Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury.
Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute ischemic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery occlusion, and evaluated the potential mechanisms underlying its effects. Pretreatment with DHI (0.9 and 1.8 mL/kg) resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upregulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI (1.8 mL/kg) administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.


Expression in Escherichia coli of a synthetic gene coding for horse heart myoglobin.
A gene for expression of horse heart myoglobin in Escherichia coli has been constructed in one step from long synthetic oligonucleotides. The synthetic gene contains an efficient translation initiation signal and used codons that are commonly found in E. coli. Unique restriction sites are placed throughout the gene. It has been inserted in a phagemid vector and is expressed from the lac promoter in E. coli at high efficiency, the soluble heme protein representing approximately 10% of soluble protein. Two versions of horse heart myoglobin were produced with aspartic acid or asparagine at residue 122. Comparison of chromatographic mobilities of these two proteins with authentic horse heart myoglobin identified aspartic acid as the correct residue 122. The availability of this gene, which is designed to facilitate oligonucleotide mutagenesis or cassette mutagenesis, will allow systematic structure-function analysis of horse heart myoglobin.


Needle electromyography of the diaphragm: a new technique.
Electrodiagnostic evaluation of diaphragmatic function has consisted of phrenic nerve stimulation and surface or esophageal recordings of the electrical activity of the diaphragm. Needle electromyography of the diaphragm has rarely been reported because of the perceived danger of this procedure. We describe a new technique for needle electromyography of the diaphragm. An EMG electrode is placed in the costal insertion of the diaphragm under the 8th, 9th, or 10th rib cartilage, distant from the major vessels, pleura, lungs, and abdominal viscera. Diaphragmatic denervation was found in 42 of 81 patients using this method. There were no complications related to the procedure. Needle electromyography of the diaphragm provides important information in the diagnosis and management of respiratory dysfunction.


The use of an intraluminal shunt for bypass grafts of the cavernous internal carotid artery. Technical note.
The authors describe an indwelling intraluminal shunt for use during graft bypass procedures of the cavernous internal carotid artery. The clinical use of this shunt in a patient with meningioma invading the right cavernous sinus is described. This shunt has also been found applicable during carotid endarterectomy, and should prove to be a useful addition to the neurosurgical armamentarium for skull-base surgery.


Regulation of growth hormone and thyrotropin secretion by somatostatin systems in rat brain.
Somatostatin inhibits growth hormone (GH) and thyrotropin (TSH) secretion in the rat. Previous studies have shown that small discrete lesions of the periventricular hypothalamic (PV) and medial-basal amygdaloid (AMG) nuclei, which contain high concentrations of somatostatin neurons, reduce somatostatin-like immunoreactivity (SLI) in the median eminence (ME) by approximately two thirds and one third, respectively. The present study assessed the function of the PV and AMG somatostatin systems in the regulation of basal episodic GH and TSH secretion. Three experiments were performed in freely behaving, chronically cannulated adult male rats. In experiment 1, bilateral electrolytic lesions (20 mC) were placed in the PV at the level of the paraventricular nucleus. In experiment 2, bilateral thermal lesions (55 degrees C X 1 min) were placed in the AMG. In experiment 3, thermal lesions were placed in both the PV and AMG (PV/AMG). Blood samples were removed from animals every 15 min for 5.5 h 14-21 days postoperatively. The ME was microdissected for determination of SLI content. PV, AMG and PV/AMG lesions reduced ME SLI by 59, 26, and 91%, respectively. PV or AMG lesions had no effect on the amplitude or frequency of GH secretory peaks, GH trough levels or the total amount of GH secreted, whereas combined PV/AMG lesions reduced GH peak levels. Lesions of the AMG caused a 34% increase in mean plasma TSH levels, while PV or PV/AMG lesions reduced TSH. The latter effect was probably caused by damage to thyrotropin-releasing hormone neurons and/or axons, which are also located in the PV region. These results suggest that PV and AMG somatostatin systems may not have a significant role in the regulation of basal episodic GH secretion and the putative AMG somatostatin system exerts a significant inhibitory influence on TSH secretion.


Spatially modulated snapshot imaging polarimeter using two Savart polariscopes.
We present a spatially modulated snapshot imaging polarimeter using two Savart polariscopes (SMSIPTS). Not only can it avoid alignment angle errors and additional phase errors of a half-wave plate (HWP), it can also avoid changing the HWP frequently when we want the target polarization state at different wavelengths and can increase some channel bandwidth to improve image quality, compared with a spatially modulated snapshot imaging polarimeter (SMSIP). The alignment angle error and additional phase errors of SMSIP and the optical layout and principle of SMSIPTS are derived first. The full Stokes polarization images can be obtained by processing the interferogram. Based on SMSIPTS, we determine the filtering method by simulation. We proved the feasibility of SMSIPTS, and the effect of SMSIPTS and SMSIP on reconstruction is compared by simulation. Last, we experimentally verified the feasibility of the theory of SMSIPTS.


Increased intracellular cAMP renders HL-60 cells resistant to cytotoxicity of taxol.
The treatment of advanced cancers with paclitaxel (taxol) is hindered by the development of drug resistance. Resistance to taxol is known to be associated with multidrug resistance (MDR) and a mutation affecting either the alpha- or beta-subunit of tubulin. In this study, we demonstrated that an intracellular cAMP level may also play an important role in resistance to taxol in HL-60, acute promyelocytic leukemia cells. Exposure of HL-60 cells to various doses of taxol for 18 hr resulted in cell death. However, pretreatment of the cells with cAMP analogs such as N6:O2-dibutyl cAMP (Db-cAMP), 8-(4-chlorophenylthio) cAMP (CPT-cAMP) and 8-bromo-cAMP (8-Br-cAMP) or an intracellular cAMP elevating agent such as forskolin apparently rendered HL-60 cells more resistant to taxol, but not with dimethyl sulfoxide (DMSO) or retinoic acid (RA), well known differentiating agents. To investigate whether protein kinase A (PKA) activated by an increase in intracellular cAMP level could be involved in increased taxol resistance of the cells, we examined the effects of PKA inhibitors, including H-89 and KT5720, on taxol resistance induced by Db-cAMP. The PKA inhibitors significantly abolished Db-cAMP-induced taxol resistance. These results suggest that cAMP analogs may render tumor cells more resistant to taxol via PKA activation.


DNA synthesis in tongue keratinocytes of hepatectomized and tumor-bearing mice.
Tongue keratinocytes have high S-phase and mitotic indices with evident circadian variation. Transplanted tumors modify the intensity and temporal structure of the S-phase index in cell populations in tumor-bearing animals; also, partial hepatectomy changes the concentrations of substances involved in cellular proliferation, leading to compensatory liver hyperplasia. The aim of our study was to analyze the interaction between tumor growth and the liver regeneration that follows partial hepatectomy, and the effects of both these processes on lingual keratinocytes. We used 380 adult male mice divided into six groups: tumor-free and tumor-bearing mice without surgery, with sham hepatectomy, and with partial hepatectomy. Each group was divided into six subgroups, which were killed at 4-h intervals until a circadian cycle was completed (from 26 until 50h post-surgery in the operated animals). Each animal was injected with 5-bromodeoxyuridine (50mg/kg) 1h before it was killed, and tongue samples were obtained and processed for histology. The sections were placed on silanized slides and incubated with the primary antibody Bu 20a (1/100 dilution). The reaction was developed using diaminobenzidine and staining was detected visually. SIs were measured as the number of labeled nuclei per thousand cells. The mean+/-S.E. of each group was calculated. Differences among experimental groups were analyzed by ANOVA and the Student-Newman-Keuls Multiple Comparisons Test. The results show that the presence of a tumor alters the normal circadian curve of SI in lingual keratinocytes, irrespective of whether the mice underwent surgery. This finding has to be considered in drug treatments for neoplasms and in experiments related to growth.


Nucleoside-(5'→P) methylenebisphosphonodithioate analogues: synthesis and chemical properties.
Nucleoside-(5'→P) methylenebisphosphonodithioate analogues are bioisosteres of natural nucleotides. The potential therapeutic applications of these analogues are limited by their relative instability. With a view toward improving their chemical and metabolic stability as well as their affinity toward zinc ions, we developed a novel nucleotide scaffold, nucleoside-5'-tetrathiobisphosphonate. We synthesized P1-(uridine/adenosine-5')-methylenebisphosphonodithioate, 2 and 3, and P1,P2-di(uridine/adenosine-5')-methylenebisphosphonodithioate, 4 and 5. Using (1)H and (31)P NMR-monitored Zn(2+)/Mg(2+) titrations, we found that 5 coordinated Zn(2+) by both N7 nitrogen atoms and both dithiophosphonate moieties, whereas 3 coordinated Zn(2+) by an N7 nitrogen atom and Pβ. Both 3 and 5 did not coordinate Mg(2+) ions. (31)P NMR-monitored kinetic studies showed that 3 was more stable at pD 1.5 than 5, with t(1/2) of 44 versus 9 h, respectively, and at pD 11 both showed no degradation for at least 2 weeks. However, 5 was more stable than 3 under an air-oxidizing atmosphere, with t1/2 of at least 3 days versus 14 h, respectively. Analogues 3 and 5 were highly stable to NPP1,3 and NTPDase1,2,3,8 hydrolysis (0-7%). However, they were found to be poor ectonucleotidase inhibitors. Although 3 and 5 did not prove to be effective inhibitors of zinc-containing NPP1/3, which is involved in the pathology of osteoarthritis and diabetes, they may be promising zinc chelators for the treatment of other health disorders involving an excess of zinc ions.


Sustainable Valorization of Tomato By-Products to Obtain Bioactive Compounds: Their Potential in Inflammation and Cancer Management.
Tomato producing and processing industries present undoubted potential for industrial discarded products valorization whether due to the overproduction of fresh tomatoes or to the loss during processing. Although tomato by-products are not yet considered a raw material, several studies have suggested innovative and profitable applications. It is often referred to as "tomato pomace" and is quite rich in a variety of bioactive compounds. Lycopene, vitamin C, β-carotene, phenolic compounds, and tocopherol are some of the bioactives herein discussed. Tomato by-products are also rich in minerals. Many of these compounds are powerful antioxidants with anti-inflammatory properties besides modulating the immune system. Several researchers have focused on the possible application of natural ingredients, especially those extracted from foods, and their physiological and pharmacological effects. Herein, the effects of processing and further applications of the bioactive compounds present in tomato by-products were carefully reviewed, especially regarding the anti-inflammatory and anti-cancer effects. The aim of this review was thus to highlight the existing opportunities to create profitable and innovative applications for tomato by-products in health context.


Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice.
Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen-derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis. We sought to determine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed murine model. First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA-specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment. IFN-gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 microg PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL-4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN-gamma production. On the other hand, PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation. These results indicate that the local application of PPD, and the subsequent induction of IFN-gamma, inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice. This suggests that pathogen-derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.


Combination of three-dimensional ultrasound measurement of foetal adrenal gland enlargement and placental alpha microglobulin-1 for the prediction of the timing of delivery within seven days in women with threatened preterm labour and preterm labour.
The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22-36+6 weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. Impact Statement What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth. What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. What are the implications of these findings for clinical practice and/or further research? The combination of a foetal adrenal gland enlargement and placental alpha microglobulin-1 may be used for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and with preterm labour.


MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes.
A combination of in vitro embryonic stem (ES) cell differentiation and targeted gene disruption has defined complex regulatory events underlying oxidative stress-induced cardiac apoptosis, a model of postischemic reperfusion injury of myocardium. ES cell-derived cardiac myocytes (ESCM) having targeted disruption of the MEKK1 gene were extremely sensitive, relative to wild-type ESCM, to hydrogen peroxide-induced apoptosis. In response to oxidative stress, MEKK1-/- ESCM failed to activate c-Jun kinase (JNK) but did activate p38 kinase similar to that observed in wild-type ESCM. The increased apoptosis was mediated through enhanced tumor necrosis factor alpha production, a response that was positively and negatively regulated by p38 and the MEKK1-JNK pathway, respectively. Thus, MEKK1 functions in the survival of cardiac myocytes by inhibiting the production of a proapoptotic cytokine. MEKK1 regulation of the JNK pathway is a critical response for the protection against oxidative stress-induced apoptosis in cardiac myocytes.


Potential association of pulmonary tuberculosis with genetic polymorphisms of toll-like receptor 9 and interferon-gamma in a Chinese population.
Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI). In this case-control study, 44 candidate SNPs were examined in a total of 600 participants (PTB patients, LTBI controls and healthy controls without M. tuberculosis infection) from Zhengzhou, China. The two groups of controls were frequency matched on gender and age with PTB patients. Genotyping was carried out by the Illumina Golden Gate assay. When comparing PTB patients with LTBI controls but not healthy controls without M. tuberculosis infection, significant associations with disease development were observed for TLR9 1174 A/G, TLR9 1635 A/G and IFNG 2109G/A. The two loci in TLR9 were in LD in our study population (r(2)=0.96, D'=1.00). A combined effect of the genotypes associated with increased risk of PTB (i.e. TLR9 1174G/G and IFNG 2109 A/A) was found when comparing PTB patients with LTBI controls (p=0.004) but not with healthy controls without infection (p=0.433). Potential associations between TLR9 and IFN-γ genetic polymorphisms and PTB were observed in a Chinese population which supports further study of the roles played by TLR9/IFN-γ pathway during the development of PTB.


Effect of isosorbiddinitrate on exogenously expressed slowly activating K+ channels and endogenous K+ channels in Xenopus oocytes.
1. The effects of isosorbiddinitrate (ISDN) were tested on membrane currents and resting potential in Xenopus laevis oocytes which were either uninjected or injected with cRNA encoding for K+ channels from three distinct families (slowly activating IsK channels, delayed-rectifying Kv1.1 or inwardly rectifying IRK1 K+ channels). 2. In uninjected oocytes ISDN (1 mM) resulted in a decrease of the holding current at potentials more positive than -100 mV and in an increase at potentials below -100 mV. Increasing extracellular K+ to 100 mM shifted the reversal potential for ISDN-mediated effects to approximately -12 mV, suggesting an inhibition of a K+ conductance by ISDN. 3. In current clamp studies ISDN (1 mM) and Ba2+ (3 mM) depolarized cell membrane. ISDN and Ba2+ had no additive effects on membrane potential when applied simultaneously. In voltage clamp studies, corresponding results were observed for the effects of ISDN and Ba2+ on the holding current with an apparent K(m) of 0.21 and 0.08 mM, respectively. 4. In contrast to ISDN, the nitric oxide (NO) donors isosorbidmononitrate (ISMN) and S-nitrosocysteine (SNOC) had no effects on the holding currents in Xenopus oocytes. Moreover, the guanylate inhibitor LY 83583 did not affect ISDN-mediated holding current alterations, suggesting that ISDN acts independently of the second messenger NO. 5. ISDN inhibited exogenously expressed IsK channels with an apparent K(m) of 0.15 mM, but at 1 mM only weakly inhibited Kv1.1 and IRK1 channels. 6. It is concluded that ISDN inhibits an endogenous K+ conductance in Xenopus oocytes with a similar potency to that shown by expressed IsK channels. These effects are independent of the second messenger NO.


Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.
We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.


Modeling of the interaction of Na+ and K+ with the binding of dopamine and [3H]WIN 35,428 to the human dopamine transporter.
Although much is known about the effects of Na+, K+, and Cl- on the functional activity of the neuronal dopamine transporter, little information is available on their role in the initial event in dopamine uptake, i.e., the recognition step. This was addressed here by studying the inhibition by dopamine of the binding of [3H]WIN 35,428 [2beta-carbomethoxy-3beta-(4-fluorophenyl)[3H]tropane], a phenyltropane analogue of cocaine, to the cloned human dopamine transporter expressed in HEK-293 cells. The decrease in the affinity of dopamine (or WIN 35,428) binding affinity with increasing [K+] could be fitted to a competitive model involving an inhibitory cation site (1) overlapping with the dopamine (or WIN 35,428) domain. The K+ IC50 for inhibiting dopamine or WIN 35,428 binding increased linearly with [Na+], indicating a K(D,Na+) of 30-44 mM and a K(D,K+) of 13-16 mM for this cation site. A second Na+ site (2), distal from the WIN 35,428 domain but linked by positive allosterism, was indicated by model fitting of the WIN 35,428 binding affinities as a function of [Na+]. No strong evidence for this second site was obtained for dopamine binding in the absence or presence of low (20 mM) Cl- and could not be acquired for high [Cl-] because of the lack of a suitable substitute ion for Na+. The K(D) but not Bmax of [3H]WIN 35,428 binding increased as a function of the [K+]/[Na+] ratio regardless of total [Cl-] or ion tonicity. A similar plot was obtained for the Ki of dopamine binding, with Cl- at > or = 140 mM decreasing the Ki. At 290 mM Cl- and 300 mM Na+ the potency of K+ in inhibiting dopamine binding was enhanced as compared with the absence of Cl- in contrast to the lack of effect of Cl- up to 140 mM (Na up to 150 mM). The results indicate that Cl- at its extracellular level enhances dopamine binding through a mechanism not involving site 1. The observed correspondence between the WIN 35,428 and dopamine domains in their inclusion of the inhibitory cation site explains why many of the previously reported interrelated effects of Na+ and K+ on the binding site of radiolabeled blockers to the dopamine transporter are applicable to dopamine uptake in which dopamine recognition is the first step.


Evaluating continuing education: options abound.
Many providers of continuing education activities perceive that there is a required evaluation form that must be completed by learners at the end of the learning activity. Although this is one approach to collecting evaluation data, it is by no means the only way. This column suggests several strategies that can be used to evaluate learning activities.


Event attributes and the content of psychotic experiences in first-episode psychosis.
Previous psychosocial stress research, contemporary cognitive models, and new cognitive behavioural treatments for psychosis converge in suggesting that stressful events influence the content of psychotic experiences. In this paper we test whether the attributes of stressful events preceding the initial onset of psychosis are associated with core themes of the illness. Forty-one people who had experienced a first episode of psychosis were assessed on the attributes of stressful events occurring in the year before onset, the themes (persecutory, depressive, and grandiose) associated with their delusions and the content of their auditory hallucinations. Principal component analysis yielded four components accounting for 72% of the variance. As hypothesized, intrusive events were associated with the development of delusions with persecutory themes. Grandiose delusions were negatively associated with loss events. Depressive delusions appear to be associated with danger events rather than loss events. There are links between stressful event attributes and core psychotic themes at first-episode psychosis. This has implications for theoretical models of, and early psychological intervention for, psychosis.


Study of ocular aberrations with age.
Aging has various effects on visual system. Vision deteriorate, contrast sensitivity decreases and ocular aberrations apparently make the optical quality worse across the years. To prospective evaluate ocular aberrations along the ages. Three hundred and fifteen patients were examined, 155 were male (39.36%) and 160 were female (60.63%). Ages ranged from 5 to 64 year-old, the study was performed from February to November, 2004. Patients were divided into 4 age-groups according to IBGE (Instituto Brasileiro de Geografia e Estatística) classification: 68 patients from 5 to 14 year-old, 55 patients from 15 to 24 year-old, 116 from 25 to 44 year-old and 76 from 45 to 67 year-old. All patients had the following characteristics: best corrected visual acuity > 20/25, emmetropia or spherical equivalent < 3.50 SD, refractive astigmatism < 1.75 CD on cycloplegic refraction, normal ophthalmologic exam and no previous ocular surgeries. This protocol was approved by Federal University of São Paulo Institutional Review Board. Total optical aberrations were measured by H-S sensor LadarWave Custom Cornea Wavefront System (Alcon Laboratories Inc, Orlando, FLA, USA) and were statistically analysed. Corneal aberrations were calculated using CT-View software Version 6.89 (Sarver and Associates, Celebration, FL, USA). Lens aberrations were calculated by subtraction. High-order (0.32 e 0.48 microm) and ocular spherical aberrations (0.02 e 0.26 microm) increased respectively in child and middle age groups. High order (0.27 microm) and corneal spherical aberrations (0.05 microm) did not show changes with age. Lens showed a statistically significant spherical aberration increase (from -0.02 to 0.22 microm). Vertical (from 0.10 to -0.07 microm) and horizontal coma (from 0.01 to -0.12 microm) presented progressively negative values with aging. High-order and spherical aberrations increased with age due to lens contribution. The cornea did not affect significantly changes observed on ocular aberrations.


Imaging of trauma in a pregnant patient.
Trauma is the number one nonobstetric cause of maternal death. This chapter presents the latest consensus from the literature on the best approach to radiographic imaging of these patients. The central issues of discussion include the rationale and protocols for screening for pregnancy in trauma setting; the effects of radiation and its risks to the fetus; obtaining informed consent; how to estimate fetal dose; and the role of ultrasound, computed tomography, and magnetic resonance imaging, including the intravenous contrast agents used for the assessment of abdominal trauma. The team approach to the management of these patients is also highlighted.


Designating longevity hotspots: cautions concerning the instability of per capita centenarian estimates.
Estimates of per capita centenarians in a Utah population varied between one per 12,864 and one per 4,675, depending on the data that were used, the population assumptions that were made, and the boundary limits that were employed. In general, caution is warranted in claims about the existence of longevity hotspots.


A qualitative study of communication during joint teleconsultations at the primary-secondary care interface.
It has been suggested that joint teleconsultations can improve communication at the primary-secondary care interface. We examined data from a qualitative analysis of social interactions in teleconsultations between specialists and general practitioners. The primary interaction was between specialists and patients. The general practitioners mostly adopted a 'back seat role', listening and observing, but not becoming actively involved. Teleconsultations create a number of interactional difficulties, which are likely to impede implementation and sustainability.


Analysis of intracorporeal knotting with invaginating suture versus endoloops in appendiceal stump closure.
Laparoscopic appendectomy is a well-described surgical technique and has gained wide clinical acceptance. Laparoscopic appendectomy offers fewer wound infections, faster recovery and an earlier return to work in comparison to open surgery. However, concerns still exist regarding the appendiceal stump closure. The aim of this study was to compare the overall incidence and specific intraoperative and postoperative complications after application of intracorporeal knotting with invaginating suture versus endoloops for stump closure in laparoscopic appendectomy. ONE HUNDRED FIFTY TWO CONSECUTIVE PATIENTS ACCORDING TO THE FOLLOWING INCLUSION CRITERIA WERE INCLUDED IN THE STUDY: 1. Laparoscopic appendectomy was performed during the study period; 2. Acute phlegmonous or gangrenous appendicitis without perforation was diagnosed during operation. Exclusion criteria - patients with acute perforated appendicitis and local or diffuse peritonitis. Data was grouped according to the appendiceal stump closure technique, with either endoloops - 112 patients (73.7 percent) or intracorporeal knotting with invaginating suture - 40 patients (26.3 per cent). The primary outcome measure was the rate of intraabdominal surgical-site infection, defined as post-operative intra-abdominal abscess. Secondary outcome variables were intraoperative and postoperative complications, duration of operation, hospital stay. There were no significant differences between the two groups in overall intraoperative and postoperative complications rate and in hospital stay. The median duration of operation was significantly shorter when the endoloop was used. The use of intracorporeal knotting with invaginating suture instead of endoloop to close the appendiceal stump decreased the total cost of laparoscopic appendectomy. According our study results, intracorporeal knotting with invaginating suture appendiceal stump closure technique is acceptable laparoscopic procedure, which intraoperative and postoperative results do not differ from endoloops technique. The total cost of this procedure is 80 € cheaper then endoloops technique.


Designing and validation of a yoga-based intervention for obsessive compulsive disorder.
Some yoga-based practices have been found to be useful for patients with obsessive compulsive disorder (OCD). The authors could not find a validated yoga therapy module available for OCD. This study attempted to formulate a generic yoga-based intervention module for OCD. A yoga module was designed based on traditional and contemporary yoga literature. The module was sent to 10 yoga experts for content validation. The experts rated the usefulness of the practices on a scale of 1-5 (5 = extremely useful). The final version of the module was pilot-tested on patients with OCD (n = 17) for both feasibility and effect on symptoms. Eighty-eight per cent (22 out of 25) of the items in the initial module were retained, with modifications in the module as suggested by the experts along with patients' inputs and authors' experience. The module was found to be feasible and showed an improvement in symptoms of OCD on total Yale-Brown Obsessive-Compulsive Scale (YBOCS) score (p = 0.001). A generic yoga therapy module for OCD was validated by experts in the field and found feasible to practice in patients. A decrease in the symptom scores was also found following yoga practice of 2 weeks. Further clinical validation is warranted to confirm efficacy.


Magnetic properties of nickel and cobalt catalysts supported on nanoporous oxides.
The aim of this work is to use magnetic measurements as a research tool in the study of possible metal-support interactions in nickel and cobalt nanoporous catalysts. Several physicochemical techniques, namely nitrogen adsorption, X-ray diffraction, temperature-programmed reduction and chemical analysis, were used to analyze the role of the preparation method and the nature of the support on the existence of such metal-support interactions and to relate them with the magnetic response of these nanoporous systems. The catalysts were prepared by incipient wetness impregnation and precipitation-deposition with two commercial oxides, gamma-Al2O3 and SiO2, as supports. The magnetic behavior of the catalysts is drastically affected by the existence of interactions between the metal and the support during the preparation procedure. The samples with weak metal-support interactions have characteristic magnetic behavior of antiferromagnetic metal oxide nanoparticles, while the ones having strong interactions display spin-glass like behavior.


[The preliminary discussions for the effect and its influence factors of nasal endoscopic surgery for the treatment of nasal inverted papilloma].
To discuss the method, effect and the influence factors of nasal endoscopic surgery for the treatment of nasal inverted papilloma. Retrospective analysis the clinical data of the 23 cases who received nasal endoscopic surgery for the treatment of nasal inverted papilloma. Only one case had recurrence after four months and was then cured by a combined treatment of external nasal approach and radiotherapy. The other 22 cases had no recurrence in the follow-up period. Endoscopic sinus surgery for the treatment of nasal inverted papilloma has satisfactory effect, so it can be regard as the first-selecting operation mode for the nasal inverted papilloma. However, it's essential to pay enough attention to such influence factors as choosing suitable case, particular preoperative examination and selecting suitable operation mode.


Are specific emotions narrated differently?
Two studies test the assertion that anger, sadness, fear, pride, and happiness are typically narrated in different ways. Everyday events eliciting these 5 emotions were narrated by young women (Study 1) and 5- and 8-year-old girls (Study 2). Negative narratives were expected to engender more effort to process the event, be longer, more grammatically complex, more often have a complication section, and use more specific emotion labels than global evaluations. Narratives of Hogan's (2003) juncture emotions anger and fear were expected to focus more on action and to contain more core narrative sections of orientation, complication, and resolution than narratives of the outcome emotions sadness and happiness. Hypotheses were confirmed for adults except for syntactic complexity, whereas children showed only some of these differences. Hogan's theory that juncture emotions are restricted to the complication section was not confirmed. Finally, in adults, indirect speech was more frequent in anger narratives and internal monologue in fear narratives. It is concluded that different emotions should be studied in how they are narrated, and that narratives should be analyzed according to qualitatively different emotions.


Daphnetin methylation by a novel O-methyltransferase is associated with cold acclimation and photosystem II excitation pressure in rye.
In plants, O-methylation of phenolic compounds plays an important role in such processes as lignin synthesis, flower pigmentation, chemical defense, and signaling. However, apart from phenylpropanoids and flavonoids, very few enzymes involved in coumarin biosynthesis have been identified. We report here the molecular and biochemical characterization of a gene encoding a novel O-methyltransferase that catalyzes the methylation of 7,8-dihydroxycoumarin, daphnetin. The recombinant protein displayed an exclusive methylation of position 8 of daphnetin. The identity of the methylated product was unambiguously identified as 7-hydroxy-8-methoxycoumarin by co-chromatography on cellulose TLC and coelution from high performance liquid chromatography, with authentic synthetic samples, as well as by UV, mass spectroscopy, (1)H NMR spectral analysis, and NOE correlation signals of the relevant protons. Northern blot analysis and enzyme activity assays revealed that the transcript and corresponding enzyme activity are up-regulated by both low temperature and photosystem II excitation pressure. Using various phenylpropanoid and flavonoid substrates, we demonstrate that cold acclimation of rye leaves increases O-methyltransferase activity not only for daphnetin but also for the lignin precursors, caffeic acid, and 5-hydroxyferulic acid. The significance of this novel enzyme and daphnetin O-methylation is discussed in relation to its putative role in modulating cold acclimation and photosystem II excitation pressure.


Cellular bases of behavioral plasticity: establishing and modifying synaptic circuits in the Drosophila genetic system.
Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity.


Mapping glucose metabolites in the normal bovine lens: Evaluation and optimisation of a matrix-assisted laser desorption/ionisation imaging mass spectrometry method.
The spatial resolution of microdissection-based analytical methods to detect ocular lens glucose uptake, transport and metabolism are poor, whereas the multiplexing capability of fluorescence microscopy-based approaches to simultaneously detect multiple glucose metabolites is limited in comparison with mass spectrometry-based methods. To better understand lens glucose transport and metabolism, a more highly spatially resolved technique that maintains the fragile ocular lens tissue is required. In this study, a sample preparation method for matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI IMS) analysis of ocular lens glucose uptake and metabolism has been evaluated and optimised. Matrix choice, tissue preparation and normalisation strategy were determined using negative ion mode MALDI-Fourier transform-ion cyclotron resonance MS of bovine lens tissue and validation performed using gas chromatography-MS. An internal standard was applied concurrently with N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC) matrix to limit cracking of the fresh frozen lens tissue sections. MALDI IMS data were collected at a variety of spatial resolutions to detect both endogenous lens metabolites and stable isotopically labelled glucose introduced by ex vivo lens culture. Using this approach, initial steps in important metabolic processes that are linked to diabetic cataract formation were spatially mapped in the bovine lens. In the future, this method can be applied to study the dynamics of glucose uptake, transport and metabolic flux to aid in the study of diabetic lens cataract pathophysiology.


[Risk factors in invasive cervical cancer among Mexican women].
To evaluate the association between invasive Cervical Cancer (CC) and high risk Human PapillomaVirus (HR-HPV) (viral load and type 16), along with other gynecological and socioeconomic factors. Individually matched case-control study (215 women with invasive CC and 420 controls). The study population was recruited between 2000 and 2001. A set of variables traditionally linked with CC (gynecological and socioeconomic factors) and two variables related to HPV infection (viral load and type 16) were assessed. Hybrid Capture II was used to detect HR-HPV DNA. Viral load was measured by light measurements expressed as relative light units (RLU) and they were categorized for analysis into four groups: negative (< 1 RLU), low viral load (1-49 RLU), middle load (50-499 RLU) and high load (>499 RLU). The analysis included univariate, bivariate and multivariate techniques being the final step the estimation of Odds Ratios (OR) by means of conditional logistic regression models. Results. The probability of having invasive CC was 78 times higher in patients with infection of HR-HPV. Risk increases with HPV type 16 (OR = 429.7) as compared with other types of HR-HPV (OR = 64.1). An important trend was observed with the increase of the viral load (from 46.6 with low viral load; to 250.7 with intermediate and 612.9 with high load). The findings also indicate significant diferences in the viral load between cases and controls according to age groups and HR-HPV types (16 versus others high risk types). Finally, the partner-demographic and obstetrical variables related to the disease increased the risk of invasive CC. No association between CC and smoking was observed in this population. This study helps in identifying women at higher risk of developing invasive CC as a subset of those patients infected with HR-HPV. The findings point strongly to the importance of the viral load in HR-HPV as a co-factor in the development of this disease. This biomarker contributes to improving the prevention and early detection of this disease and also to identify women at higher risk who carry a high viral load of HR-HPV.


Health Policies Based on Patient Satisfaction: A Bibliometric Study.
Healthcare decision-makers increasingly face a changing and ever-evolving landscape, forcing them to formulate public policies based on the results from different scientific investigations. This article evaluates the field of research on patient satisfaction as a basis for health policies. The analysis was carried out with a sample of 621 articles published between 2000 and 2020 in the Scopus database. The world's largest producer and research co-operator on patient satisfaction and health policy was the United States. However, the most prolific authors, institutions, and journals are of British origin. Regarding the themes, we find that, in economic and management matters, scientific production is scarce. To study the evolution of keywords, we divided the study period into two periods of an equal number of years. In both sub-periods, the keyword "Human" stands out. In the second sub-period, the word "Perception" stands out, which indicates the current attention paid to the patient's opinion.


Absorbed dose estimates to structures of the brain and head using a high-resolution voxel-based head phantom.
The purpose of this article is to demonstrate the viability of using a high-resolution 3-D head phantom in Monte Carlo N-Particle (MCNP) for boron neutron capture therapy (BNCT) structure dosimetry. This work describes a high-resolution voxel-based model of a human head and its use for calculating absorbed doses to the structures of the brain. The Zubal head phantom is a 3-D model of a human head that can be displayed and manipulated on a computer. Several changes were made to the original head phantom which now contains over 29 critical structures of the brain and head. The modified phantom is a 85 x 109 x 120 lattice of voxels, where each voxel is 2.2 x 2.2 x 1.4 mm3. This model was translated into MCNP lattice format. As a proof of principle study, two MCNP absorbed dose calculations were made (left and right lateral irradiations) using a uniformly distributed neutron disk source with an 1/E energy spectrum. Additionally, the results of these two calculations were combined to estimate the absorbed doses from a bilateral irradiation. Radiobiologically equivalent (RBE) doses were calculated for all structures and were normalized to 12.8 Gy-Eq. For a left lateral irradiation, the left motor cortex receives the limiting RBE dose. For a bilateral irradiation, the insula cortices receive the limiting dose. Among the nonencephalic structures, the parotid glands receive RBE doses that were within 15% of the limiting dose.


Crystal structure of Penicillium citrinum P1 nuclease at 2.8 A resolution.
P1 nuclease from Penicillium citrinum is a zinc dependent glyco-enzyme consisting of 270 amino acid residues which cleaves single-stranded RNA and DNA into 5'-mononucleotides. The X-ray structure of a tetragonal crystal form of the enzyme with two molecules per asymmetric unit has been solved at 3.3 and refined at 2.8 A resolution to a crystallographic R-factor of 21.6%. The current model consists of 269 amino acid residues, three Zn ions and two N-acetyl glucosamines per subunit. The enzyme is folded very similarly to phospholipase C from Bacillus cereus, with 56% of the structure displaying an alpha-helical conformation. The three Zn ions are located at the bottom of a cleft and appear to be rather inaccessible for any phosphate group in double-stranded RNA or DNA substrates. A crystal soaking experiment with a dinucleotide gives clear evidence for two mononucleotide binding sites separated by approximately 20 A. One site shows binding of the phosphate group to one of the zinc ions. At both sites there is a hydrophobic binding pocket for the base, but no direct interaction between the protein and the deoxyribose. A cleavage mechanism is proposed involving nucleophilic attack by a Zn activated water molecule.


Bending Genders: The Biology of Natural Sex Change in Fish.
Sexual fate is no longer seen as an irreversible deterministic switch set during early embryonic development but as an ongoing battle for primacy between male and female developmental trajectories. That sexual fate is not final and must be actively maintained via continuous suppression of the opposing sexual network creates the potential for flexibility into adulthood. In many fishes, sexuality is not only extremely plastic, but sex change is a usual and adaptive part of the life cycle. Sequential hermaphrodites begin life as one sex, changing sometime later to the other, and include species capable of protandrous (male-to-female), protogynous (female-to-male), or serial (bidirectional) sex change. Natural sex change involves coordinated transformations across multiple biological systems, including behavioural, anatomical, neuroendocrine, and molecular axes. We here review the biological processes underlying this amazing transformation, focussing particularly on its molecular basis, which remains poorly understood, but where new genomic technologies are significantly advancing our understanding of how sex change is initiated and progressed at the molecular level. Knowledge of how a usually committed developmental process remains plastic in sequentially hermaphroditic fishes is relevant to understanding the evolution and functioning of sexual developmental systems in vertebrates generally, as well as pathologies of sexual development in humans.


Experimental oral inoculations in birds to evaluate potential definitive hosts of Neospora caninum.
Experimental oral inoculations to evaluate potential definitive hosts of Neospora caninum were conducted by feeding infected rodent tissues to 9 carnivorous birds of 4 species. Birds included 2 red-tailed hawks (Buteo jamaicensis), 2 turkey vultures (Cathartes aura), 2 barn owls (Tyto alba), and 3 American crows (Corvus brachyrhynchus). The rodents (mice or rats) had been inoculated with 100,000 culture-derived tachyzoites of N. caninum 1-6 mo before feeding to the birds. Fecal samples were collected from each bird daily for 1 mo after feeding rodents and examined for oocysts by fecal flotation. In addition, processed aliquots from all avian fecal samples were fed to BALB/c mice. Five weeks after feeding, mice were bled and sera were tested for antibodies against N. caninum. One to two months later, mice were killed and brain tissue was examined microscopically for protozoal cysts. While occasional oocysts were found in avian fecal samples, these were likely not N. caninum because they were not infective to BALB/c mice. It was concluded that the bird species tested are not likely to be definitive hosts of N. caninum.


Applying DNA Barcodes to Identify Closely Related Species of Ferns: A Case Study of the Chinese Adiantum (Pteridaceae).
DNA barcoding is a fast-developing technique to identify species by using short and standard DNA sequences. Universal selection of DNA barcodes in ferns remains unresolved. In this study, five plastid regions (rbcL, matK, trnH-psbA, trnL-F and rps4-trnS) and eight nuclear regions (ITS, pgiC, gapC, LEAFY, ITS2, IBR3_2, DET1, and SQD1_1) were screened and evaluated in the fern genus Adiantum from China and neighboring areas. Due to low primer universality (matK) and/or the existence of multiple copies (ITS), the commonly used barcodes matK and ITS were not appropriate for Adiantum. The PCR amplification rate was extremely low in all nuclear genes except for IBR3_2. rbcL had the highest PCR amplification rate (94.33%) and sequencing success rate (90.78%), while trnH-psbA had the highest species identification rate (75%). With the consideration of discriminatory power, cost-efficiency and effort, the two-barcode combination of rbcL+ trnH-psbA seems to be the best choice for barcoding Adiantum, and perhaps basal polypod ferns in general. The nuclear IBR3_2 showed 100% PCR amplification success rate in Adiantum, however, it seemed that only diploid species could acquire clean sequences without cloning. With cloning, IBR3_2 can successfully distinguish cryptic species and hybrid species from their related species. Because hybridization and allopolyploidy are common in ferns, we argue for including a selected group of nuclear loci as barcodes, especially via the next-generation sequencing, as it is much more efficient to obtain single-copy nuclear loci without the cloning procedure.


Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?
To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.


Abrogation of P53 function by transfection of HPV16 E6 gene does not enhance resistance of human tumour cells to ionizing radiation.
Suppression of wild-type p53 expression has been shown to enhance the radiation resistance of human diploid fibroblasts, but results concerning the role of p53 expression in the sensitivity of human tumour cells have been conflicting. In order to address this question, we transfected four human tumour cell lines with the human papilloma virus 16 E6 gene and compared the radiosensitivity of subclones expressing E6 with that of subclones transfected with the neo gene alone. E6 binds to wild-type p53 promoting its degradation and abrogating its function. Two of these cell lines, one derived from a squamous cell carcinoma and the other an osteogenic sarcoma, expressed wild-type p53. The other two cell lines were of similar origins and histologies but expressed mutant or no p53 (null). Insertion of E6 into the cell was accomplished by two techniques: (1) to-transfection of plasmid vectors containing neo and E6; (2) infection with a retroviral vector containing neo and E6. Multiple transfected subclones were examined for each cell line. Transfection with E6 and abrogation of p53 function had no significant influence on the radiosensitivity of any of the cell lines tested. In particular, there was no evidence that loss of wild-type p53 function increased the resistance of these human tumour cell lines to ionizing radiation.


Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease.
The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14 +/- 149.53 mumol/L in patients with headache and 233 +/- 107.23 mumol/L in those without headache (P < .005). Glutamate in CSF was higher in patients with headache (4.6 +/- 1.49 mumol/L) than in patients without headache (3.11 +/- 1.18 mumol/L) (P < .001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10 +/- 52.82 mumol/L and 177.49 +/- 90.92 mumol/L in headache and nonheadache patients, respectively (P < .001). Taurine levels in CSF were 5.42 +/- 2.42 mumol/L in patients with headache and 9.27 +/- 5.31 mumol/L in those without headache (P < .001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.


Proline catalyzed sequential α-aminooxylation or -amination/reductive cyclization of o-nitrohydrocinnamaldehydes: a high yield synthesis of chiral 3-substituted tetrahydroquinolines.
A new sequential organocatalytic method for the synthesis of chiral 3-substituted (X = OH, NH2) tetrahydroquinoline derivatives (THQs) [ee up to 99%, yield up to 87%] based on α-aminooxylation or -amination followed by reductive cyclization of o-nitrohydrocinnamaldehydes has been described. This methodology has been efficiently demonstrated in the synthesis of two important bioactive molecules namely (-)-sumanirole (96% ee) and 1-[(S)-3-(dimethylamino)-3,4-dihydro-6,7-dimethoxy-quinolin-1(2H)-yl]propanone (92% ee).


Use of the intubating laryngeal mask airway in a case of ankylosing spondylitis for coronary artery bypass grafting.
The intubating laryngeal mask airway is a modification of the conventional laryngeal mask and is used as a tool for difficult intubation. It can be inserted without placing the head and neck in the Magill position and has been used successfully in cervical spine injuries. Reported is a case of successful insertion of the intubating laryngeal mask and subsequent intubation through it in a patient with ankylosing spondylitis with cervical involvement resulting in a fixed flexion deformity who underwent coronary artery bypass grafting.


Acute renal failure from spontaneous acute tumor lysis syndrome: a case report and review.
Acute tumor lysis syndrome (ATLS), a condition which results from a rapid destruction of tumor cells with massive release of cellular breakdown products, has been well described. However, only a few cases of spontaneous ATLS have been reported in the literature. Acute renal failure (ARF) from spontaneous ATLS has been reported only in three patients who were diagnosed to have Burkitt's lymphoma, adenocarcinoma, and acute myeloid leukemia. We report a similar case of a patient with non-Hodgkin's lymphoma, who developed ARF from spontaneous ATLS. ARF can complicate the clinical course of spontaneous ATLS. Since only one patient survived, patients who develop ARF from spontaneous ATLS have a poor outcome. This paper illustrates the need to anticipate the development of ARF, despite aggressive therapy, in a patient with spontaneous ATLS. Prospective studies on renal function prior to and during therapy are required in order to develop a clinical profile reliably detecting patients at risk for developing renal failure and subsequent complication.


Decree No. 147/1986 regulating the programme for the promotion of maternal and child health, 24 November 1986.
Section 1 of this Decree of Valencia, Spain, defines "promotion of maternal and child health" to mean the sequence of planned interventions for maintaining and improving the health of pregnant and parturient mothers, women in childbirth, and children, undertaken by health personnel specifically engaged in these functions. Section 2 indicates that the promotion of maternal health covers health care and educational activities based on the pregnant mother's condition, the birth, and the mother's specific needs related to her recovery during the puerperium. The following are established as minimum programs: 1) monitoring of the health of the pregnant woman; 2) education for maternity; and 3) postnatal care and the physical recovery of the mother. Details are given of the specific activities and components of each of these programs. Section 8 indicates that the promotion of child health covers the sequence of planned interventions for establishing and improving development, the application of individual preventive procedures of established effectiveness, genetic counseling, and the early detection of physical disability or disorders causing such disability. The following are established as minimum programs: 1) prevention of mental disability; 2) the monitoring of the child up to 14 years of age, including consolidation and improvement in health; and 3) the promotion of school health. Details are given of the specific activities and components of each of these programs.


Sampling rare populations.
Sampling rare populations presents many challenges. In caring for those who experience social exclusion, nurses are well placed to conduct research into these hard-to-reach populations. This article by Mary Dawood discusses some of the sampling methods used.


Affordability in individuals' healthcare decision making: A concept analysis.
This concept analysis aims to define affordability within the context of healthcare decision making. Affordability is a complex concept that influences an individual's healthcare decision making. In the year's post-Affordable Care Act, the United States has seen an increase in insured individuals, but also an increase in underinsured healthcare consumers. Evidence for the concept attributes was found by searching the Cumulative Index of Nursing and Allied Health Literature, EconLit, Family & Society Studies Worldwide, Humanities Full Text, and PsychINFO databases. Literature was synthesized using the Walker and Avant approach. A new definition was derived with four defining attributes, as well as antecedents and consequences. Three cases are forwarded: the model, borderline, and contrary. In healthcare decision making, affordability is a subjective measure that individuals use in determining the ability to engage in a healthcare service or a durable good transaction. Affordability varies based on circumstances. The context of healthcare decision making of individuals stands in contrast to the decision-making in health systems and to decisions unrelated to one's health. Affordability is a determinant of an individual's ability to engage in a transaction. As such, nurses and policymakers should attempt to understand affordability from the patient's perspective.


Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?
Ovarian sex steroids can modulate new vessel formation and development, and the clarification of the underlying mechanism will provide insight into neovascularization-related physiological changes and pathological conditions. Unlike estrogen, which mainly promotes neovascularization through activating classic post-receptor signaling pathways, progesterone (P4) regulates a variety of downstream factors with angiogenic or antiangiogenic effects, exerting various influences on neovascularization. Furthermore, diverse progestins, the synthetic progesterone receptor (PR) agonists structurally related to P4, have been used in numerous studies, which could contribute to unequal actions. As a result, there have been many conflicting observations in the past, making it difficult for researchers to define the exact role of progestogens (PR agonists including naturally occurring P4 and synthetic progestins). This review summarizes available evidence for progestogen-mediated neovascularization under physiological and pathological circumstances, and attempts to elaborate their functional characteristics and regulatory patterns from a comprehensive perspective.


Comparison of bare-metal and drug-eluting stents in patients with chronic kidney disease (from the NHLBI Dynamic Registry).
Patients with chronic kidney disease (CKD) have a disproportionate burden of coronary artery disease and commonly undergo revascularization. The role and safety of percutaneous coronary intervention (PCI) using drug-eluting stents (DESs) verses bare-metal stents in patients with CKD not on renal replacement therapy has not been fully evaluated. This study investigated the efficacy and safety of DES in patients with CKD not on renal replacement therapy. Patients were drawn from the National Heart, Lung, and Blood Institute Dynamic Registry and were stratified by renal function based on estimated glomerular filtration rate (GFR). Of the 4,157 participants, 1,108 had CKD ("low GFR" <60 ml/min/1.73 m(2)), whereas 3,049 patients had normal renal function ("normal GFR" ≥60 ml/min/1.73 m(2)). For each stratum of renal function we compared risk of death, myocardial infarction, or repeat revascularization between subjects who received DESs and bare-metal stents at the index procedure. Patients with low GFR had higher 1-year rates of death and myocardial infarction and a decreased rate of repeat revascularization compared to patients with normal GFR. Use of DESs was associated with a decreased need for repeat revascularization in the normal-GFR group (adjusted hazard ratio 0.63, 95% confidence interval 0.50 to 0.79, p <0.001) but not in the low-GFR group (hazard ratio 0.69, 95% confidence interval 0.45 to 1.06, p = 0.09). Risks of death and myocardial infarction were not different between the 2 stents in either patient population. In conclusion, presence of CKD predicted poor outcomes after PCI with high rates of mortality regardless of stent type. The effect of DES in decreasing repeat revascularization appeared to be attenuated in these patients.


Are professors of human nutrition faculty at Canadian universities representative with respect to common social constructs of gender and race?
Attributes such as sex and race/ethnicity are associated with inequities in representation. The objective of this study was to assess representation of 2 social constructs, gender and race, of professors of human nutrition in Canada. Using information publicly available October 2021, individuals with the title of assistant, associate, or full professor were identified on websites of 20 Canadian universities offering undergraduate and/or graduate degrees in human nutrition. Individuals were subjectively stratified to social constructs, i.e., white, racialized, or Indigenous, based on photographs, ethnic origin of a surname, and regional and ethnic origin disclosures on university websites, LinkedIn, social media, etc. Gender was assigned based on publicly available photographs and self-disclosed pronouns (when available). Of the 190 individuals, 80% were white, 16.4% were racialized, and 2.6% were Indigenous peoples. The majority (65.3%) were women. In a subset with established doctoral thesis dates and dates of hire at their current institution (n = 153), racialized and Indigenous professors, especially assistant and associate, had earned their doctorate and been hired more recently than their white peers. This study is limited because only individuals with professorial titles were included and the assignment of social constructs for race and gender was subjective. Nevertheless, it establishes an understanding of the proportions of professors of human nutrition who are white, racialized, Indigenous, women, and men. Novelty: Canadian universities strive to be equitable, diverse, and inclusive. One hundred and ninety professors of human nutrition were stratified using social constructs for race and gender. Findings: 65% Women, 80% white, 16.4% racialized, and 2.6% Indigenous.


Prognosis of patients after pulmonary artery plasty for non-small cell lung cancer.
We evaluated the clinical outcomes of patients after lung resection with pulmonary artery (PA) plasty for non-small cell lung cancer (NSCLC). From 1995 to 2006, 36 patients (26 males and 10 females) with NSCLC underwent lobectomy or segmentectomy with PA plasty at our institution. The mean age of the patients was 65.9 years old (range 45-87 years old). There were 17 left upper lobectomies, 10 right upper lobectomies, five left lower lobectomies, two right upper-and-middle bilobectomies, one right lower lobectomy, and one left upper division segmentectomy. Both bronchoplasty and PA plasty were performed in 15 patients. Six patients received preoperative chemotherapy, and one had preoperative radiotherapy. The postoperative morbidity rate was 27.8 % (10/36), and the mortality rate (30 days) was 2.8 % (1/36). One patient underwent completion pneumonectomy on postoperative day 13. Macroscopic residual cancer was identified in two patients at the thoracic wall and aorta, respectively; microscopic residual cancers were identified in two patients at the stumps of the pulmonary artery and in one patient at the bronchial stump. Postoperative radiation therapy was additionally given to those four patients, except one. The 5-year survival rate for all patients was 51.8 %. There was no significant difference in the 5-year survival rate between clinical N (cN) 0-1 patients and cN2 patients. However, in pathological N (pN) 0-1 patients, the 5-year survival rate was significantly better than that of pN2 patients (71.9 % versus 0.0 %; P < 0.001). PA plasty for NSCLC is acceptable and highly recommended for pN0-1 patients. Strict patient selection should be considered so as to avoid surgical operations in patients with pN2 staging.


Yields of tar and other smoke components from UK cigarettes.
Since 1972, regular six-monthly surveys of cigarettes on sale in the UK have determined the yields of tar, nicotine and carbon monoxide in mainstream smoke. During 1983-1990, a series of special studies investigated the yields of a range of additional analytes and their inter-relationships with the routinely monitored components. The results for total cyanide (as hydrogen cyanide), total aldehydes (including acetaldehyde), acrolein, formaldehyde and nitrogen monoxide are summarized, and the full data for six low-molecular weight phenols and three polycyclic aromatic hydrocarbons (PAHs) are reported. It is concluded that with the exception of nitrogen monoxide, which is strongly dependent upon the type of tobacco, and the delivery of some phenols and PAHs, which may be affected to a minor extent by the design of cigarette, the three routinely monitored smoke components provide an adequate guide to the yields of the other analytes examined, across the range of manufactured cigarettes available in the UK in the 1980s.


Positional Differences in the Most Demanding Passages of Play in Football Competition.
The aim of this investigation was to determine the position and duration specific activity of the most demanding passages of play in football players. Global positioning system data were collected from twenty-three football players across a competitive season. A total of 605 individual match files were analysed. Players were categorised based on positional groups; full-back (FB), central defender (CD), midfielder (MF), wide midfielders (WMF) and forwards (FW). The most demanding passage of a match play was analysed using a rolling average method, where maximal values were calculated for four different time durations (1', 3', 5' and 10') using distance (m·min-1), high metabolic load distance (HMLD) and average metabolic power (AMP) as variables of interest. Using distance as the criterion variable, MF and WMF positions covered greater distance, and fewer sprinting meters (>7.0 m·s-1, m·min-1). With HMLD as the criterion variable, the values for WMF and MF positions were higher than the CD and FW positions. The MF and WMF positions performed more high-intensity accelerations and decelerations when the criterion variable was AMP. These results provide an understanding of the most demanding passages of play to inform training practices for specific football playing positions.


Preoperative Meniscal Extrusion Predicts Unsatisfactory Clinical Outcomes and Progression of Osteoarthritis after Isolated Partial Medial Meniscectomy: A 5-Year Follow-Up Study.
The objective of this study was to examine the association between preoperative meniscal extrusion of patients undergoing partial medial meniscectomy with clinical outcomes and progression of osteoarthritis and to determine the extent of meniscal extrusion associated with unsatisfactory clinical outcomes and progression of osteoarthritis. Ninety-five patients who underwent partial medial meniscectomy with a minimum follow-up of 5 years were retrospectively reviewed. Preoperative meniscal extrusion was evaluated with magnetic resonance imaging. Patients were assessed preoperatively and postoperatively with Lysholm and International Knee Documentation Committee (IKDC) subjective scores for clinical outcomes and with IKDC radiographic scale for osteoarthritis. An ANOVA (Analysis of Variance) was used to analyze the variations in meniscal extrusion and the clinical and radiological outcomes. A regression analysis was performed to identify factors that affect preoperative medial meniscus extrusion and that influence results after partial meniscectomy. An optimal cutoff value for meniscal extrusion associated with unsatisfactory clinical outcomes and progression of osteoarthritis was established. Significance was set at p < 0.05. The mean ± SD preoperative and postoperative Lysholm scores were 59.6 ± 15.5 versus 83.8 ± 13.1 (p < 0.001) and the mean preoperative and postoperative IKDC subjective scores were 59.4 ± 16.8 versus 82.0 ± 15.8 (p < 0.001). Meniscal extrusion greater than 2.2 mm (sensitivity, 84%; specificity, 81%) and 2.8 mm (sensitivity, 73%; specificity, 85%) was associated with unsatisfactory (poor/fair) Lysholm and IKDC subjective scores, respectively. The progression of osteoarthritis, characterized as a change of at least one category on the IKDC radiographic scale, occurred when meniscal extrusion was greater than 2.2 mm (sensitivity, 63%; specificity, 75%). Patients with higher body mass index (BMI) had significantly greater meniscal extrusion that patients with normal BMI (p < 0.001). The medial meniscus was more extruded in patients with horizontal and root tears. In conclusion, patients with preoperative meniscal extrusion of 2.2 mm or greater had unsatisfactory clinical outcomes and progression of osteoarthritis after partial medial meniscectomy at a minimum of 5 years follow-up. Higher BMI and horizontal and root tears were associated with greater preoperative meniscal extrusion.


Probing the Interaction Between Chromatin and Chromatin-Associated Complexes with Optical Tweezers.
Single-molecule force spectroscopy is a powerful tool to analyze the architecture and interaction of large macromolecular assemblies that are refractory to high-resolution structural interrogations. Here, we describe an optical tweezers-based platform for extracting the mechanical fingerprints of individual nucleosome arrays bound with chromatin-associated complexes, such as the Polycomb repressive complex 2 (PRC2). This platform comprehensively characterizes the diverse binding modes of PRC2 on chromatin, measures their mechanical strengths, and is broadly applicable to the studies of other epigenetic machineries.


Molecular epidemiology of human rhinovirus in children with acute respiratory diseases in Chongqing, China.
Human rhinovirus-C (HRV-C) has been increasingly detected in patients with acute respiratory diseases (ARDs). Prolonged surveillance was performed on children with ARD to investigate the molecular epidemiology and clinical characteristics of HRV in Chongqing, China. Nasopharyngeal aspirates (NPA) were collected from hospitalized children with ARD during 2009-2012. HRV-C was genotyped by sequencing the VP4/VP2 coding region. Among the 1,567 NPAs obtained, 223 (14.2%) were HRV positive, and 75.3% of these 223 NPAs were co-infected with other viruses. HRV-A (54.7%) and HRV-C (39.9%) accounted for the majority of HRV infections. Logistic regression models demonstrated significant associations between HRV-A, HRV-C, and asthma attacks, as well as between HRV-C and wheezing. A phylogenetic tree showed that HRV-C2 was the predominant type of HRV-C, followed by HRV-C43, HRV-C1, and HRV-C17. Three novel genotypes were proposed on the basis of a low identity with the known HRVs. Our results showed that HRV-A and HRV-C were the predominant types of HRV infection, and HRV-C showed a high genetic variation in Chongqing, China. HRV infection was associated with asthma attacks and wheezing; furthermore, HRV infections played a minor role in causing severe pneumonia. This knowledge provides information for the prevention and control of HRV associated with ARDs.


[Endocavitary ablation for arrhythmias. New modalities of radiofrequency applications. New energy types].
Radiofrequency remains the reference energy type for catheter ablation of rhythm disorders. In the classic indications, which are atrial flutter or tachycardia, nodal re-entry and Wolff-Parkinson-White syndrome, this energy source has the best cost-efficiency-safety ratio, subject to strict conditions of use. Some new modalities of application have further improved performance, especially active irrigation of the electrode which allows induction of deeper lesions which is very useful for the ablation of difficult atrial flutters, epicardial fascicles of Kent and ischaemic ventricular tachycardias. The only emerging alternative energy type, in the framework of classical ablation, is cold, for which the principal advantages are the homogenous and slightly thrombogenic character for the lesion involved, and the possibility of reversible applications tests which are especially useful in the ablation of structures at risk. The situation is more open-ended concerning research on ablation for atrial fibrillation or the so-called new energy types, such as ultrasound and laser, whilst recognising a renewal in interest, especially for circumferential ablation of the pulmonary veins to isolate the ectopic venous foci. Mechanical energy such as luminous energy is emitted across a catheter balloon deployed at the orifice of the vein, perpendicular to its axis, aiming to reach a continuous circumferential lesion with a minimum of applications. Equally radiofrequency has been undergoing significant evolution for this application, such as by the development of porous catheter balloons with a liquid electrode, as well as by the development of deployable circumferential catheters. Ablation is use for atrial fibrillation, by endocavity atrial segmentation remains a field of research in which radiofrequency retains an important place. It is delivered via multi-electrode catheters according to the new application modalities, either pulsed or by phase interval, which secure better efficacy by better continuity of the line of block. Research is equally underway on the use of microwaves and cold in this application.


How to make more people adopt healthy behaviors? Assessing health literacy, health promoting lifestyle and their association of community residents in Shenzhen, China.
Health literacy (HL) has been concerned a key factor for determining the use of health information and promoting health. The study aimed to explore the relationship between different health literacy types and health promoting lifestyle (HPL) in different health literacy population. The survey analyzed a sample of 16,921 community residents in Shenzhen. The Chinese Citizen Health Literacy Questionnaire and health-promoting lifestyle profile II (HPLP- II) were used to assess health literacy and health promoting lifestyle. Participants were divided into different populations based on the correlation between HL and HPL. The low-HL and medium-HL populations were judged to lack health literacy, and demographic characteristics were significantly different between different HPL levels in low-HL and medium-HL populations. There were 6 types of HL, and health information literacy (β = 0.08, P < 0.001) and chronic disease literacy (β = 0.08, P < 0.001) positively predicted HPL in the low-HL population. In the medium-HL population, the results of reward and punishment analysis showed that health information was a basic factor, chronic disease was performance factor, medical care was a motivating factor for HPL; there were 6 dimensions of HPL, and health responsibility (HR), stress management (SM) and physical activity (PA) were not significantly different in medium-HL population. The results of regression analysis showed that HR and PA had a great impact on HPL (HR: β = 0.193, PA: β =0.179, β for other dimensions was 0.186, 0.176, 0.171, 0.164), but the HR and PA standardized scores were lowest in the HPL dimensions (HR: 69.42, PA: 68.5, lower than other dimensions), so it may be HR and PA that cause HPL unchanged between groups in the medium-HL population. Different HL levels have different relationships with HPL, and different HL types have different effects on HPL. Shenzhen community residents need to improve their HL, and they have great potentials for further progress to improve the population health. Public health policy makers need to consider formulating different policies for people with different HL levels.


Speech Recognition in Noise in Adults and Children Who Speak English or Chinese as Their First Language.
Speech recognition of individuals who are listening to a nonnative language is significantly degraded in the presence of background noise and may be influenced by proficiency, age of acquisition, language experience, and daily use of the nonnative language. The purpose of this study is to examine and compare speech recognition in noise performance across test conditions with varying signal-to-noise ratios (SNRs) as well as the presence of vocal and spatial cues in listeners who speak American English as a native language or Mandarin Chinese as a native language. Self-rated English proficiency and experience were collected for native Mandarin Chinese speakers to determine its relationship to performance on the test measures. A cross-sectional repeated measures design was used for the study. Four groups of participants were included in the study. The adult groups consisted of 25 adults who speak native English and 25 adults who speak native Mandarin Chinese with English as an additional language. The pediatric groups consisted of 16 children who speak native English and 16 children who speak native Mandarin Chinese with English as an additional language. Percent correct speech recognition in noise was assessed at three SNRs (-3, 0, +3 dB) using the adult or pediatric versions of the AzBio sentence test. The Listening in Spatialized Noise-Sentence (LiSN-S) test was used to determine the effect of providing spatial and vocal cues on the speech recognition in noise performance of the groups of participants. The data for each age group and test measure were analyzed with a repeated measures analysis of variance. Correlation analyses were performed to examine relationships between English proficiency and experience on performance across the speech recognition test conditions. Analysis of the data from the adult or pediatric AzBio sentence test identified a significant effect of native language for adults but no significant effect for children. The higher SNRs yielded better performance for all listeners. On the LiSN-S test, results for the adult and pediatric groups were similar and showed significantly better performance for the native English speakers in every test condition. The demographic and language characteristics that most affected speech recognition performance across the test measures included the length of time the person lived in the United States, the age of English acquisition, the number of minutes per day English was spoken by the participant, and the self-rated English proficiency. The findings in this study highlight the importance and benefit of higher SNRs as well as the provision of vocal and spatial cues for improving speech recognition performance in noise of adult and pediatric listeners who speak Mandarin Chinese as a native language.


Preparing staff to provide bereavement support.
An in-service training programme was developed to meet the needs of an NHS palliative care service for children and young people, specifically focused on bereavement work. A training day was held every six months that allowed staff to share and support each other's practice and to consider how best practice could be promoted. Each training day was evaluated by attendees, who were asked to rate the usefulness of the day and give qualitative feedback. After four training days had been completed, staff views on the impact and benefits of the programme were sought using a questionnaire that incorporated a set of statements highlighting factors important to good bereavement care. Participant evaluations indicated that the aims of the training days were being met. Responses to the questionnaire were positive, both in terms of improvement and positive outcomes in the workplace. Ongoing training and support as well as clinical supervision are essential to maintain good practice in palliative and bereavement care.


Hypnotherapy in the treatment of the chronic nocturnal use of a dental splint prescribed for bruxism.
A behavioral medicine case is described in which the patient was treated with a combined approach involving both hypnoanalytic and hypnobehavioral techniques. A 55-year-old man with bruxism was referred after 10 years of craniomandibular treatment because of his dependency on a dental splint prescribed for nocturnal use. A projective hypnoanalytic exploration helped to uncover and consequently resolve an earlier conflict that had been reactivated in the patient's work situation and which had become a constant source of mental and muscular tension. The hypnoanalytic exploration was followed by a cognitive-behavioral hypnotic intervention that was tape-recorded and prescribed for bedtime practice. Pre- and posttherapy psychological, physiological, and self-report measurements corroborated the patient's sense of well being that came with his newly found ability to sleep without the dental splint. The importance of considering multiple etiological factors in the treatment of such psychosomatic disorders as bruxism is discussed.


Nonlinear regression analysis of the time course of ligand binding experiments.
The binding and release of hormones and growth factors are often relatively slow processes under biological conditions. Consequently, a knowledge of the underlying rate constants may be of greater physiological relevance than the equilibrium constant. Here we show how, by following a single time course of binding, the rate constants for both binding and release can be determined. The ratio of these rate constants allows the binding constant to be calculated. A nonlinear regression computer program is described which facilitates these calculations and which provides estimates and standard errors of the constants determined. The method is illustrated by the binding of human growth hormone to the human growth hormone binding protein, and the binding of ovine prolactin to the rabbit prolactin receptor.


AIDS counseling on the front lines.
Skill at patient education is crucial to the battle against the spread of human immunodeficiency virus (HIV). The fight is not confined to one segment of society or to a few geographic areas. Counseling patients at risk about HIV-antibody (HIV-Ab) testing requires a full understanding of the available tests; a psychosocial profile of the patient; candid, nonjudgmental exchanges between patient and clinician; and an ability to deal with significant emotional stress. All PAs should use their talents at patient education to help contain HIV infection.


[Histopathological findings following cryo-coagulation of the ciliary body with a nitrogen-cooled probe].
A new cryoprobe was investigated in rabbits for experimental coagulation of the ciliary body. In a one-step procedure, the cyclodestructive effect was achieved by cooling the cryoprobe down to -100 degrees C without significant lens damage. The histological investigation showed extensive necrosis of the ciliary epithelium 2 h and 2 days after the freezing damage. After 2 weeks and 2 months, fibrous atrophy of the entire segment of the ciliary body could be observed.


Glucocorticoid "programming" and PTSD risk.
Epidemiological data have linked an adverse fetal environment with increased risks of cardiovascular, metabolic, neuroendocrine, and psychiatric disorders in adulthood. Prenatal stress and/or glucocorticoid excess might underlie this link. In animal models, prenatal stress, glucocorticoid exposure or inhibition/knockout of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2), the feto-placental barrier to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behavior resembling of anxiety. In humans, 11 beta-HSD-2 gene mutations cause low birth weight and placental 11 beta-HSD-2 activity correlates directly with birth weight and inversely with infant blood pressure. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. In human pregnancy, severe maternal stress affects the offspring HPA axis and associates with neuropsychiatric disorders. Posttraumatic stress disorder (PTSD) appears to be a variable in the effects. Intriguingly, some of these effects appear to be 'inherited' into a further generation, itself unexposed to exogenous glucocorticoids at any point in the lifespan from fertilization, implying epigenetic marks persist into subsequent generation(s). Overall, the data suggest that prenatal exposure to excess glucocorticoids programs peripheral and CNS functions in adult life, predisposing to some pathologies, perhaps protecting from others, and these may be transmitted perhaps to one or two subsequent generations.


Hemagglutinin and neuraminidase genes of influenza B viruses circulating in Riyadh, Saudi Arabia during 2010-2011: evolution and sequence analysis.
Influenza viruses are known as continuing threats to human public health every year worldwide. Evolutionary dynamics of influenza B viruses in humans are in a unique progression having two lineages; B/Yam and B/Vic-like viruses, which are circulating simultaneously worldwide. There is a considerable lack of data on influenza B viruses circulating in Saudi Arabia. During the winter-spring season of 2010-2011, 80 nasopharyngeal aspirates were collected from hospitalized patients with flu-like symptoms in Riyadh. Screening of samples by one-step RT-PCR identified three (3.8%) influenza B viruses. Sequencing of hemagglutinin (HA) and neuraminidase (NA) genes was performed to analyze influenza B viruses circulating in Riyadh as compared to the globally circulating strains. Several common and six unique amino acid substitutions were observed for both HA and NA genes of influenza B Saudi strains. Three unique substitutions (T182A, D196N, and K254R) were identified in HA gene of the B/Yam-like Riyadh strains. In NA gene, a unique common substitution (D53G) was found in all Riyadh strains, while two unique substitutions (L38P, G233R) were recognized only in B/Vic-like Riyadh strains. Riyadh strains were also found to contain N-glycosylation site in HA gene of both B/Vic and B/Yam lineages at positions 197-199 (NET) and 196-198 (NNK/DNK), respectively. The significance of these mutations on the antigenicity of both lineages is discussed herein. The unique changes observed in HA and NA genes of influenza B Riyadh strains support strongly the need for continuous surveillance and monitoring of new evolving strains that might pose threat to the Saudi community.


Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone.
Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αvβ3. We investigated the role of thyroid hormone-induced internalization of nuclear integrin αv monomer. Physiological concentration of thyroxine (free T4, 10(-10) M), but not 3,5,3'-triiodo-l-thyronine (T3), induced cellular internalization and nuclear translocation of integrin αv monomer in human non-small-cell lung cancer (H522) and ovarian carcinoma (OVCAR-3) cells. T4 did not complex with integrin αv monomer during its internalization. The αv monomer was phosphorylated by activated ERK1/2 when it heterodimerized with integrin β3 in vitro. Nuclear αv complexed with transcriptional coactivator proteins, p300 and STAT1, and with corepressor proteins, NCoR and SMRT. Nuclear αv monomer in T4-exposed cells, but not integrin β3, bound to promoters of specific genes that have important roles in cancer cells, including estrogen receptor-α, cyclooxygenase-2, hypoxia-inducible factor-1α, and thyroid hormone receptor β1 in chromatin immunoprecipitation assay. In summary, monomeric αv is a novel coactivator regulated from the cell surface by thyroid hormone for the expression of genes involved in tumorigenesis and angiogenesis. This study also offers a mechanism for modulation of gene expression by thyroid hormone that is adjunctive to the nuclear hormone receptor (TR)-T3 pathway.


Developmental pattern of VIP binding sites in the human hypothalamus.
We have studied the developmental patterns of vasoactive intestinal polypeptide (VIP) binding sites in the human hypothalamus. VIP recognition sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. VIP binding was generally low in the fetal and neonatal periods and a tendency in increasing densities was observed during postnatal development. The age comparison of binding density indicates variations in several structures. Thus, the densities were higher in older infants in the preoptic area, lamina terminalis, and infundibular (IN) nucleus. These differences suggest the implication of VIP receptors in the development of this brain structure and the maintenance of its various functions.


Regulation of the levels of small heat-shock proteins during differentiation of C2C12 cells.
Levels of the small heat-shock proteins (sHSPs) HSP27 and alphaB-crystallin during differentiation of mouse C2C12 cells were determined using specific immunoassays. Increases of these proteins were about 3-fold and 10-fold, respectively. Under the same conditions, however, the level of HSP70 in C2C12 cells barely increased, indicating selective accumulation of HSP27 and alphaB-crystallin with differentiation. While expression of mRNA for alphaB-crystallin was also markedly increased and that for HSP27 was but to a lesser extent, mRNA for HSP70 could barely be detected during differentiation. Activation of the heat-shock factor was not observed, in contrast to the case with heat-stressed undifferentiated cells. Various inhibitors of protein kinases affected the differentiation and the associated increase of sHSPs. Rapamycin, an inhibitor of p70 S6 kinase, completely inhibited the differentiation and suppressed the accumulation of HSP27 and alphaB-crystallin. SB203580, an inhibitor of p38 MAP kinase, also inhibited differentiation, but the accumulation of alphaB-crystallin was rather enhanced. PD98059, an inhibitor of MAP kinase kinase, significantly increased expression of a differentiation marker for muscle cells, creatine kinase M isozyme, as well as accumulation of alphaB-crystallin. These results suggest that accumulation of sHSPs during differentiation of C2C12 cells is regulated in a complex manner.