Reducing the number of unnecessary routine laboratory tests through education of internal medicine residents.
The Choosing Wisely guidelines advise against ordering routine blood tests for hospitalised patients unless they change management. Unnecessary testing can lead to adverse effects (eg, iatrogenic anaemia, poor sleep quality, risk for infections and increased cost of care). An 8-week quality initiative aimed at reducing unnecessary blood tests was implemented in three internal medicine resident inpatient services. The initiative included a 30 min educational session, reminders prior to rotation and midrotation and posters in work areas that displayed lab pricing and urged judicious testing. Residents were encouraged to justify the purpose of ordering tests in their daily progress notes. Attending physicians were made aware of the initiative. Preintervention and postintervention time points were used to compare key metrics. A >10% decrease between time periods was used as an evaluation criterion. There were 293 patient records reviewed in the preintervention period and 419 in the postintervention period. The two groups were similar in terms of age and gender. Median blood test count (complete blood count/basic metabolic profile/comprehensive metabolic profile) decreased from 4 to 2 tests per patient per day (50 % decrease) after the intervention. The median length of hospital stay decreased from 4.9 to 3.9 days (21% decrease). A decreased percentage of people requiring transfusions was also noted (2016: 6.1%, 2017: 2.9%). The frequency of unnecessary routine blood tests ordered in the hospital can be decreased by educating resident physicians, making them cost conscious and aware of the indications for ordering routine labs. Frequent reminders are needed to sustain the educational benefit.


Quality of acute stroke care improvement framework for the Paul Coverdell National Acute Stroke Registry: facilitating policy and system change at the hospital level.
The Paul Coverdell National Acute Stroke Registry prototypes baseline data collection demonstrated a significant gap in the use of evidenced-based interventions. Barriers to the use of these interventions can be characterized as relating to lack of knowledge, attitudes, and ineffective behaviors and systems. Quality improvement programs can address these issues by providing didactic presentations to disseminate the science and peer interactions to address the lack of belief in the evidence, guidelines, and likelihood of improved patient outcomes. Even with knowledge and intention to provide evidenced-based care, the absence of effective systems is a significant behavioral barrier. A program for quality improvement that includes multidisciplinary teams of clinical and quality improvement professionals has been successfully used to carry out redesign of stroke care delivery systems. Teams are given a methodology to set goals, test ideas for system redesign, and implement those changes that can be successfully adapted to the hospital's environment. Bringing teams from several hospitals together substantially accelerates the process by sharing examples of successful change and by providing strategies to support the behavior change necessary for the adoption of new systems. The participation of many hospitals also creates momentum for the adoption of change by demonstrating observable and successful improvement. Data collection and feedback are useful to demonstrate the need for change and evaluate the impact of system change, but improvement occurs very slowly without a quality improvement program. This quality improvement framework provides hospitals with the capacity and support to redesign systems, and has been shown to improve stroke care considerably, when coupled with an Internet-based decision support registry, and at a much more rapid pace than when hospitals use only the support registry.


FPGA-based digital chaotic anti-interference lidar system.
We use the chaotic signal generated by a field-programmable gate array (FPGA) to establish a digital chaotic pulse lidar system, which can achieve mid-range detection and high ranging accuracy without a complex optical structure. We employ the FPGA to generate random sequences with different modulation rates based on different chaotic iterative equations and initial values. By selecting the initial value and improved logistic equations, we successfully achieve centimeter-level ranging accuracy. Experiments have proved that the digital chaotic lidar system can effectively resist the interference of chaotic signals, square wave signals, and sine wave signals with modulation frequencies of 10 MHz, 100 MHz, 200 MHz, and 1 GHz, showing its strong anti-interference capability.


[Gene delivery using adeno-associated (AAV) vectors].
Gene transfer vectors based on the replication-defective adeno-associated virus (AAV) are emerging as promising vehicles for gene therapeutic approaches for the neurologic disease, cystic fibrosis and cancers. AAV vectors have been used to efficiently transduce genes into cells in vitro and in vivo. However, transduced recombinant AAV vectors are integrated into human chromosomes. Thus we have discussed that the review about the AAV vectors and transduction, and reported the results used AAV vectors for expression of ribozyme.


Evaluation of a safe-sex intervention programme among sex workers in Singapore.
The purpose of this study was to evaluate the effects of a brief intervention programme on STD knowledge, condom use and gonorrhoea incidence among sex workers in Singapore. A controlled before-and-after study design with non-random assignment of sex workers was used, supplemented by multivariate analysis to adjust for baseline differences. Control (n = 221, denoted C1) and experimental (n = 221, denoted E1) groups were interviewed on 2 occasions 3 months apart. Two supplementary groups were interviewed once each at the end of the 3-month period (n = 145 who had received the intervention and n = 151 who had not). Basic knowledge of STD symptoms and HIV transmission was high in all groups. There were misconceptions about casual transmission of HIV which improved dramatically at the second interview for group E1 (from 37-56% correct responses to 82-90%). Overall condom use was high (about 75%) and did not change after the intervention. Gonorrhoea rates were correspondingly low (0.4 episodes/worker/year) and also did not change. This brief intervention improved the STD knowledge of sex workers. However, behaviour as measured by reported condom use and gonorrhoea incidence did not change. Implications for future intervention programmes are discussed.


Regulation of a yeast HSP70 gene by a cAMP responsive transcriptional control element.
HSP70 genes exhibit complex regulation in response to stress and a variety of cellular and developmental events. The SSA3 HSP70 gene of Saccharomyces cerevisiae is activated at the transcriptional level under conditions of nutrient limitation. Analysis of deletions revealed that cis-acting DNA sequences present immediately upstream and downstream of the previously identified heat shock elements (UASHS) mediate this regulation. A 35 bp region of SSA3, distinct from UASHS, contains sequences capable of activating a heterologous promoter following the diauxic shift and in the stationary phase of the yeast life cycle; this region has been designated an upstream activating sequence, UASPDS. Expression driven by UASPDS is regulated by the RAS/cAMP pathway. Reduced cAMP dependent protein kinase activity results in UASPDS dependent activation of the SSA3 promoter while constitutive cAMP dependent protein kinase activity prevents UASPDS mediated transcription, even under growth conditions that would normally result in full activation. Although the heat shock element alone exhibits no UAS activity under conditions in which UASPDS promotes transcription, UASHS interacts positively with UASPDS to mediate high levels of SSA3 transcription in response to nutrient limitation and lowered intracellular cAMP concentration. This interaction is independent of the precise spacing and relative orientation of the two elements.


Increased left ventricular mass in salt-sensitive hypertensive patients.
Clinical, biochemical and echocardiographic characteristics were evaluated from 50 essential hypertensive patients classified asccording to their salt-sensitivity status. Salt-sensitive hypertension was diagnosed by means of ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20 mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake. The remaining 28 (56%) patients were considered as having salt-resistant hypertension. Compared with salt-resistant patients, salt-sensitive ones showed an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and posterior wall thickness (P = 0.0026), without differences in the internal diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed in the salt-sensitive, compared with the salt-resistant hypertensive patients. Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose, creatinine and uric acid did not differ between salt-sensitive and salt-resistant patients. We conclude that, at the same level of BP, salt-sensitive patients exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid profile. These two aspects may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.


Tissue tropisms in group A streptococcal infections.
Group A Streptococcus (GAS) is a human-specific pathogen that is highly prevalent throughout the world. The vast majority of GAS infections lead to a mild disease involving the epithelial surfaces of either the throat or skin. The concept of distinct sets of 'throat' and 'skin' strains of GAS has long been conceived. From an ecological standpoint, the epithelium of the throat and skin are important because it is where the organism is most successful in reproducing and transmitting to new hosts. This article examines key features of the epidemiology, population biology and molecular pathogenesis that underlie the tissue site preferences for infection exhibited by GAS, with an emphasis on work from our laboratory on skin tropisms. Recombinational replacement with orthologous gene forms, following interspecies transfer, appears to be an important genetic step leading up to the exploitation of new niches by GAS.


A study of the efficacy and cost-effectiveness of MRSA screening and monitoring on surgical wards using a new, rapid molecular test (EMMS).
MRSA is a significant contributor to prolonged hospital stay, poor clinical outcome and increased healthcare costs amongst surgical patients. A PCR test has been developed for rapid detection of MRSA in nasal swabs. The aims of this study are (1) to estimate the effectiveness of screening using this rapid PCR tests vs culture in reducing MRSA cross-infection rates; (2) to compare the cost of each testing strategy, including subsequent health care costs; and (3) to model different policies for the early identification and control of MRSA infection in surgical patients. The study is a prospective two-period cross-over study set in 7 surgical wards covering different surgical specialities. A total of 10,000 patients > 18 years will be tested over 16 months. The only difference between the two study periods is the method used for the detection of MRSA in each ward (rapid v conventional culture), with all other infection control practices remaining consistent between the arms. The study has been designed to complement routine practice in the NHS. Outcomes are MRSA cross-infection rates (primary outcome) and need for antibiotic therapy and MRSA-related morbidity. Parallel economic and modelling studies are being conducted to aid in the interpretation of the results and to evaluate the cost-effectiveness of the rapid PCR screening strategy. This paper highlights the design, methods and operational aspects of a study evaluating rapid MRSA screening in the surgical ward setting.


A survey of dumping symptomatology after gastric bypass with or without lesser omental transection.
Lesser omental transection during gastric bypass for morbid obesity may be associated with postoperative dumping. A survey of postoperative symptoms was performed in patients undergoing laparoscopic Roux-en-Y gastric bypass with transection vs. preservation of the lesser omentum. A written questionnaire on dumping symptoms was administered to patients 2 years after laparoscopic Roux-en-Y gastric bypass with or without transection of the lesser omentum. Statistical testing was performed to determine whether the rate of various symptoms was related to the transection of the lesser omentum. The patients without lesser omental transection had significantly less symptoms than the patients with transection for 11 out of the 17 symptoms that were queried (p < 0.05). Ingestion of sweets was associated with dumping symptoms more frequently in the group of transected patients, and this group also had a lower frequency of sweet eating (p < 0.05). This study demonstrated that transection of the lesser omentum during laparoscopic-gastric bypass was associated with more postoperative dumping symptoms compared to bypass with preservation of the lesser omentum. This association may be secondary to a partial vagotomy that may occur if the lesser omentum is transected during gastric bypass.


Synthesis and application of functional peptides as cell nucleus-directed molecules in the treatment of malignant diseases.
The unique functions of biomolecules, including transport across biological membranes (e.g. the cell membrane, the nuclear envelope), modulation of protein function, gene transcription, reconstitution of the malignant transformation, and viral, bacterial and fungal activities underlie a high pharmaceutical potential. The development of combinatorial functional peptide modules in this important area has been slow, in contrast to the rapid development in the synthesis of small biopolymers. The conjugation of a short transmembrane transport peptide module with a cell nucleus address peptide module and with any substance is attractive for preparation of BioShuttle-based peptides because of the well-established automated synthesis of peptides. Variation of the different functional modules for drug targeting and the choice of substances can be combined to create novel bioconjugates with unique properties. This article provides an overview of previous work on the BioShuttle technology and outlines the promising use of this approach in combinatorial peptide synthesis and drug discovery.


Meeting the continuing education needs of rural nurses in role transition.
The community health center (CHC) model of care delivery is gaining acceptance throughout Canada's newly created rural health regions. The resulting change in nursing functions presents a challenge to regional health authorities to ensure the attainment and maintenance of practice competencies. This qualitative study examined strategies used in selected parts of Canada to prepare and support rural diploma-prepared nurses for role transition from acute care into CHCs. In light of CHC nurses' increased degree of autonomy, skill level, and focus on community wellness, the findings indicate a need for additional educational preparation and supportive strategies for transitioning nurses. Regions should educate the public and staff about the principles of primary health care, population health, and factors that determine health to help stakeholders understand their community, the current gaps in service delivery, and the role of CHC nurses. Key players at the provincial level should work together to address competency issues and continuing education needs of nurses in career transition.


Molecular crystals vs. superatomic lattice: a case study with superalkali-superhalogen compounds.
Using a first-principles approach, we study the assembly of atomically-precise cluster solids with atomic precision. The aims are to create binary assemblies of clusters through charge transfer between neutral molecular clusters, and employing intercluster electrostatic attraction as a driving force for co-assembly. We combined pairs of complementary clusters in which one cluster is electron-donating (superalkali) and the other is electron-accepting (superhalogen). From the analysis of the binding energy between superatomic counterparts, charge transfer, and the relative size of the clusters, we analyze the resulting structures as either molecular crystals or superatomic lattices. We demonstrate that the substitution of a single atom can result in minor changes to the crystal structure of the binary solids or entirely new packing structures. The [N4Mg6Li]+[AlCl4]-, [N4Mg6Na]+[AlCl4]-, [N4Mg6K]+[AlCl4]-, [N4Mg6Li]+[AlF4]-, [N4Mg6Na]+[AlF4]-, and [N4Mg6K]+[AlF4]- compounds all form the same close-packed superatomic lattice structure through halogen bonding, with subtle differences in the orientation of the superatoms. These salts may also form molecular crystals where clusters are held to one another by electrostatic interactions. Our results emphasize how the structure of superatomic solids can be tuned upon single atom substitution.


Peyssonnosides A-B, Unusual Diterpene Glycosides with a Sterically Encumbered Cyclopropane Motif: Structure Elucidation Using an Integrated Spectroscopic and Computational Workflow.
Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A-B (1-2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.01,10.05,9] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.


Effect of lead intoxication on calcium homeostasis and calcium-mediated cell function: a review.
The interaction between lead and essential metals is a complex, well recognized, but poorly understood phenomenon. Dietary deficiencies or excesses of certain essential metals may alter the absorption, elimination, or dose response of lead. Lead, in turn, may alter the homeostasis and function of essential metals. This review will be limited to the effect of lead on calcium, an essential metal with elaborate systemic and cellular homeostatic mechanisms and innumerable second messenger and coupling-factor functions. Lead may ultimately perturb calcium-regulated or calcium-mediated functions (a) directly by interfering with calcium transport or storage processes, e.g., Ca2+ transport proteins, calcium gates, etc.; (b) indirectly by altering cell functions required for calcium homeostasis, e.g., energy production, plasma membrane permeability, etc.; (c) by substitution of Pb2+ for Ca2+ at functionally important calcium binding sites, e.g., calmodulin. While any individual study may not provide adequate experimental verification of the causal role of perturbations of calcium metabolism and function as the primary toxic lesion of lead intoxication, the collective observations of many studies do strongly support lead-calcium interactions as an important functional lesion in lead intoxicated organelles, cells, tissues, and organ systems.


Machine learning-assisted soot temperature and volume fraction fields predictions in the ethylene laminar diffusion flames.
Inferring local soot temperature and volume fraction distributions from radiation emission measurements of sooting flames may involve solving nonlinear, ill-posed and high-dimensional problems, which are typically conducted by solving ill-posed problems with big matrices with regularization methods. Due to the high data throughput, they are usually inefficient and tedious. Machine learning approaches allow solving such problems, offering an alternative way to deal with complex and dynamic systems with good flexibility. In this study, we present an original and efficient machine learning approach for retrieving soot temperature and volume fraction fields simultaneously from single-color near-infrared emission measurements of dilute ethylene diffusion flames. The machine learning model gathers information from existing data and builds connections between combustion scalars (soot temperature and volume fraction) and emission measurements of flames. Numerical studies were conducted first to show the feasibility and robustness of the method. The experimental Multi-Layer Perceptron (MLP) neural network model was fostered and validated by the N2 diluted ethylene diffusion flames. Furthermore, the model capability tests were carried out as well for CO2 diluted ethylene diffusion flames. Eventually, the model performance subjected to the Modulated Absorption/Emission (MAE) technique measurement uncertainties were detailed.


Stereotactic multiple arc radiotherapy. III--Influence of treatment of arteriovenous malformations on associated epilepsy.
Although radiosurgery obliterates the majority of arteriovenous malformations (AVMs) and cures patients of further haemorrhage, the perceived beneficial effect on the epilepsy associated with it is less certain. Two recent publications suggest that radiosurgery benefits the associated epilepsy. In a consecutive series of 101 AVM patients presenting for radiosurgery to St Bartholomew's Hospital, 24 had a history of fits; 16 were evaluable for analysis of fit control. Fifteen of the sixteen patients (94%) had improvement in fit control, 10/16 (63%) becoming fit free. This improvement appeared to correlate with response to treatment on follow-up angiography and in 11/15 patients this occurred with no change or a reduction in anticonvulsant in medication. No patient suffered a deterioration in the epilepsy. These data are discussed in the context of the only two previous reports in the literature and the mechanisms of action of treatment.


Distribution of Ochlerotatus togoi along the Pacific coast of Washington.
Before this study, the mosquito Ochlerotatus (Finlaya) togoi (Theobald) had been reported from only 2 locations within the continental United States, both of which were documented in Washington State. This study used active and passive surveillance to determine the current distribution of Oc. togoi along the Pacific Coast of Washington. Results of the study show that small, but stable, populations of Oc. togoi exist in the northern San Juan Island region of Puget Sound. Geological formations in this region are conducive to rock holes and support populations of Oc. togoi. No members of Oc. togoi were found on the southwestern Washington coast, the coast of the Olympic Peninsula, or in the lower Puget Sound.


A joint x-ray and neutron study on amicyanin reveals the role of protein dynamics in electron transfer.
The joint x-ray/neutron diffraction model of the Type I copper protein, amicyanin from Paracoccus denitrificans was determined at 1.8 A resolution. The protein was crystallized using reagents prepared in D(2)O. About 86% of the amide hydrogen atoms are either partially or fully exchanged, which correlates well with the atomic depth of the amide nitrogen atom and the secondary structure type, but with notable exceptions. Each of the four residues that provide copper ligands is partially deuterated. The model reveals the dynamic nature of the protein, especially around the copper-binding site. A detailed analysis of the presence of deuterated water molecules near the exchange sites indicates that amide hydrogen exchange is primarily due to the flexibility of the protein. Analysis of the electron transfer path through the protein shows that residues in that region are highly dynamic, as judged by hydrogen/deuterium exchange. This could increase the rate of electron transfer by transiently shortening through-space jumps in pathways or by increasing the atomic packing density. Analysis of C-HX bonding reveals previously undefined roles of these relatively weak H bonds, which, when present in sufficient number can collectively influence the structure, redox, and electron transfer properties of amicyanin.


Express with caution: Epitope tags and cDNA variants effects on hERG channel trafficking, half-life and function.
Genetic mutations in KCNH2, which encodes hERG, the alpha subunit of the potassium channel responsible for the IKr current, cause long QT syndrome (LQTS), an inherited cardiac arrhythmia disorder. Electrophysiology techniques are used to correlate genotype with molecular phenotype to determine which mutations identified in patients diagnosed with LQTS are disease causing, and which are benign. These investigations are usually done using heterologous expression in cell lines, and often, epitope fusion tags are used to enable isolation and identification of the protein of interest. Here, we demonstrate through electrophysiology techniques and immunohistochemistry, that both N-terminal and C-terminal myc fusion tags may perturb hERG protein channel expression and kinetics of the IKr current. We also characterize the impact of 2 previously reported inadvertent cDNA variants on hERG channel expression and half-life. Our results underscore the importance of careful characterization of the impact of epitope fusion tags and of confirming complete sequence accuracy prior to genotype-phenotype studies for ion channel proteins such as hERG.


Role of PIWI-like 4 in modulating neuronal differentiation from human embryonal carcinoma cells.
PIWI homologs constitute a subclass of the Argonaute family. Traditionally, they have been shown to associate with a specific class of small RNAs, piRNAs, to suppress transposable elements and protect genomic integrity in germ cells. Recent studies imply that PIWI proteins may also exert important biological functions in somatic contexts, including the brain. However, their exact role in neural development remains unknown. Hence we investigated whether PIWI proteins are involved in neuronal differentiation. By using an established cell model for studying neurogenesis, NTera2/D1 (NT2) cells, we found that a particular PIWI homolog, PIWIL4 was increasingly upregulated throughout the course of all-trans retinoic acid (RA)-mediated neuronal differentiation. During this process, PIWIL4 knockdown led to partial recovery of embryonic stem cell markers, while suppressing RA-induced expression of neuronal markers. Consistently, PIWIL4 overexpression further elevated their expression levels. Furthermore, co-immunoprecipitation revealed an RA-induced interaction between PIWIL4 and the H3K27me3 demethylase UTX. Chromatin immunoprecipitation showed that this interaction could be essential for the removal of H3K27me3 from the promoters of RA-inducible genes. By a similar mechanism, PIWIL4 knockdown also suppressed the expression of PTN and NLGN3, two important neuronal factors secreted to regulate glioma activity. We further noted that the conditioned medium collected from PIWIL4-silenced NT2 cells significantly reduced the proliferation of glioma cells. Thus, our data suggest a novel somatic role of PIWIL4 in modulating the expression of neuronal genes that can be further characterized to promote neuronal differentiation and to modulate the activity of glioma cells.


Women's alcohol consumption and risk for alcohol-exposed pregnancies in Russia.
Alcohol-exposed pregnancies (AEP) are the direct cause of fetal alcohol spectrum disorders (FASD). This study examines drinking patterns among pregnant and non-pregnant women of childbearing age in Russia, a country with one of the highest levels of alcohol consumption in the world. Cross-sectional survey. Seven public women's clinics in two locations: St Petersburg (SPB) and the Nizhny Novgorod region (NNR). A total of 648 pregnant and non-pregnant childbearing-age women. A face-to-face structured interview assessed alcohol consumption, pregnancy status/possibility of becoming pregnant and consumption before and after pregnancy recognition. Eighty-nine per cent of non-pregnant women reported consuming alcohol and 65% reported binge drinking in the past 3 months; 47% in NNR and 28% in SPB reported binges at least monthly. Women who might become pregnant consumed alcohol similarly to women who were not likely to become pregnant, and 32% of women in SPB and 54% in NNR were categorized as at risk for AEP. There was a significant decline in drinking after pregnancy identification. Twenty per cent of pregnant women reported consuming alcohol and 6% in SBP (none in NNR) reported binge drinking; however, a high prevalence of binge drinking was found among women who might become pregnant or who were trying to conceive. Russian women substantially reduce drinking after pregnancy recognition compared to pre-pregnancy levels. No reductions were found prior to pregnancy recognition, either when a woman might become pregnant or when she was trying to conceive. The pre-conception period presents a risk window and, therefore, a prevention opportunity.


Interaction of horse cytochrome c with the photosynthetic reaction center of Rhodospirillum rubrum.
Mitochondrial cytochrome c (horse), which is a very efficient electron donor to bacterial photosynthetic reaction centers in vitro, binds to the reaction center of Rhodospirillum rubrum with an approximate dissociation constant of 0.3-0.5 microM at pH 8.2 and low ionic strength. The binding site for the reaction center is on the frontside of cytochrome c which is the side with the exposed heme edge, as revealed by differential chemical acetylation of lysines of free and reaction-center-bound cytochrome c. In contrast, bacterial cytochrome c2 was found previously to bind to the detergent-solubilized reaction center through its backside, i.e., the side opposite to the heme cleft [Rieder, R., Wiemken, V., Bachofen, R., and Bosshard, H. R. (1985). Biochem. Biophys. Res. Commun. 128, 120-126]. Binding of mitochondrial cytochrome c but not of mitochondrial cytochrome c2 is strongly inhibited by low concentrations of poly-L-lysine. The results are difficult to reconcile with the existence of an electron transfer site on the backside of cytochrome c2.


The Clinical Profile and Natural History of Patients Who Fail Screening for Transcatheter Mitral Valve Replacement: Rationale and Design of the Prospective Multicenter Mitral Valve Screening Survey (MVSS).
Mitral valve disease is insidious and associated with a decreased quality of life and survival over time. Despite surgery being the standard of care, many patients are at prohibitive surgical risk. Furthermore, a substantial proportion of patients with symptomatic mitral valve disease fail stringent screening criteria for transcatheter mitral valve replacement (TMVR). The natural history of patients who fail screening is not well-characterized, and data are limited on the reasons for screen failure in this population. The Mitral Valve Screening Survey (MVSS) seeks to detail the clinical profile and natural history of patients who fail screening for TMVR. The MVSS is a prospective, multicenter registry enrolling up to 1000 consecutive subjects who, after screening for TMVR, are deemed not to be candidates. Subjects will be followed for 30 days after failing screening for TMVR and annually for up to 5 years with clinical evaluations. The primary study endpoint of the MVSS registry is all-cause mortality at 1 year. Additional secondary endpoints include all-cause mortality, hospitalizations, subsequent mitral valve intervention (transcatheter or surgical), reason for screen failure, and quality-of-life assessments at 30 days and annually up to 5 years of follow-up. The MVSS registry is the first prospective multicenter study to characterize the clinical and anatomical profile of patients who fail screening for TMVR while providing longitudinal clarification on the natural history and outcomes of these patients. CLINICAL TRIAL REGISTRATION: Mitral Valve Screening Survey (MVSS), https://clinicaltrials.gov/ct2/show/NCT04736667, NCT04736667.


Absorption of visible radiation in atmosphere containing mixtures of absorbing and nonabsorbing particles.
Recent measurements of the single-scattering albedo omega(0) of tropospheric aerosols indicate the presence of a strongly absorbing material which has tentatively been identified as graphitic carbon (soot). Theoretical calculations, based on several different models of the way in which soot might be mixed with other aerosol materials, show that a minimum of 20% soot by volume is necessary to achieve the observed urban value of omega(0) = 0.6. Rural values of the order of 0.8 can be accounted for with 1-5% soot by volume. These same values of omega can be produced by similar amounts of the iron oxide magnetite, which is shown to be virtually indistinguishable from soot by optical measurements performed on bulk samples. Calculations of phase functions for various mixtures of soot also indicate the difficulty of determining aerosol composition by optical scattering techniques. The climatic effects of these absorbing aeorosols are computed using a simple one-layer model, and the results suggest that heating rates in urban pollution layers may be of the order of 4 K/day.


The Relationship between Dietary Patterns with Blood Pressure in Iranian Army Staffs.
Hypertension is one of the most common noncommunicable diseases in the world. One of the most effective factors on blood pressure (BP) is nutrition. The aim of this study was to examine the relationship between dietary patterns and BP among military staffs. The study was carried out among 405 military staffs between 22 and 51 years old. Demographic, anthropometric information, and BP of participants were evaluated by standard methods. The dietary intakes were collected using a food frequency questionnaire (FFQ). Dietary patterns were identified using a posteriori method, factor analysis, and based on the FFQ. To check the relationship between BP and dietary patterns, we used multivariate linear regression in different models, relationship were adjusted for Age, sex, marital, smoking, income, body mass index, waist-to-hip ratio, family history of hypertension, energy intake, and physical activity level. Two dominant dietary patterns were identified in the participants: Healthy and western pattern. The association of dietary patterns with systolic BP (SBP) and diastolic BP (DBP) was exhibited in different models. There was no relationship between SBP and DBP with healthy pattern (P = 0.269 and P = 0.638, respectively) and western pattern (P = 0.648 and P = 0.315, respectively) after adjustments. Our findings indicated that dietary patterns did not have any significant relationship with SBP and DBP after adjustment for confounders in the healthy military. To identify the dietary patterns associated with BP in healthy military, more strong design studies and more participants should be conducted in the future.


Contribution of brain CT in the diagnosis of tuberculous meningitis: a case report from Djibouti.
Tuberculous meningitis, a serious disease with high mortality and morbidity, remains frequent in countries with endemic tuberculosis. Its non-specific presentation often delays the introduction of appropriate treatment. Its definitive diagnosis requires isolation of Mycobacterium tuberculosis from cerebrospinal fluid, although this test may be negative without conclusively ruling out this diagnosis. A presumptive diagnosis should be reached as soon as possible through a body of clinical evidence, including the lumbar puncture findings. Brain computed tomography (CT) with and without contrast medium injection is helpful for the diagnosis of tuberculous meningitis and its complications. We discuss the features of CT and their value in relation to a case of tuberculous meningitis in Djibouti, as well as the role of CT in managing this disease.


[Long-Term Results of Antihypertensive Therapy in Patients With Diabetes].
The article discusses the results of observational studies to evaluate the efficacy of antihypertensive drugs in patients with diabetes who participated in the randomized clinical trials. The role of such studies to clarify the tactics of application of antihypertensive drugs in patients with diabetes. The possible conditions that ensure a lasting effect of antihypertensive drugs, in particular the choice of drugs belonging to the class definition.


A model study toward the total synthesis of N-deacetyllappaconitine.
[reaction: see text] A model study leading to the preparation of the AEF rings of N-deacetyllappaconitine is described. The conjugate addition to the alpha-alkyl cyclohexenone 10 proceeded with high diastereocontrol. The Mannich cyclization of 16 to 4 was accomplished by heating with Rexyn-300 and Na(2)SO(4).


Use of a Dental Vibration Tool to Reduce Pain From Digital Blocks: A Randomized Controlled Trial.
The infiltration of local anesthetic is consistently described as painful by patients. Vibration anesthesia has been studied in the dental literature as a promising tool to alleviate the pain from dental nerve blocks. Many of these studies used a specific device, the DentalVibe. To date, there have not been any studies applying this technology to digital blocks of the hand in human subjects. We hypothesized that the use of microvibratory stimulation during digital blocks of the hand would decrease pain reported by patients. This was a randomized controlled trial of consenting adult emergency department patients who received digital block anesthesia for hand digit therapy when study authors were present. The study period was 24 months at an academic emergency department. A sample size of 50 injections (25 subjects) was necessary for a power of 80% to detect a mean difference of 2 (SD, 2.5) on the pain scale. A 2-sided dorsal injection approach was used for digital blocks. Subjects were randomized to either intervention (vibration) for the first injection or sham (device off). Both intervention and sham were held in place for 5 seconds prior to and during injection. Subjects were given 2 mL of 1% lidocaine and asked to rate the injection pain on a 1- to 10-point scale. This process was then repeated. Mean pain scores were compared using paired t tests. Our primary outcome was the difference in mean injection pain score between sham versus intervention groups. There were 25 patients in the study group (mean age, 35.52 years [range, 18-58 years]; 8 females; 11 non-Hispanic white). The mean injection pain score in the sham group was 4.28 (95% confidence interval [CI], 3.14-5.42), and in the intervention group, the mean pain score was 2.52 (95% CI, 1.62-3.42). For the primary outcome, the mean injection pain score difference between the sham and intervention groups across all subjects was 1.76 (95% CI, 0.49-3.03; P = 0.009). The mean injection pain score differences were similar across groups: females versus males (0.24; 95% CI, -2.31 to 2.79; P = 0.85), non-Hispanic whites versus other races (0.76; 95% CI, -1.78 to 3.29; P = 0.54), intervention first versus sham first (-0.43; 95% CI, -3.25 to 2.40; P = 0.75). Our results show a statistically significant difference in mean injection pain score during digital block of the hand when the DentalVibe device is used for vibration anesthesia. Larger studies are warranted to confirm our findings.


Prenatal diagnosis and fetal pathology of Tay-Sachs disease.
In 6 cases of high risk pregnancies for Tay-Sachs disease, prenatal diagnosis was successfully carried out by examining hexosaminidase A activity in the supernatant of amniotic fluid and the uncultured and cultured amniotic fluid cells. In 5 out of 6 cases, the activity of hexosaminidase A was found to be within normal or heterozygous levels. They continued their pregnancies and were delivered of healthy children. In the remaining 1 case, the activity was undetected. Her pregnancy was terminated at the 23rd week of gestation. There was no activity of hexosamindase A in the brain and liver from the aborted fetus. A moderate increase in GM2 ganglioside was found in the brain. Electron-microscopic findings revealed membranous cytoplasmic bodies in the spinal ganglion cells as well as in the nerve cells of the retina. These biochemical and histological findings of Tay-Sachs fetus suggest that the disease proceeds early in fetal period. It was found that the cultured amniotic fluid cells was the most reliable material for the prenatal diagnosis of Tay-Sachs disease, because the values of hexoxaminidase A in the cultured cells were well in accord with those in serum from the consequently bord children. Hexosaminidase pattern in the supernatant of amniotic fluid on DEAE-cellulose columnchromatogram showed a distinct difference between homozygote, heterozygote and normal. This procedure also may be useful for prenatal diagnosis of Tay-Sachs disease.


Herniated thoracic disks: treatment and outcome.
The optimal surgical approach for thoracic disk herniation is controversial, and long-term follow-up is poorly documented. We retrospectively reviewed the records of 31 patients who underwent surgery for herniated thoracic disks at our institution during a 17-year period (1975-1992). Two patients had multiple disk herniations; 16 of 33 herniated disks occurred at or below the T10-11 level. There were three surgical approaches to diskectomy: laminectomy in four patients, transpedicular surgery in 12, and costotransversectomy in 15. Weakness resolved postsurgery in nine of 18 patients. One patient transiently deteriorated neurologically after a laminectomy, three had wound infections, and two required second operations for their herniated disks. Postsurgery half the patients with symptoms continued to have pain or weakness.


Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.
Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.


Nutrient consumption and production of isoflavones in bioreactor cultures of Pueraria lobata (Willd).
This paper reports the successful culture of Pueraria lobata (Willd.) suspension cells in a bioreactor. In vitro culture of this Chinese herb has potential as an alternative production method for industrial applications. Calli of P. lobata obtained from leaf explants were cultured in a 5.0 L bioreactor for two weeks. During this period, the pH of the medium declined from 5.8 to 4.5. By the end of the run about 70% of the sugars and reducing sugars and about 50% of nitrate was consumed. Almost 70% of inorganic phosphate and about 80% of the iron was exhausted. The bioreactor results indicated an isoflavone yield of 328.9 microg/ml, with an increase of about 1.77 fold. The yield of puerarin increased about 2.42 fold and reached 73.4 microg/ml in the bioreactor culture.


Pathogenetic studies of motor fluctuations in Parkinson's disease.
Pharmacokinetic and pharmacodynamic mechanisms for levodopa have been studied in relation to the pathogenesis of the motor fluctuations which complicate advanced Parkinson's disease. Since levodopa clearance from the general circulation was found to be similar in patients with wearing-off or on-off phenomena and those with a stable response to levodopa, peripheral pharmacokinetic factors are unlikely to be involved. Efficacy half-time for levodopa, on the other hand, was significantly reduced in patients with mainly wearing-off fluctuations in comparison to those manifesting a stable response to oral levodopa; individuals with predominantly on-off phenomenon had an even more extreme reduction in the duration of the antiparkinsonian action of levodopa. Conversion from oral to intravenous levodopa treatment immediately stabilized plasma levodopa levels in both the wearing-off and on-off groups; motor variability also decreased, especially in those with wearing-off phenomenon. During 11 days of continuous intravenous levodopa therapy, additional reductions in motor fluctuations occurred in both groups, but at a significantly faster rate in patients with wearing-off than in those with on-off responses. These results suggest that wearing-off phenomenon may arise as a consequence of the degeneration of dopamine terminals due to natural disease progression with a resultant inability to buffer variations in levodopa availability; on-off phenomenon, may reflect additional postsynaptic dopamine receptor dysregulation, possibly in response to the resultant, nonphysiologic fluctuations in synaptic dopamine.


Dirac cones in a snub trihexagonal tiling lattice with reflective symmetry breaking.
The present models of the two-dimensional (2D) Dirac materials always have reflective symmetry, but the essentiality has never been proved. Here we present an exceptional case: a snub trihexagonal tiling (STT) lattice without reflective symmetry. We demonstrate the existence of Dirac cones in this reflection-symmetry-free lattice by using a single-orbital tight-binding (TB) Hamiltonian. The SST lattice is also topologically nontrivial, because the Dirac cone can be gapped by spin-orbit coupling (SOC) effect associated with robust gapless edge states. Using first-principles calculations, we predict a promising candidate 2D material, Be3C4 monolayer to realize this toy model. The Fermi velocities in this unique lattice are even higher than that in graphene. The stability and plausibility of the Be3C4 monolayer are verified by positive phonon modes, molecular dynamical simulations and mechanical criteria. This work eliminates the need for reflective symmetry in 2D Dirac materials, opening an avenue for designing new 2D Dirac materials.


Dual-Emission Reverse Change Ratio Photoluminescence Sensor Based on a Probe of Nitrogen-Doped Ti3C2 Quantum Dots@DAP to Detect H2O2 and Xanthine.
Titanium carbide quantum dots (Ti3C2 QDs) derived from two-dimensional (2D) Ti3C2Tx (MXene) are the rising-star material recently. Herein, nitrogen-doped Ti3C2 QDs (N-Ti3C2 QDs) were synthesized via a solvothermal method. The obtained N-Ti3C2 QDs exhibited excitation-dependent photoluminescence, antiphotobleaching, and dispersion stability. Furthermore, by combining the N-Ti3C2 QDs and DAP (2,3-diaminophenazine, the oxidative product of o-phenylenediamine) as a composite nanoprobe (N-Ti3C2 QDs@DAP), we developed a dual-emission reverse change ratiometric sensor to quantitatively monitor H2O2 based on photoinduced electron-transfer effects, where N-Ti3C2 QDs acted as the donor and DAP as the acceptor. On the basis of the xanthine converting into H2O2 through the catalysis of xanthine oxidase, the N-Ti3C2 QDs@DAP nanoprobe was also exploited for xanthine sensing. As a result, the proposed assay was demonstrated to be highly sensitive for H2O2 and xanthine with detection limits of 0.57 and 0.34 μM, respectively. In a word, we have investigated the application of N-Ti3C2 QDs in H2O2 and xanthine sensing and opened a new and exciting avenue for the N-Ti3C2 QDs in biosensing.


Bicycle injury documentation before and after charting intervention.
Previous studies have shown that routinely completed free-text emergency department medical records contain limited information necessary for injury surveillance. We instituted an injury documentation sheet into our emergency department records to evaluate the impact on completeness of bicycle injury documentation rates. The pretest/posttest study design used E-codes to identify bicycle-related injuries. A standardized data collection tool was utilized to review these charts. Time periods before (January 1 to December 31, 2004) and after (January 1 to June 30, 2005) institution of a standardized documentation sheet were reviewed. Data were entered into the computer program, Epistat, and scores were used for comparison. Initial review (n = 667) revealed mean age of patients 8.6 years, with 46% African American and 67% male. Helmet usage was documented in 49% of the charts (81 were wearing helmets; 245 were not wearing helmets). Mechanism of injury was documented as bicycle alone in 587, bicycle versus car in 13, and bicycle versus stationary object in 64. After implementation of an injury data sheet (n = 205), it was found that the mean age was 9.24 years, with 51% African American and 43% male. Helmet use was documented in 77% of cases (26 wearing helmets; 132 not wearing). Mechanism was documented as bicycle alone in 125, bicycle versus car in 66, and bicycle versus stationary object in 14. Helmet use was much more frequently documented after the initiation of an injury documentation reminder sheet (z = 6.97; P < 0.001; 95% confidence interval, 20.2-35.8). The use of standard injury documentation prompts increased completeness of documentation. With improved documentation, more accurate injury surveillance can be performed.


Computational thinking in life science education.
We join the increasing call to take computational education of life science students a step further, beyond teaching mere programming and employing existing software tools. We describe a new course, focusing on enriching the curriculum of life science students with abstract, algorithmic, and logical thinking, and exposing them to the computational "culture." The design, structure, and content of our course are influenced by recent efforts in this area, collaborations with life scientists, and our own instructional experience. Specifically, we suggest that an effective course of this nature should: (1) devote time to explicitly reflect upon computational thinking processes, resisting the temptation to drift to purely practical instruction, (2) focus on discrete notions, rather than on continuous ones, and (3) have basic programming as a prerequisite, so students need not be preoccupied with elementary programming issues. We strongly recommend that the mere use of existing bioinformatics tools and packages should not replace hands-on programming. Yet, we suggest that programming will mostly serve as a means to practice computational thinking processes. This paper deals with the challenges and considerations of such computational education for life science students. It also describes a concrete implementation of the course and encourages its use by others.


Reconciling irrigated food production with environmental flows for Sustainable Development Goals implementation.
Safeguarding river ecosystems is a precondition for attaining the UN Sustainable Development Goals (SDGs) related to water and the environment, while rigid implementation of such policies may hamper achievement of food security. River ecosystems provide life-supporting functions that depend on maintaining environmental flow requirements (EFRs). Here we establish gridded process-based estimates of EFRs and their violation through human water withdrawals. Results indicate that 41% of current global irrigation water use (997 km3 per year) occurs at the expense of EFRs. If these volumes were to be reallocated to the ecosystems, half of globally irrigated cropland would face production losses of ≥10%, with losses of ∼20-30% of total country production especially in Central and South Asia. However, we explicitly show that improvement of irrigation practices can widely compensate for such losses on a sustainable basis. Integration with rainwater management can even achieve a 10% global net gain. Such management interventions are highlighted to act as a pivotal target in supporting the implementation of the ambitious and seemingly conflicting SDG agenda.


The C4 and C2 but not C1 components of complement are responsible for the complement activation triggered by the Ra-reactive factor.
Ra-reactive factors (RaRF) are the name of a group of C-dependent bactericidal factors that bind specifically to Ra chemotype strains of Salmonella. These factors are present in the sera of a wide variety of vertebrates and have common characteristics. Here we investigate the C components required for the C activation induced by mouse RaRF, by using hemolysis of Ra LPS-coated E (ELPS) as a model system. It was found that C1-depleted and C1q-depleted sera were as effective as the undepleted serum in the lysis of ELPS sensitized with RaRF. Addition of the C1 component or C1q subcomponent to the depleted sera did not increase the effect. On the other hand, C4 and C2 components were found to be essential for the lysis of RaRF-sensitized ELPS. Activities of C4 and C2 remained on the sensitized cells even after washing the cells, suggesting that the classical C3 convertase, C4b2a, is generated on the RaRF-sensitized ELPS.


eMental health experiences and expectations: a survey of youths' Web-based resource preferences in Canada.
Due to the high prevalence of psychological disorders and the lack of access to care among Canadian youth, the development of accessible services is increasingly important. eMental Health is an expanding field that may help to meet this need through the provision of mental health care using technology. The primary goals of the study are to explore youth experiences with traditional and online mental health resources, and to investigate youth expectations for mental health websites. A Web-based survey containing quantitative and qualitative questions was delivered to youth aged 17-24 years. Participants were surveyed to evaluate their use of mental health resources as well as their preferences for various components of a potential mental health website. A total of 521 surveys were completed. Most participants (61.6%, 321/521) indicated that they had used the Internet to seek information or help for feelings they were experiencing. If they were going through a difficult time, 82.9% (432/521) of participants were either "somewhat likely" or "very likely" to use an information-based website and 76.8% (400/521) reported that they were either "somewhat unlikely" or "very unlikely" to visit social media websites for information or help-seeking purposes during this time. Most (87.7%, 458/521) participants rated their online privacy as very important. Descriptions of interventions and treatments was the most highly rated feature to have in a mental health-related website, with 91.9% (479/521) of participants regarding it as "important" or "very important". When presented a select list of existing Canadian mental health-related websites, most participants had not accessed any of the sites. Of the few who had, the Canadian Mental Health Association website was the most accessed website (5.8%, 30/521). Other mental health-related websites were accessed by only 10.9% of the participants (57/521). The findings suggest that despite interest in these tools, current eMental Health resources either do not meet the needs of or are not widely accessed by youth with mental health problems. In order to improve access to these resources for Canadian youth, Web-based platforms should provide information about mental health problems, support for these problems (peer and professional), and information about resources (self-help as well as ability to locate nearby resources), while protecting the privacy of the user. These findings will not only assist in the development of new mental health platforms but may also help improve existing ones.


The efficacy and safety of Laminaria japonica for metabolic syndrome: A protocol for systematic review.
Metabolic syndrome is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Conventional treatments for metabolic syndrome have limitations due to their nonselectivity, drug resistance, and low bioavailability. The brown seaweed Laminaria japonica (LJP) is a traditional medicine and food in Asia that has shown pharmacological and biochemical properties favorable to the prevention and treatment of lifestyle-related diseases. We will systematically review randomized controlled trials and in vivo preclinical studies evaluating the efficacy and safety of LJP as a useful treatment for metabolic syndrome. The following databases will be searched from inception to September 2021: MEDLINE (via PubMed), EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials and in vivo preclinical studies that analyzed LJP for the prevention and treatment of metabolic syndromes will be included. The outcome measures will include body composition, dietary habit scores, serum lipid profiles, daily nutrient intake, quality of life, number of microbiomes, gastrointestinal symptoms, and bowel function. Studies comparing LJP with any type of control intervention will be included. Data extraction using Review Manager version 5.3 and risk of bias assessment using the Cochrane Collaboration's tool for assessing risk of bias will be performed by 2 independent assessors. This systematic review will provide evidence confirming the efficacy and safety of LJP in the treatment of metabolic syndrome. Ethical approval was not required, as this study protocol does not include any personal information of the participants. DOI 10.17605/OSF.IO/G2BQK (https://osf.io/g2bqk).


Premature B-cell senescence as a consequence of chronic immune activation.
Similar features between the immune system of healthy elderly people and of younger individuals subjected to conditions of chronic immune activation are progressively being observed. This is raising the hypothesis that chronic immune activation may cause the premature aging of the immune system. Here we dissect this theory by comparing changes occurring to B-cells during healthy aging to the ones occurring during chronic immune activation in younger individuals. Moreover, we discuss how these changes may affect or predict response to vaccination in immune compromised individuals.


Two regimes of HIV/AIDS: The MMWR and the socio-political construction of HIV/AIDS as a 'black disease'.
Over the course of the HIV/AIDS epidemic, black Americans have become a central target of US public health prevention efforts. And today, HIV/AIDS is understood to disproportionately affect black Americans. This markedly contrasts with knowledge about the disease and efforts to prevent it in the first decade of the epidemic in the US, when expert and lay understandings and responses centred on white gay males. This article demonstrates that explaining these historical reversals as purely reflective of epidemiological data - or best knowledge available - is insufficient. Drawing on the concept disease regimes and utilising a discursive analysis of epidemiological results and editorial commentary published from 1981 to 1994 in the Morbidity and Mortality Weekly Reports (MMWR), this article argues for a socio-political explanation for the changing colour of HIV/AIDS. That is, it scrutinises institutional and discursive practices that within the HIV/AIDS prevention field and disease discourse constituted a 'regime of black American exclusion' (1981-1992) and a 'regime of black American inclusion (1993-present day).


Recent advances in salmonellosis treatment based on in vitro susceptibilities.
Chloramphenicol-resistant strains of Salmonella typhi (MIC 60 micrograms/ml), chloramphenicol and ampicillin-resistant strains of Salmonella typhimurium as well as multiresistant strains of various salmonella serotypes were found to be very sensitive to cephradine (MIC 0.078-0.625 micrograms/ml). Ten patients with Salmonella typhi bacteremia were successfully treated with cephradine; all the patients' strains were chloramphenicol-resistant. Cephradine appears to warrant further clinical trial for the treatment of salmonellosis.


Cytokinins beyond plants: synthesis by Mycobacterium tuberculosis.
Mycobacterium tuberculosis (M. tuberculosis) resides mainly inside macrophages, which produce nitric oxide (NO) to combat microbial infections. Earlier studies revealed that proteasome-associated genes are required for M. tuberculosis to resist NO via a previously uncharacterized mechanism. Twelve years later, we elucidated the link between proteasome function and NO resistance in M. tuberculosis in Molecular Cell, 57 (2015), pp. 984-994. In a proteasome degradation-defective mutant, Rv1205, a homologue of the plant enzyme LONELY GUY (LOG) that is involved in the synthesis of phytohormones called cytokinins, accumulates and as a consequence results in the overproduction of cytokinins. Cytokinins break down into aldehydes that kill mycobacteria in the presence of NO. Importantly, this new discovery reveals for the first time that a mammalian bacterial pathogen produces cytokinins and leaves us with the question: why is M. tuberculosis, an exclusively human pathogen, producing cytokinins?


The effects of long-term grazing exclosures on range plants in the Central Anatolian Region of Turkey.
Over the last fifty years, almost half of the steppe rangeland in the Central Anatolian Region of Turkey (CAR) has been converted to cropland without an equivalent reduction in grazing animals. This shift has led to heavy grazing pressure on rangeland vegetation. A study was initiated in June 2003 using 6 multiscale Modified-Whittaker plots to determine differences in plant composition between areas that have not been grazed in 27 years with neighboring grazed plant communities. A total of 113 plant species were identified in the study area with the ungrazed plots containing 32 plants more than the grazed plots. The major species were Astragalus acicularis, Bromus tomentellus, Festuca valesiaca, Genista albida, Globularia orientalis, Poa bulbosa, and Thymus spyleus ssp rosulans. Grazing impacts on forbs were more pronounced than for grasses and shrubs. Based on Jaccard's index, there was only a 37% similarity of plant species between the two treatments. Our study led to four generalizations about the current grazing regime and long-term exclosures in the steppe rangeland around the study area: (1) exclosures will increase species richness, (2) heavy grazing may have removed some plant species, (3) complete protection from grazing for a prolonged period of time after a long history of grazing disturbance may not lead to an increase in desirable plant species with a concomitant improvement in range condition, and (4) research needs to be conducted to determine how these rangelands can be improved.


Induction of duodenal tumors in F344 rats by continuous oral administration of N-ethyl-N-nitrosourea.
Forty male and 40 female inbred F344 rats were given a solution of 400 mg N-ethyl-N-nitrosourea/liter in their drinking water. Digestive tract tumors were induced in 32 males (an incidence rate of 80%) and in 28 females (an incidence rate of 70%). Among these digestive tract neoplasms, duodenal tumors occurred most frequently. Most were of the epithelial type, such as adenoma or adenocarcinoma. Tumors in hematopoletic organs were also found in 15 males (38% incidence) and in 17 females (43% incidence).


Exploring Anti-Prion Glyco-Based and Aromatic Scaffolds: A Chemical Strategy for the Quality of Life.
Prion diseases are fatal neurodegenerative disorders caused by protein misfolding and aggregation, affecting the brain progressively and consequently the quality of life. Alzheimer's is also a protein misfolding disease, causing dementia in over 40 million people worldwide. There are no therapeutics able to cure these diseases. Cellular prion protein is a high-affinity binding partner of amyloid β (Aβ) oligomers, the most toxic species in Alzheimer's pathology. These findings motivate the development of new chemicals for a better understanding of the events involved. Disease control is far from being reached by the presently known therapeutics. In this review we describe the synthesis and mode of action of molecular entities with intervention in prion diseases' biological processes and, if known, their role in Alzheimer's. A diversity of structures is covered, based on glycans, steroids and terpenes, heterocycles, polyphenols, most of them embodying aromatics and a structural complexity. These molecules may be regarded as chemical tools to foster the understanding of the complex mechanisms involved, and to encourage the scientific community towards further developments for the cure of these devastating diseases.


Nearly one-third of lactating mothers are suffering from undernutrition in pastoral community, Afar region, Ethiopia: Community-based cross-sectional study.
Undernutrition is responsible for a significant proportion of maternal and child morbidity and mortality. Lactating women are nutritionally vulnerable groups because this period places a high nutritional demand on the mother and leads to nutritional stress. Poor nutrition during lactation has a significant negative consequence to mothers and children's survival, growth, and development. Therefore this study aimed to assess the nutritional status of lactating mothers and associated factors in pastoral community, Afar region, Ethiopia. A community-based cross-sectional study was conducted from January 5/2020 to February 10/2020, in the Abala district. The data were collected from a sample of 366 lactating mothers whose children aged less than 24 months. Data was collected through face-to-face interviews and anthropometric measurements. Study participants were recruited using a systematic sampling technique. Anthropometric measurements (both body mass index and mid-upper arm circumference) were taken from each mother using calibrated equipment and standardized techniques. Data were entered into Epi-data version 4.2 and exported to SPSS version 22 for analysis. Predictor variables with a P-value < 0.25 at bivariable analysis were candidates for the final model. Statistical significance was declared at P-value of < 0.05 in the multivariable logistic regression. This study showed that 120(32.8%) and 122(33.3%) surveyed mothers were undernourished using a cut-off body mass index <18.5 kg/m2 and mid-upper arm circumference <23 Centimeter, respectively. Lactating mothers who didn't meet the minimum dietary diversity score were more than five (Adjusted odds ratio (AOR) = 5.103; 95% confidence interval (CI): 2.128, 12.238) times more likely to be undernourished than those who met the minimum dietary diversity score. Mothers with short birth intervals were also more than four (AOR = 4.800; 95% CI: 2.408, 9.567) time more likely to be undernourished. Nearly one-third of lactating mothers were undernourished. Undernutrition among lactating mothers was significantly associated with maternal dietary diversity score and birth interval. Health education on proper and adequate maternal dietary feeding practices, and proper family planning utilization during lactation should be emphasized.


Scrambling for access: availability, accessibility, acceptability and quality of healthcare for lesbian, gay, bisexual and transgender people in South Africa.
Sexual orientation and gender identity are social determinants of health for people identifying as lesbian, gay, bisexual and transgender (LGBT), and health disparities among sexual and gender minority populations are increasingly well understood. Although the South African constitution guarantees sexual and gender minority people the right to non-discrimination and the right to access to healthcare, homo- and transphobia in society abound. Little is known about LGBT people's healthcare experiences in South Africa, but anecdotal evidence suggests significant barriers to accessing care. Using the framework of the UN International Covenant on Economic, Social and Cultural Rights General Comment 14, this study analyses the experiences of LGBT health service users using South African public sector healthcare, including access to HIV counselling, testing and treatment. A qualitative study comprised of 16 semi-structured interviews and two focus group discussions with LGBT health service users, and 14 individual interviews with representatives of LGBT organisations. Data were thematically analysed within the framework of the UN International Covenant on Economic, Social and Cultural Rights General Comment 14, focusing on availability, accessibility, acceptability and quality of care. All interviewees reported experiences of discrimination by healthcare providers based on their sexual orientation and/or gender identity. Participants recounted violations of all four elements of the UN General Comment 14: 1) Availability: Lack of public health facilities and services, both for general and LGBT-specific concerns; 2) Accessibility: Healthcare providers' refusal to provide care to LGBT patients; 3) Acceptability: Articulation of moral judgment and disapproval of LGBT patients' identity, and forced subjection of patients to religious practices; 4) Quality: Lack of knowledge about LGBT identities and health needs, leading to poor-quality care. Participants had delayed or avoided seeking healthcare in the past, and none had sought out accountability or complaint mechanisms within the health system. Sexual orientation and gender identity are important categories of analysis for health equity, and lead to disparities in all four dimensions of healthcare access as defined by General Comment 14. Discriminatory and prejudicial attitudes by healthcare providers, combined with a lack of competency and knowledge are key reasons for these disparities in South Africa.


Surgery of prostatic carcinoma.
Seven surgical treatments for the management of prostatic cancer are briefly reviewed. A transurethral prostatic resection is of value, not only for the relief of bladder outlet obstruction, but also in the definitive management of Stage A lesions. The long-term survival for patients with Stage C disease treated by radical prostatectomy plus interstitial irradiation demonstrates the efficacy of this mode of therapy. Pelvic lymphadenectomy has yielded valuable information on the stage of the disease; long-term survival was related to the presence of lymph node metastases. Lymphadenectomy may have contributed to the 5-year survival rate of those with regional lymph node involvement, but there is no direct evidence to support this view. The early results in patients treated by cryosurgery indicate that this mode of therapy can be very effective in the ablation of the local lesion and may very well have a useful place in the surgical armamentarium for the management of prostatic cancer.


Substrate specificity of cerebral GDP-fucose: glycoprotein fucosyltransferase.
Solubilized sheep brain fucosyltransferase was shown to transfer fucose from GDP-fucose onto glycoprotein and glycopeptide acceptors, such as asialofetuin, asialotransferrin, their glycopeptides and glycopeptides from ovalbumin, but not on to monosaccharides and disaccharides such as galactose, N-acetylglucosamine and lactose. Competition studies between asialofetuin and glycopeptide V from ovalbumin provided evidence that both substrates compete for a common enzyme active site. The position of the fucosyl linkage was then investigated. Endo-beta-N-glucosaminidase D digestion of fucosylated and acetylated glycopeptide V showed that fucose is not linked to asparagine-linked N-acetylglucosamine. Hydrazinolysis and nitrous acid deamination performed on asialofetuin and glycopeptide V proved that fucose is not linked to external galactose or N-acetylglucosamine either. Thus we assume that fucose is linked to the oligomannochitobiosyl core of the glycan, and probably to the second N-acetylglucosamine.


Recurrence plot analyses suggest a novel reference system involved in newborn spontaneous movements.
The movements of newborns have been thoroughly studied in terms of reflexes, muscle synergies, leg coordination, and target-directed arm/hand movements. Since these approaches have concentrated mainly on separate accomplishments, there has remained a clear need for more integrated investigations. Here, we report an inquiry in which we explicitly concentrated on taking such a perspective and, additionally, were guided by the methodological concept of home base behavior, which Ilan Golani developed for studies of exploratory behavior in animals. Methods from nonlinear dynamics, such as symbolic dynamics and recurrence plot analyses of kinematic data received from audiovisual newborn recordings, yielded new insights into the spatial and temporal organization of limb movements. In the framework of home base behavior, our approach uncovered a novel reference system of spontaneous newborn movements.


The association between immunoglobulin G in sow colostrum and piglet plasma.
Colostrum provides newborn piglets with energy and passive immunity and is essential for survival of the piglets. The plasma concentration of immunoglobulin G (IgG) in piglets is dependent on several factors, most importantly the concentration of IgG in sow colostrum (colostrum IgG). The main aims of this study were to investigate the variation in concentration of colostrum IgG between herds and the individual sows within herd and to investigate factors associated with plasma IgG concentrations in piglets (piglet IgG). From 4 herds (A to D), 876 piglets from 62 sows were included in the study. Colostrum was sampled from sows immediately after expulsion of the first piglet and before the first suckling (t1), midway through farrowing (just after the sixth piglet was born; t2), and after the last piglet was born (t3). At d 1, 0.5 mL blood from piglets was collected in tubes containing EDTA, and IgG concentrations were analyzed. Mean colostrum IgG concentration across all herds was 53.9 g/L. Herd A had mean colostrum IgG of 38.3 g/L, whereas the other 3 herds (B,C, and D) had mean colostrum IgG of 47.4, 60.4, and 67.8 g/L, respectively. Colostrum IgG at t1, t2, and t3 across all herds was 56.2, 53.7, and 42.5 g/L, respectively. Mean concentration of piglet IgG across all samplings was 21.7 g/L. Multilevel linear regression analysis was performed with piglet IgG (g/L) as outcome. In this model, the herd effect accounted for 9% of the total variance and 34% of the variance resided at sow level. Piglet IgG was associated with herd, birth order (), body mass index (BMI) > 17 (kg/m), and colostrum IgG at t1 (g/L) with an overall -value < 0.01. Herd D had the highest predicted mean level of piglet IgG. The main model predicted that piglet IgG decreased linearly by 0.4 g/L with each piglet born ( < 0.01). The model also predicted an increase by 0.1 g/L for each gram per liter extra colostrum IgG in colostrum ( = 0.03). Piglets with a BMI above 17 kg/m had a greater piglet IgG (+4.5 g/L) than those with a BMI at 17 kg/m or below ( < 0.01). Concentrations of colostrum IgG varied largely between herds and between sows. The largest variation of piglet IgG was mainly on the piglet level, supporting the complex nature of IgG production and uptake. However, the strong association between colostrum IgG and piglet IgG shows that increased IgG level in colostrum will improve the levels of IgG in piglets and potentially increase survival of the piglets.


A comparative assessment of the impact of different occupations on workers' static musculoskeletal fitness.
An ergonomic assessment of the involvement of static muscular forces like back strength, grip strength and pinch strength in different occupations was made. A study was conducted on 45 normal adult males (15 subjects per group) which included video display terminal (VDT) operators, industrial workers and safety inspectors. Their maximum back strength, handgrip strength and pinch strength were measured with dynamometers. The observed values of back strength were significantly lower in VDT operators while significantly higher in safety inspectors and moderate in industrial workers. The values of grip strength and pinch strength of all sample groups were more or less similar. The findings clearly indicate that static muscular strength varies significantly in different occupations. Heavy static muscular load might lead to an accumulation of metabolic waste and toxins on the back resulting in lower back strength in VDT operators and industrial workers.


Wound cleansing for pressure ulcers.
Pressure ulcers (also called pressure sores, bed sores and decubitus ulcers) are areas of tissue damage that occur in the very old, malnourished or acutely ill, who cannot reposition themselves. Pressure ulcers impose a significant financial burden on health care systems and negatively affect quality of life. Wound cleansing is considered an important component of pressure ulcer care. This systematic review seeks to answer the following question:What is the effect of wound cleansing solutions and wound cleansing techniques on the rate of healing of pressure ulcers? We searched the Specialised Trials Register of the Cochrane Wounds Group (up to August 2005), and the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005). We searched bibliographies of relevant publications retrieved. We contacted drug companies and experts in the field to identify studies missed by the primary search. Randomised controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or different wound cleansing solutions, or different cleansing techniques, were eligible for inclusion if they reported an objective measure of pressure ulcer healing. Two authors extracted data independently and resolved disagreements through discussion and reference to the Cochrane Wounds Group editorial base. A structured narrative summary of the included studies was conducted. For dichotomous outcomes, relative risk (RR), plus 95% confidence intervals (CI) were calculated; for continuous outcomes, weighted mean difference (WMD), plus 95% CI were calculated. Meta analysis was not conducted, because of the small number of diverse RCTs identified. No studies compared cleansing with no cleansing. Two studies compared different wound cleansing solutions: a statistically significant improvement in Pressure Sore Status Tool scores occurred for wounds cleansed with saline spray containing Aloe vera, silver chloride and decyl glucoside (Vulnopur) compared to isotonic saline (P value = 0.025), but no statistically significant change in healing was seen when water was compared to saline (RR 3.00, 95% CI 0.21, 41.89). One study compared cleansing techniques, but no statistically significant change in healing was seen for ulcers cleansed with, or without, a whirlpool (RR 2.10, 95% CI 0.93 to 4.76). We identified only three studies addressing cleansing of pressure ulcers. One noted a statistically significant improvement in pressure ulcer healing for wounds cleansed with saline spray containing Aloe vera, silver chloride and decyl glucoside (Vulnopur) when compared with isotonic saline solution. Overall, there is no good trial evidence to support use of any particular wound cleansing solution or technique for pressure ulcers.


Efficient n-Type Small-Molecule Mixed Ion-Electron Conductors and Application in Hydrogen Peroxide Sensors.
Small-molecule semiconductors used as the channel of organic electrochemical transistors (OECTs) have been rarely reported despite their inherent advantages of well-defined molecular weight, convenient scale-up synthesis, and good performance reproducibility. Herein, three small molecules based on perylene diimides are readily prepared for n-type OECTs. The final molecules show preferred energy levels, tunable backbone conformation, and high film crystallinity, rendering them good n-type dopability, favorable volumetric capacities, and substantial electron mobilities. Consequently, the OECTs afford a record-low threshold voltage of 0.05 V and a normalized peak transconductance of 4.52 × 10-2 S cm-1, as well as impressive long-term cycling stability. Significantly, the OECTs utilized for hydrogen peroxide sensing are further demonstrated with a detection limit of 0.75 μM. This work opens the possibility of developing nonfullerene small molecules as superior n-type OECT materials and provides important insights for designing high-performance small-molecule mixed ion-electron conductors for OECTs and (bio)sensors.


A severe manifestation of primary HIV-1 infection in an adolescent.
Primary HIV infection (PHI) is symptomatic in 50-90% of patients with symptoms resembling infectious mononucleosis. The diagnosis, however, is seldom made at first presentation. Clinically severe presentations during primary HIV type 1 infection are considered to occur infrequently. We report a case of a severe manifestation of PHI with meningoencephalitis in the setting of HIV seroconversion in an adolescent girl.


Transcription-based COX-2 inhibition: a therapeutic strategy.
Potent selective cyclooxygenase-2 (COX-2) inhibitors are effective in controlling inflammatory disorders but are associated with cardiovascular complications. Their clinical use has been severely limited. We propose that transcription-based inhibition of COX-2 expression represents a therapeutic strategy that may circumvent the undesired complications of COX-2 inhibitors. Reported data from several laboratories including ours have identified C/EBPbeta as a key transactivator mediating COX-2 transcriptional activation induced by diverse pro-inflammatory mediators. Results from our recent work show that sodium salicylate at pharmacological concentrations inhibits C/EBPbeta binding to COX-2 promoter by direct inhibition of p90 ribosomal S6 kinase (RSK). RSK phosphorylates C/EBPbeta and stimulates its binding to enhancer elements. We propose that RSK1/2 is a potential target for screening drugs with novel anti-inflammatory and anti-neoplastic therapeutic potentials.


A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome.
Using targeted next generation sequencing, we have identified a splicing mutation (c.526-9_526-5del) in the SLC9A6 gene in a 9-year-old boy with mild intellectual disability (ID), microcephaly, and social interaction disabilities. This intronic microdeletion leads to the skipping of exon 3 and to an in-frame deletion of 26 amino acids in the TM4 domain. It segregates with cognitive impairment or learning difficulties in other members of the family. Mutations in SLC9A6 have been reported in X-linked Christianson syndrome associating severe to profound intellectual deficiency and an Angelman-like phenotype with microcephaly, absent speech, ataxia with progressive cerebellar atrophy, ophthalmoplegia, epilepsy, and neurological regression. The proband and his maternal uncle both have an attenuated phenotype with mild ID, attention deficit disorder, speech difficulties, and mild asymptomatic cerebellar atrophy. The proband also have microcephaly. The mutation cosegregated with learning disabilities and speech difficulties in the female carriers (mother and three sisters of the proband). Detailed neuropsychological, speech, and occupational therapy investigations in the female carriers revealed impaired oral and written language acquisition, with dissociation between verbal and performance IQ. An abnormal phenotype, ranging from learning disability with predominant speech difficulties to mild intellectual deficiency, has been described previously in a large proportion of female carriers. Besides broadening the clinical spectrum of SLC9A6 gene mutations, we present an example of a monogenic origin of mild learning disability. © 2016 Wiley Periodicals, Inc.


Is zidovudine therapy in pregnant HIV-infected women associated with gestational age and birthweight?
Prophylactic zidovudine during pregnancy and labour reduces maternal viral load and, with neonatal therapy, has been shown to reduce vertical transmission. However, zidovudine may have additional effects. Advanced HIV disease is associated with premature delivery, which in turn results in increased vertical transmission. Data from the European Collaborative Study (ECS) were analysed to investigate whether zidovudine could be associated with decreased prematurity risk and/or with a reduced frequency of low birthweight. HIV-infected pregnant women enrolled in the ECS were followed prospectively according to a standard protocol. Gestational age was assessed by ultrasound, prematurity was defined as delivery before 37 weeks and the cut-off for low birthweight was 2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on the risk of premature of low birthweight delivery. In 2299 mothers, zidovudine taken to reduce the risk of vertical transmission decreased the odds of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53-1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39-0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR values. A multivariate analysis suggested that prophylactic zidovudine and prematurity were independently associated with risk of transmission. Our findings suggest an additional health benefit of zidovudine. Even if most vertical transmission occurs around the time of delivery, therapy earlier in pregnancy could have an indirect effect on transmission rates through delaying delivery. This hypothesis needs to be confirmed or refuted by more appropriate studies.


Mesenchymal Chondrosarcoma of the Brain with Metastasis: A Case Report with Literature Review.
Mesenchymal chondrosarcoma of the brain is one of the rarest tumors with dismal prognosis. A 26-year-old man presented with headache, vomiting, and diplopia. On evaluation, a moderately enhancing extra-axial lesion was seen in right temporal region involving right greater wing of sphenoid, adjacent right maxillary sinus, and lateral wall of right orbit. Patient underwent magnetic resonance imaging of the spine and computed tomography (CT) of the chest for possible metastasis which showed lesion in lumbar vertebrae and left lung. Patient was planned for CT-guided lung biopsy which proved inconclusive. The patient was further planned for craniotomy and underwent craniotomy with microscopic excision of the mass. Histoimmunochemistry was suggestive of extraskeletal mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma of the brain is highly aggressive tumors which are difficult to differentiate radiologically. Radical excision followed by chemoradiotherapy is optimal treatment of choice.


Two- and three dimensional combinatorial chemistry from multicomponent Grignard reagents.
The conjugate addition of five component Grignard reagents to methyl ecgonidine was used to create libraries of 3-substituted tropanes. By variation in the reagent combination in 10 such 5-membered sublibraries, a library of 25 compounds was made in a two-dimensional format. Screening of this library led to identification of two new potent monoamine transporter ligands that were subsequently synthesized. The most potent compound in this library was (1R,2S,3S,5S)-3-(3,4-dimethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester, which inhibited dopamine transporter (hDAT) binding and reuptake with a K(i) of 26 and 20 nM, respectively. The conjugate addition to a 5-membered library of methyl ecgonidine analogues with variation of nitrogen substituent was also carried out and used to create 15 sublibraries of 25 compounds, which displayed 125 compounds in a three-dimensional format. From this 3D library, several potent dopamine transport inhibitors were likewise identified and synthesized. The most potent hDAT inhibitor discovered was (1R,2S,3S,5S)-3-(3,4-dimethylphenyl)-8-pentyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester. The study also showed that 3-alkyltropanes were poor inhibitors of monoamine transporters.


Prolactin and oleic acid synergistically stimulate β-cell proliferation and growth in rat islets.
Islet adaptation to pregnancy is largely influenced by prolactin and placental lactogens. In addition serum lipids are significantly increased. Here, we report the novel observation that prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth. In neonatal rat islets, prolactin increased proliferation 6-fold, oleic acid 3.5-fold, and their combination 15-fold. The expression of insulin in these dividing cells establishes them as β-cells. Similar changes were seen in islet growth. This synergy is restricted to monounsaturated fatty acids and does not occur with other islet growth factors. Oleic acid increases prolactin-induced STAT5 phosphorylation, even though by itself it is unable to induce STAT5 phosphorylation. Their effects on Erk1/2 phosphorylation are additive. Some of the synergy requires the formation of oleoyl CoA and/or its metabolites. Unexpectedly, methyl oleic acid, a non-metabolizable analog of oleic acid, also shows synergy with prolactin. In summary, prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth in rat islets, oleic acid increases prolactin-induced STAT5 activation, and requires both the metabolism of oleic acid and non-metabolized oleic acid. Since oleic acid is the most abundant monounsaturated fatty acid in serum that is elevated during pregnancy, it may contribute to increased β-cell proliferation seen during pregnancy.


[LEIOMYOSARCOMA ARISING FROM OVARIAN VEIN WITH RIGHT HYDRONEPHROSIS: A CASE REPORT].
The patient was a 37-year-old woman who had suffered from repeated pyelonephritis. Computed tomography (CT) of the abdomen revealed a 1.9 cm retroperitoneal mass with compression of the right ureter and hydronephrosis. The patient visited our medical center and admitted. The patient underwent a simple total excision of the mass and end-to-end ureteral anastomosis. The tumor involved right ovarian vein and right ureter. Histopathological diagnosis was leiomyosarcoma of the ovarian vein. At 12 months after operation, local recurrence of surroundings tissue of the right ureter and gallbladder, and inferior vena cava invasion is found. Thus, the patient underwent a right nephroureterectomy with partly resection of the inferior vena cava and en block excision of the gallbladder. While CT revealed no recurrence three months after the operation, adjuvant postoperative combination chemotherapy with gemcitabine and docetaxel was administered. Nine cases of this leiomyosarcoma arising from ovarian vein have been reported in the literature. Leiomyosarcoma arising from ovarian vein with hydronephrosis is a second example.


Physiological responses to trauma.
Stress response can be physical and psychological. Physiological responses to stress, such as a major trauma, stimulate the sympathetic nervous system. The response, although necessary to maintain life, is harmful when prolonged. Nursing and medical management is directed at controlling the etiology and reversing the side effects seen in the body organs. The physical response to stressors shall be explored in this article.


The impact of anorectal malformations on anorectal function and social integration in adulthood: report from a national database.
The impact of anorectal malformation (ARM) on bowel function and social, educational and occupational end-points was investigated in adult patients entered on a national database. Data from a national database of adult patients operated on between 1962 and 1999 for ARM were analysed. The database Malformations Ano-rectales et Pelviennes rares (MAREP) was part of a common information system, CEMARA, on rare congenital disorders. A self-administered questionnaire regarding bowel function, academic qualifications, employment and family status was mailed to patients. The type of ARM, subsequent follow-up and management including surgical interventions were retrospectively retrieved from medical records. Of 210 adult patients on the registry since 2008, 68 were included in this study. Only three (8.5%) had had regular follow-up. All reported some disturbance in bowel function. The fertility rate of 1.5 children per woman did not differ from the general population. Anorectal malformation ARM often leads to suboptimal bowel function in adulthood. This has an impact on social integration.


Association of 5p15.2 and 15q14 with high myopia in Tujia and Miao Chinese populations.
The polymorphisms rs6885224 and rs634990 have been reported to be associated with high myopia in many populations. As there is still no report on whether these two SNPs are associated with myopia in the Tujia and Miao minority areas of China, we conducted a replication study to evaluate the association of single-nucleotide polymorphisms in the regions 5p15.2 and 15q14 with high myopia in Tujia and Miao Chinese populations. We performed a comprehensive meta-analysis of 5831 cases and 7055 controls to assess whether rs6885224 in the 5p15.2 region and rs634990 in the 15q14 region are associated with high myopia. Our replication study enrolled 804 individuals. Genomic DNA was extracted from venous leukocytes, and these two SNPs were genotyped by Sanger sequencing. Allele and genotype frequencies were analysed using χ2 tests, and ORs and 95% CIs were calculated. According to the results of the meta-analysis, rs6885224 in the CTNND2 gene showed no association with myopia [p = 0.222, OR = 1.154, 95% CI (0.917-1.452)]. Conversely, rs634990 in the 15q14 region did exhibit a significant correlation with myopia [p = 7.270 × 10- 7, OR = 0.817, 95% CI (0.754-0.885)]. In our replication study, no association with high myopia in the Tujia and Miao populations was found for rs634990 or rs6885224. The following were obtained by allele frequency analysis: rs6885224, p = 0.175, OR = 0.845, and 95% CI = 0.662-1.078; rs634990, p = 0.087, OR = 0.84, and the 95% CI = 0.687-1.026. Genotype frequency analysis yielded p = 0.376 for rs6885224 and p = 0.243 for rs634990. Our meta-analysis results show that rs634990 was significantly associated with myopia but that rs6885224 was not. Nevertheless, in our replication study, these two SNPs showed no association with myopia in the Tujia and Miao Chinese populations. This is the first report involving Tujia and Miao ethnic groups from Enshi minority areas. However, the sample size needs to be expanded and more stringent inclusion and exclusion criteria need to be formulated to verify the findings.


A look to future directions in gene therapy research for monogenic diseases.
The concept of gene therapy has long appealed to biomedical researchers and clinicians because it promised to treat certain diseases at their origins. In the last several years, there have been several trials in which patients have benefited from gene therapy protocols. This progress, however, has revealed important problems, including the problem of insertional oncogenesis. In this review, which focuses on monogenic diseases, we discuss the problem of insertional oncogenesis and identify areas for future research, such as developing more quantitative assays for risk and efficacy, and ways of minimizing the genotoxic effects of gene therapy protocols, which will be important if gene therapy is to fulfill its conceptual promise.


Clinical features of recently diagnosed pulmonary paragonimiasis in Korea.
Paragonimiasis is a typical food-borne parasitic disease that is common in Southeast Asia, the Far East, Latin American, and Africa. Recently, however, this disease has been seen in many parts of the world, largely due to increases in the numbers of immigrants and overseas travelers. The purpose of this study was to evaluate the clinical and radiologic features of recently diagnosed pulmonary paragonimiasis. We retrospectively analyzed the clinical and radiologic characteristics of 36 patients (21 men and 15 women; median age 48 years; range, 19 to 75) with pulmonary paragonimiasis whose conditions were diagnosed between October 1994 and September 2004. Thirty-four patients (94%) presented with respiratory symptoms, including hemoptysis (n = 20, 56%) and cough (n = 17, 47%). However, chest pain (n = 5, 14%) and fever (n = 5, 14%) were less frequently reported. Chest radiography revealed intrapulmonary parenchymal lesions (n = 26, 72%), such as nodules (n = 14, 39%), linear opacity (n = 6, 17%), and airspace consolidations (n = 4, 11%), which occurred more commonly than did pleural lesions (n = 10, 28%). Most cases were initially suspected to be lung cancer or tuberculosis. In 13 patients with intrapulmonary parenchymal lesions who underwent bronchoscopy, bronchial luminal narrowing, coupled with congested or edematous mucosal changes, was seen in 7 patients (54%). Bronchial mucosal biopsy specimens exhibited chronic inflammation with eosinophilic infiltrations in three of these seven patients (43%). Our findings indicate that patients with pulmonary paragonimiasis presented with a variety of clinical and radiologic findings that were different from the classic presentations reported earlier, frequently mimicking those of lung cancer or tuberculosis.