[Bio-antioxidant activity of 3,5-di-tert-butylpyrocatechol and its influence on hypoxia, inflammation, pain and burns].
The bioantioxidant activity of the synthesized by us on the base of the diatomic phenol compound--3,5-di-t-butylpyrocatechol--has been studied. It was shown that this substance exhibits more pronounced antioxidant properties than tocopherol on the lipid peroxidation process in the rat brain homogenate appears in concentrations right up to 10(-8)-10(-7) M. Antioxidant effect of 3,5-di-t-butylpyrocatechol protecting action correlation has been found in the simulation of such pathological organism states as hypoxia, inflammation, burn, pain. All above mentioned results confirms the expedience of search for new drugs based on diatomic phenols.


[Endovideosurgical methods at the treatment of patients with cholelithiasis].
Experience of 10,046 laparoscopic cholecystectomies is analyzed. The were 8097 female and 1949 male patients aged 13 to 93 years. Complicated cholelithiasis was seen at 4310 (42.9%) patients including 792 patients with acute inflammation of gallbladder, 2375--with chronic empyema, 1143--with gallbladder hydrops. Choledocholithiasis was diagnosed at 502 patients, Mirizzi syndrome--at 8, biliodigestive fistulas--at 12, cancer of gall bladder--at 5 patients. Mini-invasive endoscopic methods were used at all the patients, conversion to open surgery was necessary at 23 cases. Average time of surgery was 20-35 min, hospital stay--1-6 days. Intra- and postoperative complications were diagnosed at 86 patients among the first 3000 procedures. Among successive 7000 operations (after development of prophylactic complex) there were only 3 cases of trocar puncture infection. There were 2 cases of lethal outcome due to pulmonary embolism and pancreonecrosis.


Fine-tuned grayscale optofluidic maskless lithography for three-dimensional freeform shape microstructure fabrication.
This article presents free-floating three-dimensional (3D) microstructure fabrication in a microfluidic channel using direct fine-tuned grayscale image lithography. The image is designed as a freeform shape and is composed of gray shades as light-absorbing features. Gray shade levels are modulated through multiple reflections of light in a digital micromirror device (DMD) to produce different height formations. Whereas conventional photolithography has several limitations in producing grayscale colors on photomask features, our method focuses on a maskless, single-shot process for fabrication of freeform 3D micro-scale shapes. The fine-tuned gray image is designed using an 8-bit grayscale color; thus, each pixel is capable of displaying 256 gray shades. The pattern of the UV light reflecting on the DMD is transferred to a photocurable resin flowing through a microfluidic channel. Here, we demonstrate diverse free-floating 3D microstructure fabrication using fine-tuned grayscale image lithography. Additionally, we produce polymeric microstructures with locally embedded gray encoding patterns, such as grayscale-encoded microtags. This functional microstructure can be applied to a biophysical detection system combined with 3D microstructures. This method would be suitable for fabricating 3D microstructures that have a specific morphology to be used for particular biological or medical applications.


Dynamics of B-lymphocytes in the lungs of mice exposed to aerosolized influenza virus.
Immunoglobulin-containing cells were revealed by immunofluorescence in lung sections from mice infected with influenza virus by the aerosol route. The numbers of immunoglobulin A (IgA)- and IgM-containing cells were increasing by day 3 of the infection, whereas IgG-containing cells appeared a few days later. The responding B-cell populations appeared in two principal locations: along major airways and in consolidated lesions within lung parenchyma. IgA-containing cells were the most numerous isotype, occurring predominantly in the lamina propria of the airways. IgG-containing cells were the least frequently encountered class along airways and appeared most often within consolidated lung lesions in clustered groupings. Cells staining for mu chain appeared along the airways and in lung lesions. The population of IgM-containing cells declined approximately 30 days after infection. Cells producing alpha and gamma chains were still numerous on day 46. Assays for virus-reactive antibodies in lung secretions were positive on day 8 of the infection. The IgM titers were the first to decline, but virus-binding antibodies for all classes were still present on day 33. The implications of immune responses in viral pneumonitis were considered.


Localized activity patterns in excitatory neuronal networks.
The existence of localized activity patterns, or bumps, has been investigated in a variety of spatially distributed neuronal network models that contain both excitatory and inhibitory coupling between cells. Here we show that a neuronal network with purely excitatory synaptic coupling can exhibit localized activity. Bump formation ensues from an initial transient synchrony of a localized group of cells, followed by the emergence of desynchronized activity within the group. Transient synchrony is shown to promote recruitment of cells into the bump, while desynchrony is shown to be good for curtailing recruitment and sustaining oscillations of those cells already within the bump. These arguments are based on the geometric structure of the phase space in which solutions of the model equations evolve. We explain why bump formation and bump size are very sensitive to initial conditions and changes in parameters in this type of purely excitatory network, and we examine how short-term synaptic depression influences the characteristics of bump formation.


Laparoscopic cholecystectomy in 226 cirrhotic patients. Experience of a single center in Taiwan.
Since 1987, laparoscopic cholecystectomy (LC) has been widely used as the favored treatment for gallbladder lesions. However, cirrhosis and portal hypertension have been considered relative or absolute contraindications to LC. This study aimed to assess the safety of LC in cirrhotic patients. The medical records of 226 cirrhotic patients with gallbladder lesions who had undergone LC from 1991 to 2000 were reviewed, including demographics, severity of cirrhosis, laboratory data, operative morbidity, operative mortality, and hospital stay. Furthermore, the clinical features and outcomes of 4030 patients with gallbladder lesions without cirrhosis that had undergone LC were also summarized for comparison. Of 4256 patients with gallbladder lesions that had undergone LC, 226 (5.6%) had cirrhotic livers. The cirrhotic group patients clearly exhibited the trends of older age, worse liver function, higher blood loss, and higher mortality compared to the noncirrhotic group patients. This study presents the clinical features and outcomes of 226 cirrhotic patients who underwent LC. LC, once considered contraindicated in patients with cirrhosis, is a feasible procedure for most Child's A and B patients with cholecystolithiasis. Minor morbidity, an acceptable conversion rate, and shorter hospital stay can be achieved by applying LC to treat cirrhotic patients. However, appropriate preoperative preparations and meticulous operative techniques are required to reduce blood loss during laparoscopy and even mortality.


Respirator proposal loses breath when applied to health care.
The debate continues. As Materials Management in Health Care went to press, the Occupational Safety and Health Administration was getting an earful about proposed revisions to its respiratory protection standard. The standard sets requirements for respirator use in the workplace and will be a basis for part of OSHA's proposed tuberculosis standard, which should be released later this year. Here are the American Hospital Association's comments on the proposed revisions.


Single-cell persistent activity in anterodorsal thalamus.
The anterodorsal nucleus of the thalamus contains a high percentage of head-direction cells whose activities are correlated with an animal's directional heading in the horizontal plane. The firing of head-direction cells could involve self-sustaining reverberating activity in a recurrent network, but the thalamus by itself lacks strong excitatory recurrent synaptic connections to sustain tonic reverberating activity. Here we examined whether a single thalamic neuron could sustain its own activity without synaptic input by recording from individual neurons from anterodorsal thalamus in brain slices with synaptic blockers. We found that the rebound firing induced by hyperpolarizing pulses often decayed slowly so that a thalamic neuron could keep on firing for many minutes after stimulation. The hyperpolarization-induced persistent firing rate was graded under repeated current injections, and could be enhanced by serotonin. The effect of depolarizing pulses was much weaker and only slightly accelerated the decay of the hyperpolarization-induced persistent firing. Our finding provides the first direct evidence for single-cell persistent activity in the thalamus, supporting the notion that cellular mechanisms at the slow time scale of minutes might potentially contribute to the operations of the head-direction system.


[Effect of perfusate potassium concentration on the contraction rate of the isolated rat heart during profound hypothermia].
Effect of different concentration of K+ in perfusion fluid ([K+]) (5.9 mM, 3.6 mM, 2.38 mM) and the heart temperatures of 20 degrees C and below on the rat heart rate in the Langendorf preparations, were examined in conditions of retrograde perfusion with a modified Krebs-Henseleit buffer at constant perfusion volume. The lowering of [K+] diminished the temperature/heart rate ratio and depressed the heart standstill temperature from 12.3 +/- 0.6 degrees C at [K+] 5.9 mM (n = 12) to 6.7 +/- 0.6 degrees C at [K+] 3.6 mM (n = 5) and to 2.24 +/- 0.40 degrees C at [K+] 2.38 mM (n = 5). Temperature of the cold heart standstill had the liner relationship to Ig[K+]. Change the perfusion fluid with 5.9 mM K+ after heart cold standstill by the perfusion fluid with 3.6 mM K+ restored the heart beats to the rate of 40-50 min-1 in some experiments. The second heart standstill was at the mean temperature 3.6 degrees C lower than the first one.


[Lipids, microalbuminuria and systemic blood pressure in patients with insulin-dependent diabetes mellitus].
To determine the association between lipids, microalbuminuria and systemic blood pressure. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples by radioimmunoassay. Microalbuminuria was defined when two out of three urine samples had AER ranging 20-200 micrograms/min. Lipids were determined by colorimetric methods (total cholesterol, HDL cholesterol and triglycerides). Fifty patients with insulin dependent diabetes mellitus (28 females, 22 males) aged 21.9 +/- 7 years and with diabetes duration of 6.8 +/- 5.8 years attending the outpatients diabetes clinic were studied cross-sectionally. Microalbuminuria was present in 12% of our patients. A high systolic blood pressure (SBP) was found in microalbuminuric patients (p = 0.003). No difference concerning serum lipids were found in comparison between normo and microalbuminuric patients, although 20% of all patients had increased cholesterol and LDL cholesterol and 4% had high HDL cholesterol and triglycerides levels. Stepwise multiple regression analysis showed that SBP was the only significant independent variable to influence AER (r = 0.42 r2 = 0.18 p = 0.002). Although in our study, microalbuminuria was associated only with SBP, the independent alteration of lipids in young IDDM patients must be considered as a possible additional risk factor for cardiovascular disease.


Peptide sr11a from Conus spurius is a novel peptide blocker for Kv1 potassium channels.
More than a hundred conotoxins are known today and from them, only seven conopeptides have been identified to target voltage-gated potassium channels (Kv). Conotoxin sr11a belongs to the I(2)-superfamily which is characterized by four disulfide bridges and provokes muscle stiffness when injected intracranially in mice. The aim of this work was to test the biological activity of sr11a on recombinant voltage-gated Kv1 potassium channels expressed in Xenopus laevis oocytes. Peptide sr11a was purified by high-performance liquid chromatography from the venom of the vermivorous Conus spurius. We found that peptide sr11a inhibits the delayed rectifiers Kv1.2 and Kv1.6 but had not effect on the slowly inactivating Kv1.3 channel. The functional dyad composed of a basic Lys and a hydrophobic amino acid residue is a crucial structural element, regarding the binding properties and blocking activities of more than a hundred K(+) channel toxins. Peptide sr11a does not contain Lys residues and then, it lacks the functional dyad. Molecular modeling of peptide sr11a reveals the presence of exposed basic residues of Arg and suggests that Arg17 and Arg29 are important on its biological activity.


Thiol-reactive luminescent chelates of terbium and europium.
Thiol-reactive lanthanide complexes have been synthesized that are luminescent when bound to terbium and/or europium. The complexes consist of a diethylenetriaminepentaacetate (DTPA) chelate covalently joined through one amide bond to a chromophore, carbostyril 124, and via a second amide bond to a maleimide, bromoacetamide, or pyridyldithio moiety. Site-specific attachment and characterization of the complexes attached to DNA-activating protein NtrC, to various sites on myosin, or to DNA are presented. The compounds coordinate a surprisingly large number of ligation sites of terbium when a hydrazide spacer is used between the chelate and thiol-reactive moiety, although this extra ligation can cause quenching when europium is used. Synthesis is a simple two- or three-step reaction, and purification is straightforward. The compounds should be useful as nonisotopic replacements, as long-lifetime probes in imaging, and as donors in luminescence resonance energy transfer. They are examples of a wide class of chelates that can be made conjugatable via readily available hetero- or homo-bifunctional linkers.


Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: beyond bleeding complications.
Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered the market in 2008 with the expected breakthrough potential of circumventing limitations related to treatment with vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although data derived from premarketing randomized clinical trials have largely demonstrated the clinical benefit of DOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safety in the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy, in order to assess the actual risk-benefit profile. In this critical review, we aimed to evaluate the evidence on the latest debated safety issues. In the first section, we will discuss: 1) the need for pharmacovigilance (ie, the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems in the real-world setting), and 2) the importance of properly interpreting postmarketing data to avoid unnecessary alarm. In the second section, emerging and debated safety issues potentially associated with the use of DOACs in the postmarketing setting will be assessed: 1) the potential coronary risk (which emerged during the preapproval period); 2) the occurrence of liver injury (a risk undetected in clinical trials and highlighted by case reports or series); and 3) the potential for renal damage (a still unclear safety issue). It is anticipated that hepatic and renal issues still require dedicated postauthorization safety studies to ultimately assess causality.


Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study.
The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.


The ventilatory response to modified rebreathing is unchanged by hyperoxic severity: implications for the hyperoxic hyperventilation paradox.
Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs via an oxygen (O2)-specific mechanism or secondary to carbon dioxide (CO2) retention at the central chemoreceptors remains unclear. We measured the ventilatory response to hyperoxic CO2 rebreathing with O2 clamped at increasingly higher pressures. We hypothesized that the V̇e versus Pco2 relationship is fixed and independent of Po2. On four occasions, 20 participants (10 F; mean ± SD age: 24 ± 4 yr) performed three repetitions of modified rebreathing in four, randomized, isoxic-hyperoxic conditions: mild: Po2 = 150 mmHg; moderate: Po2 = 200 mmHg; high: Po2 = 300 mmHg; and extreme: Po2 ≈ 700 mmHg. Breath-by-breath V̇e, end-tidal CO2 ([Formula: see text]), and O2 ([Formula: see text]) were measured by pneumotach and gas analyzer. For each rebreathing trial, the [Formula: see text] at which V̇e rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V̇e (V̇eBSL, L·min-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V̇eS, L·min-1·mmHg-1). For each condition, VRT, V̇eBSL, and V̇eS from like-trials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of [Formula: see text] on V̇eBSL (mild: 7.4 ± 4.2 L·min-1; moderate: 6.9 ± 4.2 L·min-1; high: 6.5 ± 3.7 L·min-1; extreme: 7.5 ± 2.7 L·min-1; P = 0.24), VRT (mild: 42.8 ± 3.2 mmHg; moderate: 42.5 ± 2.7 mmHg; high: 42.3 ± 2.7 mmHg; extreme: 41.8 ± 2.7 mmHg; P = 0.07), or V̇eS (mild: 4.88 ± 2.6 L·min-1·mmHg-1; moderate: 4.76 ± 2.2 L·min-1·mmHg-1; high: 4.81 ± 2.3 L·min-1·mmHg-1; extreme: 4.39 ± 1.9 L·min-1·mmHg-1; P = 0.41). The V̇e-Pco2 relationship is unaltered across a range of mild to extreme Po2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.NEW & NOTEWORTHY Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs directly or indirectly through heightened central carbon dioxide pressure (Pco2) or via central chemoreflex sensitization is unclear. Participants who performed modified rebreathing at high oxygen pressures (Po2) of 150, 200, 300, and ≈700 mmHg exhibited no changes to their ventilatory responses to Pco2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.


Long-term outcome in neuroZika: When biological diagnosis matters.
To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection. We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak. Eighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13-17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12-75.22; p = 0.039). NeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.


The impact of maximum rectal distention and tandem angle on rectal dose delivered in 3D planned gynecologic high dose-rate brachytherapy.
Computed tomography-based treatment planning for cervical cancer has allowed investigation into the volumetric radiation dose delivered to the rectum. The goal of intracavitary brachytherapy is to maximize the tumor dose while decreasing the dose to normal tissue like the rectum. We investigated the effects of tandem angle and maximum rectal distention on rectal dose delivered in HDR brachytherapy for locally advanced cervical cancer. Between July 2007 and January 2010, 97 brachytherapy treatment planning computed tomographic scans from the first and last implant of 51 patients with locally advanced cervical cancer were reviewed. The rectum was manually contoured from the ischial tuberosity to the bottom of the sacroiliac joint. The maximum rectal distention was determined by measuring the largest anterior-posterior diameter of the rectum superior to the tandem ring and inferior to the end of the applicator. A volumetric measurement of the maximum and mean rectal dose, dose to 2 cc (D2cc), dose to 1cc (D1cc) of the rectum was calculated. The tandem angle and the Internal Commission on Radiation Units and Measurement rectal point were recorded, and a dose volume histogram was referenced. The mean maximum rectal distention was 3.01 cm. The mean D1cc, D2cc, mean rectal dose, maximum rectal dose, and Internal Commission on Radiation Units and Measurement rectal dose were 3.03 Gy, 2.78 Gy, 4.19 cGy, 1.40 cGy, and 2.99 Gy per treatment, respectively. In a multivariate analysis controlling for surface area, tandem angle, and body mass index, there was a significant increase in D2cc with increasing rectal distention (P = 0.016). There were no significant findings when observing the effects of tandem angle on D2cc. Rectal distention significantly affects D2cc delivered in HDR brachytherapy. In contrast, tandem angle does not. Concerted efforts to decrease rectal distention should be considered during treatment planning and delivery.


[Gonadal, hormonal and spermatic function in patients treated for cryptorchidism].
This paper studies the gonadal-hormonal and spermatic function of 48 adults (over 18 years old) who were treated in childhood for cryptorchidism by medical, surgical or both treatments. We measure plasmatic levels of FSH, LH, testosterone and prolactin of 34 patients and sperm samples of 31 patients. The testicular hormonal function was not disturbed except in four patients with high levels of prolactin (> 20 ng/ml) without symptoms. The spermatic function was disturbed in bilateral cryptorchidism mainly. The better sperm quality and testicular volume were at patients treated with hormonal treatment before surgical treatment.


Effective charges and virial pressure of concentrated macroion solutions.
The stability of colloidal suspensions is crucial in a wide variety of processes, including the fabrication of photonic materials and scaffolds for biological assemblies. The ionic strength of the electrolyte that suspends charged colloids is widely used to control the physical properties of colloidal suspensions. The extensively used two-body Derjaguin-Landau-Verwey-Overbeek (DLVO) approach allows for a quantitative analysis of the effective electrostatic forces between colloidal particles. DLVO relates the ionic double layers, which enclose the particles, to their effective electrostatic repulsion. Nevertheless, the double layer is distorted at high macroion volume fractions. Therefore, DLVO cannot describe the many-body effects that arise in concentrated suspensions. We show that this problem can be largely resolved by identifying effective point charges for the macroions using cell theory. This extrapolated point charge (EPC) method assigns effective point charges in a consistent way, taking into account the excluded volume of highly charged macroions at any concentration, and thereby naturally accounting for high volume fractions in both salt-free and added-salt conditions. We provide an analytical expression for the effective pair potential and validate the EPC method by comparing molecular dynamics simulations of macroions and monovalent microions that interact via Coulombic potentials to simulations of macroions interacting via the derived EPC effective potential. The simulations reproduce the macroion-macroion spatial correlation and the virial pressure obtained with the EPC model. Our findings provide a route to relate the physical properties such as pressure in systems of screened Coulomb particles to experimental measurements.


Analysis of Pregnancy Outcomes Following Exposure to Intramuscular Interferon Beta-1a: The AVONEX® Pregnancy Exposure Registry.
There is a lack of well-controlled US studies of intramuscular (IM) interferon beta (IFNβ)-1a use in pregnant women with multiple sclerosis; however, in the European Medicines Agency region, IFNβ formulations may be considered during pregnancy if clinically needed based on data from European Union cohort registries. The AVONEX Pregnancy Exposure Registry was established to prospectively study the effects of IM IFNβ-1a on the risk of birth defects and spontaneous pregnancy loss in a US population. Pregnant women with multiple sclerosis exposed to IM IFNβ-1a within ~ 1 week of conception or during the first trimester were included. Participants were followed until there was a pregnancy outcome, live-born infants were followed until age 8-12 weeks. Data were collected on IM IFNβ-1a exposure, demographics, patient characteristics, medical history, and pregnancy outcomes, including live births (with or without birth defect), spontaneous abortions/miscarriages and fetal death/stillbirth, elective abortions (with and without birth defect), and ectopic pregnancies. A population-based birth defect surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), served as the primary external control group for evaluating the risk of birth defects. Three-hundred and two patients with a median (range) age of 31.0 (16-48) years and a median (range) gestational age at the time of enrollment of 10.1 (4-39) weeks were evaluable. Most patients (n = 278/302; 92%) reported IM IFNβ-1a exposure in the week before conception and most (n = 293/302; 97%) discontinued treatment before the end of the first trimester. Of 306 pregnancy outcomes, there were 272 live births, 28 spontaneous abortions of 266 pregnancies enrolled before 22 weeks' gestation (rate 10.5%; 95% confidence interval 7.2-15.0), five elective abortions, and one stillbirth. There were 17 adjudicator-confirmed major birth defects of 272 live births (rate 6.3%; 95% confidence interval 3.8-10.0); the pattern of birth defects observed was not suggestive of a relationship to prenatal IM IFNβ-1a exposure. This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy. ClinicalTrials.gov: NCT00168714, 15 September, 2005.


Outer membrane protein A from Klebsiella pneumoniae activates bronchial epithelial cells: implication in neutrophil recruitment.
Aside from its mechanical barrier function, bronchial epithelium plays an important role both in the host defense and in the pathogenesis of inflammatory airway disorders. To investigate its role in lung defense, the effect of a bacterial cell wall protein, the outer membrane protein A from Klebsiella pneumoniae (kpOmpA) on bronchial epithelial cells (BEC) was evaluated on adhesion molecule expression and cytokine production. Moreover, the potential implication of this mechanism in kpOmpA-induced lung inflammation was also determined. Our in vitro studies demonstrated that kpOmpA strongly bound to BEAS-2B cells, a human BEC line, and to BEC primary cultures, resulting in NF-kappaB signaling pathway activation. Exposure to kpOmpA increased ICAM-1 mRNA and cell surface expression, as well as the secretion of IL-6, CXC chemokine ligand (CXCL)1, CXCL8, C-C chemokine ligand 2, CXCL10 by BEAS-2B cells, and BEC primary cultures (p < 0.005). We analyzed in vivo the consequences of intratracheal injection of kpOmpA to BALB/c mice. In kpOmpA-treated mice, a transient neutrophilia (with a maximum at 24 h) was observed in bronchoalveolar lavage and lung sections. In vivo kpOmpA priming induced bronchial epithelium activation as evaluated by ICAM-1 and CXCL1 expression, associated with the secretion of CXCL1 and CXCL5 in bronchoalveolar lavage fluids. In the lung, an increased level of the IL-6, CXCL1, CXCL5, CXCL10 mRNA was observed with a maximum at 6 h. These data showed that kpOmpA is involved in host defense mechanism by its ability to activate not only APC but also BEC, resulting in a lung neutrophilia.


Photochemical pump and NMR probe: chemically created NMR coherence on a microsecond time scale.
We report pump-probe experiments employing laser-synchronized reactions of para-hydrogen (para-H2) with transition metal dihydride complexes in conjunction with nuclear magnetic resonance (NMR) detection. The pump-probe experiment consists of a single nanosecond laser pump pulse followed, after a precisely defined delay, by a single radio frequency (rf) probe pulse. Laser irradiation eliminates H2 from either Ru(PPh3)3(CO)(H)2 1 or cis-Ru(dppe)2(H)2 2 in C6D6 solution. Reaction with para-H2 then regenerates 1 and 2 in a well-defined nuclear spin state. The rf probe pulse produces a high-resolution, single-scan (1)H NMR spectrum that can be recorded after a pump-probe delay of just 10 μs. The evolution of the spectra can be followed as the pump-probe delay is increased by micro- or millisecond increments. Due to the sensitivity of this para-H2 experiment, the resulting NMR spectra can have hydride signal-to-noise ratios exceeding 750:1. The spectra of 1 oscillate in amplitude with frequency 1101 ± 3 Hz, the chemical shift difference between the chemically inequivalent hydrides. The corresponding hydride signals of 2 oscillate with frequency 83 ± 5 Hz, which matches the difference between couplings of the hydrides to the equatorial (31)P nuclei. We use the product operator formalism to show that this oscillatory behavior arises from a magnetic coherence in the plane orthogonal to the magnetic field that is generated by use of the laser pulse without rf initialization. In addition, we demonstrate how chemical shift imaging can differentiate the region of laser irradiation thereby distinguishing between thermal and photochemical reactivity within the NMR tube.


Non steroidal anti-inflammatory drugs and COX-2 inhibitors as anti-cancer therapeutics: hypes, hopes and reality.
Non-steroidal anti-inflammatory drugs (NSAIDs) and specific inhibitors of cyclooxygenase (COX)-2, are therapeutic groups widely used for the treatment of pain, inflammation and fever. There is growing experimental and clinical evidence indicating NSAIDs and COX-2 inhibitors also have anti-cancer activity. Epidemiological studies have shown that regular use of Aspirin and other NSAIDs reduces the risk of developing cancer, in particular of the colon. Molecular pathology studies have revealed that COX-2 is expressed by cancer cells and cells of the tumor stroma during tumor progression and in response to chemotherapy or radiotherapy. Experimental studies have demonstrated that COX-2 over expression promotes tumorigenesis, and that NSAIDs and COX-2 inhibitors suppress tumorigenesis and tumor progression. Clinical trials have shown that NSAIDs and COX-2 inhibitors suppress colon polyp formation and malignant progression in patients with familial adenomatous polyposis (FAP) syndrome. Recent advances in the understanding of the cellular and molecular mechanisms of the anti-cancer effects of NSAIDs and COX-2 inhibitors have demonstrated that these drugs target both tumor cells and the tumor vasculature. The therapeutic benefits of COX-2 inhibitors in the treatment of human cancer in combination with chemotherapy or radiotherapy are currently being tested in clinical trials. In this article we will review recent advances in the understanding of the anti-tumor mechanisms of these drugs and discuss their potential application in clinical oncology.


Impact of the Acceptance of Disability on Self-Esteem among Adults with Disabilities: A Four-Year Follow-Up Study.
This study identified the acceptance of disability's impact on self-esteem among adults with disabilities in South Korea. This is a four-year follow-up study that obtained data from the Panel Survey of Employment for Persons with Disabilities from 2017 to 2020. In total, 3329 individuals participated. Logistic regression examined the acceptance of disability's effect on self-esteem. These variables were categorized based on the acceptance of disability (high→high, low→high, high→low, and low→low) and self-esteem (low and not low). Compared to the participants with a consistently high acceptance of disability, those with constantly low acceptance were 2.35 times (95% CI 1.81-3.04) more likely to have low self-esteem. When the acceptance of disability was low→high and high→low, the low self-esteem probability was 1.23 and 1.66 times, respectively. Low self-esteem was prominent for the following: men, 50-64-year olds, married, urban, economic activists, the mid-low household income category, and those with sensory disability. Acceptance of disability can adversely affect self-esteem when it is consistently low or changes from high to low. Among socio-economic factors, there were several risk factors that could make individuals more vulnerable to low self-esteem. Therefore, it is necessary to help people accept their disabilities to maintain healthy self-esteem levels.


Electromechanical coupling and output efficiency of piezoelectric bending actuators.
Electromechanical coupling mechanisms in piezoelectric bending actuators are discussed in this paper based on the constitutive equations of cantilever bimorph and unimorph actuators. Three actuator characteristic parameters, (e.g., electromechanical coupling coefficient, maximum energy transmission coefficient, and maximum mechanical output energy) are discussed for cantilever bimorph and unimorph actuators. In the case of the bimorph actuator, if the effect of the bonding layer is negligible, these parameters are directly related to the transverse coupling factor lest. In the case of the unimorph actuator, these parameters also depend on the Young's modulus and the thickness of the elastic layer. Maximum values for these parameters can be obtained by choosing proper thickness ratio and Young's modulus ratio of elastic and piezoelectric layers. Calculation results on four unimorph actuators indicate that the use of stiffer elastic material is preferred to increase electromechanical coupling and output mechanical energy in unimorph actuators.


Developing a community-academic partnership to improve recognition and treatment of depression in underserved African American and white elders.
Reducing mental health disparities among underserved populations, particularly African American elders, is an important public health priority. The authors describe the process and challenges of developing a community/academic research partnership to address these disparities. The authors are using a Community-Based Participatory Research approach to gain access to underserved populations in need of depression treatment. The authors identify six stages: 1) Collaborating to Secure Funding; 2) Building a Communications Platform and Research Infrastructure; 3) Fostering Enduring Relationships; 4) Assessing Needs/Educating about Research Process; 5) Initiating Specific Collaborative Projects (meeting mutual needs/interests); and 6) Maintaining a Sustainable and Productive Partnership. Data from a needs assessment developed collaboratively by researchers and community agencies facilitated agreement on mutual research goals, while strengthening the partnership. A community/academic-based partnership with a solid research infrastructure has been established and maintained for 3 years. Using the results of a needs assessment, the working partnership prioritized and launched several projects. Through interviews and questionnaires, community partners identified best practices for researchers working in the community. Future research and interventional projects have been developed, including plans for sustainability that will eventually shift more responsibility from the academic institution to the community agencies. To reach underserved populations by developing and implementing models of more effective mental health treatment, it is vital to engage community agencies offering services to this population. A successful partnership requires "cultural humility," collaborative efforts, and the development of flexible protocols to accommodate diverse communities.


Comparison of Biological Screening and Diagnostic Indicators to Detect In Utero Opiate and Cocaine Exposure Among Mother-Infant Dyads.
Opioid and cocaine antenatal substance use can result in significant obstetric and pediatric health implications. Accurate detection of in utero-exposed neonates can improve patient care and health outcomes. Therefore, the effectiveness of mother-infant biological and diagnostic indicators collected at labor and delivery to provide accurate detection of in utero opiate and cocaine exposure was assessed. A retrospective medical chart review included 335 mother-infant dyads exposed to antenatal substances who were delivered between January 2009 and March 2014. Mother-infant dyads were a subset of a larger retrospective cohort of 560 substance-using mothers, who had a valid meconium drug screen (MDS) and anesthesia before delivery. Alternative biological and diagnostic indicators of maternal urine drug screens (UDS), maternal substance use International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and neonatal exposure diagnostic ICD-9-CM codes were compared against MDS. Data were analyzed using classification accuracy measures. Compared with MDS, maternal UDS had the highest sensitivity [0.52, 95% confidence interval (CI), 0.39-0.65] and specificity (0.88, 95% CI, 0.79-0.97) to detect intrauterine opiate exposure. Maternal substance use diagnosis had the highest sensitivity (0.39, 95% CI, 0.16-0.61) and maternal UDS had the highest specificity (1.00, 95% CI, 0.99-1.00) to detect intrauterine cocaine exposure. Cocaine exposure had significantly higher accuracy scores across detection methods compared with opiate exposure. Alternative indicators collected at delivery were ineffective at identifying in utero substance exposure, especially neonatal-exposed ICD-9-CM codes. Low sensitivity scores indicate that many exposed neonates could be misdiagnosed or left untreated. Accurate antenatal exposure identification at delivery is an important form of tertiary assessment that warrants the development of improved screening methodology and standardization of hospital biological drug testing.


Meeting global deaf peers, visiting ideal deaf places: deaf ways of education leading to empowerment, an exploratory case study.
In a flemish case study, deaf role models revealed a moment of awakening, indicated by the Flemish sign WAKE-UP Contact with deaf cultural rhetoric made them wake up, and deconstruct and reconstruct their lives, a process represented by a circle of deaf empowerment. Flemish deaf leaders mentioned acquiring this rhetoric during visits to deaf dream worlds (in Flemish Sign Language, WORLD DREAM): places with ideal conditions for deaf people. Such global deaf encounters (Breivik, Haualand, & Solvang, 2002) lead to the "insurrection of subjugated [deaf] knowledges" (Pease, 2002, p. 33). Whereas deaf education had never provided them with deaf cultural rhetoric and was depositing upon them oppressive societal conventions (Jankowski, 1997), a common sign language (Mottez, 1993) and global deaf experience (Breivik et al., 2002; Murray, in press) in barrier-free environments (Jankowski, 1997) provided deaf ways of deaf education (Erting, 1996; Reilly, 1995).


Effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed US guidance.
The US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience? We systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience. Systematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic.


Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain.
Although cyclooxygenases (COX) and prostaglandin E synthases (PGES) have been implicated in ischemic stroke injury, little is known about their role in intracerebral hemorrhage (ICH)-induced brain damage. This study examines the expression and cellular localization of COX-1, COX-2, microsomal PGES-1 (mPGES-1), mPGES-2, and cytosolic PGES (cPGES) in mice that have undergone hemorrhagic brain injury. ICH was induced in C57BL/6 mice by intrastriatal injection of collagenase. Expression and cellular localization of COX-1, COX-2, mPGES-1, mPGES-2, and cPGES were examined by immunofluorescence staining. In the hemorrhagic brain, COX-1, mPGES-2, and cPGES were expressed constitutively in neurons; COX-1 was also constitutively expressed in microglia. The immunoreactivity of COX-2 was increased in neurons and astrocytes surrounding blood vessels at 5 h and then tended to decrease in neurons and increase in astrocytes at 1 day. At 3 days after ICH, COX-2 was observed primarily in astrocytes but was absent in neurons. Interestingly, the immunoreactivity of mPGES-1 was increased in neurons in the ipsilateral cortex and astrocytes in the ipsilateral striatum at 1 day post-ICH; the immunoreactivity of astrocytic mPGES-1 further increased at 3 days. Our data suggest that microglial COX-1, neuronal COX-2, and astrocytic COX-2 and mPGES-1 may work sequentially to affect ICH outcomes. These findings have implications for efforts to develop anti-inflammatory strategies that target COX/PGES pathways to reduce ICH-induced secondary brain damage.


Variable deficits of bone mineral despite chronic glucocorticoid therapy in pediatric patients with inflammatory diseases: a Glaser Pediatric Research Network study.
To evaluate the relationship between chronic glucocorticoid (GC) exposure and bone mineral density (BMD) in children with rheumatic diseases and inflammatory bowel disease. Lumbar spine BMD was measured by DXA in 86 GC-treated children (66% female, age 8-20 years, mixed ethnicity) screened for a multi-center intervention trial. Predictors of spine BMD z-score and vitamin D [25(OH)D] were examined by multivariable linear regression. Mean prior year and lifetime cumulative GC exposure was 77.8 mg/kg and 224.6 mg/kg, respectively. BMD z-scores ranged from -3.7 to 2.2 SD (-1.1 +/- 1.2, mean +/- SD). Lower BMD z-scores were associated with increased prior year average daily GC dose (p = 0.03), decreased height z-score (p = 0.003), and decreased 25(OH)D concentrations (p = 0.03), but explained only a small proportion of BMD variability (adjusted R2 = 0.29). The 25(OH)D levels were <20 ng/ml in 45% of patients, and low 25(OH)D was associated with non-Caucasian ethnicity (p <0.001), increased age (p = 0.004), increased parathyroid hormone (p = 0.03), and residing in the Boston area (p <0.001). Although GC exposure is significantly associated with BMD z-score, the association is too variable to serve as a consistent predictor of reduced BMD in children. Vitamin D insufficiency is common and may contribute to skeletal deficits in this population.


Lyme disease presenting with persistent headache.
Increased intracranial pressure in patients with Lyme disease is an uncommon but reported finding. We discuss 2 patients from Lyme endemic areas who initially presented with headache, nausea, and vomiting and were eventually found to have increased intracranial pressure, a mild cerebrospinal fluid pleocytosis, and positive Lyme titers. It has been shown that increased intracranial pressure in association with neuroborreliosis can lead to blindness. In endemic areas, it is important for practitioners to consider Lyme disease when patients present with persistent headache, especially in those who have evidence of increased intracranial pressure.


Fumarate reductase is essential for Helicobacter pylori colonization of the mouse stomach.
Fumarate reductase (FRD) is the key enzyme in fumarate respiration induced by anaerobic growth of bacteria. In Helicobacter pylori, this enzyme appears to be constitutively expressed under microaerobic conditions and is not essential for its survival in vitro. In this study, the role of FRD in the colonization of H. pylori was investigated using a mouse model. The frdA gene coding for subunit A of FRD, and two control genes, copA and copP associated with the export of copper out of H. pylori, were inactivated by insertion of the chloramphenicol acetyltransferase cassette into these individual genes. The isogenic mutants of H. pylori strain AH244 were obtained by natural transformation. Seventy-five ICR mice (15 mice/group) were orogastrically dosed with either the wild type H. pylori strain AH244, its isogenic mutants, or Brucella broth (negative control). Five mice from each group were killed at 2, 4 and 8 weeks post-inoculation (WPI), respectively. H. pylori colonization was not detected in mouse gastric mucosa infected with the frdA mutant at any time point in the study by both quantitative culture and PCR. In contrast, the mice inoculated with either wild type AH244, copA or copPH. pylori mutants became readily infected. These data indicate that FRD plays a crucial role in H. pylori survival in the gastric mucosa of mice. Given that FRD, present in all H. pylori strains, is immunogenic in H. pylori -infected patients and H. pylori growth in vitro can be inhibited by three anthelmintics (morantel, oxantel and thiabendazole), this enzyme could potentially be used both as a novel drug target as well as in the development of vaccines for H. pylori prevention and eradication.


A mobile application to monitor mode, content and duration of health navigation services for people living with HIV in Guatemala.
Health navigation is increasingly being used to support people living with HIV, but timely monitoring of navigation is challenging due to the burden of reporting a high volume of diverse activities. We designed a mobile application (app) for navigators to report their interactions with men who have sex with men living with HIV (n = 374), including: (1) mode of support; (2) content; and (3) duration. We assessed sociodemographic and behavioral characteristics of the study sample and calculated monitoring system indicators. We also conducted qualitative interviews with navigators (n = 7) and used thematic analysis to assess app acceptability and usability. From January 2017 to June 2018, 95.3% of participants interacted with their navigator at least one time and 4281 reports were recorded by nine navigators. The median number of interactions per participant was 10 (range: 1-46). The majority of interactions (71.6%) occurred remotely. Most frequently covered topics included: appointment reminders (36.9%), employment (19.9%), and family (15.5%). Navigators indicated that the system was easy to use, but some did not use it in real time as intended. Timely access to navigator data enabled feedback and continuous training. These data can also facilitate analysis of intensity and content of interactions to improve tailoring and sustainability.


Differential Attachment of Salmonella enterica and Enterohemorrhagic Escherichia coli to Alfalfa, Fenugreek, Lettuce, and Tomato Seeds.
Vegetable seeds have the potential to disseminate and transmit foodborne bacterial pathogens. This study was undertaken to assess the abilities of selected Salmonella and enterohemorrhagic Escherichia coli (EHEC) strains to attach to fungicide-treated versus untreated, and intact versus mechanically damaged, seeds of alfalfa, fenugreek, lettuce, and tomato. Surface-sanitized seeds (2 g) were exposed to four individual strains of Salmonella or EHEC at 20°C for 5 h. Contaminated seeds were rinsed twice, each with 10 ml of sterilized water, before being soaked overnight in 5 ml of phosphate-buffered saline at 4°C. The seeds were then vortexed vigorously for 1 min, and pathogen populations in seed rinse water and soaking buffer were determined using a standard plate count assay. In general, the Salmonella cells had higher attachment ratios than the EHEC cells. Lettuce seeds by unit weight had the highest numbers of attached Salmonella or EHEC cells, followed by tomato, alfalfa, and fenugreek seeds. In contrast, individual fenugreek seeds had more attached pathogen cells, followed by lettuce, alfalfa, and tomato seeds. Significantly more Salmonella and EHEC cells attached to mechanically damaged seeds than to intact seeds (P < 0.05). Although, on average, significantly more Salmonella and EHEC cells were recovered from untreated than fungicide-treated seeds (P < 0.05), fungicide treatment did not significantly affect the attachment of individual bacterial strains to vegetable seeds (P > 0.05), with a few exceptions. This study fills gaps in the current body of literature and helps explain bacterial interactions with vegetable seeds with differing surface characteristics.IMPORTANCE Vegetable seeds, specifically sprout seeds, have the potential to disseminate and transmit foodborne bacterial pathogens. This study investigated the interaction between two important bacterial pathogens, i.e., Salmonella and EHEC, and vegetable seeds with differing surface characteristics. This research helps understand whether seed surface structure, integrity, and fungicide treatment affect the interaction between bacterial cells and vegetable seeds.


Factors related to attempted suicide in davanagere.
What are the factors responsible for suicidal attempts? To study the socio-demographic factors, methods and reasons for suicidal attempts. Cross-sectional study. Bapuji and C.G. Hospitals attached to J.J.M. Medical College, Davanagere. A total of 540 suicidal attempters admitted to emergency wards. A pretested proforma was administered to the subjects relating the factors responsible for the attempt. The data thus obtained was compiled and analyzed. Proportions, Z-test and Chi-square test. In this study, 61.3% were males and 38.7% were females. Peak occurrence of suicidal attempts was found in the second and third decades (15-29 years). Hindus constituted about 94.6% of the total suicidal attempters. Almost half (52.2%) of the subjects had education below or up to matriculation and 83% of them were from the lower (classes IV and V) socio-economic groups. Agriculturists, housewives and unskilled workers represented 75% of the total subjects. Fifty-five percent of the subjects were from nuclear families and most (62.4%) of them were married; frequent mode of attempting suicides was by organo-phosphorus compounds (66.3%) followed by overdosage of tablets (17.8%). Common cause was family problem (27.2%) followed by illness (27%).


Minimally invasive esophagectomy.
Esophageal resection is associated with a high morbidity and mortality rate. Minimally invasive esophagectomy (MIE) might theoretically decrease this rate. We reviewed the current literature on MIE, with a focus on the available techniques, outcomes and comparison with open surgery. This review shows that the available literature on MIE is still crowded with heterogeneous studies with different techniques. There are no controlled and randomized trials, and the few retrospective comparative cohort studies are limited by small numbers of patients and biased by historical controls of open surgery. Based on the available literature, there is no evidence that MIE brings clear benefits compared to conventional esophagectomy. Increasing experience and the report of larger series might change this scenario.


Substituted benzamide inhibitors of human rhinovirus 3C protease: structure-based design, synthesis, and biological evaluation.
A series of nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease was identified using structure-based design. The design, synthesis, and biological evaluation of these inhibitors are reported. A Michael acceptor was combined with a benzamide core mimicking the P1 recognition element of the natural 3CP substrate. alpha,beta-Unsaturated cinnamate esters irreversibly inhibited the 3CP and displayed antiviral activity (EC(50) 0.60 microM, HRV-16 infected H1-HeLa cells). On the basis of cocrystal structure information, a library of substituted benzamide derivatives was prepared using parallel synthesis on solid support. A 1.9 A cocrystal structure of a benzamide inhibitor in complex with the 3CP revealed a binding mode similar to that initially modeled wherein covalent attachment of the nucleophilic cysteine residue is observed. Unsaturated ketones displayed potent reversible inhibition but were inactive in the cellular antiviral assay and were found to react with nucleophilic thiols such as DTT.


Prediction of HER2 status via random forest in 3257 Chinese patients with gastric cancer.
The accurate evaluation of human epidermal growth factor receptor 2 (HER2) is crucial for successful trastuzumab-based therapy in individuals with gastric cancer (GC). The present study, involving a retrospective cohort (N = 2865) from Wuhan Union Hospital and a prospective cohort (N = 392) from Renmin Hospital of Wuhan University, evaluated the benefits of clinical features using random forest and logistic regression models for the detection of HER2 status in patients with GC. Patients from the Union cohort were randomly assigned to either a training (N = 2005) or an internal validation (N = 860) group. Data processing and feature selection were done in Python, which was also used to build random forest and logistic regression models for the prediction of HER2 overexpression. The Renmin cohort (N = 392) was used as the external validation group. Ten features were closely correlated with HER2 overexpression, including age, albumin/globulin ratio, globulin, activated partial thromboplastin time, tumor stage, node stage, tumor node metastasis stage, tumor size, tumor differentiation, and neuron-specific enolase (NSE). Random forest and logistic regression had areas under the curve (AUC) of 0.9995 and 0.6653 in the training group and 0.923 and 0.667 in the internal validation group, respectively. When the two predictive models were validated using data from the Renmin cohort, random forest and logistic regression had AUCs of 0.9994 and 0.627, respectively. This is the first multicenter study to predict HER2 overexpression in individuals with GC, based on clinical variables. The random forest model significantly outperformed the logistic regression model.


Fast construction of voxel-level functional connectivity graphs.
Graph-based analysis of fMRI data has recently emerged as a promising approach to study brain networks. Based on the assessment of synchronous fMRI activity at separate brain sites, functional connectivity graphs are constructed and analyzed using graph-theoretical concepts. Most previous studies investigated region-level graphs, which are computationally inexpensive, but bring along the problem of choosing sensible regions and involve blurring of more detailed information. In contrast, voxel-level graphs provide the finest granularity attainable from the data, enabling analyses at superior spatial resolution. They are, however, associated with considerable computational demands, which can render high-resolution analyses infeasible. In response, many existing studies investigating functional connectivity at the voxel-level reduced the computational burden by sacrificing spatial resolution. Here, a novel, time-efficient method for graph construction is presented that retains the original spatial resolution. Performance gains are instead achieved through data reduction in the temporal domain based on dichotomization of voxel time series combined with tetrachoric correlation estimation and efficient implementation. By comparison with graph construction based on Pearson's r, the technique used by the majority of previous studies, we find that the novel approach produces highly similar results an order of magnitude faster. Its demonstrated performance makes the proposed approach a sensible and efficient alternative to customary practice. An open source software package containing the created programs is freely available for download.


Flywheel resistance training calls for greater eccentric muscle activation than weight training.
Changes in muscle activation and performance were studied in healthy men in response to 5 weeks of resistance training with or without "eccentric overload". Subjects, assigned to either weight stack (grp WS; n = 8) or iso-inertial "eccentric overload" flywheel (grp FW; n = 9) knee extensor resistance training, completed 12 sessions of four sets of seven concentric-eccentric actions. Pre- and post-measurements comprised maximal voluntary contraction (MVC), rate of force development (RFD) and training mode-specific force. Root mean square electromyographic (EMG(RMS)) activity of mm. vastus lateralis and medialis was assessed during MVC and used to normalize EMG(RMS) for training mode-specific concentric (EMG(CON)) and eccentric (EMG(ECC)) actions at 90°, 120° and 150° knee joint angles. Grp FW showed greater (p < 0.05) overall normalized angle-specific EMG(ECC) of vastii muscles compared with grp WS. Grp FW showed near maximal normalized EMG(CON) both pre- and post-training. EMG(CON) for Grp WS was near maximal only post-training. While RFD was unchanged following training (p > 0.05), MVC and training-specific strength increased (p < 0.05) in both groups. We believe the higher EMG(ECC) activity noted with FW exercise compared to standard weight lifting could be attributed to its unique iso-inertial loading features. Hence, the resulting greater mechanical stress may explain the robust muscle hypertrophy reported earlier in response to flywheel resistance training.


Growth factors and determinants of wound repair.
The application of contemporary biochemical, analytical, and production technology have, in part, clarified the physiologic processes and identified many new factors active in wound repair. A restructuring of the sequence of the reparative events for the wound environment followed the identification of an array of hormonal polypeptides and growth factors. Deterrents of the early phases of repair include neoplasms and therapeutic doses of steroidal and cytotoxic agents. The physiological effects of these agents are rapidly reversed following their removal with a resultant enhancement of wound tear strength and wound energy. The use of synthetic growth hormone and recombinant DNA-produced polypeptide may reverse the deleterious wound healing events initiated in the injured and tumor-bearing host.


Terpenoid-lupeol of red dragon fruit (Hylocereus polyrhizus) and its immunomodulatory activity.
Red dragon fruit (Hylocereus polyrhizus, (F.A.C. Weber) Britton and Rose) has been reported to have various biological activities such as antimicrobial, anti-hypercholesterolemia, anti-diabetes mellitus, cardiovascular risk reduction, health supplement, and melanoma cell inhibitory. The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health, therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body. In order to simplify methanol extract was partition and fractionation. The active compounds of petroleum ether fraction were separated and purified using preparative thin layer chromatography. The identification of the compounds structure was conducted through spectroscopic techniques, including UV, FT-IR, 13CNMR and 1HNMR spectroscopy. The data of spectra revealed that the isolate is lupeol. The statistical analysis of macrophage activity showed that the isolate with concentrations of 100, 50, 25, 12.5 and 6.25μg/mL could activate the macrophages higher than control negative. Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol (1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [α] chrysen-9ol. In vitro test shows that the isolated compound had an immunomodulatory activity by increases macrophage phagocytosis of latex beads.


Pregnancy-specific beta 1-glycoprotein in amniotic fluid in high risk late pregnancy.
Pregnancy-specific beta 1-glycoprotein (PSBG) levels in amniotic fluid were studied by radioimmunoassay in 70 normal and 90 high risk pregnancies between 34 and 41 weeks. Most values from high risk singleton pregnancies were within the normal range. Intra-uterine growth retardation (n = 22) was associated with normal amniotic fluid PSBG levels. In twin pregnancies, the amniotic fluid PSBG values were usually above the normal mean, but within the normal range. The average ratio between amniotic fluid and maternal serum PSBG concentrations was 1:16. Amniotic fluid PSBG concentration did not correlate with the maternal serum PSBG level, and no relationship with fetal distress, infant birth weight or length, sex or placental weight was observed.


Drug-sensitivity profile of clinical Mycobacterium tuberculosis isolates--a retrospective study from a chest-disease institute in India.
Multi-drug-resistant tuberculosis (MDR-TB) is a major public-health problem, because treatment is complicated and patients remain infectious for months or years, despite receiving the best available therapy. To gain better understanding of MDR-TB, a retrospective study was initiated to determine the level of drug resistance among patients in a chest-disease institute in India. Two hundred and sixty-three isolates from treatment-failure pulmonary tuberculosis patients (20-70 years) were studied. Drug-sensitivity testing was performed by the modified-proportion method. First- and second-line drugs, along with two quinolone drugs (ofloxacin and ciprofloxacin), were tested. Patients included in this study did not improve with therapy; however, 151 isolates (57.5 %) were susceptible to all four first-line antituberculosis drugs. This study reports low resistance to fluoroquinolones among the strains present in these patients.


[Lymphoid structures in the female endometrium in ontogenesis].
Lymphoid formations of human endometrium are presented in stroma of the uterine corpus mucous membrane as lymphoid cells (so called diffuse lymphoid tissue), lymphoid nodules and interepithelial lymphocytes in glandular and covering epithelium++. Peculiarities in organization of these formations are seen as slight saturation of the endometrium with lymphoid tissue, small size of lymphoid nodules++. The lymphoid structures in question reach their maximal development during the adolescent and first mature age. During the generative period among diffusely arranged T-lymphocytes sub-populations of T-suppressors predominate. This is probably connected with participation of suppressive mechanisms of local immunity in ensuring blastocyst implantation.


Parosteal osteosarcoma: a case report.
Parosteal osteosarcoma is a low-grade malignant tumor arising from the periosteum. It involves mainly adults of third to sixth decades and the favorite site is the posterior aspect of distal femoral metaphysis. Microscopically, it is composed of woven to lamellar bone trabeculae within spindle cell stroma. We present a case of parosteal osteosarcoma that has very well-formed lamellar bone trabeculae and fat marrow under microscopic examination. Without the help of radiologic study, it is impossible to make the diagnosis of parosteal osteosarcoma.


Digital media: Promoting healthy screen use in school-aged children and adolescents.
Digital media are integrated into the everyday lives of children and adolescents, with potential benefits and risks for learning, mental and physical health, and for social life. This statement examines the cognitive, psychosocial, and physical effects of digital media on school-aged children and adolescents, with a focus on family routines, context, and activities. Evidence-based guidance for clinicians and families involves four principles: healthy management, meaningful screen use, positive modelling, and balanced, informed monitoring of screen time and behaviours.


Automatic Extraction of Hiatal Dimensions in 3-D Transperineal Pelvic Ultrasound Recordings.
The aims of this work were to create a robust automatic software tool for measurement of the levator hiatal area on transperineal ultrasound (TPUS) volumes and to measure the potential reduction in variability and time taken for analysis in a clinical setting. The proposed tool automatically detects the C-plane (i.e., the plane of minimal hiatal dimensions) from a 3-D TPUS volume and subsequently uses the extracted plane to automatically segment the levator hiatus, using a convolutional neural network. The automatic pipeline was tested using 73 representative TPUS volumes. Reference hiatal outlines were obtained manually by two experts and compared with the pipeline's automated outlines. The Hausdorff distance, area, a clinical quality score, C-plane angle and C-plane Euclidean distance were used to evaluate C-plane detection and quantify levator hiatus segmentation accuracy. A visual Turing test was created to compare the performance of the software with that of the expert, based on the visual assessment of C-plane and hiatal segmentation quality. The overall time taken to extract the hiatal area with both measurement methods (i.e., manual and automatic) was measured. Each metric was calculated both for computer-observer differences and for inter-and intra-observer differences. The automatic method gave results similar to those of the expert when determining the hiatal outline from a TPUS volume. Indeed, the hiatal area measured by the algorithm and by an expert were within the intra-observer variability. Similarly, the method identified the C-plane with an accuracy of 5.76 ± 5.06° and 6.46 ± 5.18 mm in comparison to the inter-observer variability of 9.39 ± 6.21° and 8.48 ± 6.62 mm. The visual Turing test suggested that the automatic method identified the C-plane position within the TPUS volume visually as well as the expert. The average time taken to identify the C-plane and segment the hiatal area manually was 2 min and 35 ± 17 s, compared with 35 ± 4 s for the automatic result. This study presents a method for automatically measuring the levator hiatal area using artificial intelligence-based methodologies whereby the C-plane within a TPUS volume is detected and subsequently traced for the levator hiatal outline. The proposed solution was determined to be accurate, relatively quick, robust and reliable and, importantly, to reduce time and expertise required for pelvic floor disorder assessment.


The effect of acupuncture on relieving pain after inguinal surgeries.
Postoperative pain is one of the most prevalent and bothersome issues found in the surgical department. Nowadays, there are various methods of acupuncture used for relieving pain without the complications found in some routine postoperative analgesics. These methods could be especially useful for high risk patients prone to complications from analgesics, such as transplantation recipients. The aim of this study was to evaluate the efficacy of electro-acupuncture on postoperative pain control after inguinal surgeries. Ninety male patients, who were referred to our department with indications of inguinal surgery, were included in the study and randomly divided into two groups, such as acupuncture and control. We used electro-acupuncture for the acupuncture group and no actual acupuncture (but placed needle electrodes similar to the acupuncture group) for the control group. Postoperative pain was quantified by a blind observer in both groups using a visual analogue scale (VAS) standard score before being compared. Pain intensity and analgesic use were significantly higher in the control group (P < 0.05). In the acupuncture group, the VAS pain scores were significantly lower than the control group at 0.5, 1 and 2 hours post operation. When the opioid related side effects were compared for each group, the results showed that the number of subjects who experienced dizziness in the acupuncture group was significantly lower than the control group (P < 0.05). Acupuncture in patients, after inguinal surgery, can reduce the need of analgesics, which also directly reduces the complications that may occur when analgesics are used in relieving pain postoperatively.


Intensive rehabilitation combined with HBO2 therapy in children with cerebral palsy: a controlled longitudinal study.
The present study aimed to assess the effect of intensive rehabilitation combined with hyperbaric oxygen (HBO2) therapy on gross motor function in children with cerebral palsy (CP). We carried out an open, observational, platform-independent study in 150 children with cerebral palsy with follow-up over eight months to compare the effects of standard intensive rehabilitation only (control group n = 20) to standard intensive rehabilitation combined with one of three different hyperbaric treatments. The three hyperbaric treatments used were: air (FiO2 = 21%) pressurized to 1.3 atmospheres absolute/atm abs (n = 40); 100% oxygen pressurized at 1.5 atm abs (n = 32); and 100% oxygen, pressurized at 1.75 atm abs (n = 58). Each subject assigned to a hyperbaric arm was treated one hour per day, six days per week during seven weeks (40 sessions). Gross motor function measure (GMFM) was evaluated before the treatments and at two, four, six and eight months after beginning the treatments. All four groups showed improvements over the course of the treatments in the follow-up evaluations (p < 0.001). However, GMFM improvement in the three hyperbaric groups was significantly superior to the GMFM improvement in the control group (p < 0.001). There was no significant difference between the three hyperbaric groups. The eight-month-long benefits we have observed with combined treatments vs. rehabilitation can only have been due to a beneficial effect of hyperbaric treatment.


Neuroprotective effects of melatonin administration against chronic immobilization stress in rats.
Chronic stress can impair brain functions and play a well-known role in the development of stress-related disorders such as anxiety. Melatonin (Mel) is a neurohormone which regulate several physiological processes including mood and behavior. This experimental study was designed to evaluate the effect of Mel on chronic immobilization stress (CIS) for 6 weeks in rats and to elucidate its possible underlying mechanisms. Twenty-eight adult male Wistar albino rats were divided into four equal groups: the control group, the Mel-treated group which was injected daily with Mel (10 mg/kg/day; IP) for 6 weeks, the stressed group which was subjected to CIS protocol daily for 6 weeks, and the Mel-treated stressed group which was injected with Mel and concurrently exposed to CIS protocol for 6 weeks. The Mel-treated stressed group showed reduction of both relative adrenal weight and the serum corticosterone levels, suppression of the anxiety-like behavior, increased levels of serotonin, noradrenaline and oxytocin in the frontal cortex, and improved histopathological structure and decreased chromogranin A (CgA) protein expression in the frontal cortex when compared with the chronically stressed group. We concluded that Mel is anxiolytic and this effect was mediated in part by its ability to increase the central release of oxytocin and monoamines and to downregulate CgA protein expression in the frontal cortex.


Cannabis use in adolescence and risk of future disability pension: a 39-year longitudinal cohort study.
This study aimed at examining a possible association between cannabis use in adolescence and future disability pension (DP). DP can be granted to any person in Sweden aged 16-65 years if working capacity is judged to be permanently reduced due to long-standing illness or injury. Data were obtained from a longitudinal cohort study comprising 49,321 Swedish men born in 1949-1951 who were conscripted to compulsory military service aged 18-20 years. Data on DP was collected from national registers. Results showed that individuals who used cannabis in adolescence had considerably higher rates of disability pension throughout the follow-up until 59 years of age. In Cox proportional-hazards regression analyses, adjustment for covariates (social background, mental health, physical fitness, risky alcohol use, tobacco smoking and illicit drug use) attenuated the associations. However, when all covariates where entered simultaneously, about a 30% increased hazard ratio of DP from 40 to 59 years of age still remained in the group reporting cannabis use more than 50 times. This study shows that heavy cannabis use in late adolescence was associated with an increased relative risk of labor market exclusion through disability pension.


Biochemical signature assay for use in a biosensor platform to detect bacteria in drinking water biofilms.
The objective of the study was to identify the enzymatic-biochemical (enz-bio) signatures of Escherichia coli and Salmonella for rapid detection of these bacteria in drinking water biofilms. The relative potency of lipophilic, glucosidic, and proteolytic activities in biofilms containing single bacterial species and mixture of different bacterial was used to identify the enz-bio signatures of Escherichia coli and Salmonella. The enz-bio signatures identified were: Lipophilic < Glucosidic < Proteolytic (for Escherichia coli); and Glucosidic = Lipophilic < Proteolytic (for Salmonella). The enz-bio assays were performed sequentially for detecting Escherichia coli and Salmonella in pure and mixed biofilm cultures formed on the coupons incubated in a batch reactor. The results obtained were substantiated by culture-based assays indicating comparable data. The enz-bio sensing method described here is a proof of principle and the results of this study provide a platform for the fabrication of a biosensor for bacterial detection in biofilms. The detection time required for the biosensor platform versus culture methods ranged from 10 to 120 min and 24 to 48 h, respectively.


Structure of a 7Fe ferredoxin from Azotobacter vinelandii.
The structure of the 7Fe ferredoxin from Azotobacter vinelandii has been solved from a 3.0-A multiple isomorphous replacement map. The crystals belong to space group P43212 with a = 55.22, c = 95.20 A, and Z = 1. Heavy-atom derivatives were prepared with K2PtCl4,K2[OsO2(OH)4], and Na3RhCl6. Anomalous scattering data were collected for native (Fe) and Pt derivative crystals. The figure of merit for 3,322 reflections to 3.0 A is 0.74. The structure consists of an NH2-terminal core of residues 1-50 which form the Fe-S cluster sites, and a COOH-terminal chain of residues 51-107 which wraps around this core. The [3Fe-3S] cluster is ligated by cysteines 8, 11, 16, 20, and 49 and a sixth ligand which is either glutamic acid 18 or an exogenous small molecule. The [4Fe-4S] cluster is ligated by cysteines 24, 39, 42, and 45. The coordination of both Fe-S centers has been confirmed by fitting of the cluster atoms and residues 1-50 to unbiased 2Fo-Fc Fourier maps at 2.5-A resolution. The structure of the 3Fe center has also been confirmed with anomalous scattering difference Fourier maps using both isomorphous replacement and refined phases. The partially refined structure at 2.5 A (3,490 reflections, 6.0 sigma(F)) has R = 35%.


Characterization of GFRα-1-positive and GFRα-1-negative spermatogonia in neonatal pig testis.
Type A spermatogonia, including spermatogonial stem cells, are primary cells that maintain spermatogenesis and produce spermatozoa. Many spermatogonial markers have been reported in rodents. However, few markers have been identified in pig spermatogonia. Despite the lack of information, it is necessary to separate pure spermatogonial cells from whole testicular cells to understand the mechanism of spermatogenic meiosis and to establish spermatogonial stem cells for further biotechnological studies. The purpose of this study was to identify glial cell-derived neurotrophic factor receptor alpha-1 (GFRα-1) as a surface marker for early spermatogonia in neonatal pig testes. Histological analysis of 3-day-old pig testes revealed that type A spermatogonia, which lack heterochromatin, could be distinguished in neonatal pig testes. Immunohistochemistry of neonatal pig testes with GFRα-1 antibody identified that some of the spermatogonial cells expressed GFRα-1 on the cell membrane. Co-immunostaining with both GFRα-1 and protein gene product 9.5 (PGP 9.5) detected PGP 9.5 in all spermatogonia of neonatal pig testes, whereas GFRα-1 was not detected on the surface of some PGP 9.5-positive cells, indicating that some of the spermatogonial cells were PGP 9.5 positive and GFRα-1 negative. After immunomagnetic cell sorting using a GFRα-1 antibody, both GFRα-1-positive and GFRα-1-negative cells expressed PGP 9.5. Identifying the differential mRNA expression of both GFRα-1-positive and GFRα-1-negative cells using reverse transcription-polymerase chain reaction analysis revealed the expression of promyelocytic leukaemia zinc finger, octamer-binding protein 4 and homeobox transcription factor in both cell types. These results suggest that GFRα-1-positive and GFRα-1-negative spermatogonia exist in PGP 9.5-positive spermatogonia during the early stage of pig testes spermatogenesis, and that GFRα-1 can be used for sorting PGP 9.5-expressing spermatogonia.


Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans.
There is a general consensus that overconsumption of sugar-sweetened beverages contributes to the prevalence of obesity and related comorbidities such as type 2 diabetes (T2D). Whether a similar relationship exists for no- or low-calorie "diet" drinks is a subject of intensive debate and controversy. Here, we demonstrate that consuming seven sucralose-sweetened beverages with, but not without, a carbohydrate over 10 days decreases insulin sensitivity in healthy human participants, an effect that correlates with reductions in midbrain, insular, and cingulate responses to sweet, but not sour, salty, or savory, taste as assessed with fMRI. Taste perception was unaltered and consuming the carbohydrate alone had no effect. These findings indicate that consumption of sucralose in the presence of a carbohydrate rapidly impairs glucose metabolism and results in longer-term decreases in brain, but not perceptual sensitivity to sweet taste, suggesting dysregulation of gut-brain control of glucose metabolism.


[Chemical constituents of Scurrula parasitica].
A new triterpenoid ester, 7β-hydroxyl-hop-22(29)-en-3β-O-palmitate (1), was isolated from the stems and leaves of Scurrula parasitica parasitic on Nerium indicum, along with nine known compounds, uvaol (2), 3-epi-ursolic acid (3), 3β-hydroxyl-hop-22(29)-ene (4), 3β, 15α-dihydroxyl-lup-20(29)-ene (5), lup-20(29)-en-3-O-α-D-glucoside (6), stigmasterol-3-O-β-D-glucoside (7), digitoxin-3-O-α-D-glucoside (8), behenic acid (9), octacosyl alcohol (10). Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC) and HR-ESI-MS analyses. Compounds 2-10 were isolated from this plant for the first time.


Visual mismatch response evoked by a perceptually indistinguishable oddball.
Mismatch field (MMF) is an early magnetoencephalographic response evoked by deviant stimuli within a sequence of standard stimuli. Although auditory MMF is reported to be an automatic response, the automaticity of visual MMF has not been clearly demonstrated, partly because of the difficulty in designing an ignore condition. Our modified oddball paradigm had a masking stimulus inserted between briefly presented standard and deviant stimuli (vertical gratings with different spatial frequencies). Perceptual discrimination between masked standard and deviant stimuli was difficult, but the early magnetoencephalographic response for the deviant was significantly larger than that for the standard, when the former had a higher spatial frequency than the latter. Our findings strongly support the hypothesis that visual MMF is evoked automatically.


Biobank participation and returning research results: perspectives from a deliberative engagement in South Side Chicago.
To be respectful of the public, biobank guiding principles and operations should be responsive to and inclusive of the values and beliefs of their participants. In an effort to increase knowledge and inform institutional policies, we conducted a deliberative engagement of individuals from two healthcare facilities in South Side Chicago that serve different socioeconomic communities to consider biobank policies regarding return of research results. We recruited primary caregivers of children receiving care at either a Federally Qualified Health Center or a university-based practice to attend two full-day deliberative engagement sessions, which included four educational presentations followed by focus group discussions. Surveys were administered to assess attitudes before and after the engagement, and an evaluation was conducted to assess the deliberative engagement process. All 45 participants self-identified as African-American. Focus group themes included: (1) overall interest in biobank participation, broad consent, and recontact; (2) root causes of distrust and potential biobank strategies to facilitate trust; (3) perceived positive and negative aspects of receiving research results; and (4) strong interest in receiving and managing their children's research results. Survey data indicated the same degree of interest in receiving results about themselves as about their children. Pre- and post-session findings showed mainly non-significant attitudinal changes in level of interest in biobank participation and return of research results, although there was a decrease in level of concern regarding identification from research data. Our findings reveal shared community insights important in facilitating relationships and policy discussions between biobank researchers and research participants.


Human immunodeficiency virus type 1 incorporates both glycosyl phosphatidylinositol-anchored CD55 and CD59 and integral membrane CD46 at levels that protect from complement-mediated destruction.
Human immunodeficiency virus type 1 (HIV-1) can be either resistant or sensitive to complement-mediated destruction depending on the host cells. Incorporation of different levels of host cell CD46, CD55 and CD59 may account for this differential sensitivity to complement. However, it has not been determined whether CD46, CD55 and CD59 can all be incorporated at levels which protect virions. To determine whether each of these proteins can protect HIV-1, virions were derived from CHO cells expressing either human CD46, CD55 or CD59. Virions were shown to incorporate both glycosyl phosphatidylinositol (GPI)-anchored CD55 and CD59 as well as transmembrane CD46. Importantly, all three virus preparations were significantly more resistant to complement lysis than control virus. This study demonstrates that HIV-1 incorporates both transmembrane and GPI-anchored complement control proteins from host cells and that both types of protein increase complement resistance of virus.


Myocardial infarction among professional drivers.
Professional drivers are at an increased risk of myocardial infarction but the underlying causes for this increased risk are uncertain. We identified all first events of myocardial infarction among men age 45-70 years in Stockholm County for 1992 and 1993. We selected controls randomly from the population. Response rates of 72% and 71% resulted in 1067 cases and 1482 controls, respectively. We obtained exposure information from questionnaires. We calculated odds ratios (ORs), with and without adjustment for socioeconomic status, tobacco smoking, alcohol drinking, physical inactivity at leisure time, overweight status, diabetes and hypertension. The crude OR among bus drivers was 2.14 (95% confidence interval = 1.34-3.41), among taxi drivers 1.88 (1.19-2.98) and among truck drivers 1.66 (1.22-2.26). Adjustment for potential confounders gave lower ORs: 1.49 (0.90-2.45), 1.34 (0.82-2.19) and 1.10 (0.79-1.53), respectively. Additional adjustment for job strain lowered the ORs only slightly. An exposure-response pattern (by duration of work) was found for bus and taxi drivers. The high risk among bus and taxi drivers was partly explained by unfavorable life-style factors and social factors. The work environment may contribute to their increased risk. Among truck drivers, individual risk factors seemed to explain most of the elevated risk.


Optimizing patient-centered care in breast reconstruction: the importance of preoperative information and patient-physician communication.
In breast reconstruction, achieving patient satisfaction is a central goal. While much is known about clinical variables that may influence satisfaction, little is known about how the process of care may affect patient perceptions of outcome. The aim of this study was to examine how preoperative information and interactions with the surgical and medical teams might influence patient satisfaction with the outcome. A multicenter, cross-sectional study design was used. The BREAST-Q (breast reconstruction module) was administered in a postal survey to a cohort of breast reconstruction patients in North America. The association between patient satisfaction with the process of care and satisfaction with the outcome of breast reconstruction was evaluated using linear regression. Multivariate regression models were constructed to control for confounders and to identify predictors of outcome. The study sample (n=510; response rate, 66 percent) was characterized by a mean age of 54.3±9.3 years (range, 21.0 to 81.0 years) and a mean body mass index of 25.2±4.3 (range, 16.3 to 48.9). On multivariate analysis, satisfaction with information and satisfaction with the plastic surgeon predicted higher satisfaction with breasts (information, p<0.001; plastic surgeon, p=0.003; R(2)=0.29) and higher satisfaction with overall outcome (satisfaction with information, p<0.001; satisfaction with plastic surgeon, p<0.001; R(2)=0.31). Patient-centered care is an important aspect of quality of care. Patients' levels of satisfaction with preoperative information and their interaction with their plastic surgeon significantly influence satisfaction with their breasts and overall outcome. Future research to develop methods to enhance information delivery and the surgeon-patient relationship may optimize outcomes in breast reconstruction patients. Risk, III.


Evidence that implicit assumptions of 'no evolution' of disease vectors in changing environments can be violated on a rapid timescale.
Projected impacts of climate change on vector-borne disease dynamics must consider many variables relevant to hosts, vectors and pathogens, including how altered environmental characteristics might affect the spatial distributions of vector species. However, many predictive models for vector distributions consider their habitat requirements to be fixed over relevant time-scales, when they may actually be capable of rapid evolutionary change and even adaptation. We examine the genetic signature of a spatial expansion by an invasive vector into locations with novel temperature conditions compared to its native range as a proxy for how existing vector populations may respond to temporally changing habitat. Specifically, we compare invasions into different climate ranges and characterize the importance of selection from the invaded habitat. We demonstrate that vector species can exhibit evolutionary responses (altered allelic frequencies) to a temperature gradient in as little as 7-10 years even in the presence of high gene flow, and further, that this response varies depending on the strength of selection. We interpret these findings in the context of climate change predictions for vector populations and emphasize the importance of incorporating vector evolution into models of future vector-borne disease dynamics.


Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Low-dose extrapolation and dose-related transitions are paramount in the ongoing debate regarding the quantification of cancer risks for nongenotoxic carcinogens. Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the constitutive androstane receptor (CAR) resulting in rodent liver tumors. In this study, male and female CD-1 mice administered dietary PB at 0, 0.15, 1.5, 15, 75, or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular endpoints below, at (∼75 mg/kg-day), and above the carcinogenic dose level of PB and examine these responses using benchmark dose modeling. Linear toxicokinetics were observed for all doses. Increased liver weight, hepatocellular hypertrophy, and mitotic figures were seen at 75 and 150 mg/kg-day. CAR activation, based on Cyp2b qPCR and pentoxyresorufin dealkylase activity, occurred at doses ≥ 1.5 mg/kg-day. The no-observable transcriptional effect level for global gene expression was 15 mg/kg-day. At 2 days, several xenobiotic metabolism and cell protective pathways were activated at lower doses and to a greater degree in females. However, hepatocellular proliferation, quantified by bromodeoxyuridine immunohistochemistry, was the most sensitive indicator of PB exposure with female mice more sensitive than males, contrary to sex-specific differences in sensitivity to hepatocarcinogenesis. Taken together, the identification of low-dose cellular and molecular transitions in the subtumorigenic dose range aids the understanding of early key events in CAR-mediated hepatocarcinogenesis.


Updates of Recent Vinpocetine Research in Treating Cardiovascular Diseases.
Vinpocetine is a derivative of vincamine. It has been used to prevent and treat cerebrovascular disorders such as stoke and dementia, and remains widely available in dietary supplements that often marketed as nootropics. Due to its excellent safety profile at therapeutic dose regimen, vinpocetine has raised research interest in its new applications in various experimental disease models. Here we review recent studies that uncovered novel functions of vinpocetine in cardiovascular diseases, including atherosclerosis, obesity, neointimal hyperplasia, vasoconstriction, pathological cardiac remodeling and ischemia stroke. Molecular mechanisms underlined the protective effects of vinpocetine are also discussed. These novel findings may suggest a broadened usage of vinpocetine against relevant cardiovascular diseases in human.


Repeated Parental Singing During Kangaroo Care Improved Neural Processing of Speech Sound Changes in Preterm Infants at Term Age.
Preterm birth carries a risk for adverse neurodevelopment. Cognitive dysfunctions, such as language disorders may manifest as atypical sound discrimination already in early infancy. As infant-directed singing has been shown to enhance language acquisition in infants, we examined whether parental singing during skin-to-skin care (kangaroo care) improves speech sound discrimination in preterm infants. Forty-five preterm infants born between 26 and 33 gestational weeks (GW) and their parents participated in this cluster-randomized controlled trial (ClinicalTrials ID IRB00003181SK). In both groups, parents conducted kangaroo care during 33-40 GW. In the singing intervention group (n = 24), a certified music therapist guided parents to sing or hum during daily kangaroo care. In the control group (n = 21), parents conducted standard kangaroo care and were not instructed to use their voices. Parents in both groups reported the duration of daily intervention. Auditory event-related potentials were recorded with electroencephalogram at term age using a multi-feature paradigm consisting of phonetic and emotional speech sound changes and a one-deviant oddball paradigm with pure tones. In the multi-feature paradigm, prominent mismatch responses (MMR) were elicited to the emotional sounds and many of the phonetic deviants in the singing intervention group and in the control group to some of the emotional and phonetic deviants. A group difference was found as the MMRs were larger in the singing intervention group, mainly due to larger MMRs being elicited to the emotional sounds, especially in females. The overall duration of the singing intervention (range 15-63 days) was positively associated with the MMR amplitudes for both phonetic and emotional stimuli in both sexes, unlike the daily singing time (range 8-120 min/day). In the oddball paradigm, MMRs for the non-speech sounds were elicited in both groups and no group differences nor connections between the singing time and the response amplitudes were found. These results imply that repeated parental singing during kangaroo care improved auditory discrimination of phonetic and emotional speech sounds in preterm infants at term age. Regular singing routines can be recommended for parents to promote the development of the auditory system and auditory processing of speech sounds in preterm infants.