Inhibition of human TREK-1 channels by caffeine and theophylline.
Caffeine (1,3,7-trimethylxanthine) and theophylline (1,3-dimethylxanthine) are used for therapeutic purposes and can cause life-threatening convulsive seizures due to systemic toxicity. The mechanisms for the epileptogenicity of caffeine and theophylline are not clear. TWIK-related K(+) channels (TREK-1) are highly expressed in the human central nervous system and have a major role in the control of neuronal excitability by regulating the resting membrane potential. In view of their physiological significance, inhibition of TREK-1 channels may be implicated in caffeine- and theophylline-induced seizures. We thus investigated, using whole-cell patch-clamp technique, modulation of hTREK-1 channels expressed in Chinese hamster ovary (CHO) cells by caffeine and theophylline. Caffeine and theophylline produced reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC(50)) for caffeine and theophylline were 377+/-54microM and 486+/-76microM, respectively. Caffeine and theophylline depolarized the membrane potential of CHO(TREK-1) cells in a reversible and concentration-dependent manner. Inhibition by caffeine (5mM) and theophylline (2mM) was attenuated in TREK-1 channels with mutation of the PKA consensus sequence at serine 348, suggesting the involvement of cAMP/PKA pathway in the inhibitory process. Inhibition of TREK-1 channels and consequent membrane depolarization may contribute to the convulsive seizures induced by toxic levels of caffeine and theophylline.


Fixed- versus mobile-bearing total knee arthroplasty in Indian patients.
To compare the mid-term clinical outcomes in Indian patients after total knee arthroplasty (TKA) using a fixed- or mobile-bearing prosthesis. 120 consecutive patients (50 men and 70 women) aged 55 to 76 (mean, 63) years who had arthritis of the knee with similar deformity and range of motion were randomised to undergo TKA using a fixed- or mobile-bearing prosthesis. Patients with mediolateral instability and infective arthritis were excluded. Knee Society knee and functional scores, range of motion, and the presence of flexion contracture were assessed. The mean follow-up duration was 3.5 (range, 1-4.6) years. The mid-term outcome of the 2 groups was comparable. One patient with a mobile-bearing prosthesis had recurrent dislocation at postoperative week 2, owing to iatrogenic medial collateral ligament injury. Long-term studies of both functional and radiological outcomes are needed to determine the indications for fixed- versus mobile-bearing prostheses.


Consequences of legislative restriction on the sale of compound analgesics in Newcastle (N.S.W., Australia).
In June 1979 legislation was enacted in New South Wales to restrict the sale of compound analgesics. The consequences of this legislation were assessed by a household survey in Newcastle, New South Wales, during November 1979. This survey followed an identical survey in the same community in November 1977. After legislation, a marked decrease was found in the proportion of homes having compound analgesics. A small decrease in total analgesic usage was also observed, though this was not necessarily related to the legislative restrictions. The legislative restrictions did not result in any substantial increase in use of the doctor to obtain prescriptions for compound analgesics, or any substantial increase in reported health problems. The results suggest that legislation is an effective method of inducing rapid change in health-related behavior.


(R)-12-Hydroxystearic Acid Hydrazides as Very Efficient Gelators: Diffusion, Partial Thixotropy, and Self-Healing in Self-Standing Gels.
The gelation properties of derivatives of N-alkylated (R)-12-hydroxystearic acid hydrazide (n-HSAH, n=0, 2, 6, 10; n is the length of an n-alkyl chain on the terminal nitrogen atom) in a wide variety of liquids is reported. The n-HSAH compounds were derived from a naturally occurring alkanoic acid, (R)-12-hydroxystearic acid (R-12HSA), and although they differ from the analogous N-alkyl (R)-12-hydroxystearamides (n-HSAA) only by the presence of one N-H group, their behavior as gelators is very different. For example, the parent molecule (0-HSAH) is a supergelator in ethylene glycol, in which it forms self-standing gels that are self-healing, partially thixotropic, moldable, and load-bearing; gels of 0-HSAA are not self-standing. 0-HSAH is structurally the simplest molecular gelator of which we are aware that is capable of forming both self-standing and partially thixotropic gels. Also, diffusion of the cationic dye erythrosine B and the anionic dye methylene blue in 0-HSAH/ethylene glycol gel blocks is much slower than the self-diffusion of ethylene glycol. Polarizing optical microscopy, X-ray diffraction, and FTIR studies revealed that the self-assembled fibrillar networks (SAFINs) of the gels are crystalline, and that 0-HSAH molecules may be arranged in a triclinic subcell with bilayer stacking. The SAFINs are stabilized by strong hydrogen-bonding interactions between the hydrazide groups of adjacent molecules and a perpendicular hydrogen-bonding network between the pendent hydroxyl groups of 0-HSAH. The other n-HSAH (n=2, 6, 10) molecules appear to be arranged in orthorhombic subcells with monolayers and strong hydrogen-bonding interactions between the hydrazide group of one gelator molecule and the hydroxyl group of a neighboring one. These results show how small structural modifications of structurally simple gelator molecules can be exploited to form gels with novel properties that can lead potentially to valuable applications, such as in drug delivery.


Treatment of Hemophilus vaginalis vaginitis.
Four antimicrobial agents (triple sulfa cream, doxycycline, ampicillin, and metronidazole) were studied by double-blind techniques to determine their effectiveness in the treatment of Hemophilus vaginalis vaginitis, documented by vaginal culture in 96 patients. Cure was confirmed by negative vaginal cultures 7 weeks after the start of therapy. Metronidazole proved to be effective in 20 of 22 couples (90.9%) treated. Sulfa cream, doxycycline, and ampicillin were effective in 47.8 to 63.6% of patients treated.


Interleukin-6 suppression of neutrophil apoptosis is neutrophil concentration dependent.
Apoptosis of polymorphonuclear leukocytes (PMNs) is a critical step in the resolution of tissue inflammation. PMN apoptosis has been studied extensively in vitro, and diverse inflammatory mediators have been shown to modulate the process. The reported effects of interleukin-6 (IL-6) on PMN apoptosis are inconsistent; however, analysis of published studies reveals at least one discriminating factor--the use of varied concentrations of PMNs in the experimental design. Consequently, we hypothesized that the in vitro effects of IL-6 on PMN apoptosis varied with the concentration of PMNs in culture. PMNs isolated from healthy human donors were cultured at concentrations from 1 to 20 x 10(6)/mL, and incubated with IL-6 doses from 1 to 100 ng/mL. PMNs cultured at 1-5 x 10(6)/mL were unaffected by IL-6; in contrast, IL-6 inhibited apoptosis in PMNs cultured at 10-20 x 10(6)/mL, compared with untreated similarly concentrated PMNs. These data suggest caution in interpreting in vitro studies of apoptosis; on the other hand, appropriately designed experiments may help elucidate the regulation of apoptosis in vivo.


Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals.
Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.


Does health-related quality of life improve in women following gynaecological surgery?
To measure the change in health-related quality of life (HRQOL) before and after gynaecologic surgery and to compare HRQOL to age-matched Canadian normative data. This prospective observational cohort study consisted of a convenience sample of 460 women scheduled for elective gynaecologic surgery. Women underwent surgery for a variety of reasons, including cancer, menorrhagia/dysfunctional uterine bleeding, benign uterine masses, prolapse or urinary incontinence, and chronic pelvic pain syndromes. Women were recruited preoperatively and followed for six months after surgery. HRQOL questionnaires were completed preoperatively and at six weeks and six months postoperatively, using the SF-36, and compared between time points and against normative data. Analysis included univariate statistics, repeated measures ANOVA, paired t tests, and independent samples t tests. The mean age of women in the study cohort was 49 years (± 11); the majority were married, employed, had an education beyond high school, were overweight or obese, had a hysterectomy, and had an abdominal incision. Twenty-eight percent underwent surgery for cancer. General and mental health domains showed significant improvement between the preoperative and six-week postoperative assessments, while the remaining domains showed statistically significant declines. All but one (general health) of 10 outcomes saw significant improvements from the preoperative to the six-month follow-up assessment. Preoperatively, the surgical sample scored worse on all but one (role emotional) outcome than the normative data. By six months, domain scores were much closer to normative values. Health-related quality of life improved considerably from the preoperative period to six months postoperative in women who underwent gynaecologic surgery. When compared with normative data from age-matched women, the surgical sample reported significantly reduced HRQOL preoperatively and at six weeks following surgery, but by six months after surgery HRQOL had rebounded to the point of being comparable to age-matched peers.


Excited-state dynamics of guanosine in aqueous solution revealed by time-resolved photoelectron spectroscopy: experiment and theory.
Time-resolved photoelectron spectroscopy is performed on aqueous guanosine solution to study its excited-state relaxation dynamics. Experimental results are complemented by surface hopping dynamic simulations and evaluation of the excited-state ionization energy by Koopmans' theorem. Two alternative models for the relaxation dynamics are discussed. The experimentally observed excited-state lifetime is about 2.5 ps if the molecule is excited at 266 nm and about 1.1 ps if the molecule is excited at 238 nm. The experimental probe photon energy dependence of the photoelectron kinetic energy distribution suggests that the probe step is not vertical and involves a doubly-excited autoionizing state.


Fetal surveillance in late pregnancy and during labor.
During early gestation, drugs have teratogenic effects and can be associated with structural anomalies in the fetus. Substance abuse can also have physiologic effects on the mother and fetus, including decreased uterine blood flow, increased vascular resistance, and an increase in fetal blood pressure. Women at increased risk for stillbirth should undergo antepartum fetal surveillance initiated at 32 weeks of gestation. Because of the high incidence of low birth weight, fetal anomalies, preterm delivery, and growth restriction in these patients, ultrasonography for appropriate pregnancy dating, a detailed anatomic survey, and cervical length should be performed at 20 weeks' gestation.


Contingency management treatments: Reinforcing abstinence versus adherence with goal-related activities.
Contingency management (CM) interventions usually reinforce submission of drug-negative specimens, but they can also reinforce adherence with goal-related activities. This study compared the efficacy of the 2 approaches. Substance-abusing outpatients (N = 131) were randomly assigned to 1 of 3 12-week treatments: standard treatment (ST), ST with CM for submitting negative urine toxicology screens, or ST with CM for completing goal-related activities. CM patients remained in treatment longer and achieved more abstinence than ST patients, but the CM condition that reinforced submission of negative samples resulted in better outcomes than the CM condition that reinforced goal-related activities. Abstinence at 6- and 9-month follow-ups did not differ by group, but longest duration of abstinence achieved during treatment was associated with abstinence posttreatment.


Effect of preperfusion of lead and aminophylline on digoxin cardiotoxicity.
An attempt has been made to investigate the cardiotoxicity of an interaction of Lead acetate (LA), Aminophylline (APH) and Digoxin (DGN), employing an isolated frog heart preparation. While DGN-Cardiotoxicity was potentiated by LA-preperfusion, it was antagonized by APH-preperfusion as revealed by data reflecting the mean DGN perfusion time (Sec) and mean DGN exposure (microgram/10 mg heart weight) for cardiac arrest. In an experimental group involving interaction of LA, DGN and APH, preperfusion of APH has significantly diminished but not fully abolished LA-induced potentiation of DGN-cardiotoxicity. On the other hand, perfusion of APH after LA resulted not only in annulment of LA-induced potentiation but also in an eventual residual protective effect of APH. It was striking that simultaneous preperfusion of APH and LA led to exacerbation of LA-induced potentiation. The results of this interaction study involving two widely prescribed cardioactive drugs, are considered to be of immense pharmaco-toxicological interest.


Rethinking assimilation theory for a new era of immigration.
"We argue that assimilation theory has not lost its utility for the study of contemporary immigration to the United States. In making our case, we review critically the canonical account of assimilation provided by Milton Gordon and others; we refer to Shibutani and Kwan's theory of ethnic stratification to suggest some directions to take in reformulating assimilation theory. We also examine some of the arguments frequently made to distinguish between the earlier mass immigration of Europeans and the immigration of the contemporary era and find them to be inconclusive. Finally, we sift through some of the evidence about the socioeconomic and residential assimilation of recent immigrant groups. Though the record is clearly mixed, we find evidence consistent with the view that assimilation is taking place, albeit unevenly."


A parametric approach to measuring limbus corneae from digital images.
It is difficult to demarcate the limbus borders in standard intensity images of the eye since the transition from the cornea (iris) to sclera is gradual. Non-parametric techniques that are currently used for this task are not sufficiently precise to be adopted in those ophthalmic applications where high precision in determining the limbus/pupil characteristics is required. This is the case, for example, in customized refractive corrections. Another aspect of limbus corneae characterization is the inability of measuring in vivo the outer outline of the limbus annulus without specialized illumination techniques. To overcome these limitations, we propose a parametric approach that utilizes a sigmoidal function fitted to radial intensity profiles of the limbus corneae. By the way of simulations, we show the superiority of the proposed parametric approach when compared to an optimized nonparametric technique. Further, we review the techniques for fitting ellipses to the estimated points of the limbus annulus and discuss clinical aspects of the proposed methodology. Initial clinical experiments showed close agreement between the proposed approach and limbus corneae estimates manually obtained by experienced clinicians.


To thine own self be true? Clarifying the effects of identity discrepancies on psychological distress and emotions.
After many years of research across disciplines, it remains unclear whether people are more motivated to seek appraisals that accurately match self-views (self-verification) or are as favorable as possible (self-enhancement). Within sociology, mixed findings in identity theory have fueled the debate. A problem here is that a commonly employed statistical approach does not take into account the direction of a discrepancy between how we see ourselves and how we think others see us in terms of a given identity, yet doing so is critical for determining which self-motive is at play. We offer a test of three competing models of identity processes, including a new "mixed motivations" model where self-verification and self-enhancement operate simultaneously. We compare the models using the conventional statistical approach versus response surface analysis. The latter method allows us to determine whether identity discrepancies involving over-evaluation are as distressing as those involving under-evaluation. We use nationally representative data and compare results across four different identities and multiple outcomes. The two statistical approaches lead to the same conclusions more often than not and mostly support identity theory and its assumption that people seek self-verification. However, response surface tests reveal patterns that are mistaken as evidence of self-verification by conventional procedures, especially for the spouse identity. We also find that identity discrepancies have different effects on distress and self-conscious emotions (guilt and shame). Our findings have implications not only for research on self and identity across disciplines, but also for many other areas of research that incorporate these concepts and/or use difference scores as explanatory variables.


Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany.
In a case-control study, we investigated the possible etiologic relevance to Parkinson's disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case-control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.


Turkish children's Bender-Gestalt Test performance: a pilot study and preliminary norms.
The present study was undertaken to provide preliminary data for norms on the Bender-Gestalt Test for 253 children ages 5 yr., 5 mo. to 11 yr., 10 mo. in Turkey. The Koppitz Developmental Scoring System gave mean error scores of 4.2 (SD = 3.3) for girls and 3.6 (SD = 3.0) for boys. The mean error scores obtained by all age groups are presented and compared with other cross-cultural data. These scores decreased across age groups, supporting Bender's maturational hypothesis of the test. The present sample performed at a higher developmental level than the Koppitz normative sample for the 5- and 6-year age groups, while means for other age groups were similar to the original U.S. norms. That this pattern is supported in other cross-cultural studies is discussed as well as the importance of developing local norms for visual spatial tests.


Acute intracerebral haemorrhage: circadian and circannual patterns of onset.
Hypothesis of the circannual and circadian variation in onset of intracerebral haemorrhage (CH) was verified, by means of single cosinor method and chi-square test for goodness of fit, in 161 consecutive patients (94 men and 67 women) admitted into the Institute of Neurosurgery of Ferrara Hospital, Italy, over 9 years. The majority of CH occurred in the morning between 06.00 AM and 12.00 noon (36.7% of cases, p < 0.001); when considering the specific anatomical sites, typical supratentorial haemorrhages showed a similar pattern (37.4%, p = 0.01). A similar morning behavior was found when considering subgroups by sex (men 36.2%, women 37.3%), age > or = 60 years (42.5%), no presence of hypertension (39.7%), no presence of diabetes mellitus (33.3%) and non-smokers (30.4%). The results by cosinor analysis yielded a circadian rhythmicity both for total sample and, for the men's subgroup, with a morning peak at 11.44 and 11.25, respectively. For women, however, spectral analysis found a significant ultradian cycle, having a period of 12 h (p = 0.01). A circannual periodicity, with a prevalent peak in February, was found for total sample and males subgroups, too. The results of this study confirm that intracerebral haemorrhages present a characteristic circadian and circannual pattern in onset.


Magnetic cylindrical colloids at liquid interfaces exhibit non-volatile switching of their orientation in an external field.
We study the orientation of magnetic cylindrical particles adsorbed at a liquid interface in an external field using analytical theory and high resolution finite element simulations. Cylindrical particles are interesting since they possess multiple locally stable orientations at the liquid interface so that the orientational transitions induced by an external field will not disappear when the external field is removed, i.e., the switching effect is non-volatile. We show that, in the absence of an external field, as we reduce the aspect ratio α of the cylinders below a critical value (αc≈ 2) the particles undergo spontaneous symmetry breaking from a stable side-on state to one of two equivalent stable tilted states, similar to the spontaneous magnetisation of a ferromagnet going through the Curie point. By tuning both the aspect ratio and contact angle of the cylinders, we show that it is possible to engineer particles that have one, two, three or four locally stable orientations. We also find that the magnetic responses of cylinders with one or two stable states are similar to that of paramagnets and ferromagnets respectively, while the magnetic response of systems with three or four stable states are even more complex and have no analogs in simple magnetic systems. Magnetic cylinders at liquid interfaces therefore provide a facile method for creating switchable functional monolayers where we can use an external field to induce multiple non-volatile changes in particle orientation and self-assembled structure.


YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations.
Endometrial stromal sarcomas represent the second most common mesenchymal uterine tumor. The 2003 WHO classification distinguishes low-grade and undifferentiated endometrial stromal sarcomas with different prognoses. Endometrial stromal sarcomas are a genetically heterogeneous group of sarcomas harboring different cytogenetic anomalies. Recently, a fusion between the YWHAE and FAM22A/B genes subsequent to a t(10;17) (q22;p13) has been described in endometrial sarcomas with high-grade histology. We examined YWHAE rearrangements by FISH break-apart and RT-PCR in a series of 27 undifferentiated uterine stromal sarcoma without JAZF1 rearrangements. Immunohistochemistry (IHC) was carried out with a panel of antibodies (estrogen (ER) and progesterone (PR) receptors, CD10, Cyclin D1, β-catenin, p53, and Ki-67). We identified a subgroup of endometrial sarcomas with high-grade histology and uniform morphology harboring YWHAE rearrangements. FISH break-apart was interpretable in 20 cases (74%). Twelve cases (60%) showed <10% of tumor cells with a YWHAE rearrangement, 4 cases (20%) showed between 10 and ≤20%, and 4 (20%) >20%. RT-PCR was tested on 24/27 cases (88%) and 19 cases were interpretable (79%). Five cases (26%) showed a specific fusion transcript YWHAE-FAM22A/B sequence. The best concordance rate between FISH and RT-PCR (94%) was obtained with the threshold of 20% of cells with a YWHAE rearrangement. The YWHAE-rearranged cases showed high-grade morphology with uniform appearance, spindle or round epithelioid cells, low ER and PR, CD10 expression, and a high and diffuse positivity for Cyclin D1, p53, and nuclear β-catenin negativity. Cyclin D1 was the most sensitive marker for high-grade endometrial sarcomas with YWHAE rearrangement. All undifferentiated uterine sarcomas with pleomorphic appearances did not harbor any YWHAE rearrangements, except for one case. Overall, for endometrial sarcoma cases with high-grade morphology we recommend to test for YWHAE rearrangements by FISH break-apart, a cost- and time-efficient method, and to complete the investigation by RT-PCR in borderline cases.


Confusion over similar drug names. Problems and solutions.
Confusion over similar drug names is one of the reasons for errors in the prescribing or administration of drugs. The risks of such errors could be reduced by some simple measures. National and international agencies: Licensing authorities should exercise more control over the naming of new proprietary formulations; Nonproprietary names should be internationalised; New proprietary names should be internationalised; Common prefixes in names should be avoided if possible. Pharmaceutical manufacturers: Manufacturers should play their part in ensuring that new names are carefully chosen and internationalised; Over-the-counter formulations should be given unique names; Generic formulations should be marketed under their nonproprietary names, not new proprietary names. Doctors: Should inform patients about the nature and risks of their therapy; Should issue printed prescriptions if possible, or use clearly-penned block capitals in handwritten prescriptions. In most cases they should use nonproprietary names when prescribing. Abbreviations of drug names should never be used. Pharmacists: Should discuss the nature and risks of patients' therapy with them and check that they recognise the medicines they are taking; Should ask patients to hand in their old medicines containers when they fill a new prescription; In hospital, clinical pharmacists can help to check doctors' prescriptions and to liaise between doctors and nurses, advising on correct therapy. Special cases: Special care should be taken with sulphonylureas: manufacturers should produce distinctive formulations and pharmacists should keep them in a separate section in the dispensary.


Postoperative cooling enhances composite graft survival in nasal-alar and fingertip reconstruction.
A simple method using ice-water and aluminium foil for enhancing composite graft survival is reported. Cooling the entire recipient site retards cellular degeneration in the graft until neovascularisation occurs. The success of this technique in nasal reconstruction using auricular chondrocutaneous tissue and nonmicrosurgical fingertip reattachment is presented. The potential application to thicker skin grafts is also discussed.


Combined radio-colour contrast in the examination of ballistic head models.
The conventional analysis of ballistic gelatine is performed by transillumination and scanning of 1-cm-thick slices. Previous research demonstrated the advantages of colour and radio contrast in gelatine for computed tomography (CT). The aim of this study was to determine whether this method could be applied to head models in order to facilitate their examination. Four head models of about 14 cm in diameter were prepared from two acryl hollow spheres and two polypropylene hollow spheres. Acryl paint was mixed with barium meal and sealed in a thin foil bag which was attached to the gelatine-filled sphere which was covered with about 3-mm-thick silicone. The head models were shot at using 9 mm × 19 expanding bullets from 4 m distance. The models were examined via multislice CT. The gelatine core was removed; the bullet track was photographed and cut into consecutive slices which were scanned optically. CT images were processed with Corel Photo-Paint. Optical and radiological images were analysed using the AxioVision software. The disruption of the gelatine within the head model was visualised by extensive distribution of paint up to the end of the finest cracks and fissures and along the whole bullet track. CT imaging with excellent radio contrast in the gelatine cracks caused by the temporary cavity allowed for multiplanar reconstruction. We conclude that the combination of colour contrast in gelatine with contrast material-enhanced CT facilitates accurate measurements in ballistic head models.


[Planned birth of one child only is getting more popular in Rudong County].
The planned birth of having only 1 child is getting more and more popular in Rutong County. 35,077 couples received "one child certificate" in Rutong County, Jiangsu province. In other words, 95.14% of the couples who have only 1 child received the certificate.


Assessment and treatment of the burden of migraine: a case series.
Migraine can take a significant toll on many aspects of sufferers' lives, including occupational, academic, social, and personal functioning. Individuals with migraine experience substantial pain and disability during migraine headaches (the ictal period), and many experience functional impairment and emotional consequences between attacks (the interictal period). The majority of migraine sufferers spend most of their lives in this interictal period; therefore, it is of great importance. Treatment planning must take into account both the ictal and interictal burden. Several tools have been developed to measure the burden of migraine and to assist health care professionals in making management decisions. The Migraine Disability Assessment Scale focuses exclusively on ictal burden. The Migraine Interictal Burden Scale complements the Migraine Disability Assessment Scale by measuring interictal burden. The Migraine Prevention Questionnaire was developed based on clinical guidelines to identify patients who are appropriate candidates for preventive pharmacotherapy for migraine. This article presents 4 cases selected to exemplify the ictal and interictal burden of migraine and the benefits of effective treatment. For each patient, individualized treatment strategies were developed using acute and preventive pharmacotherapy, as well as biobehavioral treatments. Migraine preventive medication and/or biobehavioral intervention may substantially improve patient health-related quality of life by reducing the frequency of migraines and the emotional and lifestyle burden produced by interictal anxiety.


Development, Optimization, and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4- d]pyrrolo[2,3- b]pyridine Scaffold.
Janus kinases are major drivers of immune signaling and have been the focus of anti-inflammatory drug discovery for more than a decade. Because of the invariable colocalization of JAK1 and JAK3 at cytokine receptors, the question if selective JAK3 inhibition is sufficient to effectively block downstream signaling has been highly controversial. Recently, we discovered the covalent-reversible JAK3 inhibitor FM-381 (23) featuring high isoform and kinome selectivity. Crystallography revealed that this inhibitor induces an unprecedented binding pocket by interactions of a nitrile substituent with arginine residues in JAK3. Herein, we describe detailed structure-activity relationships necessary for induction of the arginine pocket and the impact of this structural change on potency, isoform selectivity, and efficacy in cellular models. Furthermore, we evaluated the stability of this novel inhibitor class in in vitro metabolic assays and were able to demonstrate an adequate stability of key compound 23 for in vivo use.


Evaluation of the Transverse Displacement of the Proximal Segment After Bilateral Sagittal Split Ramus Osteotomy With Different Lingual Split Patterns and Advancement Amounts Using the Finite Element Method.
To evaluate transverse displacement of the proximal segment after bilateral sagittal split ramus osteotomy (BSSO) advancement with different lingual split patterns and advancement amounts and to determine the influential factors related to mandibular width. A 3-dimensional finite element model of the mandible including the temporomandibular joint was created for a presurgical simulation and for BSSO with lingual split patterns I (T1; Hunsuck split) and II (T2; Obwegeser split). The mandible was advanced 3 mm (A3) and 8 mm (A8) and fixated with a conventional titanium plate. Ansys software was used to measure the linear distances of the interproximal segments and to analyze the transverse displacement distribution of proximal segments after applying the load of masticatory muscle force groups. After surgical simulation, T1A3, T1A8, T2A3, and T2A8 showed increased transverse widths (mean, 2.99, 4.70, 2.36, and 4.42 mm, respectively). For transverse augmentation, there was a statistically significant difference between the 2 different mandibular advancement amounts in T1 and in T2 (P ≤ .000), but no significant differences was observed between T1 and T2 (P ≥ .058). The maximum transverse displacement distribution in the proximal segment was measured around the gonial area, and the early contact area was found near the border between the horizontal and sagittal osteotomy lines. Transverse displacements of proximal segments occur after BSSO advancement with T1 and T2 and transverse augmentation has statistically meaningful effects depending on the amount of advancement; however, no differences in transverse augmentation between T1 and T2 were identified. The fulcrum caused by the early contact between the proximal and distal segments could be an influential factor related to mandibular width.


Separation of non-ortho polychlorinated biphenyl congeners on pre-packed carbon tubes. Application to analysis in sewage sludge and soil samples.
The analysis of planar (non-ortho) polychlorinated biphenyls (PCB) by HRGC-ECD or HRGC-HRMS requires a fractionation step to avoid the interferences of the bulk of PCB, usually in much higher concentration than the planar ones. In this paper, a new method, based on the fractionation of PCB on SPE commercial tubes pre-packed with Carbopack B, has been developed. After the extract has been applied on the stationary phase, the bulk of PCD are eluted with 15 ml of hexane (fraction I), mono-ortho PCB with 20 ml of hexane/toluene 99:1 (fraction II) and planar PCB with 20 ml of toluene (fraction III) in a station under vacuum. The method has been validated: accuracy (expressed as recovery in %) is >70% and precision (expressed as % RSD) is <20% considering changes of day, analyst and batch of tubes. The method is linear in the range studied. Other advantages are that the method is simple, rapid and it can be easily automated. The application of this separation to the determination of planar PCB in fly-ash extracts from an intercalibration exercise and to sewage sludge, sediment and soil samples has been successful. In addition, this method removes hydrocarbons from the planar PCB fraction and allows its concentration to very small volumes.


Pneumococcal middle ear fluid antibodies after pneumococcal acute otitis media in infants.
Forty-one infants, who during their first (initial) acute otitis media (AOM) had culturable S. pneumoniae (Pn) in 57 middle ear fluids (MEFs) which prolonged or recurred during the follow-up, were observed for 7-15 months for the presence of Pn, Pn-antigens (Pn-ags) and initial-type/group Pn-antibodies (Pn-abs) in these MEFs. Initially, Pn-abs were found in only 3 MEFs. During the follow-up a total of 20 ears (35%) were, at various time-intervals, positive for Pn-abs; they belonged to all three major Ig-classes, but were often slight in quantity. Most regularly, and often with distinct positivity, Pn-abs were found to type 3, 9N and 14. Secretory abs were detected in 5 ears. Within one month after initial AOM, Pn-abs appeared in 9 of the 41 ears with MEF (22%); six of them cleared soon after that. MEFs with Pn-abs usually did not show initial-type Pn/Pn-ag, but new Pn/Pn-ag could later be simultaneously present in recurrent MEF. So, pneumococcal AOM may cause a local and/or systemically mediated immune response in the middle ear in infants. The response may protect the ear from homologous, but still be present in apparently non-homologous otitis media.


[Alefacept. Successful long-term therapy of a severe psoriasis].
Alefacept, a recombinant protein produced by fusion of human LFA(3 )and IgG(1), was the first biologic specially designed and approved for the treatment of psoriasis. Results of clinical trials reveal both an efficacy comparable to established systemic therapies and a high drug safety. A 62-year old male patient with psoriasis and incomplete response to several standard therapies was treated with alefacept (baseline PASI 23.1). After three courses of 15 mg alefacept i.m. weekly for 12 weeks, each followed by a 12 week post-dosing observation period, the PASI regressed to 2.0. Adverse drug reactions were not observed.


Influence of mass transfer characteristics for DNAPL source depletion and contaminant flux in a highly characterized glaciofluvial aquifer.
The transfer of contaminant mass between the nonaqueous- and aqueous-phases is a process of central importance for the remediation of sites contaminated by dense nonaqueous-phase liquids (DNAPLs). This paper describes a comparison of the results obtained with various alternative DNAPL-aqueous-phase mass transfer models contained in the literature for predicting DNAPL source-zone depletion times in groundwater systems. These dissolution models were largely developed through laboratory column experiments. To gain insight into the implications of various representations of the local-scale kinetic as well as equilibrium DNAPL dissolution processes, aquifer heterogeneity and the complex architecture of a DNAPL source-zone, the aqueous-phase contaminant concentrations and mass fluxes arriving at a down-gradient compliance boundary are analyzed in a conditional stochastic framework. The hydrogeologic setting is a heterogeneous fluvial aquifer in Southwest Germany, referred to as the aquifer analog dataset, that was intensively characterized in three dimensions for hydrogeological parameters that include permeability, effective porosity, grain size, mineralogy and sorption coefficients. By embedding the various dissolution models into the compositional, multiphase flow model, CompFlow, the relative times predicted for complete depletion of a released DNAPL source due to natural dissolution are explored. Issues related to achieving environmental benefits through, for example, partial DNAPL-zone source removal via enhanced remedial technologies are also discussed. In this context, performance metrics in the form of peak aqueous-phase contaminant concentrations and mass fluxes arriving at a down-gradient compliance boundary are compared to each other. This is done for each of the alternative mass transfer models. A significant reduction in the fractional flux at a downstream location from the DNAPL source can be achieved by partial source-zone mass reduction; however, peak concentration levels at the same location remain much higher than the United States Environment Protection Agency (US-EPA) drinking water limits. Although groundwater quality was found to improve more rapidly for the equilibrium dissolution model, it is also shown that dissolution models that promote rapid DNAPL disappearance produce greater prediction uncertainty in the aqueous-phase flux reduction.


Collegial model for clinical nurse specialists: theoretical perspective.
Organizationally based CNSs function in a wide variety of management structures. A review of the literature suggests that the steady-state career orientation typifies CNSs and is therefore compatible with the application of self-management strategies. With this in mind the Long Beach Memorial Medical Center Collegial Model for Clinical Nurse Specialists was developed and components were defined as a self-governing strategy for CNSs within a complex tertiary medical center.


The drivers of squirrelpox virus dynamics in its grey squirrel reservoir host.
Many pathogens of conservation concern circulate endemically within natural wildlife reservoir hosts and it is imperative to understand the individual and ecological drivers of natural transmission dynamics, if any threat to a related endangered species is to be assessed. Our study highlights the key drivers of infection and shedding dynamics of squirrelpox virus (SQPV) in its reservoir grey squirrel (Sciurus carolinensis) population. To clarify SQPV dynamics in this population, longitudinal data from a 16-month mark-recapture study were analysed, combining serology with real-time quantitative PCR to identify periods of acute viraemia and chronic viral shedding. At the population level, we found SQPV infection prevalence, viral load and shedding varied seasonally, peaking in autumn and early spring. Individually, SQPV was shown to be a chronic infection in >80% of grey squirrels, with viral loads persisting over time and bouts of potential recrudescence or reinfection occurring. A key recurring factor significantly associated with SQPV infection risk was the presence of co-infecting squirrel adenovirus (ADV). In dual infected squirrels, longitudinal analysis showed that prior ADV viraemia increased the subsequent SQPV load in the blood. However, there was a strong, negative association between prior ADV viraemia and subsequent SQPV shedding from the forearm, probably caused by ADV prolonging the SQPV acute viraemic phase, so delaying onset of the chronic shedding phase, and thereby altering viral shedding patterns over the time scales examined here. Hence, co-circulating ADV infection may be involved in mediating both the quantitative levels of SQPV infection and the timing and degree of subsequent infectiousness of grey squirrels.


Biophysical models of radiation bystander effects: 1. Spatial effects in three-dimensional tissues.
Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assume the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions are implemented by a mathematical formalism and computational algorithms. The model adequately describes data on bystander responses in the 3D system using a small number of adjustable parameters.


Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons.
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Synaptic vesicles are loaded with neurotransmitter by means of specific vesicular transporters. Here we show that expression of BNPI, a vesicle-bound transporter associated with sodium-dependent phosphate transport, results in glutamate uptake by intracellular vesicles. Substrate specificity and energy dependence are very similar to glutamate uptake by synaptic vesicles. Stimulation of exocytosis--fusion of the vesicles with the cell membrane and release of their contents--resulted in quantal release of glutamate from BNPI-expressing cells. Furthermore, we expressed BNPI in neurons containing GABA (gamma-aminobutyric acid) and maintained them as cultures of single, isolated neurons that form synapses to themselves. After stimulation of these neurons, a component of the postsynaptic current is mediated by glutamate as it is blocked by a combination of the glutamate receptor antagonists, but is insensitive to a GABA(A) receptor antagonist. We conclude that BNPI functions as vesicular glutamate transporter and that expression of BNPI suffices to define a glutamatergic phenotype in neurons.


Treatment of benign prostatic hyperplasia in hypertensive men.
As the proportion of the US population over the age of 65 continues to rise, it is likely that the number of individuals with concomitant benign prostatic hyperplasia and hypertension will also increase. To reduce morbidity and mortality, it is important to treat patients with hypertension optimally. Evidence from outcome trials suggests that alpha1 blockers should not be used as first-line antihypertensive therapy. Although some clinicians previously recommended alpha1 blocker monotherapy for patients with both hypertension and benign prostatic hyperplasia, the most recent American Urologic Association and Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines recommend independent treatment with the most appropriate pharmacologic agents for each condition. When treating patients with benign prostatic hyperplasia, clinicians should be aware of the potential impacts that alpha1 blockers may have on blood pressure and potential adverse events in patients who are normotensive as well as in patients with treated hypertension.


Small bowel tumours causing intussusception in childhood.
In a series of 292 children with intussusception ten (3.5 per cent) were caused by small bowel tumours. The average age of these patients was greater than in idiopathic cases; seven of the ten being older than 2 years. Intussusception due to Peutz-Jeghers hamartomas was jejunojejunal whereas other small bowel tumours causing intussusception were in the terminal ileum. The majority of these intussusceptions were either irreducible or gangrenous and all required resection of bowel. There was only one death in the entire series of 292 patients, and this was a child with lymphosarcoma.


Clinical benefits of remote versus transtelephonic monitoring of implanted pacemakers.
The purpose of this study was to evaluate remote pacemaker interrogation for the earlier diagnosis of clinically actionable events compared with traditional transtelephonic monitoring and routine in-person evaluation. Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation. The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months. The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely. The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645).


Intraocular lens power prediction for triple procedures in Fuchs' dystrophy using multiple regression analysis.
To develop a correcting term for intraocular power (IOLP) prediction for penetrating keratoplasty combined with simultaneous extracapsular cataract extraction and posterior chamber lens implantation (triple procedure). As part of a prospective clinical study, triple procedures were performed in 42 eyes with Fuchs' dystrophy. Only eyes with readable preoperative K-values were included in this study. Differences (DEV) between achieved and target refraction (TR) depending on the values of the theoretical-optical formula according to HAIGIS were investigated using multiple regression analysis in a linear anova model: DEV = a + b CP + c AL + d IOLP + e TR. CP represents central corneal power, AL represents axial length. Spherical equivalent after suture removal was - 1.39 +/- 2.86 D (TR: - 1.64 +/- 1.72 D). A multiple regression formula was developed for correction of conventionally calculated IOL power. CP (b = - 1.391, p = 0.028), AL (c = - 4.733, p = 0.007), IOLP (d = - 1.301, p = 0.009) and TR (e = - 1.804, p = 0.005) correlated significantly with DEV (a = 198.684). Proposed correcting multiple regression formula for IOL power prediction may help to improve the postoperative refractive outcome in patients undergoing triple procedures.


Thyrotropin induces G1 cyclin expression and accelerates G1 phase after insulin-like growth factor I stimulation in FRTL-5 cells.
We have investigated the mechanism by which TSH pretreatment potentiates insulin-like growth factor I (IGF-I)-induced DNA synthesis in FRTL-5 cells. As previously described, pretreatment with TSH increased IGF-I-induced DNA synthesis, suggesting that the effect of TSH is mediated through the cAMP pathway. TSH and A kinase activators required at least 12 h to precondition cells to respond to IGF-I stimulation. The presence of cycloheximide abolished the effect of TSH to increase IGF-I-induced DNA synthesis. When the time course of thymidine uptake after IGF-I addition was studied, TSH pretreatment increased the maximum DNA incorporation and shortened the G1 phase interval. These results indicated that some proteins induced by TSH are required for the effect of TSH on IGF-I activity, and the proteins are important for cell cycle progression. Cyclins are key regulators of the cell cycle; therefore, we investigated the expression of cyclins D1 and E after TSH stimulation. TSH- and A kinase-activating agents increased the expression of cyclins D1 and E after 24 h. The same amounts of cyclins D1 and E induced by IGF-I were increased after TSH pretreatment. TSH pretreatment induced the expression of G1 cyclin in FRTL-5 cells, and IGF-I caused the accumulation of enough G1 cyclins to drive the cell cycle from G1 to S phase in a short time, which accounts for the effect of TSH on IGF-I induced DNA synthesis.


Antiestrogenic action of toremifene on hormone-dependent, -independent, and heterogeneous breast tumor growth in the athymic mouse.
The antiestrogen toremifene has been used to study the growth control of hormone-dependent (MCF-7), -independent (MDA-MB-231), or mixed tumor cell populations in athymic mice. Maximal MCF-7 tumor growth was produced in ovariectomized athymic mice by circulating estradiol levels of approximately 200 pg/ml (produced by 0.5-cm silastic capsules implanted s.c.). The antiestrogen toremifene (77 +/- 4 micrograms/day from a 2-cm silastic capsule) inhibited estradiol (0.5-cm capsule)-stimulated growth by more than 70%. No tumor growth was observed in mice treated with toremifene alone, although toremifene acted as a weak partial agonist on the mouse uterus. The growth of hormone-independent MDA-MB-231 breast tumors implanted in athymic mice was not influenced by either estradiol (0.5-cm capsule) or toremifene (2-cm capsule) when administered alone or in combination. Furthermore, even very large doses of toremifene (5 mg/day p.o.) did not alter the rate of MDA-MB-231 tumor growth. Mixtures of MCF-7 and MDA-MB-231 cells in 9:1 and 99:1 ratios inoculated into athymic mice produced tumors which grew in the absence of estradiol but responded to estradiol supplementation (0.5-cm capsule) with a more rapid rate of tumor growth. Tumors grown from inoculated MCF-7:MDA-MB-231 cells (99:1 ratio) in the presence of estradiol had estrogen receptor levels of 33.2 +/- 9.2 fmol/mg of protein at Day 44 compared to 84.8 +/- 4.8 fmol/mg of protein in pure MCF-7 tumors. Toremifene (2-cm capsule) treatment inhibited the estrogen stimulation of these mixed tumors (99:1 starting ratio) to that of toremifene alone. However, toremifene-alone treatment produced a more rapid rate of tumor growth than control or tumors grown from irradiated MCF-7 cells mixed with viable MDA-MB-231 cells. Increasing the ratio of MCF-7:MDA-MB-231 cells (999:1) initially inoculated resulted in tumors which developed less rapidly than the lower ratio (99:1). Toremifene (2-cm capsule) again produced partial inhibition of 17 beta-estradiol-stimulated tumor growth while increasing tumor growth above control when the antiestrogen was administered alone. These results demonstrate that toremifene is effective in inhibiting estrogen stimulation of hormone-dependent tumors and partially successful at controlling mixed hormone-dependent/independent tumors; however, the antiestrogen cannot control the growth of a hormone-independent tumor in this model.


Use of a replication-defective vector to track cells initially infected by SIV in vivo: infected mononuclear cells rapidly appear in the draining lymph node after intradermal inoculation of rhesus monkeys.
A better understanding of the mechanisms of HIV dissemination, a key step in pathogenesis, would be possible if the cellular pathways of viral dissemination could be followed in simian immunodeficiency virus (SIV)- inoculated monkeys or HIV-infected people. In an initial attempt to follow this process using a traceable virus infection, we inoculated rhesus monkeys intradermally (ID) or directly into lymph nodes with a replication-defective SIV-based vector expressing the enhanced jellyfish green fluorescent protein (EGFP), V1EGFP. EGFP expression was detected in mononuclear cells isolated from the sites of inoculation (skin and lymph node) at 5 and 16 hr after inoculation and then cultured in vitro for 6 days to allow maximum EGFP expression. Similarly, EGFP-expressing, SIV-infected cells could be detected at 16 hr postinfection in the lymph nodes that drained the sites of ID inoculation. Since V1EGFP is a replication-defective vector, the EGFP-expressing cells are the initial target cells infected by the virions in the original inoculum. The results of flow cytometric analysis were confirmed by a nested PCR assay to detect SIV DNA and hence infection of cells and reverse transcription. These experiments indicate that 16 hr after ID inoculation newly infected cells either remain in the skin at the site of inoculation or have migrated to the draining lymph node. The results in this SIV vector model probably reflect the short time (less than 16 hr) required for HIV to move from a site of epithelial penetration to the lymphoid tissues via lymphatic vessels.


[Expression of the paternal genes for lactate dehydrogenase, glutamate dehydrogenase and acetylcholinesterase in the development of hybrid fish between species from the families of Cobitidae and Cyprinidae].
The time of expression of the paternal genes of glutamate dehydrogenase (GDH), lactate dehydrogenase (LDH) and acetylcholine esterase (AChE) was investigated in the development of fish hybrids. The species which differed by the thermostability of homologous enzymes were selected as parental pairs. The appearance of differences in the thermostability of homologous enzymes between the hybrids and the maternal species suggested the beginning of paternal enzyme synthesis in the hybrid embryos. Differences in the AChE thermostability appeared simultaneously with the enzyme activity at the stage of first muscle contractions (35 hrs of development), differences in the mitochondrial GDH thermostability appeared at the stage of hatching (50-60 hrs) and those in the LDH thermostability 12-17 days after hatching. The total activity of AChE and GDH sharply increased during the period of the paternal enzyme appearance whereas the activity of LDH suffered practically no changes. Differences in the AChE thermostability between the hybrids and the maternal species are the same for both the total AChE (in supernatant, 15,000 gX10 min.) and the solubilised AChE (in supernatant, 130,000 gX60 min.). AChE of the parental species and the hybrids have the same electrophoretic mobility. The differences in the thermostability of enzymes are preserved following the electrophoresis in polyacrilamide gel.


[Transcriptional expression of apoptosis suppression gene bcl-2 in non-small cell lung carcinoma].
To investigate the role of Bcl-2 gene in oncogenesis and progression of non-small cell lung carcinoma(NSCLC). The mRNA expressions of Bcl-2 gene in a series of 137 pulmonary tissues collected at various sites and with different properties were studied with Northern hybridization and non-radioactive digoxigenin labeling and detection system. According to the observations on benign lesions, non-cancer tissues distant from tumour, para-tumour tissues and cancer tissues, there was a tendency of mRNA expression increasing of Bcl-2 gene. Among them, Bcl-2 mRNA expression in lung cancer tissues was significantly increased, compared with that in benign lesions and tissues distant from tumour (P<0.01). The Bcl-2 mRNA expression in lymph node with cancer metastasis was significantly higher than that in lymph node without cancer metastasis(P<0.05). The Bcl-2 mRNA expression was relative to cell differentiation of the cancer, but not to the histological classification. Over expression of Bcl-2 gene might be involved in the oncogenesis and metastasis of NSCLC.


Assay of mono ADP-ribosyltransferase activity by using guanylhydrazones.
Guanylhydrazones of p-nitrobenzaldehyde and methylglyoxal serve as acceptors of ADP-ribosyl groups for the reactions catalyzed by cholera toxin. The absorption spectrum of the ADP-ribosylated p-nitrobenzylidine aminoguanidine is similar to that of a 1:1 mixture of ADP-ribose and p-nitrobenzylidine aminoguanidine. Results from fast atom bombardment mass spectrometry prove that the product is mono-ADP-ribosylated. ADP-ribosylation lowers the pKa of the p-nitrobenzylidine aminoguanidine by 0.7-0.8 pH unit. Assay methods are developed for measuring the ADP-ribosyltransferase reaction by following the rate of disappearance of p-nitrobenzylidine aminoguanidine by high-performance liquid chromatography or spectrophotometrically by monitoring the absorbance increase at 370 nm accompanying ADP-ribosylation of p-nitrobenzylidine aminoguanidine. The high-performance liquid chromatographic system can be utilized to measure ADP-ribosyltransferase activity in animal tissues. By using this procedure, the presence and quantitation of an ADP-ribosyltransferase in a homogenate of rabbit skeletal muscle is reported.


Value of endoscopic retrograde cholangiopancreatography-guided brushings in preoperative assessment of pancreaticobiliary strictures: what's new?
Brush cytology plays a prominent role in confirming the presence of extrahepatic biliary tract malignancy. However, its value is limited by its relatively low and widely variable sensitivity values. Various factors seem to influence the accuracy of cytologic diagnosis and are attributed to sampling, technical and interpretation errors. Ancillary methods, such as immunocytochemistry, flow cytometry, image analysis, fluorescence in situ hybridization (FISH) and the newly discovered method of global analysis of gene expression are helpful in resolving cases with inconclusive cytology and are vigorously investigated for their value in assessing the expression of novel tumor markers for the diagnosis and prognosis of pancreatic and bile duct carcinomas. However, their routine use in clinical practice remains in doubt. To increase the sensitivity of brush cytology and strengthen its role in the preoperative assessment of patients with pancreaticobiliary malignancies, the following are of the utmost importance: improvement of current sampling and cytopreparation techniques, introduction of a uniform system for reporting epithelial abnormalities based on strict and clearly distinct morphologic criteria for each pathologic entity and incorporation of experience and knowledge derived from standard cytologic methods and novel diagnostic technologies in clinical practice without compromising the high specificity associated with brush cytology.


Quality control of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis.
The European Lacidipine Study of Atherosclerosis (ELSA) was a prospective, randomized, double-blind, multinational interventional trial using B-mode ultrasound measurement of carotid intima-media thickness (IMT) in 2259 hypertensive individuals. ELSA showed that 4-year treatment with the calcium antagonist, lacidipine, significantly slowed down progression of carotid atherosclerosis as compared with treatment with the beta-blocker, atenolol. To report data on cross-sectional and longitudinal quality control of the ultrasound measurements implemented throughout ELSA. Patients underwent scans at baseline and at each annual visit. All endpoints were measured while the study was in progress (initial measurements). In addition to the cross-sectional quality control procedures, a longitudinal quality control procedure of re-reading 250 baseline scans at yearly intervals was implemented, to control possible reader drift. After the study had been completed, the primary endpoint was measured again under the same condition of cross-sectional quality control. Cross-sectional quality control data showed high reliability for all endpoints at all time points except for single maximum IMT (Tmax) and internal carotid IMT. Within-reader reliability was constantly better than between-reader reliability but, for the primary endpoint, between-reader reliability remained excellent. Initial and longitudinal quality control measurements showed a time trend toward lower IMT values. After application of a correction factor calculated from longitudinal quality control, all initial measurements no longer decreased with time, and the corrected IMT measurements were reasonably similar to those made after completion of the study. For long-term epidemiological studies and clinical trials, both cross-sectional and longitudinal quality control are critical to the reliability of measurements. In order to evaluate the absolute change in IMT and interpret study results without bias, both must be implemented.


Long-term durability of PSA failure-free survival after radiotherapy for localized prostate cancer.
To determine the durability of prostate-specific antigen (PSA) progression-free survival beyond 5 years in patients biochemically free of relapse 5 years after external beam radiotherapy (EBRT). This study identified 328 men treated with EBRT to the prostate who were biochemically (American Society for Therapeutic Radiology and Oncology definition) disease free 5 years after treatment. The median follow-up was 7.4 years. The patients were divided into four groups according to their PSA values 5 years after treatment: PSA <or=0.5, 0.5 to <or=1.0, 1.0 to <or=2.0, and 2.0-4.0 ng/mL. PSA progression-free rates were calculated in each subgroup at 10 years after treatment. Yearly hazard rates of biochemical progression were also calculated for the 5-10 years after treatment. The PSA progression-free survival rate was 87%, 79%, and 67%, respectively, 8, 10, and 13 years after treatment in patients biochemically free of disease 5 years after treatment. The progression-free rates at 10 years after treatment according to the PSA level at 5 years was 92% for PSA <or=0.5 ng/mL; 71% for PSA 0.5 to <or=1.0 ng/mL; 78% for PSA 1.0 to <or=2.0 ng/mL; and 56% for PSA 2.0 to <or=4.0. The lower the PSA level at 5 years, the more durable the probability of maintained biochemical disease-free survival (p <0.0001). The yearly hazard rates of biochemical progression ranged from 3.1% to 6.6% in the 5-10 years after RT. When PSA levels remain low (<2 ng/mL) 5 years after EBRT, the great majority of patients will be biochemically disease free at 10 years. The hazard rates of biochemical progression in the 6-10 years after treatment are low and are comparable to those published for prostatectomy series.


Adipose aspirates as a source for human processed lipoaspirate cells after optimal cryopreservation.
The purpose of this study was to test the authors' hypothesis that previously cryopreserved adipose aspirates collected from conventional liposuction could still be a reliable source of human processed lipoaspirate cells. Adipose aspirates were collected from 12 adult female patients after conventional liposuction of the abdomen and were then preserved by an optimal cryopreservation method with added cryoprotective agents (0.5 M dimethyl sulfoxide and 0.2 M trehalose). Cryopreservation of the adipose tissues was subsequently conducted with controlled slow cooling and then stored in liquid nitrogen (-196 degrees C). One gram of fresh or cryopreserved (after fast rewarming) adipose aspirates was processed in vitro and the resulting cell pellet, consisting of processed lipoaspirate cells, was cultured separately. The length of time until processed lipoaspirate cells became adherent to the culture plate was recorded and the number of processed lipoaspirate cells after a 2-week culture was counted. Flat, spindle-shape processed lipoaspirate cells from the cryopreserved group became adherent to the plate within 48 to 72 hours after initial culture compared with the fresh group, where the cells became adherent by 24 hours. After a 2-week culture, the cryopreserved aspirates yielded an average of 3.7 +/- 1.4 x 10(5) processed lipoaspirate cells per milliliter, equal to 90 percent of the yielded number of cells obtained from the fresh aspirates (4.1 +/- 1.4 x 10(5) cells/ml). The authors' results indicate that although there is a latency of cell growth after an optimal cryopreservation, cryopreserved adipose aspirates can yield a significant number of processed lipoaspirate cells compared with fresh aspirates and may be a reliable source of human processed lipoaspirate cells because they can still be processed later after long-term preservation.


Flow velocity vector fields by ultrasound particle imaging velocimetry: in vitro comparison with optical flow velocimetry.
We performed an in vitro study to assess the precision and accuracy of particle imaging velocimetry (PIV) data acquired using a clinically available portable ultrasound system via comparison with stereo optical PIV. The performance of ultrasound PIV was compared with optical PIV on a benchmark problem involving vortical flow with a substantial out-of-plane velocity component. Optical PIV is capable of stereo image acquisition, thus measuring out-of-plane velocity components. This allowed us to quantify the accuracy of ultrasound PIV, which is limited to in-plane acquisition. The system performance was assessed by considering the instantaneous velocity fields without extracting velocity profiles by spatial averaging. Within the 2-dimensional correlation window, using 7 time-averaged frames, the vector fields were found to have correlations of 0.867 in the direction along the ultrasound beam and 0.738 in the perpendicular direction. Out-of-plane motion of greater than 20% of the in-plane vector magnitude was found to increase the SD by 11% for the vectors parallel to the ultrasound beam direction and 8.6% for the vectors perpendicular to the beam. The results show a close correlation and agreement of individual velocity vectors generated by ultrasound PIV compared with optical PIV. Most of the measurement distortions were caused by out-of-plane velocity components.


[Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer].
Objective: To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage ⅢB/Ⅳ NSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2∶1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results: Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group (n=16) and placebo group (n=8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group (P=0.460).The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group (P=0.065).The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions: Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity. ClinicalTrials:: NCT02388919.


A Coupled Magnetoelastic Strain Sensor Array for Guiding and Monitoring Hernia Repairs.
Ventral hernia repairs using mesh prosthetics suffer from high recurrence rates, with 10%-20% of repairs failing within three years. Uneven distribution of stress within the implanted mesh prosthetic is thought to contribute to the high recurrence rate. We propose a method for providing quantitative guidance and monitoring of hernia repairs using an array of magnetoelastic strain sensors. The magnetoelastic strain sensors presented here are based on a coupled design to achieve measurements with higher signal-to-noise ratio (SNR). A first magnetoelastic element (the transducer) is bonded to the mesh prosthetic and is characterized by a strain-dependent magnetic field. The resonance frequency of a second magnetoelastic element (the resonator) encased in a rigid casing is biased by the transducer element's magneticity and can be measured noninvasively using an external interrogation coil. The coupled magnetoelastic strain sensors are assembled using a combination of photochemical machining, patterning, and heat sealing. The dynamic range of the coupled sensors can be tuned by altering the transducer geometry. Additional spring elements are integrated onto the transducer element to achieve high dynamic range measurements saturating at 74 millistrains. A coupled magnetoelastic strain sensor combines a transducer with an encased resonator element to measure strain with high SNR on an implantable flexible hernia mesh substrate. This study provides surgeons and researchers with a clinically relevant tool to quantify the strain distributions within implanted mesh prosthetics, with the ultimate goal of reducing the recurrence rate of ventral hernia repairs.


[Clinical significance and changes of serum visfatin, adiponectin and leptin levels in patients with polycystic ovarian syndrome].
To examine the serum visfatin, adiponectin and leptin levels in patients with polycystic ovarian syndrome (PCOS), and to explore the basis of the pathogenesis of PCOS. A PCOS group (n=73) and a healthy control group (n=75) were included in the study, which were matched in age and body mass index (BMI). Serum visfatin, adiponectin, leptin, sex hormone levels, and metabolic parameters were measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). Serum levels of fasting insulin(Fins), homeostatic model assessment for insulin resistance (HOMA-IR), testosterone (T), luteinizing hormone (LH), and prolactin (PRL) in the PCOS group were significantly higher than those in the healthy group(all P<0.05),and follicle-stimulating hormone (FSH) level was significantly decreased in the PCOS group. The visfatin and leptin levels in the PCOS group increased significantly than those in the healthy group [PCOS group: (95.30+/-31.90) and (11.10+/-3.87) microg/L; healthy group: (73.20+/-20.30) and (7.21+/-2.47) microg/L,P<0.001]. The adiponectin level was significantly lower than that in the healthy group [PCOS group: (4.21+/-1.17) mg/L; healthy group:( 6.39+/-1.53) mg/L,P<0.001]. Pearson correlation analysis showed that visfatin level was negatively related to adiponectin levels (r=-0.452 and -0.378, P<0.01), but positively related to leptin and HOMA-IR levels in both the PCOS group and the healthy group (r=0.379-0.556, all P<0.01). The correlation remained between the visfatin and HOMA-IR levels in the PCOS group after correcting the influence of BMI. CONCLUSION Patients with PCOS have high visfatin and leptin levels but low adiponectin levels. Visfatin levels are positively related to insulin resistance.


Hysteresis in the dynamic perception of scenes and objects.
Scenes and objects are effortlessly processed and integrated by the human visual system. Given the distinct neural and behavioral substrates of scene and object processing, it is likely that individuals sometimes preferentially rely on one process or the other when viewing canonical "scene" or "object" stimuli. This would allow the visual system to maximize the specific benefits of these 2 types of processing. It is less obvious which of these modes of perception would be invoked during naturalistic visual transition between a focused view of a single object and an expansive view of an entire scene, particularly at intermediate views that may not be assigned readily to either stimulus category. In the current study, we asked observers to report their online perception of such dynamic image sequences, which zoomed and panned between a canonical view of a single object and an entire scene. We found a large and consistent effect of prior perception, or hysteresis, on the classification of the sequence: observers classified the sequence as an object for several seconds longer if the trial started at the object view and zoomed out, whereas scenes were perceived for longer on trials beginning with a scene view. This hysteresis effect resisted several manipulations of the movie stimulus and of the task performed, but hinged on the perceptual history built by unidirectional progression through the image sequence. Multiple experiments confirmed that this hysteresis effect was not purely decisional and was more prominent for transitions between corresponding objects and scenes than between other high-level stimulus classes. This finding suggests that the competitive mechanisms underlying hysteresis may be especially prominent in the perception of objects and scenes. We propose that hysteresis aids in disambiguating perception during naturalistic visual transitions, which may facilitate a dynamic balance between scene and object processing to enhance processing efficiency.


Hypertriglyceridemic VLDL decreases plasminogen binding to endothelial cells and surface-localized fibrinolysis.
The effect of normo (NTG)- and hypertriglyceridemic (HTG)-VLDL on cultured human umbilical vein endothelial cell (HUVEC) surface-localized fibrinolysis was examined following pre-incubation with NTG-, HTG-VLDL, LDL (1-20 micrograms/mL) or buffer (control). Ligand binding assays, using 125I-labeled tcu-PA, t-PA, or Glu-plasminogen (Glu-Pmg) were carried out in the absence/presence of lipoproteins. Scatchard analyses showed that HTG-VLDL decreased the Bmax for 125I-labeled Glu-Pmg ligand binding approximately 35% [(2.11 +/- 0.39)-(1.40 +/- 0.32) x 10(6) sites/cell, p < 0.005] and increased the Kd, app approximately 5-fold (0.32 +/- 0.03 to 1.74 +/- 0.08 microM, p < 0.01), while NTG-VLDL, LDL, and buffer had no effect. 125I-labeled PA ligand binding was unaffected by these lipoproteins. Receptor-bound PA activation of cell-bound 125I-labeled Glu-Pmg was measured by quantitation of either the M(r) 20 kDa light- or M(r) 60 kDa heavy-chain of 125I-labeled plasmin, following SDS-PAGE. Kinetic analysis of these data (HTG-VLDL vs controls) indicated that HTG-VLDL decreased the V(max) of tcu-PA- and t-PA-mediated activation of plasminogen approximately 2.7-fold (0.317 +/- 0.023 vs 0.869 +/- 0.068 nM s-1, p < 0.01) and approximately 2.9-fold (0.391 +/- 0.098 vs 1.152 +/- 0.265 nM s-1, p < 0.01), respectively. Increasing concentrations of the HTG-VLDL increased 1/V(max), yielding a series of parallel plots, typical for uncompetitive inhibition with a Ki for inhibition of approximately 10 micrograms/mL. The combined ligand binding and kinetic data best fit an uncompetitive inhibition model in which the binding of the large HTG-VLDL particle to the EC surface may directly affect Glu-Pmg binding and activation, thus contributing to early fibrin deposition and the increased thrombotic risk associated with HTG.


[Effect of heliomycin on protein and nucleic acid synthesis in Escherichia coli].
Heliomycin at a concentration of 100 mcg/ml had almost no effect on the growth of Escherichia coli, which was inhibited only upon the combined action of heliomycin and ethanol that facilitated the penetration of the antibiotic into the cell. Heliomycin inhibited in these conditions the synthesis of RNA and had no effect on the synthesis of DNA in the three studied strains of E. coli. The synthesis of protein either was not inhibited by heliomycin at all or was inhibited only to a small extent.


[Animal echinococcosis in Italy: epidemiological update].
Cystic Echinococcosis (CE) is one of the most widespread parasitoses in the Mediterranean Region (MR). This is due to various factors, the most important being the close association between man, sheep and dogs in areas where open farming is practised. Although this disease has been known for several years and many studies have been carried out, nowadays in Italy there are no complete epidemiological data on its diffusion and distribution. The available data show that CE is mainly diffused in those districts where the sheep-dog cycle can be perpetuated, such as central and southern Italy, and the islands. Furthermore, no data are available on biomolecular characterisation of the strains of Echinococcus granulosus in Italy, apart form those in Sardinia, where the G1 (sheep-dog) and G7 (pig-dog) strains were recently isolated. One of the reasons why CE is a problem with no easy solution is undoubtedly the difficulty of making a certain diagnosis in the dog, the principal definitive host of E. granulosus.


The ascending branch of the lateral circumflex femoral artery. A new supply for vascularized iliac transplantation.
The ascending branch of lateral circumflex femoral a. was studied in 66 adult limbs in terms of its anatomical description and clinical relevance. The anatomical findings suggest that the ascending branch could be used as an ideal supply for vascularized iliac transplantation. This new technique has been widely used in China since 1984 with satisfactory results.


[Therapeutic ratio in combined radio-chemotherapy--radiobiological considerations].
Although much effort has been directed for obtaining a more effective way of combination in combined radio-chemotherapy, radiobiological rationales for improving the therapeutic ratio have not yet been established. Biological characteristics of solid tumors, target normal tissues in acute and chronic injuries, and also their implications in radio-chemotherapy were discussed in this review. These include cellular kinetics, pH gradient and 4 R's during the treatment course. It was considered that experimental model systems in vitro suitable for solid tumors and slowly proliferating normal tissues are required for obtaining rationales to improve therapeutic ratio.


Psychosocial stress enhances time-based prospective memory in healthy young men.
Forgetting of intentions (such as to take one's medication) is the most frequent everyday memory failure. No study so far has looked into the possible consequences stress might exert on memory for intentions (i.e., prospective memory). Twenty healthy young male adults were exposed to a psychosocial stress test and a non-stress condition. After a delay of 15 min, a time- and an event-based prospective memory task were administered during the peak of cortisol concentrations. Results show that participants performed significantly better in the time-based memory task after stress in comparison to the non-stress condition. In contrast, there was no stress effect on event-based prospective memory. The results demonstrate that prospective memory might be enhanced when participants are exposed to stress prior to the memory task and that this effect is associated to stress-related glucocorticoid effects.


Rosacea and ulcerative colitis: a possible association.
Although rosacea was formerly believed to be associated with gastrointestinal upsets, no one any longer finds a significant association between rosacea and the intestinal tract. We describe four patients with a combination of ulcerative colitis and rosacea. In all four, ulcerative colitis preceded the onset of severe papulopustular rosacea, and we therefore feel that the severity of rosacea could have been due to the associated bowel disorder. In one, the severity and poor initial response of rosacea to treatment was clearly related to the activity of the ulcerative colitis, and the rosacea improved only after proctocolectomy. While it is possible that this purported association is fortuitous, we report these cases in the hope that others may have seen this combination of diseases, to our knowledge previously unreported.


Effects of forced and spontaneous exercise on 8-hydroxydeoxyguanosine levels in rat organs.
We investigated the effects of forced and spontaneous exercise on the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a form of oxidative DNA damage, in rat organs (heart, lung, and liver). Rats were randomly assigned to one of three groups: forced exercise group (F), spontaneous exercise group (S), and sedentary control group (C). The mean levels of 8-OH-dG in the F group were 1.9-, 2.1-, and 2.4-fold higher in the heart, lung, and liver DNA, respectively, than in the S group. In the S group of rats, the distance run was not significantly correlated to the 8-OH-dG levels in the heart, lung, and liver DNA. These results demonstrate that the intensity of exercise is an important determinant in DNA damage, and suggest that spontaneous physical exercise is beneficial for maintaining a low level of oxidative DNA damage.


PUMA dependent mitophagy by Abrus agglutinin contributes to apoptosis through ceramide generation.
PUMA, a BH3-only pro-apoptotic Bcl2 family protein, is known to translocate from the cytosol into the mitochondria in order to induce apoptosis. Interestingly, the induction of PUMA by p53 plays a critical role in DNA damage-induced apoptosis. In this study, we reported mitophagy inducing potential of PUMA triggered by phytolectin Abrus agglutinin (AGG) in U87MG glioblastoma cells and established AGG-induced ceramide acts as the chief mediator of mitophagy dependent cell death through activation of both mitochondrial ROS as well as ER stress. Importantly, AGG upregulates PUMA expression in U87MG cells with the generation of dysfunctional mitochondria, with gain and loss of function of PUMA is shown to alter mitophagy induction. At the molecular level, our study identified that the LC3 interacting region (LIR) located at the C-terminal end of PUMA interacts with LC3 in order to stimulate mitophagy. In addition, AGG is also found to trigger ubiquitination of PUMA which in turn interacted with p62 for prompting mitophagy suggesting that AGG turns on PUMA-mediated mitophagy in U87MG cells in both p62-dependent as well as in p62-independent manner. Interestingly, AGG-triggered ceramide production through activation of ceramide synthase-1 leads to induction of ER stress and ROS accumulation to promote mitochondrial damage as well as mitophagy. Further, upon pre-treatment with Mdivi-1, DRP1 inhibitor, AGG exposure results in suppression of apoptosis in U87MG cells indicating AGG-induced mitophagy switches to apoptosis that can be exploited for better cancer therapeutics.


Unusual presentation of verrucous carcinoma of maxillary antrum.
Verrucous carcinoma is a rare type of squamous cell carcinoma that is most often seen in the oral cavity and larynx. This paper describes a case report of a rare tumor with an unusual presentation. This patient presented with recurrent pyoceles and was diagnosed by chance. Carcinoma of maxilla is rarely diagnosed until the bony walls are eroded. This condition should be kept in mind in patients presenting with recurrent pyocele and a biopsy carried out from the maxilla.


Wanted: your expertise.
Trustees' expertise is needed to help shape AHA policies.


Integrin expression in non-small cell carcinoma of the lung.
Alteration of integrin expression in a number of different malignant diseases has been recognized, with a trend of downregulation of collagen-laminin binding integrin expression in epithelial tumor types noted. This study evaluated the expression of a panel of integrin subunits that included subunits that form receptors that bind to collagen and laminin (alpha 2, alpha 3, alpha 6 beta 4) and subunits that form receptors that bind to fibronectin and fibrinogen (alpha 5, alpha V, beta 3, beta 6) in 51 specimens of non-small cell carcinoma (NSCCA) of the lung by use of immunohistochemistry. Integrin expression was then correlated with histologic type (squamous vs. adenocarcinoma), absence or presence of hilar or mediastinal nodal metastasis at resection, and cellular differentiation (well or poorly differentiated). In general, downregulation of the collagen-laminin binding subunits was noted in tumor cells of the NSCCA specimens when compared to the progenitor normal bronchial epithelium. No differences were noted in integrin expression between squamous cell and adenocarcinoma or between node-positive or node-negative tumors. However, downregulation of the integrin subunit alpha 3 was noted to be significantly more common in poorly differentiated tumors (p = 0.02) and several of the other collagen-laminin binding subunits also appeared to be more downregulated in poorly differentiated tumors. No upregulation was seen in the alpha 5 subunit of the fibronectin receptor or the beta 3 subunit of the vitronectin receptor, however, approximately 50% of tumors showed upregulation of the beta 6 subunit, the great majority of these being well-differentiated, node-negative tumors. Downregulation of the collagen-laminin integrins may thus be associated with differentiation of NSCCA, but not metastasis, and may serve as an adjunctive prognostic marker of disease. The beta 6 subunit appears to be associated with malignant transformation, but may serve as a positive prognostic factor.


Hospital diversification: corporate restructuring as a survival strategy.
Corporate restructuring of hospitals as a strategy for survival and continued success is described. Health-care providers' traditional orientation has been toward service and mission; now, profits and new markets in health care must be considered also. To remain competitive, hospitals must be prepared to act rapidly on opportunities. Corporate reorganization, the creation of new corporate entities that perform diversified medical and nonmedical functions, may provide the flexibility needed for quick action. Legal and accounting costs will be incurred by corporate reorganization. Tax issues, staff morale, community support, and effect on hospital managers and board members should be considered. Hospitals can cut costs through vertical integration of existing services; in this system-building strategy, new services can be added to broaden the patient base. Corporate reorganization is more important for diversification--the extension of a hospital's medical and health businesses--than for system building. Guidelines for diversification are offered. Corporate reorganization is a technique that should be considered in an institution's planning process.


Theoretical study of pyridoxine (vitamin B6) photolysis.
Two different reaction types for the photolysis of pyridoxine-aromatic ring-opening and photodissociation-have been studied in the Density Functional Theory (DFT) framework. Our results show that neither photolytic ring-opening, dehydroxymethylation, demethylation nor dehydroxylation from the aromatic ring can be induced spontaneously in UV-irradiated pyridoxine, due to the high barriers along the reaction coordinates in the excited states. However, the simultaneous dehydroxylation of the C4-bound hydroxymethyl group and dehydrogenation of the ring bound hydroxyl substituent, selectively generating ortho-quinone methide and water, does occur after UV exposure. The findings correlate very well with available experimental data. The geometries of pyridoxine, its various transition states and products are optimized in the ground and first excited states in vacuum within the TD-DFT formalism.


Timbre discrimination in normal-hearing and hearing-impaired listeners under different noise conditions.
In an attempt to quantify differences in object separation and timbre discrimination between normal-hearing and hearing-impaired listeners with a moderate sensorineural hearing loss of two different configurations, psychoacoustic measurements were performed with a total of 50 listeners. The experiments determined just noticeable differences (JND) of timbre in normal-hearing and hearing-impaired subjects along continua of "morphed" musical instruments and investigated the variance of JND in silence and different background noise conditions and on different sound levels. The results show that timbre JNDs of subjects with a steep hearing loss are significantly higher than of normal-hearing subjects, both in silence and noise, whereas timbre JNDs of flat/diagonal hearing-impaired subjects are similar to JNDs of normal-hearing subjects for signal levels above 55 dB (plus appropriate amplification for hearing-impaired). In noise (SNR=+10 dB) timbre JNDs of all subject groups are significantly higher than in silence. In the condition testing, transferability from silence to noise (i.e., the ability to imagine how the stimulus heard in silence would sound in noise), no significant JND differences across listener groups were found. The results can be explained by primary factors involved in sensorineural hearing loss and contradict the hypothesis that hearing-impaired people generally have more problems in object discrimination than normal-hearing people.


Higher Rate of Barrett's Detection in the First Year After Successful Endoscopic Therapy: Meta-analysis.
Endoscopic eradication therapy (EET) is highly effective in treating dysplastic Barrett's esophagus (BE). Current surveillance intervals after complete remission of intestinal metaplasia (CRIM) are based on expert opinion. We performed a meta-analysis to compare BE detection in the first year to the subsequent ones METHODS: We searched MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials through 1 August 2017 for studies reporting IM and neoplasia detection after CRIM. Pooled incidence rate (IR) of IM detection was calculated for each year after CRIM. We compared IM, dysplasia, and high grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) detection in the first year after CRIM to the years after. Twenty two studies were included involving 1973 patients with follow-up of 5176 patient-years. IM detection IR per patient-year in the 1st year was 12% (95% CI: 8-17%), in the 2nd year 7% (95% CI: 4-11%), and in the 3rd year 3% (95% CI: 1-7%). IM detection rate in the first year was significantly higher compared to the years after (relative risk (RR) 1.8 (95% CI: 1.29-2.49)). Dysplasia detection IR in the first year after achieving CRIM was 3% per patient-year (95% CI: 2-5%). Dysplasia detection IR after the first year was 1% (95% CI: 1-2%) and significantly higher in the first year compared to the years after (RR: 1.92 (95% CI: 1.32-2.8). HGD/EAC detection was 1 %/patient-year (95% CI: 0-2%) in the first year after CRIM compared to 0%/patient-year (95% CI: 0-1%) in subsequent years. HGD/EAC IR was higher in the first year (RR: 1.58 (95% CI: 0.94-2.65)). Neoplasia detection after successful treatment of BE appears more common within the first year of surveillance. This appears to be due to incompletely treated prevalent rather than recurrent disease. More intensive surveillance in the first year following CRIM is warranted.


Direct measurement of effective indices of guided modes in LiNbO(3) waveguides using the Cerenkov second harmonic.
Second-harmonic generation in the form of Cerenkov radiation has been used to make direct, contact-free measurements of the effective indices of guided modes in LiNbO(3) channel waveguides. X-cut substrates were used, and channels oriented along the y axis were formed by either proton exchange or titanium indiffusion. For end-fire TE excitation, the Cerenkov harmonic radiates forward at a shallow angle into the substrate, leaves the output facet of the substrate, and appears as bright bands in the far field. These bands are seen to form a one-to-one correspondence with the m lines that are due to guided modes when a prism coupler is simultaneously clamped to the sample surface. The effective indices of the guided modes can be obtained by a simple calculation that involves only the substrate index and the angle at which the Cerenkov harmonic is radiated into the substrate. This technique permits effective index measurements of cladded waveguides where prism coupler measurements cannot be made. Examples of the technique in which index oil is used as a guide overlayer are given.


In vitro testing method of polymers candidate destined for contact with blood.
Research aiming at obtaining athromobogenic biomaterials destined for contact with blood have been the subject of interdisciplinary studies carried out since 1980. When testing candidate materials, it is advisable that preliminary classification as well as elimination of materials not conforming to the requirements of athromobogenesis should be performed. Practicable laboratory methods were selected facilitating in vitro evaluation of materials of modified surface and conforming to the definite requirements. The testing of candidate materials of athromobogenic properties comprises basic research methods enabling instantaneous classification. The applied experimental model comprises the following: scanning electron microscopy (SEM), thromboelastography (TEG), formula: [see text] examining clotting systems by determining calcium, cephalincalcium times as well as the amount of blood platelets, biochemical examination. Application of the above-mentioned methods enables objective preliminary evaluation of candidate materials that may be applied in obtaining implantation products and medical appliances for the contact with blood.