention.
Early response to obesity intervention consistently predicts long-term BMI reductions. However, little is known about how changes in weight at other times in an intervention may impact long-term outcomes. This study examined the relationship between weight-related changes that occurred early and later during an intervention and the association between these changes with overall outcomes. A secondary analysis of a school-based obesity intervention with replicated efficacy among Hispanic middle school students was conducted (n = 174). Linear regression models were developed in which first and second semester changes in BMI represented as a percentage of the 95th BMI percentile (%BMIp95) were separately used to predict overall %BMIp95 outcomes. First semester changes in %BMIp95 were used to predict subsequent %BMIp95 change (i.e., second semester). Changes in %BMIp95 during both the first and second semesters were independently associated with overall changes from baseline (e.g., at 24 months: first semester, β = 0.59, P < 0.01; second semester, β = 1.02, P < 0.001). First semester %BMIp95 change was not associated with second semester change (β = -0.07, P = 0.32). Change at any point during the intervention was predictive of overall weight outcomes. Additional research is needed to understand patterns of weight changes throughout interventions to better understand long-term outcomes.


Usefulness of nicardipine as monotherapy for chronic, stable angina.
Using a double-blind, Latin square protocol designed to detect dose response, nicardipine hydrochloride, a new calcium antagonist, was studied as monotherapy for stable exertional angina. Eighty-one patients were enrolled in the trial and 62 patients were included in greater than or equal to 1 primary efficacy analyses. Patients received 1 to 2 weeks of placebo run-in, then 5 weeks of treatment with placebo and with 10, 20 and 30 mg of nicardipine given 3 times daily. Patients completed symptom diaries, were monitored with 24-hour electrocardiographic Holter monitors and underwent serial exercise treadmill tests. By 1 hour, 10, 20 and 30 mg of nicardipine administered 3 times daily produced statistically significant, dose-related improvements in all key exercise parameters, which persisted at the 4-hour evaluation. The systolic blood pressure at rest and during exercise decreased, but the pulse slightly increased. The peak rate-pressure product was unchanged. The side effects were not severe. Nicardipine hydrochloride is an effective, well-tolerated medication for the treatment of stable exertional angina, and is a good alternative to currently available calcium antagonists.


LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.


Uptake and metabolism of androgens by bovine spermatozoa.
Spermatozoa from bovine ejaculates and cauda epiditymidis were incubated with either tritiated 17 beta-hydroxy-5 alpha-androstane-3-one (DHT) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol). Examination of the medium incubations demonstrated metabolic conversion of both DHT and 3 alpha-diol when these steriods were incubated with ejaculated sperm. In addition to this interconversion, the following metabolities were identified: 5 alpha-androstane-3 beta, 17 beta-diol, (3 beta-diol), androsterone and 5 alpha-androstane-3, 17-dione (5 alpha-A-dione). Incubations with cauda spermatozoa showed similar metabolic patterns. Androgen binding was exhibited by both sperm types. Examination of the washed cauda sperm pellet, following incubations with 3 alpha-diol showed that the incubated steroid was the most abundantly bound. DHT and 5 alpha-androst-16-en-3 alpha-ol (delta 16-3 alpha-ol1 were also detected. The major part of the radioactivity bound in the sperm pellet was identified as DHT when this steroid was used as the substrate; the remaining radioactivity consisted of 3 alpha-diol and delta 16-3 alpha-ol. Investigations of ejaculated sperm pellets gave similar results apart from the additional identification of 5 alpha-androst-16-en-3 one (delta 16-3-one) and 5 alpha-androst-16-en-3 beta-ol (delta 16-3 beta-ol (delta 16-3 beta-ol).


Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone.
This study investigated the hypothesis that, in benign prostatic hyperplasia (BPH), upregulated oestrogen receptors (ER) and the action of androgens differentially regulate expression of stromal growth factors. Eight human prostatic stromal cell strains were subjected to a procedure to upregulate their ER by exposing them to 1 micromol 17beta-estradiol for 10 days followed by passage and growth in the absence of steroids. Four of the cell strains instead received 100 nmol dihydrotestosterone for 48 h. Immunoexpression of ERalpha, AR and six growth factors was quantified by flow cytometry in each case. Expression of ERalpha was significantly increased in six of eight cell strains. Expressions of six growth factors (FGF-2, FGF-7, IGF-1, TGF-beta1 NGF and e NOS) were elevated but only for FGF-7 was it significant. There was a significant positive correlation between the change in ERalpha and the change in FGF-2 and FGF-7, but not the other growth factors. Exposure to dihydrotestosterone reduced expression of ERalpha and all six growth factors, compared with oestrogen-treated cells but not significantly. It is concluded that upregulated ERalpha in prostatic stroma may have a greater modulating influence on synthesis of certain growth factors than the direct action of androgens and, by enhancing synthesis of FGF-2 and FGF-7, could play a significant role in the development of BPH.


Reversible binding of the cooked food mutagen MeIQx to lignin-enriched preparations from wheat bran.
The binding of the mutagen 3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline-2-amine (MeIQx) to various fibre preparations from wheat bran was studied. The physical structures of wheat bran and lignin-enriched preparations were determined by scanning electron microscopy. With increasing mutagen concentration from 0.5-16 micrograms/ml, the fraction of MeIQx bound to cellulase-treated lignin was nearly constant, for a certain lignin density. The binding between cellulase-treated lignin and MeIQx was reversible. Incubation temperature influenced the rate at which the equilibrium between lignin and MeIQx was established, but had less effect on the equilibrium itself. With increasing fibre densities and a constant mutagen concentration, complete binding was apparently reached at a high fibre density. This was illustrated by plotting the data according to Scatchard. Increased binding of the MeIQx was obtained with increased enrichment of lignin in different fibre preparations.


Pharmacokinetic analysis of the plasma disappearance of ovine follitropin and analogues in the male rat.
Ovine follitropin (oFSH) and its chemically deglycosylated (DG) or the asialo analogue were injected as a single bolus (2.5 micrograms) to intact mature male rats and plasma levels measured by radioimmunoassay. Semi-logarithmic plots of the plasma disappearance curves were all biphasic. For all substances tested, the data were best fitted to a biexponential equation and the following parameters were calculated: the half-lives of the distribution and elimination phases and the metabolic clearance rate (MCR) at steady state. It was found that the distribution phase of oFSH was much slower than for deglycosylated (DG) alpha + beta recombinant, DG-oFSH and asialo-oFSH. The elimination half-lives for asialo-oFSH and DG alpha + beta recombinant were much shorter than for oFSH and DG-oFSH. oFSH had the lowest MCR, followed by DG alpha + beta, DG-oFSH and asialo-oFSH. This study clearly shows that sugar residues internal to sialic acid also play a significant part in the clearance of the hormone.


Impact of Peritoneal Interposition Flap on Patients Undergoing Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies. To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence. In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints. Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low. PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC. A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap.


Development of an economical, autonomous pHstat system for culturing phytoplankton under steady state or dynamic conditions.
Laboratory investigations of physiological processes in phytoplankton require precise control of experimental conditions. Chemostats customized to control and maintain stable pH levels (pHstats) are ideally suited for investigations of the effects of pH on phytoplankton physiology, for example in context of ocean acidification. Here we designed and constructed a simple, flexible pHstat system and demonstrated its operational capabilities under laboratory culture conditions. In particular, the system is useful for simulating natural cyclic pH variability within aquatic ecosystems, such as diel fluctuations that result from metabolic activity or tidal mixing in estuaries. The pHstat system operates in two modes: (1) static/set point pH, which maintains pH at a constant level, or (2) dynamic pH, which generates regular, sinusoidal pH fluctuations by systematically varying pH according to user-defined parameters. The pHstat is self-regulating through the use of interchangeable electronically controlled reagent or gas-mediated pH-modification manifolds, both of which feature flow regulation by solenoid valves. Although effective pH control was achieved using both liquid reagent additions and gas-mediated methods, the liquid manifold exhibited tighter control (±0.03pH units) of the desired pH than the gas manifold (±0.10pH units). The precise control provided by this pHstat system, as well as its operational flexibility will facilitate studies that examine responses by marine microbiota to fluctuations in pH in aquatic ecosystems.


Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008.
Validamycin A (VAL-A) is an important and widely used agricultural antibiotic. In this study, statistical screening designs were applied to identify significant medium variables for VAL-A production and to find their optimal levels. The optimized medium caused 70% enhancement of VAL-A production. The difference between optimized medium and original medium suggested that low nitrogen source level might attribute to the enhancement of VAL-A production. The addition of different nitrogen sources to the optimized medium inhibited VAL-A production, which confirmed the importance of nitrogen concentration for VAL-A production. Furthermore, differences in structural gene transcription and enzyme activity between the two media were assayed. The results showed that lower nitrogen level in the optimized medium could regulate VAL-A production in gene transcriptional level. Our previous study indicated that the transcription of VAL-A structural genes could be enhanced at elevated temperature. In this work, the increased fermentation temperature from 37 to 42 °C with the optimized medium enhanced VAL-A production by 39%, which testified to the importance of structural gene transcription in VAL-A production. The information is useful for further VAL-A production enhancement.


Vitamin-A-dependent zinc-binding protein and intestinal absorption of Zn in chicks.
It was demonstrated that the development of experimental avitaminosis A in chicks led to secondary zinc deficiency. The balance of Zn in the chick became negative, while the Zn content of various tissues decreased. Thus in vitamin-A-deficient chicks the serum Zn content was 1258 (SD 26.3) micrograms/l which was considerably lower than 1652 (SD 97.8) micrograms/l in controls. Zn absorption was considerably reduced throughout the entire small intestine of vitamin-A-deficient chicks and most markedly in the ileal region. Within 72 h after retinyl acetate administration Zn absorption was fully restored in this region of the intestine. The 65Zn-binding capacity of soluble proteins, present in the supernatant fraction of ileal-mucosa homogenates of vitamin-A-deficient chicks, was found to increase 2.6 times by 72 h after the administration of a single dose of retinyl acetate. A vitamin-A-dependent Zn-binding protein (ZnBP), absent in vitamin-A-deficient chicks, was isolated from the ileal mucosa after their repletion with vitamin A. Competitive-binding studies (calcium, cadmium, copper) showed the protein to be highly specific for Zn ions. The molecular weight of ZnBP was 83 kDa. The association constant of the protein-Zn complex was 0.8 X 10(6)/mol. The protein was acidic with approximately 20% of its amino acid residues belonging to dicarboxylic acids. ZnBP was found to be a glycoprotein, and it contained hexose as a carbohydrate component. It is suggested that ZnBP is involved in the binding of Zn in the ileal mucosa of chicks.


Pre-surgical bronchoscopic treatment for typical endobronchial carcinoids.
Carcinoids are tumors that originate from diffuse neuroendocrine system cells (APUD cells) and represent 1-2% of all pulmonary tumors. Although surgical resection remains the mainstay of treatment, bronchoscopic radical resection of typical carcinoids in selected cases exhibiting endoluminal growth and small implant base has also been explored. Bronchoscopic removal of endobronchial lesions may also reduce the risk of post-obstructive infections and improve pulmonary function, allowing the patient to undergo surgery in better clinical and respiratory state. In this paper we have evaluated the impact on surgical planning and outcome of preoperative bronchoscopic resection in treatment of endobronchial typical carcinoids. Our observations further support the role of bronchoscopic treatment before surgery in endobronchial typical carcinoids.


A control-matched comparison of flap off and flap on laser-assisted subepithelial keratectomy (LASEK) for the treatment of myopia and myopic astigmatism.
To compare the visual and refractive outcomes of flap off and flap on, Laser Assisted Subepithelial Keratectomy (LASEK) for low to moderate myopia. A prospective non-randomized control-matched study was conducted in which 53 patients underwent LASEK for the treatment of low to moderate myopia and myopic astigmatism. Right eye of each patient had the flap removed (flap off) while in the left eye the flap was recapped (flap on). Equal number (N = 53) of flap on was matched with flap off having preoperative manifest refraction spherical equivalent within ±0.75 Diopters (D). Primary outcome variables included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA) and manifest refraction. Preoperatively, the mean spherical equivalent (SE) was -3.59 ± 1.46 D for flap off and -3.67 ± 1.51 D for flap on (p = 0.779). The mean preoperative sphere was -3.32 ± 1.58 D for flap off group and -3.36 ± 1.61 D for flap on group (p = 0.338) whereas, the mean preoperative cylinder was -0.55 ± 0.70 D and -0.63 ± 0.68 D for flap removal and flap preservation groups respectively (p = 0.576). Postoperatively, the mean LogMAR UCVA was -0.035 ± 0.079 for flap off and -0.043 ± 0.085 for flap on. The percentages of eyes that had UCVA of 20/40 or better were 98.1% for flap off group and 100% for flap on group (p = 0.317). Mean postoperative SE was 0.00 ± 0.19 D for flap off group and -0.03 ± 0.43 D for flap on group. In flap removal group, 100% eyes were within ±0.50 D of the intended correction while in flap preservation group, 92.5% and 100% eyes were within ±0.50 D and ±1.00 D of the intended correction, respectively. Mean postoperative LogMAR BSCVA was -0.013 ± 0.044 for flap removal group and -0.016 ± 0.049 for flap preservation group (p = 0.727). The differences in the visual and refractive results between flap preservation and flap removal groups were not clinically significant. Both procedures seemed safe and effective for the treatment of myopia and myopic astigmatism.


Anthropometric measurement standardization in the US-affiliated pacific: Report from the Children's Healthy Living Program.
Anthropometric standardization is essential to obtain reliable and comparable data from different geographical regions. The purpose of this study is to describe anthropometric standardization procedures and findings from the Children's Healthy Living (CHL) Program, a study on childhood obesity in 11 jurisdictions in the US-Affiliated Pacific Region, including Alaska and Hawai'i. Zerfas criteria were used to compare the measurement components (height, waist, and weight) between each trainee and a single expert anthropometrist. In addition, intra- and inter-rater technical error of measurement (TEM), coefficient of reliability, and average bias relative to the expert were computed. From September 2012 to December 2014, 79 trainees participated in at least 1 of 29 standardization sessions. A total of 49 trainees passed either standard or alternate Zerfas criteria and were qualified to assess all three measurements in the field. Standard Zerfas criteria were difficult to achieve: only 2 of 79 trainees passed at their first training session. Intra-rater TEM estimates for the 49 trainees compared well with the expert anthropometrist. Average biases were within acceptable limits of deviation from the expert. Coefficient of reliability was above 99% for all three anthropometric components. Standardization based on comparison with a single expert ensured the comparability of measurements from the 49 trainees who passed the criteria. The anthropometric standardization process and protocols followed by CHL resulted in 49 standardized field anthropometrists and have helped build capacity in the health workforce in the Pacific Region. Am. J. Hum. Biol. 28:364-371, 2016. © 2015 Wiley Periodicals, Inc.


In vitro fecal fermentation characteristics of bamboo insoluble dietary fiber and its impacts on human gut microbiota.
Bamboo contains abundant hemicellulose, cellulose, and lignin, which are a high-quality insoluble dietary fiber (IDF) raw material. To investigate IDF- induced changes in the production of short-chain fatty acids (SCFAs) and the composition of human gut microbiota, IDF was extracted by alkaline hydrogen peroxide (named BIDF), complex enzymatic hydrolysis method (named OIDF) from bamboo, and commercial bamboo fiber BF90. The in vitro fecal fermentation characteristics of BIDF, OIDF, BF90 and its impacts on human gut microbiota were studied for the first time. Results showed that BIDF, OIDF, and BF90 could promote the production of total SCFAs after 24 h fermentation. Additionally, BIDF could alter the composition and microbial diversity of gut microbiota, especially increase the relative abundance of Bacteroides and decrease the ratio of Firmicutes to Bacteroidetes (F/B) value. These results revealed that the IDF from bamboo could be partially utilized by specific bacteria in human intestines and provide a reference for the study of the effects of IDF fermentation on SCFAs production and microbial composition.


Dealing with soy sauce precipitation at submicron-/nano-scale: An industrially feasible approach involving enzymolysis with protease and alkaline conditions.
This study proposes an industrially feasible approach to handle the heating-induced soy sauce precipitates (SSPs) during soy sauce production. Protein (32.59%; containing a large amount of hydrophobic amino acid) and sugar (26.86%) were found to be the main composition of SSPs, and high content of mineral elements were also discovered in SSPs. A pH adjustment to 8-12 along with an enzymolysis step with alkaline protease seemed beneficial for this purpose while offering opportunities to manipulate the soy sauce quality. The pH adjustment decreased SSPs particle size from micron-scale to submicron- or nano-scale, and improved significantly the efficiency of SSPs protein enzymatic hydrolysis and protein recovery (up to 80%). The enzymolysis with alkaline protease enabled the generation of pyrazines while affecting the contents of phenols, alcohols, furans, pyrroles and sulfur-containing compounds. Interactions occurred between amino acids and sugars, among volatiles, and between volatiles (like aldehydes) and other monomers under such alkaline conditions. This study presents an efficient approach that is of practical significance to dealing with SSPs in soy sauce production and reuse of SSPs.


Genomic analysis of the F3031 Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius by PCR-based subtractive hybridization.
PCR-based subtractive genome hybridization produced clones harboring inserts present in Brazilian purpuric fever (BPF) prototype strain F3031 but absent in noninvasive Haemophilus influenzae biogroup aegyptius isolate F1947. Some of these inserts have no matches in the GenBank database, while others are similar to genes encoding either known or hypothetical proteins. One insert represents a 2.3-kb locus with similarity to a Thermotoga maritima hypothetical protein, while another is part of a 7.6-kb locus that contains predicted genes encoding hypothetical, phage-related, and carotovoricin Er-like proteins. The presence of DNA related to these loci is variable among BPF isolates and nontypeable H. influenzae strains, while neither of them was detected in strains of types a to f. The data indicate that BPF-causing strain F3031 harbors unique chromosomal regions, most of which appear to be acquired from unrelated microbial sources.


Phase space localization and matrix element distributions in systems with mixed classical phase space.
We consider distributions of diagonal matrix elements for smooth observables in systems whose classical phase space has a mixture of chaotic and nearly integrable regions. The quantum distributions agree very well with distributions obtained from classical trajectory segments whose length is the Heisenberg time. Non-Gaussian wings in the distributions can be linked to classical trapping in certain parts of phase space, sometimes connected to islands, but also to regions separated by other barriers to transport. Thus classical deviations from ergodicity are quantitatively reflected in quantum matrix elements. The relation to scars is discussed.


Applying World Dental Federation Theoretical Framework for Oral Health in a General Population.
The World Dental Federation (FDI) has recently proposed a new definition and theoretical framework of oral health. The theoretical framework includes 4 main components and describes the relationships amongst them. In 2020, an international work group proposed the minimum Adult Oral Health Standard Set (AOHSS) of variables to measure oral health, which was mapped onto the FDI's theoretical framework. By using an empirical data set, the proposed variables in the AOHSS and the potential interactions amongst the components of the FDI's theoretical framework can be tested. The purpose of this research was to investigate structural relations of the components of the FDI's theoretical framework of oral health based on data from a general adult population. Data from a previously conducted Swedish cross-sectional study focusing on oral health were utilised (N = 630; women, 55.2%; mean age, 49.7 years [SD, 19.2]). Variable selection was guided by the AOHSS. Structural equation modeling was used to analyse relationships amongst the components of the FDI's theoretical model (core elements of oral health, driving determinants, moderating factors, and overall health and well-being). The Oral Health Impact Profile (OHIP)-14, xerostomia, and aesthetic satisfaction had statistically significant direct effects on overall health and well-being (p < .05). Driving determinants and moderating factors had statistically significant direct effects on all core elements of oral health (p < .05) except aesthetic satisfaction (p = .616). The predictors explained 24.1% of the variance of the latent variable overall health and well-being. Based on several indices, the proposed model showed acceptable model fit. The FDI's theoretical framework can be used to describe different components of oral health and the relationship amongst them in an adult general population. Further research based on the FDI's theoretical framework in other populations and settings is needed to explore complex interactions and possible relationships that form oral health and to investigate other or additional important social determinants.


First myocardial infarction in patients under 60 years old: the role of exercise tests and symptoms in deciding whom to catheterise.
To determine the role of exercise tests and assessment of angina in the detection of potentially threatening disease in young patients with infarcts. Elective readmission of patients at a mean (SD) of 60 (30) days after acute myocardial infarction for assessment of angina, treadmill exercise tests, and cardiac catheterisation. Cardiology department of a teaching hospital. 186 consecutive survivors, aged under 60 years and discharged from the coronary care unit after a first myocardial infarction. Coronary arteriography, presence of angina, result of exercise tests, and referral for revascularisation. 31% of patients had either two vessel disease (with proximal left anterior descending involvement), three vessel disease, or left main stem disease. 49% of all patients had angina. Of the 173 patients who had an exercise test 34% had 1 mm and 24% had 2 mm of exercise induced ST depression. Thirty percent had no angina and a negative exercise test: after a mean (SD) follow up of 16 (4) months none of this symptom free sub-group had died, had experienced a further myocardial infarction, or had been referred for revascularisation. 79% of patients with either two vessel disease (with proximal left anterior descending involvement), three vessel disease, or left main stem disease had either angina or a 1 mm ST depression during the exercise test. Patients without cardiac pain after myocardial infarction and without ST changes during an exercise do not need arteriography.


Association of acute-phase reactants with arterial stiffness in patients with type 2 diabetes mellitus.
The relationship between chronic low-grade inflammation and atherosclerotic progress in patients with diabetes mellitus has not been confirmed. We determined whether acute-phase reactants are associated with arterial stiffness in diabetic patients. Relationships of blood inflammatory markers [high-sensitivity C-reactive protein (CRP), amyloid A protein (SAA), sialic acid, fibrinogen and white blood cells (WBC)] with atherosclerosis were investigated in a cross-sectional study using 114 subjects with type 2 diabetes. The degree of atherosclerosis was evaluated by arterial stiffness measured using cardio-ankle vascular index (CAVI), a new index of arterial stiffness, which is compatible with conventional aortic pulse-wave velocity. CRP, SAA, sialic acid, fibrinogen and WBC showed significant correlations with CAVI. CAVI was significantly higher in the highest tertile of sialic acid, fibrinogen and WBC compared with the lowest tertile or lowest and middle tertiles. This association was independent of age, sex and smoking. By logistic regression analysis, the highest levels of these acute-phase reactants showed increased risk of high CAVI, while CRP and SAA were not associated with an increased risk in this analysis. CAVI was also significantly correlated with duration of diabetes, blood pressure and serum total cholesterol. Acute-phase reactants, such as CRP, SAA, sialic acid, fibrinogen and WBC, are associated with arterial stiffness in patients with type 2 diabetes mellitus.


Characterization of estrogen receptor beta2 and expression of the estrogen receptor subtypes alpha, beta1, and beta2 in the protandrous black porgy (Acanthopagrus schlegeli) during the sex change process.
Estrogens play an important role in many physiological processes in both female and male vertebrates, mediated by specific nuclear receptor, estrogen receptors (ERs). We have isolated a third ER (ERbeta2), which was found to contain 2004 nucleotides including an open reading frame that encodes 667 amino acids. We have also cloned ERalpha and ERbeta1 from the published information (GenBank accession nos. AY074780 and AY074779) and investigated the expression pattern of these ER subtypes in the gonads during gonad sex change of black porgy by quantitative polymerase chain reaction. Maturity stages can be divided into five stages during the sex change process from immature male to female (immature male, mature male, male of mostly testis, male of mostly ovary and mature female). The expression of ERalpha mRNA was highest in the ovary of mature female, followed by the testis of mature male and testicular portion of mostly testis. ERbeta1 expression was higher in the mature testis and ovary than in the gonads of other maturity stages. In contrast to that, ERbeta2 was highest in the ovary of mature female, and significantly lower levels of ERbeta2 expression were observed in the gonads of the other maturity stages. The present study describes the molecular characterization of ERbeta2, and documents the expression changes of three ER subtypes during sex change process of the protandrous black porgy.


Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency-related COPD.
No consistent data are available regarding the effect of inhaled corticosteroids (ICS) in alpha(1)-antitrypsin-deficiency (AATD)-related COPD. Recent data report inflammatory effects of the polymers of alpha(1)-antitrypsin on the peripheral lung. The aim of this study was to assess the effectiveness of an extra-fine ICS, hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) with a mass median aerodynamic diameter of 1.1 microm, on lung function and exercise tolerance in COPD patients with AATD when added to long-acting bronchodilators (LABAs). After a 1-week washout, 8 steroid-naïve COPD patients with AATD (ZZ genotype), within a double-blind randomized cross-over study, were assigned to one of the following 16-week treatments: (1) HFA-BDP 400 microg b.i.d., salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d. or (2) placebo, salmeterol 50 microg b.i.d. and oxitropium bromide 200 microg t.i.d; after a 2-week washout period they received the other treatment. In weeks 1, 17, 19 and 35, patients took a spirometry assessment (breathing air and heliox) and a shuttle walking test (SWT) with dyspnea assessed by the modified Borg scale. Significant differences in improvement were found in FEV(1), FVC, IC, distance covered and dyspnea perceived during SWT between the 2 treatments and baseline values (p < 0.05; Friedman's test). However, further analysis showed that only the LABAs + ICS condition showed significant increases in the FEV(1), FVC, IC, DeltaMEF(50%) and distance covered during SWT along with a reduction in maximum isostep exertional dyspnea (p < 0.05; Wilcoxon test). A greater distance was walked at the end of the SWT with LABA + ICS than LABAs alone (301 +/- 105 vs. 270 +/- 112 m; p < 0.05). In AATD-related COPD patients (ZZ genotype) the addition of extra-fine ICS to LABAs decreases airway narrowing, mostly in the small airways, further reducing dynamic hyperinflation with a marked improvement in exercise tolerance and dyspnea, suggesting that a peripheral inflammatory process contributes to airflow obstruction in these patients.


Safety of zidovudine dose reduction in treatment-naïve HIV infected patients. A randomized controlled study (MiniZID).
Since September 2014, zidovudine (ZDV)-based therapy for HIV has been the preferred second-line WHO regimen in Cameroon, but its use is limited by the risk of anaemia at standard dosage. We assessed the safety of a reduced vs. standard dose of ZDV to decrease the risk of anaemia in treatment-naïve, HIV-infected individuals. In a prospective, randomized, open-label trial in an HIV clinic in Cameroon, 142 eligible adults (CD4 count < 350 cells/μL) were randomized to receive 24 weeks of a regimen comprising lamivudine plus nevirapine with either a reduced (400 mg) or standard dose (600 mg) of ZDV. The primary endpoint was the proportion of participants with new/worsening anaemia. Median age was 35 years; 58.5% were women; median body mass index was 23.2 kg/m(2) . At baseline, median haemoglobin was 11.6 g/dL, median CD4 cell count was 163 cells/μL, and median plasma HIV-1 RNA load was 5.4 log10 copies/mL. The proportion of participants with new/worsening anaemia was 37.5% (400 mg ZDV) and 32.9% (600 mg ZDV) (P = 0.563). Ten patients with severe anaemia required a switch from ZDV to tenofovir (11.4% in standard-dose arm vs. 2.8% in low-dose arm; P = 0.054). At 24 weeks, there was no significant difference between treatment groups, including median CD4 T-cell count increases. No significant difference was observed in the overall rate of anaemia between HIV-infected individuals starting a ZDV-based treatment according to a standard- or reduced-dose regimen. Severe anaemia and treatment switches related to study drug, however, were more frequent with 600 mg than 400 mg ZDV.


Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.
Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency.


Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI.
This study examined regional structural changes in the whole brain in 45 medicated patients with schizophrenia (23 males and 22 females), comparing with 42 age- and sex-matched healthy volunteers (22 males and 20 females). Automated voxel-based analysis on three-dimensional magnetic resonance imaging (MRI) was conducted using statistical parametric mapping (SPM). Compared with the controls, relative gray matter in the patients was significantly reduced in the left superior temporal, left middle and inferior frontal, right inferior frontal, and bilateral anterior cingulate and medial temporal areas. Gray matter reductions in the left superior temporal and prefrontal areas were found predominantly in the male patients, while the anterior cingulate gray mater reduction was more striking in the female patients. On the contrary, significant gray matter increases in the patients were found in the parietal areas and the cerebellum. In the white matter, significant reduction was found in the bilateral anterior limbs of the internal capsule and the superior occipitofrontal fasciculus, whereas the bilateral parietal white matter showed significant increases. These results suggest that a pathological process in schizophrenia predominantly affects the fronto-temporolimbic-paralimbic regions. Reduced white matter in the connecting bundles, which was first found in this study, may imply morphological substrates for abnormalities in the fronto-thalamic and fronto-temporolimbic connectivity in schizophrenia.


Multistate outbreak of Salmonella serotype Typhimurium infections associated with consumption of restaurant tomatoes, USA, 2006: hypothesis generation through case exposures in multiple restaurant clusters.
Multiple salmonellosis outbreaks have been linked to contaminated tomatoes. We investigated a multistate outbreak of Salmonella Typhimurium infections among 190 cases. For hypothesis generation, review of patients' food histories from four restaurant-associated clusters in four states revealed that large tomatoes were the only common food consumed by patients. Two case-control studies were conducted to identify food exposures associated with infections. In a study conducted in nine states illness was significantly associated with eating raw, large, round tomatoes in a restaurant [matched odds ratio (mOR) 3·1, 95% confidence interval (CI) 1·3-7·3]. In a Minnesota study, illness was associated with tomatoes eaten at a restaurant (OR 6·3, mid-P 95% CI 1·05-50·4, P=0·046). State, local and federal regulatory officials traced the source of tomatoes to Ohio tomato fields, a growing area not previously identified in past tomato-associated outbreaks. Because tomatoes are commonly eaten raw, prevention of tomato contamination should include interventions on the farm, during packing, and at restaurants.


Correction of mammary ptosis with glandular atrophy.
Excess skin and insufficient gland are two problems posed by the correction of the small ptotic breast. A single-stage operation can resolve these problems. Our technique used for 20 patients proved satisfactory with a low rate of complications.


Stress fiber sarcomeres of fibroblasts are contractile.
Living cultured fibroblasts were microinjected with rhodamine-labeled smooth muscle alpha-actinin and visualized by video-intensified fluorescence microscopy. The alpha-actinin incorporated into the stress fibers and exhibited a regularly striped arrangement. The fluorescently labeled stress fibers remained intact despite glycerol or digitonin extraction of the cells; furthermore, these cell models contracted upon addition of MgATP. During this process, sections of alpha-actinin-labeled stress fibers contracted up to 25%; shortening proceeded in the nonfluorescent part of the stress fiber sarcomeres. In glycerol-extracted cell models, adenylylimidodiphosphate, ADP and pyrophosphate inhibited but vanadate, N-ethylmaleimide-modified heavy meromyosin, cytochalasin B, colchicine, phalloidin and DNAase I did not. Cytochalasin B was inhibitory when added to the intact cells before glycerol extraction. These morphological and biochemical findings demonstrate that stress fiber sarcomeres of fibroblasts are contractile elements and support the concept that an actomyosin system may be involved.


Sarcocystis gigantea lectin--mitogen and polyclonal B-cell activator.
The present study further examined the in vitro response of human mononuclear cells (MNC) to the Sarcocystis gigantea lectin (SGL). The results confirm our previous report that SGL is mitogenic for human MNC. We now report that SGL is not only a potent mitogen but also a polyclonal activator for human peripheral B cells. As was true for pokeweed mitogen (PWM, 2 micrograms/ml), the addition of SGL (25 micrograms protein/ml) to cultures of MNC caused lymphocyte proliferation and B-cell maturation, indicated by a marked increase in IgG and IgM production. As measured by the [3H]-thymidine incorporation assay, SGL induced significantly higher proliferative responses than PWM (P less than 0.01, n = 24). The values obtained by SGL and PWM for IgG and IgM synthesis were essentially identical. As opposed to SGL, the sarcotoxin-containing fraction (SGTF) did not induce antibody formation or proliferative responses in human MNC.


Expression and Purification of Dengue NS1 Protein in Sf9-Baculovirus System.
It is well known that glycosylations of Dengue NS1 protein are important for its structure, oligomerization, and immunogenicity. One of the major challenges in heterologous NS1 protein expression is the difference in glycosylation patterns amongst different organisms. The two major natural hosts for Dengue virus are humans and mosquitoes, which are capable of producing very complex glycosylation motifs. This chapter presents an optimized protocol for heterologous expression and purification of Dengue NS1 protein in Sf9 cells infected with baculovirus. NS1 protein obtained from this protocol is glycosylated and capable of forming soluble hexamers that can be used for structural and functional assays.


Association between SMAD3 gene polymorphisms and osteoarthritis risk: a systematic review and meta-analysis.
Several studies have been performed to investigate the association between SMAD3 gene polymorphism and osteoarthritis (OA), but the results were inconclusive. This study aims to determine whether SMAD3 polymorphism is associated with risk of OA. A comprehensive literature search in PubMed, Embase, and ISI Web of Science for relevant studies was performed. After extracting data from eligible studies, we chose the fixed or random effect model according to the heterogeneity test. Estimation of publication bias and sensitivity analysis were conducted to confirm the stability of this meta-analysis. In total, 10 studies from 6 articles with 5093 OA patients and 5699 controls were enrolled in this meta-analysis. The combined results revealed significant association between SMAD3 rs12901499 polymorphism and the risk of OA (allele model: OR 1.21, 95% CI 1.07-1.38). Subgroup analysis revealed that G allele increased the risk of OA in Caucasians, but not in Asians (allele model: Caucasians: OR 1.31, 95% CI 1.18-1.44; Asians: OR 1.24, 95% CI 0.95-1.61). And the pooled results revealed significant association between SMAD3 rs12901499 polymorphism and both knee and hip OA (knee OA: OR 1.18, 95% CI 1.04-1.34; hip OA: OR 1.31, 95% CI 1.18-1.44). The current meta-analysis revealed that the G variant of SMAD3 rs12901499 polymorphism increased the risk of OA in Caucasians. Further well-designed studies with larger sample size in different ethnic populations are required to confirm these results.


Appendiceal abscess masquerading as acute urinary retention in children.
Two boys with acute urinary retention were found to have a persistent pelvic mass after bladder decompression. Evaluation in each disclosed a large pelvic abscess secondary to a ruptured appendix. The diagnosis of appendicitis may be difficult and appendiceal abscess presenting with acute urinary retention in children has been reported previously in only 7 instances. History, physical examination, laboratory studies, and radiographic and ultrasonic evaluations should lead to the correct diagnosis, and surgical intervention restores normal voiding.


IgE-mediated 14C-serotonin release from rat mast cells modulated by morphine and endorphins.
The formaldehyde method was used to examine the interaction of PGE1 with morphine, beta-endorphin and Met-enkephalin on rat mast cells by their effects on IgE-mediated 14C-serotonin release. PGE1 (2x10(-8) -2x10(-5) M) caused a dose-related inhibition of the mediator release 1 min after an antigen challenge, and morphine (3x10(-7) -3x10(-5) M) reversed this PGE1 effect dose-dependently and stereospecifically; naloxone (2x10(-4) M) antagonized this action of morphine. Beta-Endorphin (3x10(-7) -10(-5) M) and Met-enkephalin (3x10(-6) -10(-4) M) mimicked this morphine action dose-dependently and were antagonized by naloxone (2x10(-4) M). These results suggest that morphine and endorphins modulate immunological mediator release from rat mast cells through opioid receptors.


Phosphorothioate-linked guanine/cytosine-based stem-loop oligonucleotides induce the extracellular release of mitochondrial DNA from peritoneal B1a cells.
It has been previously demonstrated that phosphorothioate-linked GpC-based stem-loop oligonucleotides (GC-SL ODN) induce the release of mitochondrial DNA (mtDNA) from chronic lymphocytic leukemia (CLL) B cells. Although CLL B cells are believed to originate from CD5+ B cells because of their phenotypic similarities, it remains unclear whether GC-SL ODN can stimulate CD5+ B1 cells to secrete mtDNA. To explore this possibility, we compared the frequency of the mtDNA-producing population among peritoneal cells after GC-SL ODN treatment. We found that mtDNA-releasing cells are enriched for peritoneal CD19+ B cells upon GC-SL ODN challenge. Among peritoneal CD19+ B cells, the CD5+ B1a subpopulation was a primary cellular source of mtDNA secretion in GC-SL ODN-elicited immune responses. GC-SL ODN-stimulated mtDNA release by B1a cells was positively regulated by MyD88 and TRIF signaling pathways. In vivo GC-SL ODN treatment increased lipopolysaccharide-induced activation of innate immune cells such as NK cells, suggesting the immune-enhancing effects of mtDNA secretion. Furthermore, the loop size formed by GC-SL ODNs was a critical factor in inducing mtDNA release by B1a cells. Taken together, our results identified GC-SL ODN as promising biomaterials for enhancing immune responses.


MRI Screening for Optic Gliomas in Neurofibromatosis Type 1.
Investigators from Cincinnati Children's Hospital, OH, analysed retrospectively the utility of screening brain/orbital MRIs in 826 children with NF1 (ages 1-9 years; 402 female, 424 male) seen over a 20-year period between 1990 and 2010.


Significant Lifetime Enhancement in QLEDs by Reducing Interfacial Charge Accumulation via Fluorine Incorporation in the ZnO Electron Transport Layer.
ZnO nanoparticles are widely used for the electron transport layers (ETLs) of quantum dots light emitting devices (QLEDs). In this work we show that incorporating fluorine (F) into the ZnO ETL results in significant enhancement in device electroluminescence stability, leading to LT50 at 100 cd m-2 of 2,370,000 h in red QLED, 47X longer than the control devices. X-ray photo-electron spectroscopy, time-of-flight secondary ion mass spectroscopy, photoluminescence and electrical measurements show that the F passivates oxygen vacancies and reduces electron traps in ZnO. Transient photoluminescence versus bias measurements and capacitance-voltage-luminance measurements reveal that the CF4 plasma-treated ETLs lead to increased electron concentration in the QD and the QD/hole transport layer interface, subsequently decreasing hole accumulation, and hence the higher stability. The findings provide new insights into the critical roles that optimizing charge distribution across the layers play in influencing stability and present a novel and simple approach for extending QLED lifetimes.


Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.
Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells.


Attitudes and knowledge regarding episiotomy use and technique in vacuum extraction: A web-based survey among doctors in Sweden.
Correct episiotomy use and technique may prevent obstetric anal sphincter injuries. We aimed to explore the attitudes, use, and technique regarding episiotomy among doctors in Sweden, and their willingness to contribute to a randomized controlled trial of lateral episiotomy or no episiotomy in vacuum extraction in nulliparous women. A web-based survey was sent to members of the Swedish Society of Obstetrics and Gynecology (n = 2140). The survey included 31 questions addressing personal characteristics, use of episiotomy, a two-dimensional picture on which the respondents drew an episiotomy, and questions regarding attitudes towards episiotomy and participation in a randomized controlled trial. We calculated the proportion of supposedly protective episiotomies (fulfilling criteria of a lateral or mediolateral episiotomy and a length ≥ 30 mm). We compared the results between obstetricians, gynecologists, and residents using Chi-square and Kruskal-Wallis tests for differences between groups, and logistic regression to estimate the odds ratio (OR) of drawing a protective episiotomy. We received 432 responses. Doctors without a vacuum delivery in the past year were excluded, leaving 384 respondents for further analyses. In all, 222 (57.8%) doctors reported use of episiotomy in<50% of vacuum extractions. We obtained 308 illustrated episiotomies with a median angle of 53°, incision point distance from the midline of 21 mm, and length of 36 mm, corresponding to a lateral episiotomy. Few doctors combined these parameters correctly resulting in 167 (54.2%) incorrectly drawn episiotomies. Residents drew shorter episiotomies than obstetricians and gynecologists. Doctors ranked episiotomy the least important intervention to prevent obstetric anal sphincter injuries in vacuum extraction. Doctors contributing to an ongoing randomized controlled trial of lateral episiotomy or no episiotomy in vacuum extraction were more able to draw a protective episiotomy (OR 3.69, 95% confidence interval 1.94-7.02). Doctors in Sweden reported restrictive use of episiotomy in vacuum extraction and depicted lateral type episiotomies, although the majority were incorrectly drawn. Preventive episiotomy was ranked of low importance. Our results imply a need for education, training, and guidelines to increase uptake of correct episiotomy technique, which could result in improved prevention of obstetric anal sphincter injuries.


Restoration of the poor oxygen transport function of ACD-stored blood by pyridoxal 5'-phosphate.
Pyridoxal 5'-phosphate is easily incorporated into ACD-stored erythrocytes without decrease of ATP, and restores the poor oxygen transport function with a similar effect to 2,3'-diphosphoglycerate.


Nonlinear Method to Predict the Distribution of Structurally Diverse Compounds between Blood and Tissue.
In this work, methods for predicting the distribution of compounds between blood and tissue were investigated using nonlinear regression analysis. For the tissue/blood partition coefficient, 282 compounds and 810 activity data for seven tissues were selected. Twenty-four parameters were studied for each state of the compound. A study set with the most compounds and activity data in similar studies was established, and a model with good prediction ability was obtained. A total of 773 data points were randomly divided into two data sets: the training set contained 623 data points (n = 623, r = 0.822, s = 0.438, F = 142.2, and Q = 0.814) and the test set contained 150 data points (n = 150, r = 0.814, and s = 0.334). Furthermore, individual tissue/blood distribution coefficients were also studied in depth to obtain separate models for predicting the distribution coefficient of a drug between blood and a tissue. By applying these models, not only can the tissue/blood distribution coefficient or single tissue/blood distribution coefficient of the seven tissues and organs of the human body be predicted, but the distribution of the drug molecules in different states (neutral, cation, and anion) in the three tissue components can also be predicted.


A novel strategy using MASCOT Distiller for analysis of cleavable isotope-coded affinity tag data to quantify protein changes in plasma.
A novel strategy consisting of cleavable Isotope-Coded Affinity Tag (cICAT) combined with MASCOT Distiller was evaluated as a tool for the quantification of proteins in "abnormal" patient plasma, prepared by pooling samples from patients with acute stroke. Quantification of all light and heavy cICAT-labelled peptide ion pairs was obtained using MASCOT Distiller combined with a proprietary software. Peptides displaying differences were selected for identification by MS. These preliminary results show the promise of our approach to identify potential biomarkers.


Gene expression profiling of the venom gland from the Venezuelan mapanare (Bothrops colombiensis) using expressed sequence tags (ESTs).
Bothrops colombiensis is a highly dangerous pit viper and responsible for over 70% of snakebites in Venezuela. Although the composition in B. colombiensis venom has been identified using a proteome analysis, the venom gland transcriptome is currently lacking. We constructed a cDNA library from the venom gland of B. colombiensis, and a set of 729 high quality expressed sequence tags (ESTs) was identified. A total number of 344 ESTs (47.2% of total ESTs) was related to toxins. The most abundant toxin transcripts were metalloproteinases (37.5%), phospholipases A2s (PLA2, 29.7%), and serine proteinases (11.9%). Minor toxin transcripts were linked to waprins (5.5%), C-type lectins (4.1%), ATPases (2.9%), cysteine-rich secretory proteins (CRISP, 2.3%), snake venom vascular endothelium growth factors (svVEGF, 2.3%), L-amino acid oxidases (2%), and other putative toxins (1.7%). While 160 ESTs (22% of total ESTs) coded for translation proteins, regulatory proteins, ribosomal proteins, elongation factors, release factors, metabolic proteins, and immune response proteins. Other proteins detected in the transcriptome (87 ESTs, 11.9% of total ESTs) were undescribed proteins with unknown functions. The remaining 138 (18.9%) cDNAs had no match with known GenBank accessions. This study represents the analysis of transcript expressions and provides a physical resource of unique genes for further study of gene function and the development of novel molecules for medical applications.


Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.
Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis. To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model. TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction. We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice. We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.


Urethral duplication--a wide spectrum of anomalies.
Urethral duplications are rare lower urinary tract anomalies, with multiple anatomical variants described. This paper aims to separate this complex anomaly into different diseases, each with distinct clinical forms according to the disturbance during embryogenesis, yet noting a few similarities that may be helpful in their management. The classification system of urethral duplication is also discussed. Twelve urethral duplication cases over a 14-year period were reviewed. Clinical presentation, the imaging studies used to ascertain anatomical details, type of urethral duplication and surgical correction used in the treatment of patients are presented. Nine patients had urethral duplication in the sagittal plane and three patients in the coronal plane. Of the patients with sagittal urethral duplication, 3 had pre pubic sinus, 3 had epispadiac urethral duplication, 1 had a dorsal urethral duplication deviated from the midline and 2 had hypospadiac urethral duplication. All the patients with coronal urethral duplication had associated bladder duplication. The surgical correction of the patients with sagittal urethral duplication included excision of the pre pubic sinus, excision of the duplicated urethra, and urethroplasty. Excision of the hemibladders' septum and closure of one bladder neck was the treatment for patients with coronal urethral duplication and bladder duplication. Urethral duplication is a complex anomaly and the different manifestations probably have different embryological origins. Each group, sagittal or coronal, has a few similarities that may be helpful in their management, although every diagnosed case presents a unique anatomy and surgical treatment must be individualized.


Health information technology adoption in New Zealand optometric practices.
Health information technology (HIT) has the potential to fundamentally change the practice of optometry and the relationship between optometrists and patients and to improve clinical outcomes. This paper aims to provide data on how health information technology is currently being used in New Zealand optometric practices. Also this paper aims to explore the potential benefits and barriers to the future adoption of health information technology in New Zealand. One hundred and six New Zealand optometrists were surveyed about their current use of health information technology and about potential benefits and barriers. In addition, 12 semi-structured interviews were carried out with leaders of health information technology in New Zealand optometry. The areas of interest were the current and intended use of HIT, the potential benefits of and barriers to using HIT in optometric offices and the level of investment in health information technology. Nearly all optometrists (98.7 per cent) in New Zealand use computers in their practices and 93.4 per cent of them use a computer in their consulting room. The most commonly used clinical assessment technology in optometric practices in New Zealand was automated perimeter (97.1 per cent), followed by a digital fundus/retinal camera (82.6 per cent) and automated lensometer (62.9 per cent). The pachymeter is the technology that most respondents intended to purchase in the next one to five years (42.6 per cent), followed by a scanning laser ophthalmoscope (36.8 per cent) and corneal topographer (32.9 per cent). The main benefits of using health information technology in optometric practices were improving patient perceptions of 'state of the art' practice and providing patients with information and digital images to explain the results of assessment. Barriers to the adoption of HIT included the need for frequent technology upgrades, cost, lack of time for implementation, and training. New Zealand optometrists are using HIT broadly in their practices and expect HIT use to increase over time.


School-based obesity prevention in Chilean primary school children: methodology and evaluation of a controlled study.
To assess the impact of a 6 months nutrition education and physical activity intervention on primary school children through changes in adiposity and physical fitness. Longitudinal school-based controlled evaluation study. Children from 1st to 8th grade, 2141 in intervention and 945 in control schools. Nutrition education for children and parents, 'healthier' kiosks, 90 min of additional physical activity (PA) weekly, behavioral PA program and active recess. Adiposity indices (BMI, BMI Z-score, triceps skinfold thickness (TSF), waist circumference and physical fitness (20 m shuttle run test and lower back flexibility). Positive effect on adiposity indices (except TSF) was observed in boys (P<0.001 for BMI Z), while both physical fitness parameters increased significantly in both boys (P<0.001 for each test) and girls (P<0.0001 for each test). A differential effect in BMI Z was observed according to baseline nutritional status. This intervention showed a robust effect on physical fitness in both genders and decreased adiposity only in boys.


Prevalence and factors associated with percutaneous injuries and splash exposures among health-care workers in a provincial hospital, Kenya, 2010.
Accidental occupational exposure of healthcare workers to blood and body fluids after skin injury or mucous membrane contact constitutes a risk for transmission of blood-borne pathogens. Such pathogens include Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV). We conducted a study to determine the prevalence and associated factors for percutaneous injuries and splash exposures among health-care workers in Rift Valley provincial hospital. A cross-sectional study was carried out from October to November 2010. Self reported incidents, circumstances surrounding occupational exposure and post-exposure management were sought by use of interviewer administered questionnaire. Descriptive, bivariate and multiple logistic regression (forward stepwise procedure) analyses were performed. The level of significance was set at 0.05. Twenty five percent of health-care workers interviewed (N=305) reported having been exposed to blood and body fluids in the preceding 12 months. Percutaneous injuries were reported by 19% (n=305) and splash to mucous membrane by 7.2%. Higher rates of percutaneous injuries were observed among nurses (50%), during stitching (30%), and in obstetric and gynecologic department (22%). Health workers aged below 40 years were more likely to experience percutaneous injuries (OR=3.7; 95% CI=1.08-9.13) while previous training in infection prevention was protective (OR=0.52; 95% CI=0.03-0.90). Forty eight percent (n=83) reported the incidents with 20% (n=83) taking PEP against HIV. Percutaneous injuries and splashes are common in Rift Valley Provincial hospital. Preventive measures remain inadequate. Health institutions should have policies, institute surveillance for occupational risks and enhance training of health care workers.


Bone scintigraphy, radiographic survey and prostatic acid phosphatase in patients with prostatic carcinoma. A comparison of sensitivity.
In 62 patients with histologically confirmed carcinoma of the prostate bone scintigraphy, radiographic survey and serum prostatic acid phosphatase determinations were carried out to evaluate the progression of the disease and to compare the relative sensitivity of the diagnostic tools. Thirty-five patients had scintigraphic evidence of skeletal metastases, whereas abnormal X-ray survey and elevated prostatic acid phosphatase levels were found in only 4 and 19 patients, respectively, all of whom had positive scintigraphic findings. Radiographic evidence of metastases was not found in any of the patients with normal scintigraphy, while elevated prostatic acid phosphatase was found in two patients. It is concluded that bone scintigraphy is far more sensitive than either radiographic survey or determination of prostatic acid phosphatases in the diagnosis of skeletal involvement in prostatic carcinoma, and should be the method of choice for this purpose.


Self diffusion of interacting membrane proteins.
A two-dimensional version of the generalized Smoluchowski equation is used to analyze the time (or distance) dependent self diffusion of interacting membrane proteins in concentrated membrane systems. This equation provides a well established starting point for descriptions of the diffusion of particles that interact through both direct and hydrodynamic forces; in this initial work only the effects of direct interactions are explicitly considered. Data describing diffusion in the presence of hard-core repulsions, soft repulsions, and soft repulsions with weak attractions are presented. The effect that interactions have on the self-diffusion coefficient of a real protein molecule from mouse liver gap junctions is also calculated. The results indicate that self diffusion is always inhibited by direct interactions; this observation is interpreted in terms of the caging that will exist at finite protein concentration. It is also noted that, over small distance scales, the diffusion coefficient is determined entirely by the very strong Brownian forces; therefore, as a function of displacement the self-diffusion coefficient decays (rapidly) from its value at infinite dilution to its steady-state interaction-averaged value. The steady-state self-diffusion coefficient describes motion over distance scales that range from approximately 10 nm to cellular dimensions and is the quantity measured in fluorescence recovery after photobleaching experiments. The short-ranged behavior of the diffusion coefficient is important on the interparticle-distance scale and may therefore influence the rate at which nearest-neighbor collisional processes take place. The hard-disk theoretical results presented here are in excellent agreement with lattice Monte-Carlo results obtained by other workers. The concentration dependence of experimentally measured diffusion coefficients of antibody-hapten complexes bound to the membrane surface is consistent with that predicted by the theory. The variation in experimental diffusion coefficients of integral membrane proteins is greater than that predicted by the theory, and may also reflect protein-induced perturbations in membrane viscosity.


Kinetic studies of oestradiol 17 beta-hydroxysteroid dehydrogenase in MCF-7 mammary cancer cells.
The kinetic properties of oestradiol 17 beta-dehydrogenase have been studied in the MCF-7 human breast cancer cell line. The activity of the enzyme was found to be linear with respect to time for at least 2 h and with respect to protein concentrations over the range 40-300 micrograms protein per tube. The enzyme was able to utilize both NAD and NADP as cofactors but at higher concentrations NAD was the more effective. The apparent Km was estimated to be 13.4 microM which is approximately two-fold higher than found for breast tumour tissue.


Validation of International Classification of Diseases coding for bone metastases in electronic health records using technology-enabled abstraction.
The accuracy of bone metastases diagnostic coding based on International Classification of Diseases, ninth revision (ICD-9) is unknown for most large databases used for epidemiologic research in the US. Electronic health records (EHR) are the preferred source of data, but often clinically relevant data occur only as unstructured free text. We examined the validity of bone metastases ICD-9 coding in structured EHR and administrative claims relative to the complete (structured and unstructured) patient chart obtained through technology-enabled chart abstraction. Female patients with breast cancer with ≥1 visit after November 2010 were identified from three community oncology practices in the US. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of bone metastases ICD-9 code 198.5. The technology-enabled abstraction displays portions of the chart to clinically trained abstractors for targeted review, thereby maximizing efficiency. We evaluated effects of misclassification of patients developing skeletal complications or treated with bone-targeting agents (BTAs), and timing of BTA. Among 8,796 patients with breast cancer, 524 had confirmed bone metastases using chart abstraction. Sensitivity was 0.67 (95% confidence interval [CI] =0.63-0.71) based on structured EHR, and specificity was high at 0.98 (95% CI =0.98-0.99) with corresponding PPV of 0.71 (95% CI =0.67-0.75) and NPV of 0.98 (95% CI =0.98-0.98). From claims, sensitivity was 0.78 (95% CI =0.74-0.81), and specificity was 0.98 (95% CI =0.98-0.98) with PPV of 0.72 (95% CI =0.68-0.76) and NPV of 0.99 (95% CI =0.98-0.99). Structured data and claims missed 17% of bone metastases (89 of 524). False negatives were associated with measurable overestimation of the proportion treated with BTA or with a skeletal complication. Median date of diagnosis was delayed in structured data (32 days) and claims (43 days) compared with technology-assisted EHR. Technology-enabled chart abstraction of unstructured EHR greatly improves data quality, minimizing false negatives when identifying patients with bone metastases that may lead to inaccurate conclusions that can affect delivery of care.


Comparison of analytical techniques to quantitate the capsid content of adeno-associated viral vectors.
Adeno-associated virus (AAV) vectors, which contain a DNA transgene packaged into a protein capsid, have shown tremendous therapeutic potential in recent years. An inherent characteristic of the manufacturing process is production of empty capsids that lack the transgene and are therefore unable to provide the intended therapeutic benefit. The effect of empty capsids on clinical outcomes is not well understood, but there are immunogenicity and efficacy concerns, and these empty capsids are considered a product-related impurity. Therefore, empty capsids should be controlled during the manufacturing process and monitored through analytical testing, but there are limited techniques available that are capable of quantifying capsid content and even fewer that are amenable to validation and implementation as registered release tests in a regulated environment. In addition, there is currently not a widely accepted gold standard technique for quantifying capsid content, and the understanding of how the results compare between different orthogonal technologies is limited. The current study utilizes a comprehensive assessment to evaluate diverse analytical techniques for their ability to quantitate capsid content.