Characteristics of Older Adults Who Consume Alcohol While on Antidepressants.
Determine the characteristics of older Americans who self-report consuming alcohol and taking at least one antidepressant. This study utilized cross-sectional analyses. The University of Michigan Health and Retirement Study and its subsurvey Prescription Drug Study (PDS). Those who reported taking at least one antidepressant prescription medication, were 65 years of age or older, and were enrolled in Medicare or Medicaid between 2002 and 2004. Chi-square tests were conducted between demographic groups and alcohol consumption variables. Relationships between antidepressant quantity and behaviors of those consuming alcohol while taking antidepressants were also addressed. Demographics, alcohol consumption, number of antidepressants, psychiatric problem status, and alcohol behaviors. There were 412 subjects from the 2007 PDS (N = 3,536) who self-reported taking at least one antidepressant prescription medication. A total of 102 (24.8%) of the 412 subjects taking antidepressants reported using alcohol. Ethnicity, education level attained, and geographic region all showed a statistical difference between alcohol drinkers and nondrinkers. Most subjects were only on one antidepressant medication. Also, none of the subjects felt they needed to cut down on their drinking though they also did not feel annoyed by criticism from others about their drinking habits. This study showed that 24.8% of older Americans in the community were consuming some amount of alcohol while on antidepressants. These results show that there is an opportunity for consultant pharmacists to educate older American adults about the safety concerns with alcohol consumption and antidepressant use.


Multi-stage perturbation theory for compensating intra-channel nonlinear impairments in fiber-optic links.
A recursive perturbation theory to model the fiber-optic system is developed. Using this perturbation theory, a multi-stage compensation technique to mitigate the intra-channel nonlinear impairments is investigated. The technique is validated by numerical simulations of a single-polarization single-channel fiber-optic system operating at 28 Gbaud, 32-quadrature amplitude modulation (32-QAM), and 40 × 80 km transmission distance. It is found that, with 2 samples per symbol, the multi-stage scheme with eight compensation stages increases the Q-factor as compared with linear compensation by 4.5 dB; as compared with single-stage compensation, the computational complexity is reduced by a factor of 1.3 and the required memory for storing perturbation coefficients is decreased by a factor of 13.


[Diagnostic and therapeutic blockade of the celiac ganglia].
Neurolytic celiac plexus block is the therapy of choice for visceral upper abdominal pain that is resistant to therapy. In order to ensure that the treatment is indicated a temporary block for diagnostic purposes (application of a local anesthetic) has to be carried out. A diagnostic block can be performed as a blind puncture according to anatomic criteria if new computed tomograms are available providing the necessary information on the patient's anatomy. In 18 patients who underwent a diagnostic block by this procedure no side effects could be observed. If neurolytic substances (e.g. ethanol 96%) are used, a contrast medium should be added to make roentgen control and documentation possible. Computed tomography is a very suitable procedure for these purposes. The location, angle and depth of the puncture can be calculated by the computer tomograph. Of 14 patients in whom we performed a CT-guided block of the celiac ganglion, 10 were free from pain afterwards or showed considerably reduced pain symptoms. The side effects that could be observed were but slight and passed after a few days.


Central nervous system aspergillosis in an immunocompetent patient.
A 12-year-old girl was admitted to the Emergency Department with seizures and headache for 2 months. A CT scan and MRI showed a mass in the right frontal lobe with obvious mass effect. Surgery was carried out, and the resultant pathology was found to be aspergillosis. This study reports aspergillosis in an immunocompetent host following recurrent fungal otitis media. Although this condition is rare, it should be considered in patients with a history of fungal infections.


Rapid in situ cross-linking of hydrogel adhesives based on thiol-grafted bio-inspired catechol-conjugated chitosan.
In this paper, a novel chitosan derivative, thiol-grafting bio-inspired catechol-conjugated chitosan was synthesized. The chemical structure of the synthesized catechol-conjugated chitosan was verified by 1H NMR, and its contents of thiol group and catechol group were determined by UV-vis spectrum. Four percent of catechol-conjugated chitosan aqueous solution could form hydrogels rapidly in situ in 1 min or less with the addition of sodium periodate. Rheological studies showed that the mechanical properties depend on the concentrations of catechol-conjugated chitosan and the molar ratio of sodium periodate to catechol groups. Additionally, the adhesive properties of the resulting adhesives were evaluated, and the adhesion strength of obtained adhesives was as high as 50 kPa because of the complex and multiple interactions, especially the anti-oxidation mechanism of thiol group. The in vitro cytotoxicity assays demonstrated an excellent biocompatibility of the catechol-conjugated chitosan hydrogels. Benefiting from the in situ fast cured, desired mechanical strength, biocompatibility and relatively high adhesion performance, these properties suggested that catechol-conjugated chitosan hydrogel adhesives have potential applications as tissue adhesive for soft tissues.


Research of differential expression of sIL1RAP in low-grade gliomas between children and adults.
Glioma is the most common intracranial malignant tumor. Low-grade gliomas (LGG) occupy almost 80% in all of the gliomas. The prognosis of LGG in children is much better than in adult, however, the molecular mechanism is still unclear. In our investigation, it was first found that the level of soluble IL1RAP (sIL1RAP) was significantly higher in the LGG from children than that from adult. We also revealed that sIL1RAP could induce the apoptosis of U251. In cells with overexpression of sIL-1RAP, the cell proliferation promoted by IL-1 was significantly inhibited. These decreased tumor growth ability and better prognosis of low-grade gliomas in children patients than that in adult patients. The expression level of sIL1RAP may become one of the potential indexes for determining the prognosis of low-grade gliomas.


Fatty Acids of CLA-enriched Egg Yolks Can Induce Mitochondrial Pathway of Apoptosis in MCF-7 Breast Cancer Cells.
Fatty acids from conjugated linoleic acid (CLA)-enriched egg yolk suppressed the viability of the MCF-7 cancer line more effectively than non-enriched egg yolk. Herein we aimed to determine the molecular mechanisms by analysing the expression and activation of proteins involved in cellular stress and apoptosis signaling. Forty-eight Isa Brown laying hens (26-week-old) were fed a fortified (0.75% CLA) or a control diet (0% CLA) for 4 months. Collected eggs were used to obtain CLA-enriched (EFA-CLA) or non-enriched (EFA) fatty acid extracts for the treatment of the MCF-7 cancer cell line. Protein levels were analysed by PathScan® Stress and Apoptosis Signalling Antibody Array and western blot method. Treatment with EFA-CLA led to activation of caspase signalling as main effector of apoptosis. It also increased levels of pro-apoptotic B-cell lymphoma 2 family proteins as well as promoted the release of cytochrome c, second mitochondria-derived activator of caspase and mitochondrial serine protease from mitochondria to the cytoplasm. EFA-CLA increased levels of tumour protein 53 and mothers against decapentaplegic homolog 2 tumour suppressors, and activated p38 mitogen-activated protein kinases and stress-activated protein kinase/c-Jun NH2-terminal kinase proteins. Finally, treatment down-regulated anti-apoptotic extracellular signal-regulated protein kinases 1 and 2, RAC-alpha serine/threonine-protein kinase, heat-shock protein 27, inhibitor of nuclear factor κβ, transforming growth factor beta-activated kinase 1 and survivin proteins. Taken together, our results suggest that activation of the mitochondrial apoptotic pathway may be a potential mechanism of EFA-CLA action.


Effectiveness of Trauma-Focused Cognitive Behavioral Therapy Among Trauma-Affected Children in Lusaka, Zambia: A Randomized Clinical Trial.
Orphans and vulnerable children (OVC) are at high risk for experiencing trauma and related psychosocial problems. Despite this, no randomized clinical trials have studied evidence-based treatments for OVC in low-resource settings. To evaluate the effectiveness of lay counselor-provided trauma-focused cognitive behavioral therapy (TF-CBT) to address trauma and stress-related symptoms among OVC in Lusaka, Zambia. This randomized clinical trial compared TF-CBT and treatment as usual (TAU) (varying by site) for children recruited from August 1, 2012, through July 31, 2013, and treated until December 31, 2013, for trauma-related symptoms from 5 community sites within Lusaka, Zambia. Children were aged 5 through 18 years and had experienced at least one traumatic event and reported significant trauma-related symptoms. Analysis was with intent to treat. The intervention group received 10 to 16 sessions of TF-CBT (n = 131). The TAU group (n = 126) received usual community services offered to OVC. The primary outcome was mean item change in trauma and stress-related symptoms using a locally validated version of the UCLA Posttraumatic Stress Disorder Reaction Index (range, 0-4) and functional impairment using a locally developed measure (range, 0-4). Outcomes were measured at baseline and within 1 month after treatment completion or after a waiting period of approximately 4.5 months after baseline for TAU. At follow-up, the mean item change in trauma symptom score was -1.54 (95% CI, -1.81 to -1.27), a reduction of 81.9%, for the TF-CBT group and -0.37 (95% CI, -0.57 to -0.17), a reduction of 21.1%, for the TAU group. The mean item change for functioning was -0.76 (95% CI, -0.98 to -0.54), a reduction of 89.4%, and -0.54 (95% CI, -0.80 to -0.29), a reduction of 68.3%, for the TF-CBT and TAU groups, respectively. The difference in change between groups was statistically significant for both outcomes (P < .001). The effect size (Cohen d) was 2.39 for trauma symptoms and 0.34 for functioning. Lay counselors participated in supervision and assessed whether the intervention was provided with fidelity in all 5 community settings. The TF-CBT adapted for Zambia substantially decreased trauma and stress-related symptoms and produced a smaller improvement in functional impairment among OVC having experienced high levels of trauma. clinicaltrials.gov Identifier: NCT01624298.


Characteristics and risk factors of infections after glaucoma filtering surgery.
To define characteristics and potential risk factors of endophthalmitis and blebitis after glaucoma filtering surgery in adults. A chart review of all cases of endophthalmitis or blebitis treated at the Duke University Eye Center for 6 years (January 1993 to December 1998) was performed to identify patients with a history of incisional glaucoma surgery. Twenty patients were identified. The filtering bleb was located superiorly in all patients. Blebitis but not endophthalmitis developed in 3 (15%) of 20 patients, and all had visual outcomes of at least 20/25. Endophthalmitis (blebitis and vitritis) occurred in 17 (85%) of 20 patients. Cases of blebitis were treated with topical antibiotics. All cases of endophthalmitis were treated with intravitreal antibiotics, and 3 (18%) of 17 patients also underwent immediate vitrectomy. Initial visual acuity was less than hand motions in 5 (29%) of 17. Final visual acuity was less than 20/200 in only one case of endophthalmitis. In 15 (75%) of 20 patients, the bleb was noted to be thin, avascular, or both. On presentation, 11 (55%) of 20 blebs had Seidel-positive leaks with hypotony. A history of recurrent bleb leaks was documented in 7 (33%) of 20 patients. Pseudophakia was present in 13 (65%) of 20 eyes, and 7 (35%) of 20 had undergone combined cataract and filtering surgery. A prodrome, such as a browache, headache, or external eye inflammation or infection, was documented in previous physician visits in 7 (35%) of 20 patients. No cases occurred in eyes with glaucoma implants. Patients in whom endophthalmitis develops after trabeculectomy do poorly, even with aggressive medical and surgical intervention. As expected, several patients had thin, avascular, leaking blebs. In addition, hypotony, recurrent bleb leaks, pseudophakia, and more than one filtering surgery may also be associated with blebitis or endophthalmitis after glaucoma filtering surgery. In a surprising number of patients, prodromal signs or symptoms were documented by ophthalmologists days or weeks before the diagnosis of blebitis or endophthalmitis was made.


Arachidonic acid increases intracellular calcium in erythrocytes.
Recently, we have measured in erythrocytes a voltage-modulated and dihydropyridine-inhibited calcium influx. Since arachidonic acid and other polyunsaturated fatty acids influence the activities of most ion channels, we studied their effects on the erythrocyte Ca(2+) influx. It was measured on fresh erythrocytes, isolated from healthy donors, using the fluorescent dye Fura 2 as indicator of [Ca(2+)](i). AA (5-50 microM) and EPA (20-30 microM) stimulated a concentration-dependent increase in [Ca(2+)](i), deriving from extracellular calcium (1 mM), without affecting the intra- and extracellular pH and membrane voltage. The Ca(2+) influx rate varied from 0.5 to 3 nM Ca(2+)/s in the presence of AA and from 0.9 to 1.7 nM Ca(2+)/s with EPA. The Ca(2+) influx elicited by AA and EPA was not inhibited by dihydropyridines, while cyclooxygenase inhibitors were effective and PGE1 or PGE2 did not produce any effect. We conclude that AA could activate an erythrocyte voltage-independent Ca(2+) transport via an intermediate product of cyclooxygenase pathway; however, a direct interaction with the membrane lipid-protein cannot be excluded.


Bone morphogenetic protein (BMP)1-3 enhances bone repair.
Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair.


Transient acantholytic dermatosis (Grover's disease) in a renal transplant patient.
Grover's disease ("transient acantholytic dermatosis") is a transient dermatosis of unknown cause manifesting clinically as a papular skin eruption located usually on the anterior chest and abdomen and histologically with dyskeratosis and acantholysis. Grover's disease has occasionally been reported in patients with chronic renal failure, HIV infection, hematological malignancies and bone-marrow allotransplantation. We report herein a new case of Grover's disease that developed in a renal transplant patient. To the best of our knowledge, this is the first observation of Grover's disease developing in the setting of solid organ transplantation.


[An evaluation of some of the relationships between thought-action fusion, attributional styles, and depressive and obsessive-compulsive symptoms].
Thought-action fusion (TAF) is a cognitive bias presumed to underlie the development of obsessional problems. Two domains of TAF have been identified. The first, TAF-moral, is characterized by the belief that having morally unacceptable thoughts is as bad as actually carrying them out. The second, TAF-likelihood, refers to the belief that certain thoughts cause particular events. The event can be related to one's self (likelihood-self) or to someone else (likelihood-others). The other cognitive variable of the study is attributional style. The theory of attributional styles, in terms of the causes of good and bad events, is taken into account especially in the context of depression and has four dimensions: internality-externality, stability-instability, globality-specifity, and importance-unimportance. The first objective of the present study was to investigate the relationships between TAF, and attributional style, and depressive and obsessive-compulsive symptoms. The second objective was to determine the predictors of TAF when the effects of depressive and obsessive-compulsive symptoms are statistically controlled. The sample consisted of 312 students randomly selected from different departments at Hacettepe University. The Thought-Action Fusion Scale (TAFS), Attributional Style Questionnaire (ASQ), Maudsley Obsessive-Compulsive Inventory (MOCI), and Beck Depression Inventory (BDI) were administered to these students. The correlations among all the subtypes of TAF (TAF-moral, likelihood-self, and likelihood-others), and the global attributions for bad events, BDI, and MOCI were significant. In addition, the correlation between TAF-moral and the importance of the attribution for bad events was significant. TAF-likelihood-others and TAF-likelihood-self were predicted by global attributions for bad events and TAF-moral was predicted by the importance of the attributions for bad events. TAF, and attributional styles, and depressive and obsessive-compulsive symptoms may be related to each other. The results also suggest a possible effect of other variables not controlled in this study, both on TAF and the dimensions of attributional styles.


Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections.
The steady increase in resistant organisms is related to the widespread use of antibiotics in community and hospital settings. New therapeutic options are needed, including treatments for infections caused by antibiotic-resistant gram-positive organisms. Quinupristin-dalfopristin, the first formulation of a distinct class of antibiotics known as the streptogramins, has activity against a range of gram-positive bacteria that are usually resistant to other agents, including vancomycin-resistant Enterococcus faecium. The pharmacodynamic (postantibiotic effect) and pharmacokinetic characteristics of quinupristin-dalfopristin allow dosing at eight- to 12-hour intervals. The safety profile of the formulation is generally favorable, with no demonstrable ototoxicity, nephrotoxicity, bone marrow suppression, or cardiovascular adverse effects. Reversible arthralgias, myalgias, and peripheral venous irritation are the formulation's major side effects. A potential for drug interactions exists because quinupristin-dalfopristin significantly inhibits the cytochrome P450-3A4 enzyme system. Quinupristin-dalfopristin has been shown to be effective in the management of documented severe infections caused by vancomycin-resistant E. faecium, nosocomial pneumonia, and infections related to the use of intravascular catheters.


Pear-shaped bladder caused by large iliopsoas muscles.
A case of pear-shaped bladder resembling pelvic lipomatosis was shown to be caused by large iliacus and psoas muscles.


Metal content of drinking water supplied to the city of Maracaibo, Venezuela.
Total dissolved aluminum, calcium, iron, potassium, magnesium and sodium were evaluated in the drinking water supplied to the city of Maracaibo, Venezuela, to ascertain the water quality for human consumption. Mean concentrations (+/- S.D.) of 533 +/- 313 micrograms/l Al, 32 +/- 4 mg/l Ca, 167 +/- 104 micrograms/l Fe, 2 +/- 1 mg/l K, 5 +/- 2 +/- 1 mg/l K, 5 +/- 1 mg/l Mg and 16 +/- 4 mg/l Na were obtained during a 4-month sampling period that included dry (January-February 1991) and wet (March-April 1991) seasons. Significant seasonal variations (P < 0.002) for aluminium, potassium and magnesium were as follows: 641 +/- 275 and 445 +/- 340 micrograms/l aluminium, 3 +/- 0.5 and 2 +/- 0.5 mg/l potassium and 4 +/- 0.2 and 6 +/- 2 mg/l magnesium for the wet and dry seasons, respectively. The concentration of aluminum was consistently higher than the levels accepted by most international water quality criteria (approximate acceptable value < 300 micrograms/l aluminum), probably because of the inadequate flocculation treatment given to the raw water at the water plant. The rest of the metals under consideration complied with international guidelines of quality criteria for drinking water. The presence of an elevated concentration of humic material (22 +/- 2 mg/l of total organic carbon) in the drinking water should be a matter of public concern.


Seasonal allergic rhinitis and antihistamine effects on children's learning.
Children suffering from seasonal allergic rhinitis and matched normals were instructed on the use of a didactic computer simulation in a realistic classroom situation. Groups of atopic children received different treatments before instruction; ie, sedating (diphenylhydramine HCl) or nonsedating (loratadine) antihistamines or placebo. All returned after 2 weeks for an examination measuring factual and conceptual knowledge and the application of a learned strategy. Examination results showed large and consistent impairing effects of the allergic reaction on prior learning. Both the placebo and diphenhydramine groups learned significantly less than normal controls. The loratadine group's learning performance was superior to either of the other atopic groups' but still inferior to the normals'. Our conclusions are that the allergic reaction reduces learning ability in children and that this effect is partially counteracted by treatment with loratadine and aggravated by diphenhydramine.


[Stalking: a new traumatic syndrome?].
Stalking is a recently described syndrome including a pattern of repeated intrusion and seeking for intimate relationship with another person that is unwanted. Such behaviour is perceived as an explicit threat from a victim who experiences fear. Recent studies indicate that stalking is an important legal and clinical issue with elevated prevalence rates especially among women (10%) eventually with dramatic consequences. Furthermore stalking situation are important in psychiatric practice especially among patients referred to emergency room and crisis intervention. A specific form of "treatment barrier" comes along with stalking and will be discussed. Judiciary actions are often necessary before it is possible to plan a treatment.


Spatio-temporal expression of MRF4 transcripts and protein during Xenopus laevis embryogenesis.
Whereas there have been extensive studies of the expression of XMyf5 and XMyoD during Xenopus embryogenesis, nothing is known about the spatio-temporal accumulation of XMRF4 transcripts and protein. In this report, we describe the cloning and characterization of two full-length MRF4 cDNAs and of their proximal promoters in Xenopus laevis. The comparison of the relative transcript levels of the XMRF4-a and -b genes in developing and adult muscles is highly suggestive of specific functions for the corresponding XMRF4 proteins. Whole-mount embryo in situ hybridization revealed the first XMRF4 transcripts in the more differentiated anterior myocytes of the embryo when the myosin heavy chain E3 mRNA begins to be detectable. XMRF4 mRNA accumulation later extended posteriorly but was never detected in the posterior unsegmented mesoderm, in contrast to XMyoD and XMyf-5. Whole-mount embryo immunohistochemistry revealed that XMRF4 protein accumulated in somite nuclei slightly after XMRF4 transcripts.


Stroke Incidence by Major Pathological Type and Ischemic Subtypes in the Auckland Regional Community Stroke Studies: Changes Between 2002 and 2011.
Major pathological stroke types (ischemic stroke [IS], primary intracerebral hemorrhage [ICH], and subarachnoid hemorrhage) and IS subtypes, have differing risk factors, management, and prognosis. We report changes in major stroke types and IS subtypes incidence during 10 years using data from the ARCOS (Auckland Regional Community Stroke Study) III performed during 12 months in 2002 to 2003 and the fourth ARCOS study (ARCOS-IV) performed in 2011 to 2012. ARCOS-III and ARCOS-IV were population-based registers of all new strokes in the greater Auckland region (population aged >15 years, 1 119 192). Strokes were classified into major pathological types (IS, ICH, subarachnoid hemorrhage, and undetermined type). Crude annual age-, sex-, and ethnic-specific stroke incidence with 95% confidence intervals was calculated. ISs were subclassified using TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria into 5 etiologic groups. Rate ratios with 95% confidence intervals were calculated for differences in age-standardized rates between the 2 studies. In ARCOS-IV, there were 1329 (81%) ISs, 211 (13%) ICHs, 79 (5%) subarachnoid hemorrhages, and 24 (1%) undetermined type strokes. The proportional distribution of IS subtypes was 29% cardioembolism, 21% small-vessel occlusion, 15% large-artery atherosclerosis, 5% other determined etiology, and 31% undetermined type. Between 2002 and 2011, age-standardized incidence decreased for subarachnoid hemorrhage (rate ratios, 0.73; 95% confidence intervals, 0.54-0.99) and undetermined type (rate ratios, 0.14; 95% confidence intervals, 0.09-0.22). Rates were stable for IS and ICH. Among IS subtypes, large-artery atherosclerosis and small-vessel occlusion rates increased significantly. The frequency of all risk factors increased in IS. Ethnic differences were observed for both stroke subtype rates and their risk factor frequencies. A lack of change in IS and ICH incidence may reflect a trend toward increased incidence of younger strokes. Increased rates of large-artery atherosclerosis and small-vessel occlusion are associated with increased smoking and high blood pressure. Ethnic differences in the proportional distribution of pathological stroke subtypes suggest differential exposure and susceptibility to risk factors.


Dynamic laser light scattering of papain-treated thick filaments from limulus striated muscle in suspension.
Using quasielastic light scattering we have previously shown an increase in high frequency internal motion of isolated thick filament upon activation. This we have attributed to cross-bridge motion. Here we show that after cleavage of the S1 moiety of myosin from isolated filaments with papain, calcium ions no longer activate the isolated filaments to produce high-frequency motions.


Two cases of non-Hodgkin's lymphoma in the accessory parotid gland.
Primary malignant lymphomas in the salivary glands are relatively rare and tumors of the accessory parotid gland comprise only 1% of parotid tumors. We present two cases with a painless swelling of the cheek region. In both cases histological diagnoses of primary non-Hodgkin's lymphoma were made following complete excision of the accessory parotid gland tumor.


Effect of thaw temperatures in reducing enzyme activity in human thyroid tissues.
An identified impediment to the advancement of science in the field of proteomics is the deterioration of proteins in tissue upon removal of the tissue from its natural state. To reduce this degradation, human tissues are frozen and stored in either liquid nitrogen or -80°C environments. It is believed that frozen tissue in ultralow temperatures preserves proteins against enzyme degradation. Various molecular, biophysical, and biochemical analytical studies require that frozen tissues be thawed before being used for analyses. Depending on downstream analyses, tissues are thawed at different temperatures (37°C, room temperature or 4°C). However, there is very little literature that describes the effects of different thaw temperatures on enzymatic inactivation in tissue lysates. We investigated the effects of preprocessing variable thaw temperature on postprocessed lysates using tyrosine phosphatase and phosphatase and tensin homolog activity assays. In our study we examined the thawing of frozen human thyroid tissues at the traditional temperatures of 4°C (on ice), 37°C (in an oven), and the novel temperature of 95°C (using Stabilizor T1™). The tissue lysates were processed without the addition of enzymatic inhibitors. Our results showed that in benign, malignant, and diseased tissues, high temperature thawing is effective in reducing enzymatic activity. In normal tissue, the reduction is dependent on individual enzymes. This suggests that if tissue lysates are to be obtained from frozen tissues without the addition of inhibitors, high temperature thawing might have marked improvement in downstream non-enzymatic analyses of diseased and neoplastic tissues.


The pudendal nerve-evoked response in axial muscle.
In 39 Urethane-anesthetized rats we have recorded the afferent volley in the dorsal roots and the electrical activity of the lateral longissimus muscle and its motor nerves during electrical stimulation of a cutaneous branch of the pudendal nerve. Male and female rats were used; the females were ovariectomized and either pretreated with estradiol or left without hormonal treatment. Conduction velocities in the pudendal nerve were 54 m/s for the largest A-beta fibers and averaged 10 m/s for A-delta fibers. Excitation of pudendal nerve afferents strongly potentiated the firing of axial motoneurons, at stimulus currents below threshold for A-delta fibers. Trains of three shocks to the pudendal nerve were considerably more effective than double or single shock trains. Repetition rates as low as 1/s had a long lasting excitatory effect on the lateral longissimus muscle and the magnitude of the responses increased gradually for several seconds with continued stimulation. Recordings from the axons of the epaxial motoneurons of female rats showed a strong activation of neuronal firing with an onset latency of 5.8 ms from the last shock of a three ms, three shock train; the onset in male rats, 8.4 ms, differed significantly. Peak spike activity occurred at mean latencies of 11, 22 and 102 ms in both sexes. A period of depressed firing was usually present from 34 to 50 ms. Males differed in having a larger peak in activity at 102 ms, but the overall profile of the responses was similar in males and females. No differences were seen in the overall response patterns of the estrogen-treated and untreated females. Responses of comparable magnitude were seen with ipsilateral or contralateral pudendal nerve stimulation; these were facilitated by bilateral stimulation. In electromyographic recordings, the onset of unit firings was seen at 6.4 ms latency in response to pudendal nerve stimulation. This unit activity was consistent with the firing pattern seen in the muscle nerves.


Erythema elevatum diutinum. Response to dapsone.
A patient with a 20-year history is presented as a classic example of erythema elevatum diutinum, with a dramatic response to dapsone therapy, and with interesting features of improvement during pregnancies and occurrence of giant cell tumors of soft tissue, neither of these latter features having been previously reported.


Biofilm formation of Candida albicans on the surfaces of deteriorated soft denture lining materials caused by denture cleansers in vitro.
Candidal colonization and subsequent biofilm formation on denture materials are important in the development of pathogenesis, such as denture stomatitis. Routine use of denture cleansers is one of the most effective methods of denture plaque control, although the incompatibility of soft liners and denture cleansers cause damage to the materials. The present study, biofilm formation of Candida albicans on the surfaces of soft denture lining materials, immersed in denture cleansers for 180 days were studied. Seven commercially available soft denture lining materials, were artificially deteriorated by immersion into three commercially available denture cleansers for 180 days, and subsequent fungal growth and biofilm formation were studied by measuring pH of the media and by the use of adenosine triphosphate (ATP) analysis. Fungal biofilm formation on the deteriorated soft liners varied depending upon the combination of the soft liners and denture cleansers. Several combinations of soft liners with denture cleansers exhibited the significantly high colonization capacity as compared with each sample immersed in distilled water, used as individual controls. The relationship between the biofilm formation on the samples of each material and the surface roughness of the soft lining materials was analyzed. However, no significant correlation was observed. The results, taken together, suggested that fungal colonization could be predominantly regulated by the combination of lining material with denture cleansers. In clinical terms, our findings suggests that daily cleansing of soft lining materials with mismatched denture cleansers promoted the subsequent biofilm formation of fungi on the materials.


[Purely phasic neurons of the medial geniculate body--markers of changes in the signal].
The majority of neurons in the medial geniculate body responded with short bursts of activity to increments of the noise signal, and some of them--to decrements of the signal as well. Responses to changes in the signal envelope were only observed in narrow intensity range different for different neurons. The data suggest that division of neurons into groups acting within local dynamic ranges related to the cochlear nerve level, remains on the medial geniculate body level so as the ability of the organism to detect small changes in the signal envelope is maintained by the convergence of information from local detectors.


[Spectral analysis method for precisely measuring specific rotation of quartz].
A spectral analysis method for precisely measuring specific rotation of quartz is proposed. The measuring principle is analyzed by using the method of optical matrix. The result indicates that the specific rotation of quartz can be exactly calculated by measuring the transmittance curve of a sample quartz plate sandwiched between two paralleled polarizing prisms, and the correctness of the method is validated by a designed experiment using a spectrophotometer. The data is analyzed, and the rotary dispersion formula of quartz is fitted. Compared with Lowry' formula, our formula is more accurate in visible spectral scope. Errors in the experiment is analyzed and the result shows that the measuring accuracy will be improved by choosing thicker quartz plate, longer wave band, lower scan speed, and smaller slit width.


Sudden unexpected death from pulmonary thromboembolism--examination of antemortem chest X-ray.
An autopsy case of a woman who died suddenly from undiagnosed and untreated pulmonary thromboembolism (PTE) on her way home from the hospital is described in this report. She had complained of chest pain and dyspnea on exertion when she visited the hospital and a chest X-ray taken at that time showed remarkable manifestation of right heart failure and PTE, compared with former X-rays taken during previous visits to the hospital. In this report we present the findings of four chest X-rays of this patient, which had been taken both before and after the development of PTE.


NMR constrained solution structures for laminin peptide 11. Analogs define structural requirements for inhibition of tumor cell invasion of basement membrane matrix.
Peptide 11, CDPGYIGSR-NH2, is a segment of laminin which blocks tumor cell invasion. A high affinity laminin receptor in tumor cells is thought to be blocked by the carboxyl-terminal YIGSR, and conformational energy calculations suggest that the glycine in YIGSR allows an important conformational bend. We replaced the YIGSR glycine residue in peptide 11 with either D-alanine or L-alanine to allow or disfavor the proposed glycine bend. We found the Gly7-->D-Ala7 analog to be equal to peptide 11 in inhibiting tumor cell invasion of basement membrane matrix. The Gly7-->L-Ala7 analog was much less capable of invasion inhibition. Two-dimensional 1H-1H NMR was used to study the solution conformations of the peptide 11 analogs. NOESY experiments revealed close NH-NH contacts in peptide 11 and the D-Ala7 analog, but not in the L-Ala7 analog. Molecular dynamics generated low energy structures with excellent NOE agreement for peptide 11 and its analogs. Both peptide 11 and the D-Ala7 analog, but not the less active L-Ala7 analog, were predicted to have similar bends around Gly7 or D-Ala7. These results suggest that a bend in the YIGSR region of peptide 11 may be important for the binding of laminin to its metastasis-associated receptor.


Frequency of migraine and the risk of cardiovascular disease for women: limited evidence of an association.
Evaluation of: Kurth T, Schurks M, Logroscino G et al. Migraine frequency and risk of cardiovascular disease in women. Neurology 73, 581-588 (2009). There is substantial evidence that migraine with aura (MA) is associated with ischemic stroke and myocardial infarction in women. The mechanisms of this association are poorly understood. Analysis of data from the Women's Health Study, from 27,798 women over 45 years of age who were initially free of cardiovascular disease, found that women with baseline MA at a frequency of less than monthly had increased risk of major cardiovascular disease (HR: 2.28; 95% CI: 1.70-3.07) relative to women without migraine, and those who reported MA with a frequency of more than weekly had more than four-times the risk of ischemic stroke (HR: 4.25; 95% CI: 1.36-13.29) compared with those without migraine. Low numbers of outcome events in each of the frequency categories and lack of information on migraine frequency during follow-up limit the interpretation of these findings, but they suggest that frequency of migraine may be a moderating factor in the link between MA and cardiovascular disease.


X-ray structure of acarbose bound to amylomaltase from Thermus aquaticus. Implications for the synthesis of large cyclic glucans.
As a member of the alpha-amylase superfamily of enzymes, amylomaltase catalyzes either the transglycosylation from one alpha-1,4 glucan to another or an intramolecular cyclization. The latter reaction is typical for cyclodextrin glucanotransferases. In contrast to these enzymes, amylomaltase catalyzes the formation of cyclic glucans with a degree of polymerization larger than 22. To characterize the factors that determine the size of the synthesized cycloamyloses, we have analyzed the X-ray structure of amylomaltase from Thermus aquaticus in complex with the inhibitor acarbose, a maltotetraose derivative, at 1.9 A resolution. Two acarbose molecules are bound to the enzyme, one in the active site groove at subsite -3 to +1 and a second one approximately 14 A away from the nonreducing end of the acarbose bound to the catalytic site. The inhibitor bound to the catalytic site occupies subsites -3 to +1. Unlike the situation in other enzymes of the alpha-amylase family, the inhibitor is not processed and the inhibitory cyclitol ring of acarbose, which mimicks the half chair conformation of the transition state, does not bind to catalytic subsite -1. The minimum ring size of cycloamyloses produced by this enzyme is proposed to be determined by the distance of the specific substrate binding sites at the active site and near Tyr54 and by the size of the 460s loop. The 250s loop might be involved in binding of the substrate at the reducing end of the scissile bond.


Quality indicators in digestive endoscopy: introduction to structure, process, and outcome common indicators.
The general goal of the project wherein this paper is framed is the proposal of useful quality and safety procedures and indicators to facilitate quality improvement in digestive endoscopy units. This initial offspring sets forth procedures and indicators common to all digestive endoscopy procedures. First, a diagram of pre- and post-digestive endoscopy steps was developed. A group of health care quality and/or endoscopy experts under the auspices of the Sociedad Española de Patología Digestiva (Spanish Society of Digestive Diseases) carried out a qualitative review of the literature regarding the search for quality indicators in endoscopic procedures. Then, a paired analysis was used for the selection of literature references and their subsequent review. Twenty indicators were identified, including seven for structure, eleven for process (five pre-procedure, three intra-procedure, three post-procedure), and two for outcome. Quality of evidence was analyzed for each indicator using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification.


[Endovascular closure of defects of the interatrial septum and patent foramen ovale].
Endovascular occlusion of defects of the interatrial septum and patent foramen ovale has increasingly been gaining ground in surgical practice. This is predetermined by a shortened hospital stay of the patients and the lack of any cosmetic defects left, as compared with the conventionally performed surgical management. The present review analyses both Russian and foreign literature related to the problem concerned. Indications for and contraindication to this type of operative treatment are determined herein. Also described is the technique of implantation for the present-day types of occluders. A comparative assessment of efficacy and safety of various occlusion systems is given.


Protein lateral mobility as a reflection of membrane microstructure.
The lateral mobility of membrane lipids and proteins is presumed to play an important functional role in biomembranes. Photobleaching studies have shown that many proteins in the plasma membrane have diffusion coefficients at least an order of magnitude lower than those obtained when the same proteins are reconstituted in artificial bilayer membranes. Depending on the protein, it has been shown that either the cytoplasmic domain or the ectodomain is the key determinant of its lateral mobility. Single particle tracking microscopy, which allows the motions of single or small groups of membrane molecules to be followed, promises not only to reveal new features of membrane dynamics, but also to help explain longstanding puzzles presented by the photobleaching studies, particularly the so-called immobile fraction. The combination of the two complementary technologies should measurably enhance our understanding of membrane microstructure.


Estrogen induction of progestophilins in rat estrogen-sensitive cells grown in media supplemented with sera from castrated rats and from rats bearing an alpha-fetoprotein-secreting hepatoma.
The purpose of this work was to study the effect of alpha-fetoprotein (AFP) over cell multiplication and the induction of an estradiol-17 beta (E2)-dependent marker, i.e., progestophilins in E-sensitive cells C2(9)RAP derived from a W/Fu rat pituitary tumor. These cells proliferate in isogeneic hosts under the influence of E2, while they proliferate in culture regardless of the presence of E2. C2(9)RAP cells were grown in medium supplemented with 10% horse serum. Progestophilin levels were measured 48 h after adding serum (20% horse, or castrated rat, or AFP-secreting tumor-bearing rat) and estrogen to the 10% horse serum-supplemented medium in which the cells were growing. Maximal induction of progestophilins was obtained at 3 X 10(-10) M E2 in cells grown in medium containing horse or castrated rat serum. In contrast, maximal induction of progestophilins required 3 X 10(-8) M E2 in cells grown in medium supplemented with the serum of Morris hepatoma 7777-bearing rats. This serum contained AFP levels comparable to those present at birth in the rat. 11-Methoxy-17 beta ethynylestradiol (R2858), a synthetic estrogen with little affinity for AFP, was also tested for its ability to induce progestophilins. The degree of maximal induction of progestophilins expressed as percentage of the respective control, was similar for all experimental groups, both with E2 and with R2858. In addition, we compared the free E2 levels in the culture medium with the progestophilin levels and the cell proliferation rate. We found that the progestophilin levels were maximal at free E2 concentrations above 11 pg E2/ml, whereas there was no correlation between the free E2 levels and the proliferation rate. Moreover, the proliferation rate of cells in medium supplemented with horse or castrated rat serum was maximal at concentrations of free E2 below 0.4 pg/ml; whereas cell proliferation was inhibited with hepatoma serum even at concentrations of free E2 of 44 pg/ml. We conclude that the effect of hepatoma serum on the E2 induction of progestophilins seems to be mediated by the effect of AFP on the availability of free estrogen, since it is abolished by the addition of both natural and synthetic estrogens. The inhibitory effect of hepatoma serum upon cell proliferation is not reversed by estrogens and thus seems to be mediated by mechanisms other than E2 trapping by AFP.


Detection of enterovirus RNA in clinical samples by nested polymerase chain reaction for rapid diagnosis of enterovirus infection.
Employing a nested polymerase chain reaction with primers from the 5' non-translated region of the enterovirus genome, we detected enteroviral RNA from patients with a variety of enterovirus-associated clinical syndromes. This technique was found to be sensitive (detecting enteroviral RNA extracted from 0.1 50% tissue culture infectious dose) and specific; no specific PCR product was detected from RNA extracts of a variety of non-enterovirus isolates. Although the technique is of comparable sensitivity to single round polymerase chain reaction followed by Southern blot hybridization, it was more rapid, since it enabled a diagnosis to be made within 1 day. Thus, using nested polymerase chain reaction we were able to detect enteroviral RNA in 31 of 46 clinical specimens from 17 of 23 patients with suspected enterovirus infections. The samples included cerebrospinal fluid, throat swabs, stool, vesicle fluid, peripheral blood lymphocytes, whole blood and pericardial effusion. In contrast virus was isolated in only 17 of 42 clinical specimens from 12 of 22 these patients. In preliminary studies, restriction endonuclease analysis of polymerase chain reaction products enabled us to distinguish between non-polio enteroviruses and poliovirus types 1, 2, and 3. This additional technique may be useful in distinguishing between such infections in polio-endemic countries where rapid public health measures may be required.


[Investigation of the vesical sphincter and genital-sexual autonomic pathways. Techniques, normal values, and application to pathology].
Parasympathetic and sympathetic pathways may be assessed by using different electrophysiologic tests. Sympathetic skin potentials (SSP) are elicited with peripheral electrical stimulation (e.g. median nerve or pudendal nerve). SSP are recorded from the skin of the hand and foot and from the genital skin. Skin responses were always obtained from normal volunteers. Absence of SSP is one of the earliest findings in neurogenic impotence. Electromyography of corpora cavernosa is described with a new method. A new corpora cavernosa response to pudendal nerve stimulation is described. This test appear to have application in the evaluation of neurogenic impotence.


Role of intravoxel incoherent motion parameters in gastro-esophageal cancer: relationship with 18F-FDG-PET, CT perfusion and MR perfusion imaging parameters.
Identification of pre-therapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F- FDG-PET, CT perfusion and dynamic contrast enhanced MRI in patients with gastro- esophageal cancer and investigated their histopathological correlation. Thirty-one consecutive patients (28 male; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (n=22) and esophageal squamous cell carcinoma (n=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum- slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. IVIM and PET parameters showed significant negative correlations: MTV & bval (rs = -0.643, p = 0.002), TLG & bval (rs = -0.699, p < 0.01) and TLG & fp (rs = -0.577, p = 0.006). Positive correlation was found for TLG & D (rs = 0.705, p = 0.000). Negative correlation was found for bval & staging (rs = 0.590, p = 0.005). Positive correlation was found for positive enhancement interval & BV (rs = 0.547, p = 0.007), BF & regression index (rs = 0.753, p = 0.005) and for time-to-peak & staging (rs = 0.557, p = 0.005). IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.


Induced death of Escherichia coli encapsulated in a hollow fiber membrane as observed in vitro or after subcutaneous implantation.
The encapsulation of bacteria may be used to harness them for longer period of time in order to make them viable, while antibiotic treatment would result in controlled release of therapeutic molecules. Encapsulated bacteria Escherichia coli GFP (green fluorescent protein) (E. coli GFP) were used here as a model for therapeutic substance - GFP fragments release (model of bioactive substances). Our aim was to evaluate the performance of bacteria encapsulated in hollow fibers (HF) treated with antibiotic for induction of cell death. The polypropylene surface modified HF was applied for E. coli encapsulation. The encapsulated bacteria were treated with tetracycline in vitro or in vivo during subcutaneous implantation into mice. The HF content was evaluated in flow cytometer, to assess the bacteria cell membrane permeability changes induced by tetracycline treatment. It was observed that applied membranes prevent release of bacteria through the HF wall. The encapsulated in HF E. coli GFP culture in vitro proves the tetracycline impact on bacteria viability and allows recognition sequence of events within process of bacteria death. Treatment with tetracycline of the SCID mice for 8 hours proves the tetracycline impact on bacteria viability in vivo, rising the necrotic bacteria releasing GFP fragments. It was concluded, that the bacteria may be safely enclosed within the HF at site of implantation, and when the animal is treated with antibiotic bacteria may act as a local source of bioactive factor.


[Screening of differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells during osteoporosis and their function in stem cell differentiation].
To screen differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells (BMMSCs) during osteoporosis and their function in stem cell differentiation. The osteoporosis model was induced by ovariectomy in mice.The differentially expressed microRNAs in BMMSCs during osteoporosis were screened with microRNA microarray chip and their expressions during osteogenesis and adipogenesis were detected by RT-PCR. Ten differentially expressed microRNAs were detected in BMMSC during osteoporosis. The expression of 5 specific microRNAs altered significantly during osteogenic differentiation and 3 microRNAs altered during adipogenic differentiation. A serials of differentially expressed microRNAs may be involved in functional defects of BMMSC during osteoporosis.


Extended lymphadenectomy for gastric cancer: results in a teaching hospital.
Lymphadenectomy including second-echelon lymph nodes (D2 resection) for gastric cancer has not been widely adopted partly as a result of a reported increase in operative morbidity and mortality. In the present study we examined the operative risk of D2 resection in a public teaching hospital. From 1995 to 1998, 57 patients underwent exploratory laparotomy for gastric neoplasm: nine with curative D2 resection (Group I), 17 with curative but less than D2 resection (Group II), 16 with palliative resection (Group III), and 15 with no resection (Group IV). Among the four groups, patients with curative D2 resection (Group I) were older and had increased operative time and estimated blood loss, but their need for blood transfusion, the operative morbidity and mortality, and the mean hospital stay were not increased. In contrast, those patients with palliative resection (Group III) had the highest morbidity among all groups, the only fatality, and prolonged hospital stay. Therefore, curative D2 resection can be performed safely even with significant resident involvement. The advanced patient age or the extensive dissection does not increase its surgical risk. Hence, D2 dissection should be considered whenever curative resection is feasible because it allows accurate staging with the added benefit of possible improvement in patient survival.


[Lysine deficiency and carnitine biosynthesis in the rat].
Male rats weanling fed 20% gluten diet for 90 days of demonstrate to have about one-third lower level of carnitine per gram of skeletal muscle and heart muscle than the group which received the same diet supplemented with 1% of lysine. The carnitine level of the liver, however, was significantly higher in the unsupplemented versus the lysine supplemented groups.


[Intratumoral heterogeneity in renal cell carcinoma. Molecular basis and translational implications].
Advanced clear cell renal cell carcinoma is characterized by extensive intratumoral genomic heterogeneity and branched as well as convergent evolutionary traits with genomically different subclones evolving in parallel in the same tumor. Distinct driver mutations can be found in spatially separated subclones, which may hinder the development of novel targeted therapies. However, truncal mutations of the VHL tumor suppressor gene and chromosome 3p loss were ubiquitously detected and will hence continue to be a focus of future drug development. Nevertheless, genomic instability, enhanced tumor genome plasticity and intratumoral heterogeneity are likely to represent major challenges towards biomarker development and personalized patient care.


How Reliable Is Microscopy and Culture for the Diagnosis of Gonorrhea? An 11-Year Experience from INDIA.
Positivity of microscopy and culture was greater (P < 0.0001) in men with urethral discharge syndrome (65.8%) than in women with vaginal/cervical discharge (0.5%), indicating that basic diagnostic tests may not be cost-effective for diagnosis of vaginal/cervical discharge syndrome. Microscopy when compared with culture showed sensitivity, specificity, positive predictive value and negative predictive value of 95.4%, 77.6%, 84.6%, and 95.3%, in men, whereas in women, it was 77.8%, 99.9%, 92.1%, and 99.9%, respectively.


A survey of breast imaging fellowship programs: current status of curriculum and training in the United States and Canada.
The Society of Breast Imaging and the Education Committee of the ACR Breast Commission conducted a survey of breast imaging fellowship programs to determine the status of fellowship curricula, help identify strengths and potential areas for improvement, and assess the current demand for fellowship programs. In 2012, a two-part survey was emailed to breast imaging fellowship directors from 72 fellowship programs. Of the 66 respondents, a total of 115 positions were identified. There were 90 positions with 9-12 months of breast imaging, and 25 positions with 6 months focused on breast imaging. Approximately two-thirds of programs reported an increase in the number of fellowship applicants, with three-quarters having 3 or more applicants for each position. All programs offered digital mammography, breast MRI, and diagnostic ultrasound services, and nearly all provided experience with interventional procedures. Approximately one-third provided breast screening ultrasound training. More than two-thirds required at least a 1-day rotation with a breast surgeon. Important nonclinical areas of training were not addressed in many programs. Approximately 40% of programs did not offer training related to the practice audit, and one-third of programs did not provide formal training related to quality control. Breast imaging fellowships are currently in higher demand than in the past. Most fellowship programs provide training in the key imaging modalities and interventional procedures. Potential gaps in training for many programs include the practice audit, quality control procedures, breast positioning, and mammography technical factors.


The prevalence and determinants of drug-resistance-associated mutations in the HIV-1-infected MSM population of Henan Province in China.
To estimate the prevalence of human immunodeficiency virus (HIV) drug resistance (DR) in a population of men who have sex with men (MSM) from Henan Province of China and to identify the DR-associated HIV-1 mutations in these MSM. The HIV-positive status of the MSM subjects in this study was confirmed using ELISA and Western blotting. The MSM subjects were classified into non-treatment group (n = 106) and treatment group (n = 313). CD4(+) T-lymphocyte counts were obtained by flow cytometry, and viral load was measured by branched DNA (bDNA) signal amplification assay. HIV-1 genotypic resistance tests were performed by sequence analysis of the HIV-1 protease and reverse transcriptase genes. In the non-treatment group, 15 patients (14.2 %) displayed DR to non-nucleoside reverse transcriptase inhibitor (NNRTI). In the treatment group, the failure rate of viral suppression was 38.33 % and the DR rate was 33.2 %, which was higher than the rate observed in the non-treatment group (P < 0.05). The incidence of mutations corresponding to NNRTI resistance was significantly higher than the incidence of mutations corresponding to nucleoside reverse transcriptase inhibitor (NRTI) resistance (32.9 % vs. 26.5 %) in the cohort. After antiretroviral therapy (ART), the frequencies of K103N, G190A, Y181C, and V106A mutations were highly elevated. Logistic regression analysis results showed that duration of treatment, poor treatment compliance, drug abuse and homosexual orientation are the major risk factors for DR in this MSM population (all P < 0.05). Our results showed that DR-associated mutations in the HIV-1-infected MSM population increased significantly after ART. Furthermore, duration of treatment, poor treatment compliance, drug abuse and homosexual orientation were identified as the risk factors for DR in the MSM population from Henan Province in China.


Multiple imputation to estimate the association between eyes in disease progression with interval-censored data.
In many ophthalmologic studies, progression of diseases such as diabetic retinopathy, age-related maculopathy, cataract, and glaucoma is only noted when each eye is examined at intervals that commonly vary between subjects. Such data are often analysed using continuous time survival methods with observed progression assumed to occur at the end of the interval. Tied times of progression can lead to substantial bias in estimation of the association between progression in right and left eyes. We describe a multiple imputation strategy to create multiple data sets without ties, based on drawing interval-censored progression times from a parametric gamma frailty model that accounts for continuous and discrete covariates. We illustrate the method with data from 478 patients with insulin-dependent diabetes mellitus who were followed for progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution of tied failure times allows for valid estimation of the hazard of progression in one eye given the progression status of the other eye. A simulation study suggests that the method performs well. Results highlight the advantage of multiple imputation that data imputed under one model can be analysed under several alternative models.


Topical carbonic anhydrase inhibitors IV: Relationship between excised corneal permeability and pharmacokinetic factors.
Ethoxzolamide (1) and two analogues, representing a hydroxyethoxy and a hydrogen substitution on the 6-position of the benzene ring (2 and 3), were applied to rabbit eyes using a topical infusion method designed to provide a constant rate into aqueous humor. Statistical-moment theory was applied to the topical infusion data to describe disposition of each compound within the rabbit eye. For each analogue, it was possible to compare the corneal absorption rate constant (ka), aqueous humor elimination rate constant (k10), disposition mean residence time (MRTd), apparent steady-state volume of distribution (Vdss), and total ocular clearance (Qe). In vivo ocular ka values were related to maximum in vitro corneal penetration rates determined across excised rabbit corneas. In particular, 2 had a much longer residence time and a slower clearance than 1 and 3, which may be responsible for its ability to lower intraocular pressure when dosed topically to the rabbit eye, whereas 1 and 3 show no activity.


Hollow microsphere with mesoporous shell by Pickering emulsion polymerization as a potential colloidal collector for organic contaminants in water.
Submicrometer hollow microspheres with mesoporous shells were prepared by a simple one-pot strategy. Colloidal silica particles were used as a particle stabilizer to emulsify the oil phase, which was composed of a polymerizable silicon monomer (TPM) and an inert organic solvent (PEA). The low interfacial tension between colloidal silica particles and TPM helped to form a Pickering emulsion with small droplet sizes. After the polymerization of TPM, the more hydrophobic PEA formed a liquid core, leading to a hollow structure after its removal by evaporation. BET results indicated that the shell of a hollow particle was mesoporous with a specific surface area over 400 m(2)·g(-1). With PEA as the core and silica as the shell, each resultant hollow particle had a hydrophobic cavity and an amphiphilic surface, thus serving as a good colloidal collector for hydrophobic contaminants in water.


[Experimental design in phase I (AUTHOR'S TRANSL)].
Clinical pharmacology has its domain during phase I. The formalisation of phase I is not very advanced. Sometimes it is argued that the design of experiments during that phase is unnecessary. Just the opposite is true. Trying a new substance for the first time in man poses a special necessity for the design of experiments in a scientific context. Phase I is described in a formal way. The design of experiments with a single subject -- the first one to be exposed to a new substance -- is described. Finally Latin squares are dealt with as a useful tool for phase I.


Lutein improves cell viability and reduces Alu RNA accumulation in hydrogen peroxide challenged retinal pigment epithelial cells.
Dysfunction of the microRNA (miRNA)-processing enzyme DICER1 and Alu RNA accumulation are linked to the pathogenesis of age-related macular degeneration (AMD). This study determined the optimal dose of lutein (LUT) and zeaxanthin (ZEA) to protect human retinal pigment epithelium (RPE) cells against hydrogen peroxide (H2O2). The effect of the optimal dose of LUT and ZEA as DICER1 and Alu RNA modulators in cultured human RPE cells challenged with H2O2 was investigated. ARPE-19 cells were pre-treated with LUT, ZEA, or both for 24 h before 200 μM H2O2 challenge. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. DICER1 and Alu RNA were quantified by western blotting and real-time polymerase chain reaction, respectively. H2O2 increased cell Alu RNA expression and decreased cell viability of ARPE-19, but had no significant impact on the DICER1 protein level. LUT, alone and in combination with ZEA pre-treatment, prior to H2O2 challenge significantly improved cell viability of ARPE-19 and reduced the level of Alu RNA compared to the negative control. These results support the use of LUT alone, and in combination with ZEA, in AMD prevention and treatment. This study is also the first to report LUT modulating effects on Alu RNA.


Endovascular treatment of excessive spasticity from spinal cord injury. A case report.
We report a new treatment for excessive spasticity using an endovascular technique. A 52-year-old woman with intractable spasticity of the hip joints and abdominal muscles was treated with an injection of 70% alcohol into Adamkiewicz's artery, which destroyed the spinal cord fed by Adamkiewicz's artery and cut the reflex arcs of excessive spasticity. Immediately after the treatment a significant change was noticed in muscle tonicity of the lower extremities, and intractable spasticity disappeared. Skin necrosis and muscle damage occurred because of the alcohol that leaked into the muscle branch of the subcostal artery. However, these complications could be treated by simple necrotomy. No recurrence was observed during the follow-up period. We believe this endovascular treatment will become a new strategy for excessive spasticity arising from spinal cord injury.


Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent.
Early cross-sex hormonal interventions (that is, between 16 and 18) as a treatment for young transsexuals are often considered to be risky. However, the delay of such treatment until after the development of secondary sex characteristics has obvious drawbacks for transsexual individuals. This paper reports a postoperative follow-up case-study of a female-to-male transsexual who was treated with a combination of an LHRH agonist (which delayed her secondary sex characteristics development) and psychotherapy at age 13, and subsequently underwent sex reassignment at 18.


Parenting knowledge among adolescent mothers.
The parenting knowledge of first-time adolescent mothers who chose to receive special services from the public school system was measured. These data are thought to be the first reported on the adolescent's awareness that parenting influences the present and future well-being of the infant and mother. Knowledge level was high and no different from that of adult primiparous mothers of comparable socioeconomic status. Correct response to individual items on the infant Caregiving Inventory (ICI) ranged from 84% to 96% for adolescents. These results are contrary to the previous reports of deficient parenting by adolescents. They reflect the need for continuing investigation of adolescent mothers' parenting knowledge in evaluating their effectiveness as parents.


Blood pressure-lowering effects of angiotensin receptor antagonist monotherapy and in combination with other anti-hypertensive drugs in primary care settings in Japan.
Combination therapy with multiple anti-hypertensives is required to achieve target blood pressure (BP) control and is recommended as the first-line therapy in hypertension. Although angiotensin receptor blockers (ARBs) may be combined with other anti-hypertensives, it is unclear how the effects of ARBs are influenced by co-administered anti-hypertensives. We investigated the effect of olmesartan medoxomil (OLM) when it is given alone (monotherapy) or concomitantly with other anti-hypertensives in 6507 OLM-naive Japanese in "real world" clinical practice. After a 12-week treatment, BP was significantly reduced from baseline in both the monotherapy group and the combination therapy group (P < 0.0001). The BP-lowering efficacy after treatment and achievement rates of target BP were similar in both groups. In the combination therapy group, no significant difference of achieved BP level was detected between patients taking Calcium channel blockers and any other class of anti-hypertensive drugs. This study suggests that ARBs such as OLM-elicits BP-lowering efficacy as either a first- or second-line agent and its effects are minimally influenced by co-administered anti-hypertensives.


Association between DNA cleavage during apoptosis and regions of chromatin replication.
We have addressed the association between the site of DNA cleavage during apoptosis and DNA replication. DNA double strand breaks were introduced into chromatin containing pulse labeled nascent DNA by the induction of apoptosis or autocleavage of isolated nuclei. The location of these breaks in relation to nascent DNA were revealed by Bal31 exonuclease digestion at the cut sites. Our data show that Bal31 accessible cut sites are directly linked to regions enriched in nascent DNA. We suggest that these regions coincide with the termini of replication domains, possibly linked by strong DNA-matrix interactions with biophysically defined topological structures of 0.5-1.3 Mbp in size. The 50 kbp fragments that are commonly observed as products of apoptosis are also enriched in nascent DNA within internal regions but not at their termini. It is proposed that these fragments contain a subset of replicon DNA that is excised during apoptosis through recognition of their weak attachment to the nuclear matrix within the replication domain.


Electrochemical oxidation of butein at glassy carbon electrodes.
The electrochemical oxidation of flavonoid butein is studied at glassy carbon electrodes in phosphate and citrate buffer solutions of different pH values, and 1M perchloric acid aqueous solutions by cyclic and square wave voltammetries. The oxidation peak corresponds to the 2e(-), 2H(+) oxidation of the 3,4-dihydroxy group in B ring of butein, given the corresponding quinone species. The overall electrode process shows a quasi-reversible behavior and an adsorption/diffusion mixed control at high butein bulk concentrations. At low butein concentrations, the electrode process shows mainly an adsorption control. Butein surface concentration values were obtained from the charge associated with the adsorbed butein oxidation peaks, which are in agreement with those values expected for the formation of a monolayer of adsorbate in the concentration range from 1 to 5μM. Square wave voltammetry was used to perform a full thermodynamic and kinetics characterization of the butein surface redox couple. Therefore, from the combination of the "quasi-reversible maximum" and the "splitting of the net square wave voltammetric peak" methods, values of (0.386±0.003) V, (0.46±0.04), and 2.7×10(2)s(-1) were calculated for the formal potential, the anodic transfer coefficient, and the formal rate constant, respectively, of the butein overall surface redox process in pH4.00 citrate buffer solutions. These results will be then used to study the interaction of butein, and other flavonoids with the deoxyribonucleic acid, in order to better understand the potential therapeutic applications of these compounds.


Reliability of Entire Corneal Thickness Mapping in Normal Post-Laser in situ Keratomileusis and Keratoconus Eyes Using Long Scan Depth Spectral Domain Optical Coherence Tomography.
To investigate the repeatability and reproducibility of mapping the entire corneal thickness using spectral domain optical coherence tomography (SD-OCT). Thirty normal eyes, 30 post-laser in situ keratomileusis (LASIK) surgery eyes, and 30 keratoconus eyes were analyzed. A custom-built long scan depth SD-OCT device was used to obtain entire corneal images. Ten-millimeter-diameter corneal thickness maps were generated by an automated segmentation algorithm. Intraclass correlation coefficients of repeatability (ICC1) and reproducibility (ICC2), and coefficients of repeatability (CoR1) and reproducibility (CoR2), were calculated to quantify the precision and accuracy of corneal pachymetry measurements using the Bland-Altman method. For SD-OCT measurements in healthy subjects, CoR1 and CoR2 were less than 5.00 and 5.53 μm. ICC1 and ICC2 were more than 0.997 and 0.996. For SD-OCT measurements in LASIK patients, CoR1 and CoR2 were less than 5.09 and 5.34 μm. ICC1 and ICC2 were more than 0.997 and 0.996. For SD-OCT measurements in keratoconus patients, CoR1 and CoR2 were less than 11.57 and 10.92 μm. ICC1 and ICC2 were more than 0.995 and 0.996. The measurements of corneal pachymetric mapping by long scan depth SD-OCT can be assessed over the entire corneal area with good repeatability and reproducibility.


Intranasal lidocaine to prevent headache following migraine aura.
To report the consistent effect of intranasal lidocaine 4% on preventing headache following aura in one individual. A treatment that could prevent the headache which follows an aura would be an important advance in the treatment of migraine. No migraine abortive treatment has been shown to have such an effect. A 15-year-old adolescent boy with a history of recurrent headache since aged 2, fulfilling the criteria for migraine with aura, was seen in consultation. Intranasal lidocaine 4% was used during the aura phase to prevent the headaches. Before using intranasal lidocaine, the patient invariably experienced a migraine following a typical visual aura. The episodes occurred approximately weekly, with a stable pattern for several years. When given during the aura, intranasal lidocaine prevented the headache following the aura, and remained successful on all but two occasions over 1 1/2 years of use (approximately 75 episodes). There was no effect on the duration of the aura itself. Intranasal lidocaine consistently prevented the development of headache symptoms following aura in this individual. Such an effect suggests a role for the sphenopalatine ganglion in the development of migraine pain.


Domperidone-induced tardive dyskinesia and withdrawal psychosis in an elderly woman with dementia.
To report a case of probable domperidone-induced tardive dyskinesia and withdrawal psychosis in an elderly woman. A 75-year-old woman was first assessed for cognitive decline and personality changes. On clinical examination, diffuse choreoathetoid movements were noted. Chronic domperidone use seemed the most likely cause for the movement disorder and was abruptly discontinued. Within a few days, she developed a severe psychotic syndrome with Capgras delusions; the movement disorder continued unabated. Both the movement disorder and psychotic symptoms promptly remitted with risperidone treatment. Domperidone has, on rare occasions, been associated with acute extrapyramidal syndromes, especially in young children, but, to our knowledge, this is the first case of domperidone-induced tardive dyskinesia and withdrawal psychosis, adverse effects associated with chronic central nervous system dopaminergic blockade. Domperidone is a dopamine D₂ receptor antagonist that does not usually cross the blood-brain barrier. However, blood-brain barrier alterations occur with aging and dementia, which may explain central nervous system penetration of domperidone in our patient, diagnosed with probable frontotemporal dementia. The association was rated as probable on the Naranjo probability scale. Chronic use of domperidone may, on rare occasions, induce neuropsychiatric syndromes similar to those seen with the use of antipsychotics. This may be more likely in situations in which the blood-brain barrier is damaged, as in vascular and degenerative dementias.


Myocardial ischemia: correlation of mitochondrial adenine nucleotide and respiratory function.
State 3 respiration of rat heart mitochondria decreased approximately 60% after 20 min normothermic in vitro ischemia. After 20 min ischemia, the levels of intramitochondrial adenine nucleotides (ATP + ADP + AMP) decreased to approximately 20% of control values, with a rapid loss between 10 and 20 min. Also, the exchangeable adenine pool of the mitochondria decreased 60% after 20 min ischemia. State 4 respiration was not affected by the ischemic insult. The adenine nucleotide translocase activities of mitochondria from control and ischemic hearts were too high to measure accurately. Therefore, the effects of ischemia on adenine nucleotide translocase activity could not be established. However, 1 microM carboxyatractyloside did not impair state 3 respiration of control mitochondria, but did inhibit the adenine translocase activity by at least 80%. Moreover, titration of state 3 respiration with carboxyatractyloside produced sigmoidal curves for mitochondria from control and ischemic tissue. State 3 respiration correlated well with the total mitochondrial adenine nucleotides and the exchangeable adenine pool (r = 0.63 and 0.78, respectively). Data collected from isolated perfused rat hearts also showed a good correlation between state 3 respiration and the exchangeable adenine nucleotides (r = 0.92). In this study, mitochondria were isolated from hearts that were either perfused, made ischemic for 30 min by aortic cross-clamp, or reperfused for 10 min after the aortic cross-clamp. The slopes and y-intercepts of the regression lines were similar for the in vitro ischemic and the perfusion studies. There was no significant difference between the effects of ischemia on the state 3 and uncoupled respiratory rates.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood concentrations of everolimus are markedly increased by ketoconazole.
The authors sought to quantify the influence of the CYP3A and P-glycoprotein inhibitor ketoconazole on the pharmacokinetics of everolimus in healthy subjects. This was a 2-period, single-sequence, crossover study in 12 healthy subjects. In period 1, subjects received the reference treatment of a single 2-mg dose of everolimus. In period 2, they received the test treatment of ketoconazole 200 mg twice daily for a total of 8 days and a single dose of everolimus coadministered on the fourth day of ketoconazole therapy. The test/reference ratio and 90% confidence interval were derived for everolimus maximum concentration and area under the curve. During ketoconazole coadministration, everolimus maximum concentration increased 3.9-fold (90% confidence interval, 3.4-4.6) from 15 +/- 4 ng/mL to 59 +/- 13 ng/mL. Everolimus area under the curve increased 15.0-fold (90% confidence interval, 13.6-16.6) from 90 +/- 23 ng*h/mL to 1324 +/- 232 ng*h/mL. Everolimus half-life was prolonged by 1.9-fold from 30 +/- 4 hours to 56 +/- 5 hours. Everolimus did not appear to alter ketoconazole predose concentrations. Given the magnitude of this drug interaction, use of ketoconazole should be avoided if possible in everolimus-treated patients.


An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings.
An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.


Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence.
Acetylcholinesterase, an essential enzyme of the nervous system, rapidly terminates the action of acetylcholine released into the synapse. Acetylcholinesterase is also found (in lower abundance) in extrajunctional areas of muscle and nerve and on erythrocyte membranes. Hydrodynamic analyses of the native enzyme and characterization of its dissociated subunits have revealed multiple enzyme forms which can be divided into two classes: dimensionally asymmetric forms which are usually found within the synapse and contain a collagen-like structural subunit disulphide-linked to the catalytic subunits; and globular forms which appear to be widely distributed on the outer surface of cell membranes. Both forms have been characterized in the ray Torpedo californica and, although their catalytic behaviours seem to be identical, they differ slightly in amino-acid composition, peptide maps and reactivity with certain monoclonal antibodies. Here, we report the complete amino-acid sequence of an acetylcholinesterase inferred from the sequence of a complementary DNA clone. The 575-residue protein shows significant homology with the C-terminal portion of thyroglobulin.


Empirical investigation of two assumptions in the diagnosis of DSM-IV major depressive episode.
The aim of the current study was to examine two major assumptions behind the DSM-IV diagnosis of major depressive episode (MDE): that depression represents a distinct category defined by a valid symptom threshold, and that each depressive symptom contributes equally to the diagnosis. Data were from the Australian National Survey of Mental Health and Wellbeing. Participants consisted of a random population-based sample of 10 641 community volunteers, representing a response rate of 78%. DSM-IV diagnoses of MDE and other mental disorders were obtained using the Composite International Diagnostic Interview, version 2.0. Analyses were carried out on the subsample of respondents who endorsed either depressed mood or loss of interest (n =2137). Multivariate linear regression analyses examined the relationship between the number and type of symptoms and four independent measures of impairment. The relationship between the number of depressive symptoms and the four measures of impairment was purely linear. Three individual symptoms (sleep problems, energy loss, and psychomotor disturbance) were all independent predictors of three of the four measures of impairment. Counting symptoms alone is limited in guiding a clear diagnostic threshold. The differential impact of individual symptoms on impairment suggests that impairment levels may be more accurately estimated by weighting the particular symptoms endorsed.


Interaction in vivo and in vitro between the yeast fimbrin, SAC6P, and a polymerization-defective yeast actin (V266G and L267G).
A mutant yeast actin (GG) has decreased hydrophobicity in a subdomain 3/4 hydrophobic plug believed to be involved in a hydrophobic cross-strand "plug-pocket" interaction necessary for actin filament stability. This actin will not polymerize in vitro but is compatible with cell viability. We have assessed the ability of Sac6p, the yeast homologue of the actin filament stabilizing and bundling protein fimbrin, to restore polymerization in vitro and to facilitate GG-actin function in vivo. Sac6p rescues GG-actin polymerization at 25 degrees C but not at 4 degrees C. The actin polymerizes into bundles at room temperature with a fimbrin:actin molar ratio of 1:4. At this ratio, every actin monomer contacts a Sac6p actin binding domain. Following cold-induced depolymerization, actin/Sac6p mixtures repolymerize beginning at 15 degrees C instead of the 25 degrees C required for de novo assembly, because of the presence of residual actin-Sac6p nuclei. Generation of haploid Deltasac6/GG-actin cells from either diploid or haploid cells was unsuccessful. The facile isolation of cells with either mutation alone indicates a synthetic lethal relationship between this actin allele and the SAC6 gene. Sac6p may allow GG-actin function in vivo by stabilizing the actin in bundles thereby helping maintain sufficient levels of an otherwise destabilized actin monomer within the cell.


Molecular systematics and evolution of Regina and the thamnophiine snakes.
Snakes of the tribe Thamnophiini represent an ecologically important component of the herpetofauna in a range of habitats across North America. Thamnophiines are the best-studied colubrids, yet little is known of their systematic relationships. A molecular phylogenetic study of 32 thamnophiine species using three complete mitochondrial genes (cytochrome b, NADH dehydrogenase subunit 2, and 12S ribosomal DNA) recovered a well-supported phylogeny with three major clades: a garter snake group, a water snake group, and a novel semifossorial group. The historically contentious genus Regina, which contains the crayfish-eating snakes, is polyphyletic. The phylogeographic pattern of Thamnophis is consistent with an hypothesis of at least one invasion of northern North America from Mexico.


Matrix Metalloproteinase 14 Overexpression Is Correlated with the Progression and Poor Prognosis of Nasopharyngeal Carcinoma.
Matrix metalloproteinase 14 (MMP14) has been identified to play a significant role in several types of cancers, but little is known about the significance of MMP14 in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to explore the association of MMP14 expression with clinicopathologic features and prognosis in NPC. MMP14 mRNA and protein expressions were examined in NPC and nasopharyngeal tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of MMP14 expression levels with clinical features and prognosis of NPC patients was analyzed. MMP14 mRNA expression was markedly higher in NPC tissues than in nasopharyngeal epithelium tissues (p = 0.002). Using immunohistochemistry, staining for MMP14 protein was found in the normal nasopharyngeal epithelial cells and malignant epithelial cells, but increased expression of MMP14 was observed in NPC samples compared with normal nasopharyngeal epithelium samples (p = 0.027). In addition, high levels of MMP14 protein were positively correlated with the status of clinical stage (p = 0.009), N classification (p = 0.006), and distant metastasis (p = 0.005) of NPC patients. Patients with higher MMP14 expression had a significantly shorter overall survival time than did patients with low MMP14 expression. Multivariate analysis indicated that the level of MMP14 expression was an independent prognostic indicator (p < 0.001) for the survival of patients with NPC. MMP14 overexpression is a potentially unfavorable prognostic factor for NPC patients.


Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins.
Epidemiological studies suggest that statins reduce the risk of developing Alzheimer disease. Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing of amyloid precursor protein. To our knowledge, the mechanism for statins in risk reduction of Alzheimer disease is unknown. To test the effect of statin treatment on beta-amyloid (A beta) metabolism in humans. A prospective, randomized, dose-finding 36-week treatment trial with statins. Plasma samples were taken at baseline (week 0) and at weeks 6, 12, and 36. Outpatient clinical study at a university hospital. Thirty-nine patients who met the criteria for hypercholesterolemia. Patients were randomized to oral treatment with either simvastatin or atorvastatin calcium according to the following regimen: simvastatin, 40 mg/d, or atorvastatin, 20 mg/d, for 6 weeks; followed by simvastatin, 80 mg/d, or atorvastatin, 40 mg/d, for 6 weeks; and finally, simvastatin, 80 mg/d, or atorvastatin, 80 mg/d, for 24 weeks. Plasma levels of A beta(1-40) and A beta(1-42) were measured using 2 enzyme-linked immunosorbent assays, and total A beta was quantified by Western blotting. Treatment with both statins reduced total plasma cholesterol levels by 56% (P =.00). The plasma levels of A beta(1-40), A beta(1-42), and total A beta were stable in individual patients during the treatment period. No significant change in the level of A beta(1-40), A beta(1-42), or total A beta was found. This study questions the effect of statins on the processing of amyloid precursor protein in humans.


Mechanics of increased support of weight by the hindlimbs in primates.
Quadrupedal primates support most of their weight on their hindlimbs during locomotion. Neither the position of their center of gravity nor the average position of their foot contacts is substantially different from that of other quadrupeds supporting most of their weight on their forelimbs. Arguments are presented to support the theory that high levels of hindlimb retractor activity will produce this shift of support to the hindlimbs. If this muscular activity is appropriately timed, it will generate only low horizontal accelerations, which can be offset by small changes in the average position of the limbs. Estimates of muscular force are derived from force plate and kinematic data, which indicate that primates in fact do exhibit the postulated pattern of muscular activity. It is suggested that this shift occurs to reduce the compressive forces on the forelimbs.


Electron-induced chemistry of 5-chlorouracil.
Dissociative electron attachment to 5-chlorouracil cannot proceed directly , since the dissociative σ* state is too short-lived and autodetachment occurs rapidly. Effcient fragmentation of the chlorouracil anion radical is only possible if a nondissociative π* state is formed initially that undergoes an intersection with the σ* state at an elongated C-Cl distance.


Improving Small RNA-seq: Less Bias and Better Detection of 2'-O-Methyl RNAs.
The study of small RNAs (sRNAs) by next-generation sequencing (NGS) is challenged by bias issues during library preparation. Several types of sRNA such as plant microRNAs (miRNAs) carry a 2'-O-methyl (2'-OMe) modification at their 3' terminal nucleotide. This modification adds another difficulty as it inhibits 3' adapter ligation. We previously demonstrated that modified versions of the 'TruSeq (TS)' protocol have less bias and an improved detection of 2'-OMe RNAs. Here we describe in detail protocol 'TS5', which showed the best overall performance. TS5 can be followed either using homemade reagents or reagents from the TS kit, with equal performance.


Gallium Bromide-Promoted Dearomative Indole Insertion in 3-Indolylmethanols: Chemoselective and (Z/E)-Selective Synthesis of 3,3'-Bisindole Derivatives.
Gallium bromide (GaBr3)-promoted dearomative indole insertion in 3-indolylmethanols has been established, which chemoselectively constructs a biologically important 3,3'-bisindole framework bearing an all-carbon quaternary center in high yields and excellent (Z)-selectivities (up to 99% yield, all >95:5 Z/E). The reaction pathway was suggested to include a tandem sequence of Michael addition/C-C bond cleavage/nucleophilic addition, wherein the strong acidity of GaBr3 played a crucial role in the key step of C-C bond cleavage. This reaction not only provides a new strategy for dearomatization of indoles, but also represents a new reaction category for 3-indolylmethanols, which involves a rarely reported late-stage C-C bond cleavage of 3-indolylmethanol derivatives. In addition, this approach also offers an efficient method for the synthesis of biologically important 3,3'-bisindole derivatives.


Is popular radio a source of exposure to alcohol references in mid to later life? A content analysis.
There is concern around alcohol consumption in mid to later life yet little understanding about what influences this behaviour. No previous research has explored the extent to which adults in mid to later life may be exposed to alcohol references in the media. This project aimed to determine the frequency of alcohol references on radio stations with a high proportion of listeners in mid to later life. Content analysis of alcohol references on four popular UK music-based radio stations with a high proportion of listeners aged 55-64 years over three time points. Alcohol references occur frequently, but vary by time of year and type of radio station. When alcohol is mentioned its consumption is portrayed as the norm, without negative consequences. On three commercial stations, the majority of mentions came from advertising, whereas on BBC Radio 2 nearly all references were talk-based. All adverts for direct promotion of alcohol were by supermarkets. Alcohol was frequently associated with celebrations, socializing or something to consume for its own sake. Adults in the age group 55-64 may be exposed to references to alcohol that could serve to reinforce norms of consumption of alcohol and promote purchases of cheap alcohol.


Comparison between bolus injection and infusion of secretin and pancreozymin in the diagnosis of chronic pancreatic disease (one hour test).
There is no agreement in the literature as regards the carrying out of the Secretin-Pancreozymin test in order to achieve the greatest accuracy in the diagnosis of pancreatic insufficiency. In this study the results obtained by bolus i.v. injection of Secretin and Pancreozymin GIH are compared with those obtained by i.v. infusion of the hormones. The test - always prolonged for one hour - was done in 125 subjects, divided into two groups matched for sex, age and pancreatic or digestive disease. Volume, pH, bicarbonates, calcium and amylase were measured in the juice collected. The results showed that bolus i.v. injection of Secretin and Pancreozymin has greater diagnostic sensitivity (94%) than the infusion method (84%). If infusion is used, it is necessary to protract the test for more than one hour.


Anti-inflammatory effects by transdermal application of triamcinolone acetonide gel using phonophoresis in rats.
The present study was carried out to determine the feasibility of using gel formulations for the transdermal delivery of triamcinolone acetonide (TA), which is one of the synthetic glucocorticoids, in conjunction with phonophoresis, and to develop the carbopol gels of TA. For this purpose, the anti-inflammatory effects of the gel containing TA after the adoption of ultrasound were evaluated by investigating the in vivo change in the serum creatine phosphokinase (CPK) and histological findings. Following a muscle injury, the serum CPK activity decreased significantly in the TA gel group with phonophoresis, comparing with that in the control group and the commercial gel group given ultrasound. In the gross finding, after a muscle injury, the TA gel group with phonophoresis showed rapid moderation of the injury compared with the three other groups. The histological findings showed that the inflammation was relieved within 72 h after the injury from the TA gel group with phonophoresis. These effects were considerably higher in the phonophoresis group than in the other three groups. Overall, a TA gel using phonophoresis might be used as a new transdermal delivery technique providing enhanced anti-inflammatory effects.


Effect of desialylated human chorionic gonadotropin (hCG) on the bioactivity of rat Leydig cells.
Human chorionic gonadotropin is a glycoprotein hormone that, like LH, stimulates steroidogenesis in gonadal cells. Using a desialylation process. 95 per cent of the sialic acid residues from an intact standard hCG molecule were eliminated and then the electrophoretic properties and the bioactivity of the desialylated hCG were determined. Using rat Leydig cells as a biological model, the binding affinity to LH receptors of Leydig cell membranes, steroidogenic activity and second messenger production were studied. The results indicate that the loss of sialic acid from the hCG molecule slightly increases the binding activity to LH receptors and results in steroidogenic activity with an increased ED50. Cyclic AMP production was significantly reduced however and arachidonic acid release was not observed. Several possible mechanisms that could explain these results are discussed.


Vascular pattern of the mammalian ovary with special reference to the three-dimensional architecture of the spiral artery.
Casts of blood vessels in the ovaries of the female rat, pig and monkey were made with methacrylate, dissected out under a dissecting microscope and observed in a scanning electron microscope (SEM). The ovarian arteries and their branches were characterized by the presence of a spiral configuration. The spiral course of the arteries, however, varied greatly in detail among the different species. The arteries in the pig and monkey ovaries had tightly spiraling configurations, while there was only an image suggestive of a spiral in the rat ovarian arteries. The former species showed a rich plexus of the spiral arteries in the hilus and medulla of the organ. Their branches straightened at the transitional region between the medulla and cortex but again showed spiral configurations in the cortex. Further, the arterial branches supplying the growing and mature follicles showed a much more marked extent to the spiral configurations as compared with those of the corpus luteum. In this paper morphological findings shall be discussed in correlation with their physiological implications.