Laser-induced carotid artery injury model in the rat for therapeutic agent screening.
The aims of this study were to establish a rat model of carotid artery injury and to evaluate its suitability for evaluating therapeutic agents active against endothelial proliferation. Wistar-Kyoto rats were injected intravenously with the photochemically reactive dyes rose bengal or Evans blue, and the carotid artery was then focally irradiated with laser light of the appropriate wavelength. Histological sections of the carotid artery were analyzed to determine the appropriate parameters for this model. Ferulic acid was used to assess the suitability of this model for drug screening. No animal died as a result of the photochemical treatment. Endothelial proliferation in the carotid artery was observed in rats injected with rose Bengal and exposed to green laser light. Ferulic acid (400 mg/kg per day) significantly (p<0.05) reduced endothelial proliferation in the carotid artery 28 days after injury in dye-treated animals compared with vehicle-treated animals. This simple experimental rat model is suitable for studying factors inhibiting endothelial thickening after vessel damage and for developing therapeutic strategies active against endothelial proliferation.


How does plasmid DNA penetrate cell membranes in artificial transformation process of Escherichia coli?
Artificial transformation of Escherichia coli with plasmid DNA in presence of CaCl2 is a widely used technique in recombinant DNA technology. However, exact mechanism of DNA transfer across cell membranes is largely obscure. In this study, measurements of both steady state and time-resolved anisotropies of fluorescent dye trimethyl ammonium diphenyl hexatriene (TMA-DPH), bound to cellular outer membrane, indicated heat-pulse (0 degrees C42 degrees C) step of the standard transformation procedure had lowered considerably outer membrane fluidity of cells. The decrease in fluidity was caused by release of lipids from cell surface to extra-cellular medium. A subsequent cold-shock (42 degrees C0 degrees C) to the cells raised the fluidity further to its original value and this was caused by release of membrane proteins to extra-cellular medium. When the cycle of heat-pulse and cold-shock steps was repeated, more release of lipids and proteins respectively had taken place, which ultimately enhanced transformation efficiency gradually up to third cycle. Study of competent cell surface by atomic force microscope showed release of lipids had formed pores on cell surface. Moreover, the heat-pulse step almost depolarized cellular inner membrane. In this communication, we propose heat-pulse step had two important roles on DNA entry: (a) Release of lipids and consequent formation of pores on cell surface, which helped DNA to cross outer membrane barrier, and (b) lowering of membrane potential, which facilitated DNA to cross inner membrane of E. coli.


Functional bracing of Colles' fractures: a prospective study of immobilization in supination vs. pronation.
In a prospective study, 156 Colles' fractures were treated with a functional Orthoplast brace. Approximately one-half were braced in pronation and one-half in supination. One hundred and four were available for follow-up. Results were analyzed by type of fracture and position of immobilization (pronation versus supination). In evaluating the results, we found that: (1) displaced Colles' fractures without articular involvement (Type II) braced in supination yielded superior anatomic results when compared with those treated in pronation; (2) Type IV (displaced intra-articular) fractures braced in supination obtained a significantly higher percentage of excellent functional and anatomic results than those braced in pronation. In general, treatment with functional bracing yielded 90% excellent or good functional results.


Managing In-Session "Surprises:" Provider Responses to Emergent Life Events during Evidence-Based Treatment Implementation.
This study aimed to: (1) pilot a psychotherapy coding system for provider responses to emergent life events (ELEs; unexpected events that have a significant negative impact on the client), (2) examine the impact of ELEs on evidence-based treatment (EBT) delivery in community settings. Raters coded 30 randomly-sampled EBT session recordings with and without reported ELEs. Inter-rater reliability and validity for the system were generally high. When an ELE occurred, providers were significantly less likely to deliver the EBT, and when they did, they rarely linked the EBT to the event. Findings highlight the potential for ELEs to disrupt EBT implementation.


Heterochrony and geometric morphometrics: a comparison of cranial growth in Pan paniscus versus Pan troglodytes.
Heterochrony, the classic framework in which to study ontogeny and phylogeny, in essence relies on a univariate concept of shape. Though principal component (PC) plots of multivariate shape data seem to resemble classical bivariate allometric plots, the language of heterochrony cannot be translated directly into general multivariate methodology. We simulate idealized multivariate ontogenetic trajectories and explore their appearance in PC plots of shape space and size-shape space. Only if the trajectories of two related species lie along exactly the same path in shape space can the classic terminology of heterochrony apply and pure dissociation of size change against shape change be detected. Regional heterochrony--the variation of apparent heterochrony by region--implies a dissociation of local growth fields and cannot be identified in an overall PC analysis. We exemplify a geometric morphometric approach to these issues using adult and subadult crania of 48 Pan paniscus and 47 Pan troglodytes specimens. On each specimen, we digitized 47 landmarks and 144 semilandmarks on facial curves and the external neurocranial surface. We reject the hypothesis of global heterochrony in the cranium of Pan as well as regional heterochrony for the lower face, the upper face, and the neurocranium.


Inclusion complex formation between high amylose corn starch and alkylresorcinols from rye bran.
The formation of high amylose corn starch (HACS)-alkylresorcinol (AR) inclusion complexes was demonstrated using HACS and a crude AR extract from rye bran, and was confirmed by complementary characterization techniques. Inclusion complex was extracted using hot 2-propanol/water (3:1), and thirteen different AR homologs were identified in the 2-propanol/water extract. However, this extraction regime was insufficient to remove all guests from the inclusion complexes, but did result in annealing of the V-type crystallinity, yielding an endotherm with higher onset and peak temperatures and dissociation enthalpy. The remaining guest compounds were recovered by disruption of the inclusion complexes with DMSO followed by liquid-liquid extraction. A total of nine AR homologs were recovered and two saturated long alkyl chain AR homologs (C21:0 and C19:0) were obviously enriched in the complexes compared to the crude AR extract. The formation of HACS-AR inclusion complexes may have the potential to inhibit staling in baked goods.


Progestin regulation of human endometrial function.
A well-orchestrated sequence of events enables the human endometrium to become receptive to embryo implantation during a defined period in the menstrual cycle. Ovarian steroids, oestradiol and progesterone, regulate many of these functions in a highly co-ordinated manner. There are no experimental systems for critically examining the regulation of endometrial functions by steroid hormones, especially those responses restricted to the epithelium. Using an experimental xenograft model where the steroid responses of normal endometrium could be predictably recapitulated, the role of progesterone in the regulation of alpha crystallin B in the glandular epithelial cells of human endometrium was established.


The death of a healthy volunteer in a human research project: implications for Australian clinical research.
A healthy 19-year-old United States college student volunteer in a clinical research program underwent a bronchoscopy and died as a result of acute lignocaine toxicity. The major contributing factor in the tragedy was that the research protocol failed to specify an upper dose limit for lignocaine spray, although previous versions of the protocol had done so. We look at the implications of this case for Australian institutional ethics committees.


Shaping patients' decisions.
Many physicians struggle to strike an acceptable balance between respecting patient autonomy and guiding patients' decisions toward what is in their best interests based on their expressed values and long-term goals. Over the past 40 years, the ethical principle of respect for autonomy has gained primacy in Western medicine, but judgments about the appropriate dose of influence on patient decisions have been clouded by misconceptions about patient autonomy. In this article, we consider three such misconceptions with the goal of helping physicians to optimally promote their patients' interests.


The effect of different types of smoking habits on periodontal attachment.
The association between different types of smoking (cigarette, Shesha and Argela) and periodontal attachment loss was investigated in the Riyadh area. The study group included 150 subject 20-60 years of age. Of this, 27.5% were cigarette smokers, 20.3% were Shesha smokers, 20.3% were Argela smokers, and 32% were non-smokers (females 24.2%: 74% males). The study was based on clinical examination, periodontal parameters recorded by one examiner (AS) and included measurement of pocket depth (PD 1) followed by measurement of recession from the CEJ to gingival margin (GR 2). Attachment loss (AL) was calculated by adding recession or by subtracting gingival overgrowth to measurements of probing depth. The readings were taken from buccal and lingual surfaces of all teeth except third molars. The influence of age, sex and different types of smoking consumption on these periodontal parameters was statistically evaluated using an analysis of variance (ANOVA). The effect of smoking on periodontitis showed no association with sex, but it was associated with age. By performing both univariate and multivariate tests. P-value for smoking and periodontitis were GR (p = 0.0001), PD (p = 0.0001), and AL (p = 0.0001). The result showed that there is increased loss of attachment in smokers than non-smokers. However, when comparing Shesha smokers to cigarette smokers it was found that Shesha smokers had a greater attachment loss (p = 0.0001), recession (p= 0.0001) and deeper pocket depth (p = 0.001) than cigarette and Argela smokers. These findings suggest that all types of tobacco consumption increase periodontal disease severity and Shesha smoking had a greater effect than cigarette and Argela smoking on disease severity. This study confirms that tobacco is an important risk factor for periodontal disease. Since Shesha smoking is widely used among Saudi subjects of both sexes, additional studies should be conducted to study the effect of Shesha smoking on the periodontium.


Vascularization of left kidney by single vessel originating from splenic artery.
According to the literature, sole renal arteries always originate from the aorta. In multiple renal arteries, the origin of an accessory renal artery may be expected from the splenic artery on theoretical basis. This origin, however, never is described. A patient is presented with a sole left renal artery, originating from the splenic artery. The diagnosis is made by angiography and confirmed by computed tomography and surgery.


Inhibition of cell proliferation by the cholecystokinin antagonist L-364,718.
Specific cholecystokinin (CCK) receptor and gastrin receptor antagonists were used to assess what role, if any, these receptors have in autocrine cell growth. Although the cholecystokinin receptor antagonist, L-364,718, inhibited cell proliferation in a broad spectrum of cell lines, the gastrin antagonist, L-365,260, had no effect on cell proliferation. In addition neither added gastrin17, nor sulfated cholecystokinin8, could reverse the inhibitory action of L-364,718. It is proposed that L-364,718 inhibits cell proliferation independently of classical gastrin/CCK receptors.


Executive functions in the elderly with mild cognitive impairment: a systematic review on motor and cognitive inhibition, conflict control and cognitive flexibility.
Mild Cognitive Impairment (MCI) is a syndrome characterised by mild cognitive decline, on one or more domains, but which does not compromise daily functions. Several studies have investigated the relationship between MCI and deficit in executive functions (EFs) but, unlike robust evidence in the mnestic domain, the nature of executive deficits in the MCI population remains uncertain. This systematic review aims to evaluate EFs in patients with MCI, considering inhibition (motor and cognitive), conflict control and cognitive flexibility. The databases used for the search were PUBMED, PsycINFO, PsycARTICLES and MEDLINE. Eligibility criteria: use of specific paradigms for EFs assessment ('Wisconsin Card Sorting Test', 'Stroop Task', 'Go/No-Go Task', 'Flanker Task'); age over 65, studies published in English. presence of dementia; psychiatric disorders; stroke; cranial trauma; inclusion of participants with MCI in groups with healthy elderly or those with dementia. Fifty-five studies were selected, namely: Stroop Task (N = 30), WCST (N = 14), Go/No-Go (N = 9), Flanker Task (N = 2). Results have shown in people with MCI deficits in all the EFs considered. The results of this review support the applicability of the four experimental tasks examined for the study of EFs in people with MCI. These paradigms are useful in research, diagnosis and therapeutic purposes, allowing obtaining an articulated EFs profile that can compromise the daily life in elderly. These EFs are not generally evaluated by standard assessment of MCI, but their evaluation can lead to a better knowledge of MCI and help in the diagnosis and treatment.


Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents?
The gastric and tracheal flora of 142 consecutive patients receiving stress ulcer prophylaxis were investigated, identifying identical isolates by typing. Furthermore, the growth pattern of normal respiratory bacteria and organisms causing ventilation pneumonia at different pH values and the in vitro effect of sucralfate and bismuth subsalicylate on these bacteria in simulated gastric fluid were studied. The results obtained were as follows: (1) with rising gastric pH bacterial counts in gastric aspirates, especially gram-negatives, increased significantly; (2) in 45 (31.7%) of the patients identical organisms were first isolated in gastric samples and one to two days later in tracheal secretions; (3) ventilation pneumonia was significantly more frequent in patients with high gastric pH; (4) pathogens causing ventilation pneumonia grew well in simulated gastric fluid at higher pH values, unlike normal respiratory organisms; and (5) sucralfate and bismuth subsalicylate showed antibacterial activity against frequent causative organisms of ventilation pneumonia.


Exercise in osteoarthritis: moving from prescription to adherence.
Exercise is recommended for the management of osteoarthritis (OA) in all clinical guidelines irrespective of disease severity, pain levels, and functional status. For knee OA, evidence supports the benefits of various types of exercise for improving pain and function in the short term. However, there is much less research investigating the effects of exercise in patients with OA at other joints such as the hip and hand. It is important to note that while the magnitude of exercise benefits may be considered small to moderate, these effects are comparable to reported estimates for simple analgesics and oral nonsteroidal anti-inflammatory drugs for OA pain but exercise has much fewer side effects. Exercise prescription should be individualized based on assessment findings and be patient centered involving shared decision making between the patient and clinician. Given that patient adherence to exercise declines over time, appropriate attention should be pain as reduced adherence attenuates the benefits of exercise. Given this, barriers and facilitators to exercise should be identified and strategies to maximize long-term adherence to exercise implemented.


Influence of crown-implant ratio on implant success rates and crestal bone levels: a 36-month follow-up prospective study.
The aim of this prospective study was to determine how the crown-implant ratio (C/I ratio) influences crestal bone loss and implant success rates after a 3-year follow-up, using implants with a sintered porous surface (SPS). On the basis of preestablished inclusion and exclusion criteria, 151 of a cohort of 160 patients with single or partial edentulism were selected as eligible for the study. The 151 patients were treated consecutively from 2005 to 2007 using 280 SPS implants, which were restored with a single crown or a partial fixed denture. The data collection included both clinical and anatomical C/I ratios; other implant prosthetic factors were also recorded. Implants were divided into three groups according to the C/I ratio. Clinical and radiographic examinations were scheduled over a 36-month follow-up of functional loading according to a well-established protocol generally applied to determine implant success rates and crestal bone levels. Statistical analysis was used to determine any significant differences or correlations (P = 0.05). A total of 259 SPS implants in 136 patients were followed up for 36 months. According to the success criteria, the overall implant-based success rate was 98.1%, and the mean peri-implant bone loss (PBL) was 0.48 ± 0.29 mm. Statistical analysis revealed significant correlation between implant success rate and C/I ratio (P < 0.05) and between PBL and C/I ratio (P < 0.05). The critical threshold value of the anatomical and clinical C/I ratio for avoiding excessive bone loss or implant failure was 3.10 and 3.40. This prospective cohort study revealed that SPS implants offer a predictable solution for implant prosthetic rehabilitation in patients with edentulism characterized by different alveolar bone atrophy. From the biomechanical point of view, the C/I ratio would appear to be the main parameter capable of influencing implant success and crestal bone loss. Consequently, it is important not to exceed the threshold values in order to avoid excessive stress at the bone-implant interface capable of resulting in excessive crestal bone loss or implant failure.


[Early treatment of acute nephrotic syndrome in patients with acute post-streptococcal glomerulonephritis].
In the period of five years 54 patients with acute poststreptococcal glomerulonephritis were treated. Acute nephritic syndrome was manifested in 45 (almost 4/5 of all) patients. Edema and hematuria were found in all patients, hypertension in 89%, and acute renal failure in 49% of patients with the acute nephritic syndrome. For successful treatment of acute nephritic syndrome of decisive importance have been application of measures intended primarily to correction of positive sodium and water balance by dietetic regimes, diuretics and antihypertensives and rest, while the application of the dialysis has not been necessary even in patients with acute renal failure.


LPS-induced clustering of CD14 triggers generation of PI(4,5)P2.
Bacterial lipopolysaccharide (LPS) induces strong pro-inflammatory reactions after sequential binding to CD14 protein and TLR4 receptor. Here, we show that CD14 controls generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in response to LPS binding. In J774 cells and HEK293 cells expressing CD14 exposed to 10-100 ng/ml LPS, the level of PI(4,5)P2 rose in a biphasic manner with peaks at 5-10 min and 60 min. After 5-10 min of LPS stimulation, CD14 underwent prominent clustering in the plasma membrane, accompanied by accumulation of PI(4,5)P2 and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region. Clustering of CD14 with antibodies, without LPS and TLR4 participation, was sufficient to trigger PI(4,5)P2 elevation. The newly generated PI(4,5)P2 accumulated in rafts, which also accommodated CD14 and a large portion of PIP5K Iα and PIP5K Iγ. Silencing of PIP5K Iα and PIP5K Iγ, or application of drugs interfering with PI(4,5)P2 synthesis and availability, abolished the LPS-induced PI(4,5)P2 elevation and inhibited downstream pro-inflammatory reactions. Taken together, these data indicate that LPS induces clustering of CD14, which triggers PI(4,5)P2 generation in rafts that is required for maximal pro-inflammatory signaling of TLR4.


A comparative study of sagittal correction with the Herbst appliance in two different ethnic groups.
The dentofacial morphology of Chinese is different from Caucasians. The purpose of this investigation was to assess the skeletal and dental changes contributing to the sagittal correction in group of consecutive Chinese children who were treated with the Herbst appliance. A comparison was made between 14 Chinese and 14 Swedish subjects who all had Herbst appliance treatment. All subjects were corrected from the Class II division 1 malocclusion to an overcorrected Class I or Class III dental relationship within a 6-8 month period. Lateral cephalograms taken before and immediately after the Herbst treatment were analysed. In general, the skeletal and dental changes during treatment were comparable between both ethnic groups. However, individual variations within the two groups were wide. It can be concluded that the Herbst appliance was equally successful in Southern Chinese children and similar treatment changes as those achieved in Swedish children could be found.


Contribution of iodized salt to total iodine and total salt intake in Germany.
Salt reduction campaigns without a parallel increase of iodine fortification will lead to a worsened iodine status in countries with a relevant salt iodization. A decline in iodine supply bears the risk of higher prevalences of goiter, thyroid nodules, and cognitive delay in children. Against this background, we analyzed the contribution of iodized salt to total iodine and salt intake in Germany and compared the results with data from Switzerland. Analyses were performed with data of the representative German Health-Interview and Examination-Survey for Adults (DEGS1, 2008-2011) using spot urine measurements of creatinine, iodine, and sodium (n = 6738). Median daily iodine and salt intakes were calculated by estimating 24-h iodine and sodium excretions from urinary analyte/creatinine ratios. Linear regressions were used to deduce iodine intake that originates from iodine containing foods (i.e., salt-independent iodine). From this, ingested iodine originating from salt and the proportion of iodized salt to total salt intake were calculated. Data from Switzerland were obtained from the literature. In Germany, only 42% (52.2 µg/d) of the predicted median total iodine intake (126.2 µg/d), i.e., 12% less than in Switzerland, were found to originate from salt, whereas 73.7 µg/d came from iodine containing foods. 28% (2.6 g/d) of the median salt intake (9.3 g/d) of the German population was calculated to represent iodized salt against 43% in Switzerland. Along with an almost identical inherent iodine intake in Germany and Switzerland, the average total iodine intake, the contribution of iodized salt to total iodine intake, and the proportion of iodized salt to total salt are higher in Switzerland than in Germany. Despite this, iodine fortification of table salt has recently been increased in Switzerland from 20 to 25 mg/kg to ensure iodine sufficiency in the population, whereas in Germany fortification still remains at a mean level of 20 mg/kg implying a growing risk of increasing iodine deficiency rates if general salt intake drops.


Auditory brain stem responses in patients with vertigo.
Sixty-two patients with vertigo were examined with ABR. Eight of the 30 patients with vestibular neuronitis had abnormal ABR indicating brain stem dysfunction. Most of the patients with abnormal ABR showed continued ABR abnormality after recovery from the disease. Only one patient with epidemic vertigo had abnormal ABR, the remaining 15 patients had no signs of brain stem involvement. All 16 patients with benign positional vertigo had normal ABR.


Sleep quality and disturbances in patients with different-sized rotator cuff tear.
The literature is unanimous in saying that shoulder pain, due to rotator cuff tear (RCT), may be mostly at night; to our knowledge, this statement is not supported by scientific evidence. Our aim was to investigate sleep quality and disturbances in patient with RCT and in a control group. A case-control design study was used. We enrolled 324 consecutive patients (Group A) (156M-168F, mean age ± SD: 64.94 ± 6.97; range 47-74) who underwent arthroscopic rotator cuff repair. Tear size was determined intraoperatively. The control group (Group B) included 184 subjects (80M-104F, mean age ± SD = 63.34 ± 6.26; range 44-75) with no RCT. All participants were submitted to two standardized self-reported questionnaires evaluating sleep quality and disturbances: the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Data were submitted to statistics. We found no significant differences between the two groups according to both PSQI (Group A: 5.22 ± 2.59; Group B: 5.21 ± 2.39) and ESS (Group A: 2.59 ± 2.54; Group B: 5.76 ± 2.63), p > 0.05. Patients with small tears had average PSQI and ESS higher than patients with large and massive lesions (p < 0.005). Pearson's test showed that tear severity was negatively correlated with both sleep latency (r 2 = -0.35, β = 0.069, p < 0.005) and sleep disturbances (r 2 = -0.65, β = 0.053, p < 0.001). RCT is only one of the responsible causes for sleep disturbance in middle-aged and elderly subjects. Patients with small tears have a poorer sleep quality with respect to those with a more severe tear; particularly, they not only take more time to fall asleep, but also have a more disturbed sleep compared to patients with large and massive tears. III.


The acute effect of perindopril upon effort capacity in congestive heart failure.
A number of 21 patients with congestive heart failure (CHF) of various etiologies were studied. All patients were subjected to a classical exercise testing (ET) on cycloergometer. The ET was repeated 24 hrs later, 6 hrs after the administration of 2 mg Perindopril (Coversyl). No statistically significant differences in duration and intensity of ET before and after Perindopril were noted for the whole group. But in 9 patients (42.8%) at least one effort level was gained. In these patients the peak double product (DP) was similar before and after Perindopril, but at submaximal effort DP was, at each level, lesser after Perindopril, suggesting a mechanism of afterload reduction in the improvement of effort capacity.


CYP3A-mediated apoptosis of dauricine in cultured human bronchial epithelial cells and in lungs of CD-1 mice.
Dauricine is the major bioactive component isolated from the root of Menispermum dauricum DC and has shown promising pharmacologic activities with a great potential for clinical use. Recently, we found that intraperitoneal exposure of dauricine produced selective pulmonary injury in mice. A quinone methide metabolite of dauricine was identified and is suggested to be associated with the pulmonary toxicity of dauricine. The present study evaluated the apoptotic effect of dauricine in cultured cells and mice, determined the change in cellular glutathione (GSH) contents after exposure to dauricine, investigated the role of GSH depletion in dauricine-induced cytotoxicity and apoptosis, and examined the role of CYP3A in dauricine-induced GSH depletion and apoptosis. Dauricine was found to induce apoptosis in NL-20 cells. Additionally, intraperitoneal administration of dauricine caused GSH depletion and apoptosis in lungs of mice. Treatment with ketoconazole, an inhibitor of CYP3A, reversed cellular GSH depletion in lungs of mice given dauricine and showed protective effect on dauricine-induced apoptosis in lungs of mice. This indicates that metabolic activation is involved in dauricine-induced GSH-depletion, cytotoxicity and apoptosis. The glutathione depletor L-buthionine sulfoximine showed potentiating effect on cytotoxicity and apoptosis induced by dauricine. We propose that dauricine is metabolized to a quinone methide intermediate which depletes cellular GSH, and the depletion of GSH may trigger and/or intensify the cytotoxicity and apoptosis induced by dauricine.


[Geographic distribution and gene sequencing of Paragonimus westermani in some areas of Guangdong Province].
To investigate the current distribution of Paragonimus westermani in Guangdong Province. Snails and crabs collected from mountain streams in regional survey sites were dissected to detect cercarial and metacercarial infections of P. westermani. Domestic cats and dogs artificially infected with the collected metacercariae were also dissected to detect adult worms of P. westermani. The COI and ITS2 gene sequences of those adult worms were compared with those of known Paragonimus specimen deposited in the GenBank. All of the first intermediate hosts in five survey sites of Liangkou, Nankun, Mountain, Dadong, Muxi, Guowu, were identified as Semisulcospira libertina, whose cercariae infection rates were 0.33%, 0.15%, 0.058%, 0.10%, and 0.05%, respectively; the second intermediate hosts in above five sites were all identified as Sinopotamon denticulatum, whose metacercariae infection rates were 100%, 100%, 38.09%, 55.36%, and 65.26%, respectively. The numbers of metacercariae in the five sites were 79.4, 105.66, 9.16, 16.18, and 15.6 per positive crab, respectively, and 11.12, 7.87, 0.58, 0.69, and 0.85 per gram of crab, respectively. All the metacercariae were identical to those of P. westermani. Adult worms and eggs of P. westermani were found in both reservoir hosts of domestic cats and dogs infected artificially. By comparing the COI genes of five representative samples from each survey site with that of Paragonimus #AF219379.21, AF540958.1 from GenBank, we found out the homology to be 99%, 99%, 99%, 98%, and 99%, respectively. In addition, a comparison of the ITS2 gene sequences between the above five samples and Paragonimus #DQ836243.1, DQ351845.1, AB354217.1 from GenBank revealed 98%, 99%, 98%, 98%, and 98% gene homology, respectively. Two ultra-high and three high endemic areas of P. westermani are discovered in Guangdong Province. No obvious differences were found among the types of P. westermani in the above five endemic areas.


Effect of FGFs on adult bovine Muller cells: proliferation, binding and internalization.
A new method for culturing retinal Muller cells from adult bovine tissue is described. The identification of these glial cells was based on immunocytochemical analysis of specific Muller cell markers. Cultured cells from fourth to ninth passage showed positive labelling for S 100 protein, carbonic anydrase (CAA), glutamine synthetase (GS), alpha cristallin (alpha C) and polyclonal glial fibrillary acidic protein (GFAP) antibody, but were negative for both monoclonal GFAP antibody and also for Muller cells in the retina. Investigation of the effect of acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and epithelial growth factor (EGF) on the proliferation of the Muller cells revealed that bFGF was the most potent mitogen (EC50 = 14 pM). Binding data revealed the presence of two classes of binding sites for aFGF and bFGF: (1) a high affinity binding site (Kd of 14 pM and 27 pM for aFGF and bFGF respectively); (2) a low affinity binding site (Kd of 3.2 nM and 0.6 nM for aFGF and bFGF respectively with great variability in the number of binding sites). In addition, the cross-linking experiments revealed the presence of high molecular weight FGF receptors (110-140 kDa). After aFGF or bFGF binding to Muller cells, aFGF and bFGF-cell surface receptors were rapidly downregulated with a half-life for disappearance of 35-50 min. Internalization and degradation of 125I-bFGF bound to the Muller cell receptors did not occur at 4 degrees C. At 37 degrees C, however, there was a rapid decrease in receptor-bound 125I-bFGF due to the downregulation of bFGF receptors. Concomitantly 125I-bFGF appeared inside the Muller cells. After 2 h, 125I-bFGF began to be degraded and after 6 h three fragments of 16 kDa, 8 kDa and 5.5 kDa were discernible. Degradation of bFGF appeared to occur in the lysosomal compartment since it was inhibited by chloroquine, an inhibitor of lysosomal proteases; aFGF internalization and degradation followed the same kinetics as bFGF with the appearance of 7 kDa and 5 kDa fragments. These results suggest that Muller cells may be the target for aFGF and bFGF contained in other cells of the retina. The fact that aFGF could be released from rod outer segment by a phosphorylation-dependent mechanism, and that apical prolongation of the Muller cells is connected with the photoreceptor cells suggest that these factors may be the mediators involved in the communication between glial cells and neurons.


Thymoma--an important differential diagnosis of mediastinal tumours.
A 69-year-old man with slight dyspnoea underwent routine X-ray examination by his primary care physician. The X-ray and the CT showed a homogenous mass at the right side of the anterior mediastinum. The benignity and the origin of the tissue were still unknown. Therefore, we performed a CT-guided fine needle aspiration biopsy of the mediastinal mass. Histopathological examination finds out a spindle-cell or type A thymoma. Based on these findings we decide for a thoracoscopic resection of the thymoma. After the surgical intervention the patient was completely asymptomatic. In conclusion, because thymomas are prone to ectopic occurrence, they should be considered in the differential diagnosis of mediastinal tumors.


Effect of caloric restriction on the 24-hour plasma DHEAS and cortisol profiles of young and old male rhesus macaques.
Although dietary caloric restriction (CR) can retard aging in laboratory rats and mice, it is unclear whether CR can exert similar effects in long-lived species, such as primates. Therefore, we tested the effect of CR on plasma levels of dehydroepiandrosterone sulfate (DHEAS), a reliable endocrine marker of aging. The study included six young (approximately 10 years) and ten old (approximately 25 years) male rhesus macaques, approximately half of the animals in each age group having undergone >4 years of 30% CR. Hourly blood samples were collected remotely for 24 hours, through a vascular catheter, and assayed for DHEAS and cortisol. Both of these adrenal steroids showed a pronounced diurnal plasma pattern, with peaks occurring in late morning, but only DHEAS showed an aging-related decline. More importantly, there was no significant difference in plasma DHEAS concentrations between the CR animals and age-matched controls. These data fail to support the hypothesis that CR can attenuate the aging-related decline in plasma DHEAS concentrations, at least not when initiated after puberty.


Relationship between composite fracture toughness and bond strengths to enamel and dentine.
This study aimed to evaluate the association between the fracture toughness of two nanofilled-hybrid resin composites (Clearfil Majesty Esthetic [CME], Kuraray Medical, Japan; Estelite Σ [ES], Tokuyama, Japan) and their bond strengths to enamel and dentine mediated by a self-etching primer system (Clearfil SE Bond [CSE]; Kuraray). Twenty-four permanent human molars were sectioned into enamel and dentine specimens and finished with 600-grit silicon carbide paper, bonded with CSE and either CME or ES, for μ-shear bond strength (μSBS) and μ-tensile bond strength (μTBS). The specimens were tested until failure at a cross-head speed of 1 mm/min, failure loads recorded, bond strengths calculated and results analysed using independent samples t-tests. Eight single-notched bar-shaped specimens, 30 mm × 5.2 mm × 2.2 mm, were prepared for each resin composite and fracture toughness measured using four-point bending at a cross-head speed of 0.5 mm/min. Results were analysed using independent samples t-tests. For μSBS and μTBS, there was no significant difference between the resin composites for enamel or dentine. The fracture toughness of CME was significantly higher than that of ES. For both enamel and dentine, resin composite fracture toughness affected neither μTBS nor μSBS to enamel or dentine.


Structural specificity of alkoxy radical formation in crystalline carbohydrates.
A DFT study of radiation induced alkoxy radical formation in crystalline α-l-rhamnose has been performed to better understand the processes leading to selective radical formation in carbohydrates upon exposure to ionizing radiation at low temperatures. The apparent specificity of radiation damage to carbohydrates is of great interest for understanding radiation damage processes in the ribose backbone of the DNA molecule. Alkoxy radicals are formed by deprotonation from hydroxyl groups in oxidized sugar molecules. In α-l-rhamnose only one alkoxy radical is observed experimentally even though there are four possible sites for alkoxy radical formation. In the present work, the origin of this apparently specific action of radiation damage is investigated by computationally examining all four possible deprotonation reactions from oxygen in the oxidized molecule. All calculations are performed in a periodic approach and include estimates of the energy barriers for the deprotonation reactions using the Nudged Elastic Band (NEB) method. One of the four possible radical sites is ruled out due to the lack of a suitable proton acceptor. For the other three possible sites, the reaction paths and energy profiles from primary cationic radicals to stable, neutral alkoxy radicals are compared. It is found that deprotonation from one site (corresponding to the experimentally observed radical) differs from the others in that the reaction path is less energy demanding. Hence, it is suggested that the alkoxy radical formation is not necessarily site specific, but that the observed radical is formed in much greater abundance than the others due to the different energetics of the processes and reaction products.


Docking study, synthesis, and in vitro evaluation of fluoro-MADAM derivatives as SERT ligands for PET imaging.
In order to predict affinity of new diphenylsulfides for the serotonin transporter (SERT), a molecular modeling model was used to compare potential binding affinity of new compounds with known potent ligands. The aim of this study is to identify a suitable PET radioligand for imaging the SERT, new derivatives, and their precursors for a C-11 or F-18 radiolabeling, were synthesized. Two fluorinated derivatives displayed good in vitro affinity for the SERT (K(i)=14.3+/-1 and 10.1+/-2.7 nM) and good selectivity toward the other monoamine transporters as predicted by the docking study.


Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development.
Hermansky-Pudlak syndrome is an autosomal recessive disease characterized by pigment dilution and prolonged bleeding time. At least 15 mutant mouse strains have been classified as models of Hermansky-Pudlak syndrome. Some of the genes are implicated in intracellular vesicle trafficking: budding, targeting, and secretion. Many of the Hermansky-Pudlak syndrome genes remain uncharacterized and their functions are unknown. Clues to the functions of these genes can be found by analyzing the physiologic and cellular phenotypes. Here we have examined the morphology of the melanosomes in the skin of 10 of the mutant mouse Hermansky-Pudlak syndrome strains by transmission electron microscopy. We demonstrate that the morphologies reflect inhibition of organelle maturation or transfer. The Hermansky-Pudlak syndrome strains are classified into morphologic groups characterized by the step at which melanosome biogenesis or transfer to keratinocytes is inhibited, with the cappuccino strain observed to be blocked at the earliest step and gunmetal blocked at the latest step. We show that all Hermansky-Pudlak syndrome mutant strains except gunmetal have an increase in unpigmented or hypopigmented immature melanosomal forms, leading to the hypopigmented coat colors seen in these strains. In contrast, the hypopigmentation seen in the gunmetal strain is due to the retention of melanosomes in melanocytes, and inefficient transfer into keratinocytes.


{Social support and the help offered by mothers to their psychologically troubled sons or daughters}.
We describe in this paper the everyday support mothers give to their adult sons or daughters suffering from psychotic disorders. We also describe the support these women receive from their social network regarding specific needs related to their children's disorders. Ninety-nine women, representing all socioeconomic groups, were interviewed. They were recruited through hospitals and self-help groups. The results of this study highlight the fact that participants give a substantial amount of support to their children, that they have considerable concern for their children's well-being, and that members of their family are their main source of emotional and practical support, and of advice. Mental health professionals give primarily informational support to respondents, in part through community-based agencies. The respondents who belong to self-help groups have significantly more needs related to their children's disorders and have more concern for their children's well-being than do the other respondents.


Gender-based issues in interventional cardiology: a consensus statement from the Women in Innovations (WIN) initiative.
Cardiovascular disease is the leading cause of mortality in women yet studies have suggested it is often under-recognized. Of particular concern is the apparent suboptimal treatment of women in comparison to men, with less revascularization and use of evidence-based medications. The Women in Innovations group of cardiologists, aims to highlight these issues and change perceptions to optimize the treatment of female patients with cardiovascular disease, support future research, and encourage and guide the training of female interventional cardiologists.


Interaction of Bile Salts with β-Cyclodextrins Reveals Nonclassical Hydrophobic Effect and Enthalpy-Entropy Compensation.
Herein, we present an endeavor toward exploring the lacuna underlying the host:guest chemistry of inclusion complex formation between bile salt(s) and β-cyclodextrin(s) (βCDs). An extensive thermodynamic investigation based on isothermal titration calorimetry (ITC) demonstrates a dominant contribution from exothermic enthalpy change (ΔH < 0) accompanying the phenomenon of inclusion complex formation, along with a relatively smaller contribution to total free energy change from the entropic component. However, the negative heat capacity change (ΔCp < 0) displays the hallmark for a pivotal role of hydrophobic effect underlying the interaction. Contrary to the classical hydrophobic effect, such apparently paradoxical thermodynamic signature has been adequately described under the notion of "nonclassical hydrophobic effect". On the basis of our results, the displacement of disordered water from hydrophobic binding sites has been argued to mark the enthalpic signature and the key role of such interaction forces is further corroborated from enthalpy-entropy compensation behavior showing indication for almost complete compensation. To this end, we have quantified the interaction of two bile salt molecules (namely, sodium deoxycholate and sodium glycocholate) with a series of varying chemical substituents on the host counterpart, namely, βCD, (2-hydroxypropyl)-βCD, and methyl βCD.


The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.
In asymptomatic end-stage renal disease (ESRD) patients undergoing vasodilator stress myocardial perfusion imaging (MPI) prior to renal transplantation (RT), the impact of pre-transplant heart rate response (HRR) to vasodilator stress on post-RT outcomes is unknown. We analyzed a retrospective cohort of asymptomatic patients with ESRD who underwent a vasodilator stress SPECT-MPI and subsequently received RT. Blunted HRR was defined as HRR <28% for regadenoson stress and <20% for adenosine stress. The primary endpoint was major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. Clinical risk was assessed using the sum of risk factors set forth by the AHA/ACCF consensus statement on the assessment of RT candidates. Among 352 subjects, 140 had an abnormal pre-transplant HRR. During a mean follow-up of 3.2 ± 2.0 years, 85 (24%) MACEs were observed. Blunted HRR was associated with increased MACE risk (hazard ratio 1.72; 95% confidence interval 1.12-2.63, P = 0.013), and remained significant after adjustment for gender, sum of AHA/ACCF risk factors, summed stress score, baseline heart rate, and β-blocker use. HRR was predictive of MACE in patients with normal MPI and irrespective of clinical risk. Blunted HRR was associated with a significant increase in post-operative (30-day) MACE risk (17.9% vs 8.5%; P = 0.009). In asymptomatic ESRD patients being evaluated for RT, a blunted pre-transplant HRR was predictive of post-RT MACE. HRR may be a valuable tool in the risk assessment of RT candidates.


Retinoic acid modulates IL-5 receptor expression and selectively inhibits eosinophil-basophil differentiation of hemopoietic progenitor cells.
IL-5 plays a central role in eosinophil and basophil differentiation, exerting its effects through the IL-5 receptor (IL-5Ralpha). Currently, little is known concerning regulation of IL-5Ralpha expression in the context of commitment of hemopoietic progenitor cells to the eosinophil and basophil lineages. Because all-trans retinoic acid (ATRA) is known to modulate some aspects of hemopoietic differentiation, we examined the effects of ATRA on eosinophil-basophil differentiation and IL-5Ralpha expression. Progenitor cells were obtained from bone marrow aspirates and cord blood samples. Enriched populations of CD34(+) cells were isolated by means of positive immunomagnetic selection with MACS beads. In semisolid methylcellulose cultures of normal human bone marrow, ATRA (10(-6) mol/L) selectively suppressed eosinophil-basophil colony-forming units but had no effect on granulocyte-macrophage colony-forming units. Similarly, ATRA (10(-6) mol/L) inhibited eosinophil-basophil differentiation of cord blood CD34(+) cells in liquid culture, whereas neutrophil differentiation proceeded without impediment. Most importantly, these effects of ATRA (10(-8) to 10(-6) mol/L) on CD34(+) cells were associated with a dose-dependent inhibition of IL-5Ralpha but no change in GM-CSF receptor expression, as detected with flow cytometry. These findings indicate that retinoids can differentially regulate expression of IL-5Ralpha, but not GM-CSF receptor, and that these effects have functional consequences in vitro on eosinophil and basophil differentiation.


The response of the tyrosine hydroxylase gene to cyclic AMP is mediated by two cyclic AMP-response elements.
Tyrosine hydroxylase (TH) gene transcription rate is stimulated by cyclic AMP in cultured rat pheochromocytoma cells. This effect is at least partially due to the interaction of transcription factors with the canonical cyclic AMP-response element (CRE) at position -45 to -38 within the TH gene promoter. In this study we test whether a region of the TH gene promoter, which is adjacent to and upstream of the canonical TH CRE, also participates in the response of the promoter to cyclic AMP. Using electrophoretic mobility shift assays, we demonstrate that nuclear proteins from rat pheochromocytoma cell lines bind to the region of the TH gene from -102 to -73. A comparison of promoter sequences indicates that sequences within this region of the TH gene are highly homologous to proenkephalin promoter sequences (between -110 and -80) designated ENKCRE-1 and ENKCRE-2. We designated the TH gene sequence homologous to ENKCRE-1 as TH E1 and the sequence homologous to ENKCRE-2 as TH E2. Competition displacement binding assays suggest that protein binding to the -102/-73 region of the TH gene is critically dependent on the TH E1 sequence. Transient transfection assays using minimal promoter constructs demonstrate that this region acts as a cyclic AMP-responsive element. Mutagenesis of the TH E1 sequence within the normal context of the TH gene proximal promoter leads to a 50% decrease in the cyclic AMP inducibility of the promoter. These results support the hypothesis that the full response of the TH gene to cyclic AMP requires both the canonical TH CRE and this newly discovered element, which we term TH CRE2.


No difference in time-dependent improvement in functional outcome following closing wedge versus opening wedge high tibial osteotomy: a randomised controlled trial with two-year follow-up.
The aim of this prospective randomised study was to compare the time course of clinical improvement during the first two years following a closing or opening wedge high tibial osteotomy (HTO). It was hypothesised that there would be no differences in clinical outcome between the two techniques. Between 2007 and 2013, 70 consecutive patients were randomly allocated to undergo either a closing or opening wedge HTO. All patients had medial compartment osteoarthritis (OA), and were aged between 30 years and 60 years. They were evaluated by independent investigators pre-operatively and at three and six months, and one and two years post-operatively using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Oxford Knee Score (OKS), the Lysholm score, the Tegner activity score, the University of California, Los Angeles (UCLA) activity scale and range of movement (ROM). There were no significant differences at any time between the two techniques for any clinical outcome score (p > 0.05). The mean scores for all the systems, except UCLA and Tegner, significantly improved until six months post-operatively (p < 0.001). For some scores, the improvement continued until one and two years. This prospective randomised study suggests that there are no differences in the time course of the clinical improvement between the closing and opening wedge techniques for HTO during the first two post-operative years. Patients can expect continued improvement in physical function for between six months and one year after HTO regardless of the technique used. Cite this article: Bone Joint J 2017;99-B:1157-66.


Two-step adsorption on jungle-gym-type porous coordination polymers: dependence on hydrogen-bonding capability of adsorbates, ligand-substituent effect, and temperature.
A preliminary study of isopropanol (IPA) adsorption/desorption isotherms on a jungle-gym-type porous coordination polymer, [Zn(2)(bdc)(2)(dabco)](n) (1, H(2)bdc = 1,4-benzenedicarboxylic acid, dabco =1,4-diazabicyclo[2.2.2]octane), showed unambiguous two-step profiles via a highly shrunk intermediate framework. The results of adsorption measurements on 1, using probing gas molecules of alcohol (MeOH and EtOH) for the size effect and Me(2)CO for the influence of hydrogen bonding, show that alcohol adsorption isotherms are gradual two-step profiles, whereas the Me(2)CO isotherm is a typical type-I isotherm, indicating that a two-step adsorption/desorption is involved with hydrogen bonds. To further clarify these characteristic adsorption/desorption behaviors, selecting nitroterephthalate (bdc-NO(2)), bromoterephthalate (bdc-Br), and 2,5-dichloroterephthalate (bdc-Cl(2)) as substituted dicarboxylate ligands, isomorphous jungle-gym-type porous coordination polymers, {[Zn(2)(bdc-NO(2))(2)(dabco)]·solvents}(n) (2 ⊃ solvents), {[Zn(2)(bdc-Br)(2)(dabco)]·solvents}(n) (3 ⊃ solvents), and {[Zn(2)(bdc-Cl(2))(2)(dabco)]·solvents}(n) (4 ⊃ solvents), were synthesized and characterized by single-crystal X-ray analyses. Thermal gravimetry, X-ray powder diffraction, and N(2) adsorption at 77 K measurements reveal that [Zn(2)(bdc-NO(2))(2)(dabco)](n) (2), [Zn(2)(bdc-Br)(2)(dabco)](n) (3), and [Zn(2)(bdc-Cl(2))(2)(dabco)](n) (4) maintain their frameworks without guest molecules with Brunauer-Emmett-Teller (BET) surface areas of 1568 (2), 1292 (3), and 1216 (4) m(2) g(-1). As found in results of MeOH, EtOH, IPA, and Me(2)CO adsorption/desorption on 2-4, only MeOH adsorption on 2 shows an obvious two-step profile. Considering the substituent effects and adsorbate sizes, the hydrogen bonds, which are triggers for two-step adsorption, are formed between adsorbates and carboxylate groups at the corners in the pores, inducing wide pores to become narrow pores. Interestingly, such a two-step MeOH adsorption on 2 depends on the temperature, attributed to the small free-energy difference (ΔF(host)) between the two guest-free forms, wide and narrow pores.


Neurophysiological index as a biomarker for ALS progression: validity of mixed effects models.
Our objective was to evaluate the neurophysiological index (NI) as a biomarker for amyotrophic lateral sclerosis (ALS) and to assess the validity of linear mixed effects models for describing longitudinal changes. Functional assessment and nerve conduction studies were undertaken in 58 ALS patients. Neurophysiological data were collected on four occasions over 12 weeks (baseline, weeks 4, 8 and 12). The NI was calculated for the abductor digiti minimi and ulnar nerve at the wrist. NI declined at a rate of 0.04 per week (S.E. 0.006, p < 0.0001). Patients with bulbar-onset disease had 0.88 greater NI than patients with upper limb-onset disease over the follow-up period (S.E. 0.39, p = 0.03). There were no differences in the rates of decline among patients with different disease phenotypes. Rates of change in NI and functional impairment were weakly correlated (Spearman's p = 0.29, p = 0.03). Linear mixed effects models were appropriate for detailing the longitudinal changes in NI. The present findings support incorporation of NI as an outcome measure for ALS clinical trials conducted over short time periods.


Association of Prostatic Volume and Carotid Intima-media Thickness in Patients With Benign Prostatic Hyperplasia.
To assess cardiovascular risk factors and carotid intima-media thickness in patients with benign prostatic hyperplasia. One hundred and twenty-three patients who were evaluated for the presence of benign prostatic hyperplasia with accompanying symptoms were included in the study. Patients were also examined by cardiology department to assess and measure cardiovascular risk factors, left ventricular functions, and carotid intima-media thickness. Cardiovascular risk factors adjusted carotid intima-media thickness was found to be different between 3 groups, being highest in the severely symptomatic group and lowest in the mildly symptomatic group. Significant correlation of prostatic volume was shown with carotid intima-media thickness after adjusting prostatic volume for body mass index and age, and carotid intima-media thickness for cardiovascular risk factors (r = 0.75 P = .01). Linear regression analysis revealed that carotid intima-media thickness significantly associated with prostatic volume (beta coefficient: 0.628; confidence interval: 37.02-60.1; P = .001). We have demonstrated that prostatic tissue has significant association with carotid intima-media thickness in patients with benign prostatic hyperplasia.


Body fat distribution in women with polycystic ovary syndrome.
To investigate body fat distribution in women with polycystic ovary syndrome (PCOS). Body weight, body mass index (BMI), and six indices of body fat measured by dual-energy x-ray absorptiometry were compared in 40 women with PCOS and 97 age-matched controls. The possible correlations between the body fat characteristics and serum androgen levels were evaluated in the 40 PCOS women. Body fat distribution was classified into upper- (N = 24) and lower-half body type (N = 16), and androgen levels and the incidence of hirsutism were compared in the two types. The BMI, body fat ratio, upper-half body fat ratio, and upper-half/lower-half body fat ratio were significantly higher in PCOS women than in controls. After adjustment for age, height, and body weight, the upper-half/lower-half body fat ratio was still significant (P < .001). The PCOS subjects exhibited a significant positive correlation between the upper-half/lower-half body fat ratio and dehydroepiandrosterone-sulfate (DHEA-S) levels (r = 0.607, P < .01) as well as testosterone levels (r = 0.585, P < .05). Dehydroepiandrosterone-sulfate and testosterone levels were significantly higher in those with the upper-half body type than in those with the lower-half body type (P < .001). After adjustment for confounding variables, only DHEA-S was still significantly higher in this body type (P < .05). Serum DHEA-S levels seem to be associated with upper-half body fat distribution in women with PCOS, irrespective of body weight.


Update on cardiovascular screening: can we prevent sudden cardiac death in adolescent athletes?
Cardiovascular screening of athletes to prevent sudden death has been a subject of ongoing debate. In the United States, such screening is currently based on history and physical examination. The International Olympic Committee and the European Sports Council require an electrocardiogram (ECG) as part of screening athletes. The 2010 European Society of Cardiology guidelines and recent US studies suggest the usefulness of ECG in screening athletes. This article provides an overview of key aspects of cardiovascular screening currently recommended in the United States and the recommendations for the use of ECG.


Role of IgA, IgG, and IgM antibodies against Haemophilus parainfluenzae antigens in IgA nephropathy.
We have recently demonstrated glomerular deposition of outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of IgA antibody against OMHP in patients with IgA nephropathy (IgA-N). In this study, we analyzed IgA-, IgG-, and IgM-classes of antibodies against OMHP, and the relationship between these antibodies and renal lesions in IgA-N. The subjects included 44 patients with IgA-N and 62 patients with outer glomerular diseases (OGD); the latter group consisted of 23 patients with predominantly IgG or IgM deposits and small amounts of IgA in the mesangium (group A), and 39 with IgG or IgM deposits without IgA (group B). IgA, IgG, and IgM antibodies against OMHP in patients sera were detected by enzyme-linked immunosorbent assay (ELISA). Immunoblotting demonstrated that the IgA, IgG, and IgM antibodies against OMHP in the sera of IgA-N patients bound to components of OMHP with molecular weights of 19.5, 30, and 40.5 kD. The amino acid compositions of these three OMHP components were similar to those reported for the outer membrane protein (OMP) P6 precursor, OMP P5, and OMP P2 (porin) of Haemophilus influenzae. Both IgA-N and group A patients, (i.e. those with IgA-related renal disease), demonstrated a significantly higher level of IgA antibodies against OMHP than did group B patients. However, only IgA-N patients revealed a significant correlation between the IgA-antibody titer and degree of glomerular changes. IgA-N patients with macroscopic hematuria or arterio(lo)sclerosis had a significantly higher IgA antibody titer than other IgA-N patients. There was no relationship between renal lesions and IgG or IgM antibody titers in any group. These findings suggest that IgA antibodies against OMHP are significantly increased in patients with IgA-related renal disease compared to those without mesangial IgA deposits and that a significant relationship between these antibodies and renal lesions exists only in patients with IgA-N.


Intravital microscopy on a closed cranial window in mice: a model to study trigeminovascular mechanisms involved in migraine.
The purpose of the study was to develop a mouse model to study trigeminovascular mechanisms using intravital microscopy on a closed cranial window. In addition, we studied exogenous and endogenous calcitonin gene-related peptide (CGRP)-mediated vasodilation in dural arteries. Arteries in C57BL/6Jico mice were constricted with endothelin-1, which reduced the baseline diameter by 65-75%. Subsequently, vasodilation was induced by alpha-CGRP, capsaicin or transcranial electrical stimulation of perivascular trigeminal nerves in the absence or presence of different concentrations of BIBN4096BS or sumatriptan. Both alpha-CGRP and capsaicin induced vasodilation in preconstricted arteries. Transcranial electrical stimulation also induced current-dependent relaxation of dural arteries with 100 microA producing maximal dilation in the control group. BIBN4096BS blocked the responses evoked by alpha-CGRP and capsaicin, as well as electrical stimulation, whereas sumatriptan attenuated only vasodilation induced by electrical stimulation. This model is likely to prove useful in dissecting elements of the trigeminovascular system and for exploring pathophysiological aspects of migraine, especially in future studies using transgenic mice with mutations relevant to those observed in patients with migraine.


Mouse round spermatids developed in vitro from preexisting spermatocytes can produce normal offspring by nuclear injection into in vivo-developed mature oocytes.
It has been shown that mature oocytes injected with nuclei from round spermatids collected from mouse testis can generate normal offspring and that round spermatids can develop in vitro. An undetermined issue is whether spermatids developed in vitro are capable of generating fertile offspring by nuclear injection into oocytes. Herein, we report the production of normal and fertile offspring by nuclear injection using haploid spermatid donors derived from mouse primary spermatocyte precursors cocultured with Sertoli cells. Cocultured spermatogonia and spermatocytes were characterized by their nuclear immunoreactive patterns determined by an antibody to phosphorylated histone H2AX (gamma-H2AX), a marker for DNA double-strand breaks. Cocultured round spermatid progenies display more than one motile flagellum, whose axonemes were recognized by antitubulin immunostaining. Flagellar wavelike movement and flagellar-driven propulsion of round spermatids developed in vitro were documented by videomicroscopy (http://www.sci.ccny.cuny.edu/ approximately kier). We also show that breeding of male and female mouse offspring generated by spermatid nuclear injection produced fertile offspring. In addition to their capacity to produce fertile offspring, cocultured, flagellated round spermatids can facilitate the analysis of the mechanisms of centriolar polarity, duplication, assembly, and flagellar growth, including the intraflagellar transport of cargo proteins.


Evoked responses to sinusoidal gratings in the pigeon optic tectum.
Tectal evoked potentials (TEPs) in response to sinusoidal gratings of different contrast, spatial and temporal frequency have been recorded from the tectal surface of the pigeon. Responses have been digitally filtered in order to isolate transient oscillatory (fast) potentials (50-150 Hz), transient slow potentials (1-50 Hz), and the steady-state second-harmonic component (16.6 Hz). Transient slow potentials, as well as the steady-state second-harmonic component, are band-pass spatially tuned with a maximum at 0.5 cycles/deg and attenuation at higher and lower spatial frequencies. The high spatial frequency cutoff is 4-5 cycles/deg. Both transient slow potentials and the steady-state second-harmonic component increase in amplitude as a function of log contrast and saturate at about 20% contrast. The contrast sensitivity, as determined by extrapolating TEP amplitude to 0 V is 0.1-0.2%. These characteristics of spatial-frequency selectivity and contrast sensitivity are similar to those reported for single tectal cells. Unlike slow potentials, oscillatory potentials are not band-pass spatially tuned. In addition, their contrast response function does not saturate at moderate contrast. These differences suggest that tectal evoked slow and fast potentials reflect the activity of different neuronal mechanisms.


[Interaction between microflora and nitrogen nutrients in large intestine and its impacts on host health].
Proteins are not only the main building blocks for the construction of tissue, but also crucial for metabolic activity in animals. The microbial community colonized in the gastrointestinal tract plays an important role in host nutrients metabolism, especially nitrogen nutrients. Bacteria in small intestine could metabolize parts of amino acids (AAs), which further affects the systemic AAs metabolism of host. Compared with that in small intestine, the density of bacteria is much higher and the retention time of chyme is much longer in large intestine. On the one hand, the metabolism and community structure of microflora could be affected by nitrogen nutrients entering the large intestine. Thus, the metabolism of nitrogen nutrients by large intestinal microflora can lead to the formation of several metabolites, which are generally presumed to be detrimental for the host health. This review summarized the effects of dietary protein on the community structure of large intestinal microflora, the microbial metabolites of AAs in large intestine and their impacts on intestinal physiology and host health.


[A case - control study of gallstone disease in female population in Taicang].
To investigate the risk factors of gallstone disease in female population in Taicang. A case - control study conducted on 144 cases and 371 controls aged 35 - 79 years in five villages. Diagnosis of gallstone disease was assessed by real - time ultrasonography. The case was considered as presence of gallstones at echograph and previous cholecytectomy. The controls were selected from a random sample of female participates. Through univariate and multivariate analysis, gallstone disease was significantly associated with age (OR = 1.80), family history of gallstone disease (OR = 3.66), hypertension (OR = 1.93), fat intake (OR = 1.77), number of pregnancies (OR = 1.44) and menopause (OR = 1.67). Drinking water from deep well (OR = 0.54) was inversely associated with gallstone disease. The main risk factors of female gallstone disease were age, family history of gallstone disease, fat intake, number of pregnancy and menopause. Drinking water from deep well was a protective factor of gallstone disease.


Angiogenesis by endothelial cell transplantation.
Myocardial angiogenesis may improve regional perfusion and perhaps function after cardiac injury. We evaluated the effect of endothelial cell transplantation into a myocardial scar on angiogenesis and ventricular function, as an alternative to angiogenic gene or protein therapy. A transmural myocardial scar was created in the left ventricular free wall of rat hearts by cryoinjury. Allogeneic aortic endothelial cells were injected into the scar 2 weeks after cryoinjury. A cluster of transplanted cells was identified at the site of injection 1 day and 1 week after transplantation, but not after 2 weeks. The size of this cluster of transplanted cells decreased as vascular density in the transplanted scar tissue increased with time. Six weeks after transplantation, vascular density was significantly greater in transplanted hearts than in control hearts. Regional blood flow, by microsphere analysis, was greater in the transplanted rats. Systolic and diastolic ventricular function was similar between groups. In a second series of experiments, syngeneic aortic endothelial cells labeled with bromodeoxyuridine were transplanted 2 weeks after cryoinjury. Vascular density in the transplanted scar was greater than in controls. Labeled transplanted endothelial cells were identified forming part of the newly developed blood vessels. No difference in vascular density was found between allogeneic and syngeneic cell transplantation. Vascular endothelial growth factor was not expressed at greater levels in the transplanted cells or the myocardial scar. Transplanted endothelial cells stimulated angiogenesis, were incorporated into the new vessels, and increased regional perfusion in myocardial scar tissue, but did not improve global function in this cryoinjury rat model.


Surface Hydrogenation of Boron-Doped Diamond Electrodes by Cathodic Reduction.
Boron-doped diamond (BDD) has attracted much attention as a promising electrode material especially for electrochemical sensing systems, because it has excellent properties such as a wide potential window and low background current. It is known that the electrochemical properties of BDD electrodes are very sensitive to the surface termination such as to whether it is hydrogen- or oxygen-terminated. Pretreating BDD electrodes by cathodic reduction (CR) to hydrogenate the surface has been widely used to achieve high sensitivity. However, little is known about the effects of the CR treatment conditions on surface hydrogenation. In this Article, we report on a systematic study of CR treatments that can achieve effective surface hydrogenation. As a result, we found that the surface hydrogenation could be improved by applying a more negative potential in a lower pH solution. This is because hydrogen atoms generated from protons in the CR treatment contribute to the surface hydrogenation. After CR treatments, BDD surface could be hydrogenated not completely but sufficiently to achieve high sensitivity for electrochemical sensing. In addition, we confirmed that hydrogenation with high repeatability could be achieved.


Short- and long-term outcomes of hepatectomy with or without radiofrequency-assist for the treatment of hepatocellular carcinomas: a retrospective comparative cohort study.
The objective of this study was to compare the short- and long-term outcomes of radiofrequency-assisted liver resection (RFLR) and conventional clamp-crushing liver resection (CCLR) and to evaluate the safety and efficiency of RFLR. Between January 2008 and December 2012, a total of 597 patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy were identified. A total of 272 patients underwent RFLR, and 325 patients received CCLR. The short- and long-term outcomes were compared. The patients in the RFLR and CCLR groups showed similar baseline characteristics. The RFLR group showed less intraoperative blood loss (485.5 vs. 763.2 mL, p = 0.003), a lower transfusion requirement rate (19.1 vs. 31.7%, p ≤ 0.01), shorter surgery duration (211 vs. 296 min, p ≤ 0.01) and a lower vascular inflow occlusion rate (25.7 vs. 33.8%, p = 0.032). No significant postoperative changes in bilirubin or liver enzymes were observed in the two groups. The degree of postoperative complications and morbidity did not significantly differ between the two groups. There were no significant differences in the 1-, 2- and 3-year overall survival rates (73.8%, 58.5%, and 55.7% vs. 80.8%, 65.8%, and 56.2%, respectively) or disease-free rates (51.9%, 47.2%, and 46.0% vs. 54.5%, 44.9%, and 38.5%, respectively) between the RFLR and CCLR groups. These results suggested RFLR was a safe and efficient method for patients with HCC. RFLR was associated with decreased blood loss, fewer blood transfusions, shorter surgery times and less vascular inflow occlusion application. The RFLR group did not show increased liver injury or postoperative morbidity or mortality.


Dilated cardiomyopathy.
On account of the rapidly progressive nature of the disease, the high incidence of systemic embolism and arrhythmias, and the risk of sudden death, dilated cardiomyopathy is inconsistent with aircrew duties. In the small proportion of subjects who apparently make a satisfactory recovery , re-licensing may be considered once there is no requirement for medication and chest X-ray, electrocardiogram, echocardiogram, exercise electrocardiogram, 24 h ambulatory electrocardiogram and left ventricular ejection fraction are all normal. These tests should initially be repeated annually and be associated with cardiological review.


p53 directs conformational change and translation initiation blockade of human fibroblast growth factor 2 mRNA.
Tumour suppressor p53 has been shown to inhibit fibroblast growth factor 2 expression post-transcriptionally in cultured cells. Here we have investigated the mechanism responsible for this post-transcriptional blockade. Deletion mutagenesis of the FGF-2 mRNA leader revealed the requirement of at least four RNA cis-acting elements to mediate the inhibitory effect of p53 in SK-Hep-1 transfected cells, suggesting the involvement of RNA secondary or tertiary structures. Recombinant wild-type, but not Ala(143) mutant p53, was able to specifically repress FGF-2 mRNA translation in rabbit reticulocyte lysate, in a dose dependent manner. Sucrose gradient experiments showed that p53 blocks translation initiation by preventing 80S ribosome formation on an mRNA bearing the FGF-2 mRNA leader sequence. Interaction of wild-type and mutant p53 with different RNAs showed no significant correlation between p53 RNA binding activity and its translational inhibiting effect. However, by checking the accessibility of the FGF-2 mRNA leader to complementary oligonucleotide probes, we showed that the binding to RNA of wild-type, but not mutant p53, induced RNA conformational changes that might be responsible for the translational blockade. This strongly suggests that p53 represses FGF-2 mRNA translation by a direct mechanism involving its nucleic acid unwinding-annealing activity.


Highly Branched Poly(β-Amino Esters): Synthesis and Application in Gene Delivery.
Highly branched poly(β-amino esters) (HPAEs) are developed via a facile and controllable "A2+B3/B2" strategy successfully. As nonviral gene delivery vectors, the performance of HPAEs is superior to the well-studied linear counterpart as well as the leading commercial reagent Superfect. When combined with minicircle DNA construct, HPAEs can achieve ultrahigh gene transfection efficiency, especially in keratinocytes.


Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.
Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority.


[Silver impregnation of astrocytes in paraffin sections].
A method is described based on mordantiation with a sodium carbonate solution and a physical developing technique.


Comparison of prostate-specific antigen and prostatic acid phosphatase in the management of prostatic cancer.
Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostatic cancer. All patients, who participated in a phase III trial (n = 110), had disseminated disease and received first line endocrine treatment of either orchidectomy or a monthly injection of a depot luteinizing hormone-releasing hormone analogue (Zoladex). Serum samples were analyzed for PSA and PAP at 0, 3, 6, and 12 months and patients were clinically assessed at 6 and 12 months. At diagnosis, 72 and 97% of all patients had elevated PAP and PSA concentrations (greater than 4 ng/ml), respectively. Patients with progressive disease had significantly higher PSA and PAP levels at both assessments. A small number of patients in the "complete remission" group had both PSA and PAP levels within the normal range after 3 months of treatment. Similarly, both PSA and PAP levels steadily declined in the group of patients who had partial regression of the disease. The patients with stable disease, however, had a significant rise only in their PSA levels at the 12-month assessment. This data suggest that PSA is more sensitive than PAP in those patients who have a "slow progression" of the disease.


Continuous long-term anti-TNF therapy does not lead to an increase in the rate of new bone formation over 8 years in patients with ankylosing spondylitis.
Compare the radiographic progression of ankylosing spondylitis (AS) patients treated with infliximab (INF) versus historical controls (Herne cohort, HC) never treated with tumour necrosis factor (TNF)-blockers over 8 years. Patients were selected based on the availability of lateral cervical and lumbar radiographs at baseline (BL) and after 8 years. Radiographs were scored by two blinded readers using modified Stokes AS spinal score (mSASSS). Mixed linear models were applied to compare radiographic progression between cohorts after adjustment for baseline status. Patients in INF (n=22) and HC (n=34) did not differ in the mSASSS status: 13.2 ± 17.6 in INF versus 14.2 ± 13.8 in HC (p=0.254). Both showed progression at 8 years: mean mSASSS 20.2 ± 21.4 in INF and 25.9 ± 17.8 in HC. After adjustment for baseline damage the mean mSASSS (SEM) at 8 years was 21.0 (1.4) in INF and 25.5 (1.1) HC (p=0.047). The mean mSASSS difference was similar in the groups between baseline and 4 years but was more pronounced in HC between 4 and 8 years (p=0.03 between groups). The mean number of syndesmophytes, although similar at baseline, differed significantly at 8 years: 1.0 ± 0.6 new syndesmophytes/patient in INF versus 2.7 ± 0.8 in HC (p=0.007). Adjustment for age, symptom duration, HLA-B27, Bath AS disease activity index and Bath AS function index at baseline had no influence. Despite limitations of patient numbers and retrospective study design, these data show increase in new bone formation in both patients treated with anti-TNF and those who did not. However, since there was even less bone formation in the INF treated group after 8 years, these data argue against a major role for the TNF-brake hypothesis.


Trypanosoma brucei mitochondrial ribosomal RNA synthesis, processing and developmentally regulated expression.
The steady-state levels of the mitochondrial ribosomal RNAs of Trypanosoma brucei are repressed in the early bloodstream developmental stage of the parasite and accumulate approximately 30-fold during differentiation to the stage found in the midgut of the insect vector. In order to determine the mechanism regulating this developmental process, we have examined the transcription and processing of the 9S and 12S mitochondrial rRNAs of T. brucei. A short-lived RNA was detected in pulse labeling experiments which contains the mature 12S and 9S rRNAs and at least 1200 nucleotides of RNA transcribed from upstream of the 12S rRNA gene. This putative processing precursor RNA was identified in both intact cells and in run-on experiments using isolated mitochondria. The transcripts containing the upstream sequences are unstable and reach isotopic equilibrium within 15 min. Mature rRNAs in the insect developmental stage are stable and show no detectable turnover during a 36-h chase. Comparison of rRNA synthesis in bloodstream and insect life-stages indicates that mitochondrial rRNA levels are controlled not at the transcriptional level, but rather by a mechanism which likely modulates the stability of the mature rRNAs. These results suggest that a short-lived rRNA precursor is synthesized and processed at comparable rates in both bloodstream and insect stages of the parasite. Thus, it appears that differential stability of the mature 9S and 12S rRNAs plays a major role in modulating mitochondrial gene expression during the developmental cycle of T. brucei.


Potential of human gammadelta T lymphocytes for immunotherapy of cancer.
T lymphocytes are classified into 2 subsets based on their T-cell receptor (TCR) expression. The vast majority of T cells expresses an alphabeta TCR heterodimer. These alphabeta T cells recognize antigenic peptides presented by MHC class I (for CD8(+) T cells) or MHC class II molecules (for CD4(+) T cells). Concepts of cancer immunotherapy are mostly concerned with activation of these MHC-restricted alphabeta T cells. Until recently, a numerically small subset of T cells, which expresses an alternative TCR composed of a CD3-associated gammadelta heterodimer, has received far less attention as a potential agent in cancer therapy. These gammadelta T cells share with alphabeta T cells certain effector functions such as cytokine production and potent cytotoxic activity but recognize different sets of antigens, usually in a non-MHC-restricted fashion. Different subsets of human gammadelta T cells recognize stress-inducible MHC class I-related molecules frequently expressed on epithelial tumor cells or phosphorylated metabolites which can be generated by tumor cells. In line with this, many tumor cells are highly susceptible to gammadelta T-cell mediated lysis. In our article, we summarize the available evidence for a contribution of human gammadelta T cells in tumor defense and discuss potential strategies for the immunotherapy of tumors based on the endogenous activation and/or adoptive transfer of tumor-reactive gammadelta T lymphocytes.


Degenerative lumbar stenosis: the neurosurgical perspective.
Degenerative lumbar stenosis is a complex entity caused by predictable patterns of degenerative pathoanatomy. Patients with spinal stenosis are treated by orthopaedic surgeons and neurosurgeons, who often have slightly different ideas regarding treatment strategies. However, data exist to support several recommendations, regarding fusion with or without instrumentation, surgical versus conservative treatment, and limitation of procedures to symptomatic levels. In the current study, the typical patterns of degenerative disease and surgical treatment and a view of the neurosurgical perspective of the treatment of patients with lumbar stenosis are presented.


Peroral susceptibility of Aedes albifasciatus and Culex pipiens complex mosquitoes (Diptera: Culicidae) from Argentina to western equine encephalitis virus.
The transmission cycle of western equine encephalitis (WEE) virus in South America is unknown. A WEE virus strain was isolated from Aedes albifasciatus in Argentina during the WEE epizootic of 1982-83. Also, Culex pipiens from Argentina was reported to be able to transmit WEE virus experimentally, but other results indicate that Cx. pipiens from the USA is refractory to this virus. We determined the susceptibility of Argentina strains of Ae. albifasciatus and Culex pipiens complex mosquitos to infection by WEE virus by the oral route. Adult females were fed on chicks infected with a WEE virus strain isolated in Cordoba Province, Argentina, or were fed on a blood/virus suspension. Each mosquito ingested between 10(1.6) to 10(6.4) vero cell plaque-forming units of virus. Each of 28 Ae. albifasciatus was positive for virus from the fourth day postfeeding, and there was evidence for virus replication. In contrast, 0/44 Cx. p. quinquefasciatus and only 1/15 Cx. p. pipiens was positive. Aedes albifasciatus is susceptible to infection by WEE virus and should be considered a potential vector of this virus in Argentina. Both subspecies of Cx. pipiens are refractory to peroral infection by WEE virus and probably do not play a role in the WEE virus cycle in Argentina.


[The beneficial effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms].
To investigate the effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms. 90 New Zealand white rabbits were divided randomly into 3 groups: group I (balloon injury group), group II (pAdtrackCMV group) and group III (pAdtrackCMV-VEGF165 group). All animals were given hypercholesterol diet for 7 days before experiment and continued to receive hypercholesterol diet until being killed. Each group was further divided into five subgroups according to the sacrifice time (3 days, 1, 2, 4 and 8 weeks after transfection). Blood samples and arteries were harvested for further analysis. At the end of 2 weeks, areas of neointima plus media of group III were smaller than those of group I and II (P < 0.05). The areas under external elastic membrane were larger in group III at 4 weeks and lumen stenosis rates were significantly lower than group I and II (P < 0.05 or 0.01). In group III, VEGF165, metalloproteinases (MMPs) -1, -2, -9 and their tissue inhibitors (TIMPs) 1, 2 could be detected from 3 days after gene transfer and reached the highest level at 2 weeks time and could not be detected by 8 weeks time. In groups I and II, MMP-2 and TIMP-1, -2 could be detected during the whole procedure and the value of TIMP1/MMP1 was significantly higher than in group III (P < 0.01). Remodelling is the main reason for restenosis (RS) after vascular balloon injury. Local pAdtrackCMV-VEGF165 transfer can specifically change the expression of MMPs and facilitate the positive remodelling process, hence, inhibiting restenosis.


Coordination-Triggered Hierarchical Folate/Zinc Supramolecular Hydrogels Leading to Printable Biomaterials.
Printable hydrogels desired in bioengineering have extremely high demands on biocompatibility and mechanic strength, which can hardly be achieved in conventional hydrogels made with biopolymers. Here, we show that on employment of the strategy of coordination-triggered hierarchical self-assembly of naturally occurring small-molecule folic acid, supramolecular hydrogels with robust mechanical elastic modulus comparable to synthetic double-network polymer gels can be made at concentrations below 1%. A sequence of hierarchical steps are involved in the formation of this extraordinary hydrogel: petrin rings on folate form tetramers through hydrogen bonding, tetramers stack into nanofibers by π-π stacking, and zinc ions cross-link the nanofibers into larger-scale fibrils and further cross-link the fibril network to gel water. These supramolecular qualities endow the hydrogel with shear-thinning and instant healing ability, which makes the robust gel injectable and printable into various three-dimensional structures. Owing to the excellent biocompatibility, the gel can support cells three-dimensionally and can be used as an ideal carrier for imaging agent (Gd3+), as well as chemodrugs. In combination with its easy formation and abundant sources, this newly discovered metallo-folate supramolecular hydrogel is promising in various bioengineering technological applications.


Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia.
Schizophrenia is a complex neurodevelopmental disorder that is thought to be induced by an interaction between predisposing genes and environmental stressors. To identify predisposing genetic factors, we performed a targeted (mostly neurodevelopmental) gene approach involving the screening of 396 selected non-synonymous single-nucleotide polymorphisms (SNPs) in three independent Caucasian schizophrenia case-control cohorts (USA, Denmark and Norway). A meta-analysis revealed ten non-synonymous SNPs that were nominally associated with schizophrenia, nine of which have not been previously linked to the disorder. Risk alleles are in TRKA (rs6336), BARD1 (rs28997576), LAMA5 (rs3810548), DKK2 (rs7037102), NOD2 (rs2066844) and RELN (rs2229860), whereas protective alleles are in NOD2 (rs2066845), NRG1 (rs10503929), ADAM7 (rs13259668) and TNR (rs859427). Following correction for multiple testing, the most attractive candidate for further study concerns SNP rs6336 (q=0.12) that causes the substitution of an evolutionarily highly conserved amino acid residue in the kinase domain of the neurodevelopmentally important receptor TRKA. Thus, TRKA signaling may represent a novel susceptibility pathway for schizophrenia.


Ozone-induced production of nitric oxide and TNF-alpha and tissue injury are dependent on NF-kappaB p50.
Ozone-induced lung injury is associated with increased production of reactive nitrogen intermediates and TNF-alpha, which have been implicated in the pathogenic process. Generation of these mediators is regulated in part by transcription factors, e.g., NF-kappaB and CCAAT/enhancer-binding protein (C/EBP). The present studies used NF-kappaB p50 knockout mice to assess the role of this transcription factor protein in ozone-induced inflammatory mediator production and toxicity. Treatment of wild-type (WT) mice with ozone (0.8 ppm, 3 h) resulted in a rapid increase in NF-kappaB binding activity in alveolar macrophages that peaked after 6-12 h. This response was attenuated in NF-kappaB p50(-)/(-) mice. In WT mice, but not NF-kappaB p50(-)/(-) mice, C/EBP was also markedly increased in macrophages following ozone inhalation. Ozone also induced changes in the mobility of C/EBP in gel shift assays, suggesting alterations in the transcription factor complex that may be important in controlling inflammatory gene expression. Whereas macrophages from WT mice produced increased quantities of nitric oxide and TNF-alpha following ozone inhalation, this was not observed in cells from NF-kappaB p50(-)/(-) mice. Ozone-induced decreases in expression of the anti-inflammatory cytokine IL-10 were also prevented in NF-kappaB p50(-)/(-) mice. In WT mice, ozone inhalation caused an increase in bronchoalveolar lavage protein, a marker of tissue damage. This was not evident in NF-kappaB p50(-)/(-) mice. There was also no evidence of peroxynitrite-mediated lung injury in these mice. These findings demonstrate that NF-kappaB and possibly C/EBP signaling are important in ozone-induced production of reactive nitrogen intermediates and TNF-alpha and in tissue injury.


Central Role of Bicarbonate Anions in Charging Water/Hydrophobic Interfaces.
Aqueous interfaces are ubiquitous in Nature and play a fundamental role in environmental or biological processes or modern nanotechnologies. These interfaces are negatively charged, and despite several decades of research, the rationale behind this phenomenon is still under debate. Two main controversial schools of thought argue on this issue; the first relies on the adsorption of hydroxide anions on hydrophobic surfaces, whereas the second one supports a self-rearrangement of water molecules at the interface bearing hydronium ions. Here, we report on two series of independent experimental studies (nanoprecipitation and interfacial tension measurements) that demonstrate that in the pH 5-10 range the negative interfacial charge of the colloids mostly stems from bicarbonate ions, whereas at lower and higher pH, protons and hydroxide ions contribute, with bicarbonate ions, to the interfacial charging. This new interpretation complies with previous studies and opens new perspectives to this striking physical chemical issue.


Different respiratory behaviors disclosed by induced bronchoconstriction in mild asthma patients.
Respiratory responses to bronchoconstriction in asthma have been partially assessed and their significance is unclear. In 44 mild asthma patients we investigated respiratory responses during increasing levels of methacholine-induced bronchoconstriction. Inspiratory muscle activity, tidal volume, inspiratory and expiratory times were continuously monitored; breathing discomfort was rated. Mean inspiratory flow, respiratory frequency and ventilation were calculated. Lung function was assessed prior to and at maximum bronchoconstriction. Bronchoconstriction "dose-dependently" increased inspiratory muscle activity and breathing discomfort (P<0.01). In 37 patients (84.1%), the increase in inspiratory muscle activity was associated with increases in mean inspiratory flow and ventilation (P<0.01) because of selective rises in breathing depth (volume responders), or rate (frequency responders) or both (dual responders). In seven patients (15.9%) ventilation was unchanged. Individual respiratory responses were reproducible. With bronchoconstriction, frequency responders displayed greater hyperinflation and stronger breathing discomfort than volume responders (P<0.01). Analysis of the responses to induced bronchoconstriction disclosed distinctive and reproducible respiratory adjustments that may identify functionally different asthma subpopulations.


[Cortical somatosensory evoked potential associated with experimental chronic cord compression by epidural neoplasm in rabbits].
An experimental model of spinal cord compression was developed in rabbits by epidural neoplasms which were injected anterior to the T 13 vertebral body and grew into the spinal canal through the intervertebral foramina. With this experimental model, the neurological condition of the animals was monitored using a scale and changes of somatosensory evoked potentials (SEPs) were studied to evaluate the neurophysiological effect of experimental chronic cord compression. The animals were immobilized with pancuronium bromide and artificial respiration was maintained through a tracheostomy. SEPs were recorded by silver ball electrodes which were positioned epidurally over the somatosensory cortex through small burr holes. A subcutaneous needle placed at the nose served as a reference electrode. Right hind paw was stimulated via two percutaneous needles with 0.1 msec rectangular impulses sufficiently strong to produce motor responses, ranging from 10 to 20 volt in control rabbits. Electrical stimuli were delivered at a rate of 1 Hz. The intensity of electrical stimulation was raised up to 300 volt, when no consistent SEP was observed in the rabbit with spinal neoplasm. The SEP was summated by averaging 50 successive cortical transients with the analysis time of 200 and 500 msec. The cortical SEPs in the rabbit normally consisted of a positive-negative sequence, which we labelled P1, N1, P2, N2 and so on. Early peaks, P1 and N1, were observed constantly with average latencies of 30.1 and 53.3 msec respectively in normal rabbits. The variability of amplitudes seen even in control animals made them a less useful measure of function than latencies. Normal SEPs were preserved until the animals demonstrated moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and electrical characterization of magnetic bilayer graphene intercalate.
We report synthesis and transport properties of the minimal graphite intercalation compound, a ferric chloride (FeCl(3))(n) island monolayer inside bilayer graphene. Chemical doping by the intercalant is simultaneously probed by micro-Raman spectroscopy and Hall measurements. Quantum oscillations of conductivity originate from microscopic domains of intercalated and unintercalated regions. A slight upturn in resistance related to magnetic transition is observed. Two-dimensional intercalation in bilayer graphene opens new possibilities to engineer two-dimensional properties of intercalates.


Site-specific development of periodontal disease is associated with increased levels of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in subgingival plaque.
Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (previously T. forsythensis), which are regarded as the principal periodontopathogenic bacteria, exist as a consortium in subgingival biofilms. We aimed to examine quantitative relationships between P. gingivalis, T. denticola, and T. forsythia in subgingival biofilms and the relationship between the quantity and prevalence of these three bacteria and site-specific periodontal health. This study was cross-sectional. The study population consisted of 35 adult subjects who visited the Kyushu Dental College Hospital. Plaque samples were collected from 105 periodontal pocket sites. Quantitative analyses of each of the three periodontopathogenic bacteria were performed using real-time polymerase chain reaction with species-specific primers and hybridization probes. The plaque samples were divided into four groups based on the presence or absence of a periodontal pocket (probing depth [PD] > or =4 mm) and bleeding on probing (BOP), regardless of attachment loss. The proportions of all three target bacteria detected in samples from sites of periodontal disease (with PD and BOP) were markedly higher than those in the other sample groups. Cell numbers of P. gingivalis, T. denticola, and T. forsythia in the subgingival plaque of each sampling site were significantly mutually correlated and were increased in the plaque of sites of periodontal disease with PD > or =4 mm and BOP. The symbiotic effects of P. gingivalis, T. denticola, and T. forsythia, which coaggregate and exist concomitantly in subgingival biofilms, may be associated with the local development of periodontitis.


Evaluating the triptans.
The debilitating effect of migraine has fueled the search for more specific agents to treat its characteristic and associated symptoms. Second-generation oral triptans have shown an improved efficacy profile in comparison with the pioneer sumatriptan and with the over-the-counter medications and prescription analgesics that have been staples of migraine treatment. Although all triptans exert effects through the 5-hydroxytryptamine 1B/1D receptors, each triptan has distinctive pharmacokinetic properties that determine its efficacy and tolerability profile. Empirical findings based on clinical trials have led to associations between triptan pharmacology and efficacy. With the expanded treatment choices, the onus is on healthcare providers (especially primary care physicians, who see the majority of patients with migraine) to determine which treatment has an efficacy profile that best suits the individual patient's needs. Patients prefer pharmacotherapy with a rapid onset of action that facilitates complete pain relief and no recurrence. Data from published comparator trials, based on commonly used efficacy end points and pharmacokinetic properties underlying patient-preferred outcomes, are reviewed in this article.