Nurses' Perspectives on Family Caregiver Medication Management Support and Deprescribing.
Nurses who care for patients with life-limiting illness operate at the interface of family caregivers (FCGs), patients, and prescribers and are uniquely positioned to guide late-life medication management, including challenging discussions about deprescribing. The study objective was to describe nurses' perspectives about their role in hospice FCG medication management. Content analysis was used to analyze qualitative interviews with nurses from a parent study exploring views on medication management and deprescribing for advanced cancer patients. Ten home and inpatient hospice nurses, drawn from 3 hospice agencies and their referring hospital systems in New England, were asked to describe current practices of medication management and deprescribing and to evaluate a pilot tool to standardize hospice medication review. Analysis of the 10 interviews revealed that hospice nurses are receptive to a standardized approach for comprehensive medication review upon hospice transition and responded favorably to opportunities to discuss medication discontinuation with FCGs and prescribers. Effective framing for discussions included focus on reducing harmful and nonessential medications and reducing caregiver burden. Results indicate that nurses who care for hospice-eligible and enrolled patients are willing to discuss deprescribing with FCGs and prescribers when conversations are framed around medication harms and their impact on quality of life.


Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy.
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A(1c) . Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A(1c) levels were observed (−0.99, −1.11, and −1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA(1c) . With the 10 mg dose, the benefits (glucose & HgA(1c) lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.


Concentration of tissue inhibitor of metalloproteinases (TIMP)-1 in ovine follicular fluid and serum.
Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA and protein localize within granulosal cells of post-gonadotropin-surge follicles and luteal tissue in ewes. Our objectives were to test the hypotheses that 1) follicular fluid concentration of TIMP-1 increases following a gonadotropin surge induced by LHRH agonist (Exp. 1) and 2) luteal status affects peripheral serum concentration of TIMP-1 (Exp. 2 and 3). In Exp. 1, the concentration of TIMP-1 within antral fluid from post-surge follicles (28.7 +/- 6.65 microg/mL) was greater (P < .02) than from pre-surge follicles (2.37 +/- 2.47 microg/mL). In Exp. 2, serum concentration of TIMP-1 did not differ among d 0 to 6 (1.27 +/- .55 microg/mL) of the estrous cycle or among periods of luteal maintenance (1.29 +/- .06 microg/mL), spontaneous luteal regression (1.19 +/- .09 microg/mL), or luteal development (1.22 +/- .08 microg/mL). However, serum concentration of TIMP-1 was greater ( P < .001) during the period of luteal maintenance (1.14 +/- .04 microg/mL) than during PGF2alpha-induced luteolysis (d 26; .85 +/- .06 microg/mL) and induced luteal absence (d 27 to 33; .95 +/- .05 microg/mL). In Exp. 3, ewes (n = 14) were bled daily from d 1 to 19 (d 0 = estrus) and at 12-min intervals for 6 h on d 3, 10, and 17. Although concentration of TIMP-1 varied considerably within and among ewes, mean concentration of TIMP-1 per ewe per day increased ( P < .05) from d 3 to 17. These data indicate that follicular fluid concentration of TIMP-1 increases following a gonadotropin surge, but the contribution of ovarian derived TIMP-1 to peripheral serum concentration is negligible.


Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding.
During epididymal maturation, sperm acquire the ability to swim progressively by interacting with proteins secreted by the epididymal epithelium. Beta-defensin proteins, expressed in the epididymis, continue to regulate sperm motility during capacitation and hyperactivation in the female reproductive tract. We characterized the mouse beta-defensin 41 (DEFB41), by generating a mouse model with iCre recombinase inserted into the first exon of the gene. The homozygous Defb41(iCre/iCre) knock-in mice lacked Defb41 expression and displayed iCre recombinase activity in the principal cells of the proximal epididymis. Heterozygous Defb41(iCre/+) mice can be used to generate epididymis specific conditional knock-out mouse models. Homozygous Defb41(iCre/iCre) sperm displayed a defect in sperm motility with the flagella primarily bending in the pro-hook conformation while capacitated wild-type sperm more often displayed the anti-hook conformation. This led to a reduced straight line motility of Defb41(iCre/iCre) sperm and weaker binding to the oocyte. Thus, DEFB41 is required for proper sperm maturation.


Prenatal and postnatal production of IgM and IgA antibodies to rubella virus studied by antibody capture immunoassay.
Rubella virus-specific IgM and IgA antibodies were quantitated by antibody capture immunoassay in adults after primary infection and after experimentally induced reinfection. Antibodies to rubella virus were also detected in fetuses whose mothers had rubella before week 18 of pregnancy. IgM and IgA concentrations in fetal blood were determined by radial immunodiffusion and enzyme immunoassay, respectively. In primary postnatal infection, IgM antibodies were consistently found until week 8 after onset of the disease, and after week 14 these antibodies were usually no longer detected. The time of disappearance of rubella virus-specific IgA varied with each individual. After vaccination of previously immune volunteers, no change was noted in level of IgA antibody, and no IgM antibody was detected. In infected fetuses, total IgM and IgA concentrations rose significantly, and rubella virus-specific IgM and IgA antibodies were detected as early as week 22 of pregnancy.


Prostaglandin E2 induces retinoic acid receptor-β up-regulation through MSK1.
The pharmacological modulation of putative renoprotective factors hypoxia-inducible factor-1α (HIF-1α) and HIF-1α-regulated vascular endothelial growth factor-A (VEGF-A) in the kidney has therapeutic interest. In human renal proximal tubular HK2 cells, prostaglandin E2 (PGE2) up-regulates HIF-1α and VEGF-A through epidermal growth factor receptor (EGFR)-dependent up-regulation of retinoic acid receptor-β (RARβ). Here we studied the role of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 and their target kinase, mitogen- and stress activated kinase-1 (MSK1), in the signaling cascade. Treatment of HK2 cells with PGE2 resulted in increased phosphorylation of EGFR, the three studied kinases and the histone H3 (Ser10) at the RARβ gene promoter (the latter has been proposed as a molecular signature of the activated RARβ gene promoter). Prevention of the phosphorylation of EGFR, ERK1/2, p38 MAPK or MSK1 is by incubating, respectively, with AG1478, PD98059, SB203580 or H89 allowed to elucidate the precise phosphorylation order in the signaling cascade triggered by PGE2: first, EGFR; then, ERK1/2 and p38 MAPK and, finally, MSK1. Phosphorylation of MSK1 led to that of Ser10 in histone H3 and to activation of RARβ gene transcription (and the consequent increase in the expression of HIF-1α and VEGF-A), which was suppressed by H89 or by transfecting cells with a vector encoding for a dominant-negative mutant of MSK1. These results highlight the relevance of MSK1 in the up-regulation of RARβ by PGE2. They also may contribute to new therapeutic approaches based upon the pharmacological control of HIF-1α/VEGF-A in the proximal tubule through the modulation of the PGE2/EGFR/MAPK/MSK1/RARβ pathway.


Malignant mixed müllerian tumor of the ovary and false negative punctures.
Malignant mixed müllerian tumour (MMMT) of the ovary is a rare and aggressive tumour with a poor prognosis. We present a case of a 57-year-old woman with a large pelvic mass, omental cake, ascites and pleural effusions, clinically highly suspect of an ovarian neoplasm. Paracentesis and ultrasound-guided biopsy of the ovary were negative for malignant disease. Therefore a CT-guided true cut biopsy was performed. The latter gave a histopathologic diagnosis of an endometrioid adenocarcinoma of the ovary. However after cytoreductive surgery anatomopathologic examination revealed a malignant mixed müllerian tumour of the ovary with heterologous differentiation. Apparently only one of the two components was found in the puncture. Adjuvant chemotherapy, active against the sarcomatous and the carcinomatous component, was given. At present the patient is well and disease free 35 months after the initial diagnosis. Cytological examination of ascites may be negative in the presence of malignant disease. If a tumour consists of two components, puncture can miss one, which may lead to undertreatment. Punctures should be discouraged as a diagnostic tool in patients in whom an ovarian malignancy is suspected.


Fractional intestinal absorption and retention of calcium measured by whole-body counting. Application of a power function model.
By application of a power function model, fractional intestinal calcium absorption was investigated with a new technique involving whole-body counting after successive oral and intravenous administration of standard doses of 47Ca. The fractional calcium retention 7 days after the oral load of 47Ca was also measured. Fractional calcium retention averaged 30.3% in normal subjects and 11.5% in 11 patients with intestinal malabsorption. In the same groups fractional calcium absorption averaged 46.6% and 16.4%, respectively. Fractional calcium retention and intestinal calcium absorption were significantly correlated to body surface area, and there was a well-defined relation between fractional retention and absorption of calcium...


Effects of ketanserin on blood pressure and platelet aggregation in elderly men with mild hypertension.
Thirteen men, age 60 +/- 2 years (mean +/- SEM) with mild hypertension, 151 +/- 4/95 +/- 3 mm Hg, completed a randomized, double-blind, placebo-controlled crossover trial of ketanserin therapy. In comparison to placebo, ketanserin treatment at 40 mg bid for 6 weeks lowered systolic and diastolic blood pressure, 148 +/- 4/92 +/- 3 vs. 140 +/- 6/86 +/- 3 mm Hg, P = 0.19/0.02. The rate of platelet aggregation in response to ADP and epinephrine was unchanged while the response to serotonin was greatly diminished. Neither the systemic pressor response nor the pupillary mydriatic response to phenylephrine was significantly altered. Plasma norepinephrine concentration declined significantly. Ketanserin reduced blood pressure, particularly the diastolic component, in elderly men with mild hypertension. While antagonism of serotonin's effects on platelet aggregation was evident, blockade of alpha 1-receptor-mediated events was not apparent. The results suggest that during chronic therapy the antihypertensive effects of ketanserin were mediated by serotonergic blockade and a possible lytic effect on sympathetic drive. The dual effects of ketanserin on blood pressure and platelet aggregation may be beneficial in reducing cardiovascular complications in hypertensive patients.


Coronary stenting early before non-cardiac surgery: is the endothelial progenitor cell capturing coronary stent a solution?
The authors report, for the first time, immediate and mid-term outcome of early antiplatelet therapy discontinuation followed by uneventful non-cardiac surgery and endovascular aortic repair, few days after successful deployment of an endothelial progenitor cell capturing coronary stent, in three consecutive patients.


l(p)-Multiresolution analysis: how to reduce ringing and sparsify the error.
We propose to design the reduction operator of an image pyramid so as to minimize the approximation error in the l(p)-sense (not restricted to the usual p=2), where p can take noninteger values. The underlying image model is specified using shift-invariant basis functions, such as B-splines. The solution is well-defined and determined by an iterative optimization algorithm based on digital filtering. Its convergence is accelerated by the use of first and second order derivatives. For p close to 1, we show that the ringing is reduced and that the histogram of the detail image is sparse as compared with the standard case, where p=2.


High-performance liquid chromatographic determination of alpha-tocopheryl nicotinate in cosmetic preparations.
alpha-Tocopheryl nicotinate (alpha-TN) accelerates blood circulation and stimulates hair follicle cells, hence it is an active ingredient in a broad range of cosmetic products. A reversed-phase high-performance liquid chromatographic method was developed to determine alpha-TN in cosmetic preparations with alpha-tocopheryl acetate as internal standard. The method was found to be rapid, precise and specific.


Attrition and housing improvements: A study of post-disaster housing after three years.
This research is part of an effort to monitor houses built for victims of hurricane Fifi in 1975. After 3 years (1978) we interviewed the residents to determine the rate of continued occupancy and the amount of housing improvement and the correlates of both. We found that a significant number of small families, Protestants, and families that had not participated in the construction of the housing had moved. From what we could determine, moving was primarily related to seeking work and improving one's financial position. Nearly 90% of the permanent occupants had improved their houses with either indigenous or manufactured materials. Non-improvement of houses was concentrated among families with few members. The largest number of unimproved houses was located in the project that sewed the poorest victims and contained the cheapest housing.


Membrane potentials in cell-free preparations from guinea pig cerebral cortex: effect of depolarizing agents and cyclic nucleotides.
The distribution of [3H]triphenylmethylphosphonium ion between the medium and vesicular entities was examined in a cell-free, particulate preparation from guinea pig cerebral cortex. This distribution followed the Nernst relationship with regard to the external potassium ion concentration and, in physiological media, indicated the maintenance of a mean trans-membrane potential ranging from -58 to -78 mV. The neurotoxins batrachotoxin, veratridine, and grayanotoxin I, partially depolarized the preparation. Tetrodotoxin blocked the depolarization by batrachotoxin, veratridine, and gray-anotoxin I. The depolarization by these neurotoxins was potentiated by the presence of anemone toxin II and presumably reflected the response of vesicular components of neuronal origin. An additional potassium-sensitive depolarization probably represented the response of vesicular components of glial origin with an apparent transmembrane potential of -8 to -35 mV. No correlation could be demonstrated between changes in transmembrane potential and stimulation of cyclic AMP generation by a variety of agents in this preparation.


Comparative p53 mutational spectra in aerodigestive tract tumors in Hong Kong Chinese patients.
The p53 mutations in colorectal, esophageal and lung carcinomas from Hong Kong were studied previously. The availability of mutation data for these cancers in one geographical region prompted investigations into special features of these p53 alterations. Mutations in codons 175, 176, 248 and 273 accounted for 35% of all mutations detected. A hot spot at codon 176 observed in esophageal carcinomas was not detected in any of the other aerodigestive tract tumors studied and appeared to be uniquely restricted to Chinese esophageal cancers. Other unique mutation sites, and a notably higher frequency of insertions and deletions in each of these cancers, were also detected in Chinese patients as compared to Caucasians.


Management of parapneumonic effusion and empyema: medical thoracoscopy and surgical approach.
Parapneumonic effusions or empyemas are frequently seen in patients with lower respiratory tract infections. The condition is associated with significant morbidity and mortality. Since Gram stains and bacterial cultures are usually negative, treatment focuses on empiric antibiotic treatment and chest tube drainage. The role of intrapleural fibrinolytics is still a matter of debate. Medical thoracoscopy is a simple and effective therapeutic alternative associated with better outcome and fewer complications than conservative treatment. Furthermore, it can be performed in analgo-sedation in a bronchoscopy suite. Video-assisted thoracic surgery carries the advantage of providing optimal visibility of the pleural cavity, thus allowing better debridement. Thoracotomy is the treatment of choice when thoracoscopic cleaning is not satisfactory.


Prognosis in intracerebral hemorrhage.
Intracerebral hemorrhage (ICH) is the most devastating type of stroke with the greatest mortality rate. Unfortunately there are no clinically proven therapies, and treatment is typically supportive. Given the poor prognosis, many families are faced with the decision to limit or withdraw care from those who have had an ICH. Many clinical grading systems have been developed to help stratify patients with ICH and aid in predicting prognosis. The ICH scale was the first to be developed to predict 30-day mortality and has been validated by different cohorts around the world. Since its inception in 2001, numerous other scales have been developed to predict mortality, and more importantly, functional outcome. However, in the development of these scales, patients who had care withdrawn were included in the analysis. It has been shown that the concept of poor prognosis leads to do-not-resuscitate orders, less invasive care, and eventually death. Most of these patients have care withdrawn within the first two hospital days, despite evidence to suggest early interventions may improve outcomes. As a result, the most recent guidelines suggest waiting more than 24 hours before deciding to withdraw care. The use and interpretation of these ever-advancing scales may allow physicians to better predict outcome and assist families in making important care-related decisions.


MR and CT appearance of nodular fasciitis.
Nodular fasciitis is a common soft-tissue tumor that remains almost unreported in the radiology literature. We retrospectively reviewed all available imaging studies on three patients with nodular fasciitis studied by MR at our institution. The lesions were round to oval in configuration, ranging in size from 1 to 4.5 cm. Two were intramuscular and one was subcutaneous in location. Both intramuscular lesions were poorly defined on CT, with a tissue attenuation less than that of skeletal muscle. The single subcutaneous lesion was well defined by surrounding fat. Conversely, all lesions were well defined on MR, although the appearance was otherwise nonspecific and varied according to the histology of the lesion. Both intramuscular lesions were mucoid or cellular and were hyperintense to skeletal muscle on T1-weighted and hyper-intense to fat on T2-weighted spin-echo (SE) MR images. The subcutaneous lesion was fibrous and markedly hypointense to skeletal muscle on all SE pulse sequences. Findings on three-phase bone scan, arteriography, and ultrasound are discussed. Because there are no unique radiologic findings in nodular fasciitis, this entity must be included in the preoperative differential diagnosis of small soft-tissue masses occurring in the extremities of young adults.


Charge excitations in cuprate and nickelate in resonant inelastic x-ray scattering.
We analyze the resonant inelastic x-ray scattering (RIXS) spectra at the Cu and Ni K-edges in La(2)CuO(4) and La(2)NiO(4), respectively. We make use of the Keldysh-Green function formalism, in which the RIXS intensity is described by a product of the incident-photon-dependent factor and the density-density correlation function in the 3d states. The former factor is calculated using the 4p density of states given by an ab initio band structure calculation and the latter using the wavefunctions given by a Hartree-Fock calculation of a multiorbital tight-binding model. The initial state is described within the Hartree-Fock approximation and the electron correlations on charge excitations are treated within the random phase approximation. The calculated RIXS spectra reproduce well several characteristic features in the experiments. Although several groups have interpreted the RIXS peaks as bound excitons, our calculation indicates that they should be interpreted as band-to-band excitations augmented by electron correlations. The difference in RIXS spectra between La(2)CuO(4) and La(2)NiO(4) is explained from this point of view.


Recurrent hepatocellular carcinoma successfully treated with laparoscopic thermal ablation.
Aggressive treatment of intrahepatic recurrence of hepatocellular carcinoma (HCC) increases patients' survival. This study aimed to evaluate laparoscopic thermal ablation (TA) in the treatment of intrahepatic HCC recurrences. A retrospective analysis was performed on 88 patients (REC group) who underwent laparoscopic TA after prior TA (66 patients.) or partial hepatic resection (HR) (22 patients) as initial local treatment. Another 170 patients with primary HCC tumors (PRIM group) were regarded as the control group. The postoperative morbidity rates were similar for the patients with prior TA (18%) and those with prior HR (21%) (nonsignificant difference [NS]). The overall survival rates were not significantly different between the two groups (3-year survival rates of 59 and 78%, respectively; P = 0.1662). Moreover, the disease-free survival (DFS) rates did not differ significantly between the patients with prior TA and those with prior HR (3-year DFS of 21 and 8%, respectively; P = 0.1911). The incidences of morbidity in the whole REC (21%) and PRIM (20%) groups were similar (P = NS), and no mortality occurred in either group (0%). The cumulative 3-year survival rate was 63% in the REC group and 59% in the PRIM group (P = 0.5739), whereas the 3-year DFS rate was 17% in the REC group and 22% in the PRIM group (P = 0.5266). Laparoscopic TA can be performed safely and may be effective for intrahepatic HCC recurrence after prior TA or HR. It leads to survival and DFS rates similar to those obtained using laparoscopic TA for primary HCC without increasing morbidity. Laparoscopic TA could be proposed as first-line treatment of intrahepatic HCC recurrence for selected patients.


Use of customized fiber posts for the aesthetic treatment of severely compromised teeth: a case report.
The introduction of fiber posts has improved the treatment of endodontically treated teeth, increasing retention, and distributing the stress along the root in order to reduce the risk of fracture. This clinical case describes the use of posts during the prosthetic rehabilitation of severely compromised teeth in the anterior segment.


UK surveillance: provision of quality assured information from combined datasets.
Surveillance information is most useful when provided within a risk framework, which is achieved by presenting results against an appropriate denominator. Often the datasets are captured separately and for different purposes, and will have inherent errors and biases that can be further confounded by the act of merging. The United Kingdom Rapid Analysis and Detection of Animal-related Risks (RADAR) system contains data from several sources and provides both data extracts for research purposes and reports for wider stakeholders. Considerable efforts are made to optimise the data in RADAR during the Extraction, Transformation and Loading (ETL) process. Despite efforts to ensure data quality, the final dataset inevitably contains some data errors and biases, most of which cannot be rectified during subsequent analysis. So, in order for users to establish the 'fitness for purpose' of data merged from more than one data source, Quality Statements are produced as defined within the overarching surveillance Quality Framework. These documents detail identified data errors and biases following ETL and report construction as well as relevant aspects of the datasets from which the data originated. This paper illustrates these issues using RADAR datasets, and describes how they can be minimised.


Effects of metabotropic glutamate receptor stimulation on cerebral O2 consumption and blood flow during focal cerebral ischemia in rats.
This investigation was performed to evaluate the effects of ACPD [(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid], a metabotropic glutamate receptor agonist, on cerebral O2 consumption during focal cerebral ischemia. Male Wistar rats were placed in control (n = 7) and ACPD (n = 7) groups under isoflurane anesthesia. Twenty minutes after middle cerebral artery (MCA) occlusion, gauze sponges with 10(-5) M ACPD or normal saline were placed on the ischemic cortex (IC) for a period of 40 min and were changed every 10 min. One hour after MCA occlusion, regional cerebral blood flow (rCBF) was determined using the C14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined using microspectrophotometry. There were no statistical differences in vital signs, blood gases, and hemoglobin between the groups. In the control group, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 45 +/- 11 vs. 110 +/- 11 ml/min/100 g, O2 consumption: 2.9 +/- 0.4 vs. 5.4 +/- 1.1 ml O2/min/100 g). ACPD did not change regional cerebral blood flow of the IC, but did significantly increase the oxygen extraction (7.8 +/- 0.2 vs. 6.9 +/- 0.3 ml O2/100 ml) and oxygen consumption of the IC (4.3 +/- 1.5 vs. 2.9 +/- 0.4) compared to the control IC. Our data demonstrated that topical application of 10(-5) M ACPD to the ischemic area worsened cerebral O2 balance. These data suggest that metabotropic glutamate receptors are not maximally activated during ischemia in the temporal cortex.


Trajectories of physical health in the first 5 years after traumatic brain injury.
The aims of the study were to examine whether self-reported physical health changes over the first 5 years after traumatic brain injury (TBI), and whether the trajectories of physical health over that time period could be predicted by demographic and injury-related variables. A longitudinal cohort study was conducted with 97 individuals with moderate-to-severe TBI who had been admitted to a Trauma Referral Centre in 2005/2007. Patients were followed up at 1, 2 and 5 years post-injury. Physical health-related quality of life (HRQL) (i.e., physical health) was measured by four subscales of the Medical Outcomes 36-Item Short Form Health Survey (SF-36): Physical Functioning, Role-Physical, Bodily Pain and General Health. Only the Physical Functioning domain showed statistically significant improvements across time. Women had lower scores on Role-Physical, Bodily Pain (more pain) and General Health. Unemployment prior to injury and having been in a "blue collar" physical job was associated with lower Physical Functioning and General Health, while greater TBI severity was associated with lower Physical Functioning, but better Role-Physical. Bodily Pain, Role-Physical and General Health remained fairly stable over time, despite the improvement in Physical Functioning. There were a number of significant injury-related and demographic predictors across the four trajectories of physical health. A better understanding of factors influencing these domains over the first 5 years after TBI and effective pain reducing rehabilitation strategies are needed.


Charge and magnetization inhomogeneities in diluted magnetic semiconductors.
It is predicted that III-V diluted magnetic semiconductors can exhibit stripelike modulations of magnetization and carrier concentration. This inhomogeneity results from the strong dependence of the magnetization on the carrier concentration. Within Landau theory, a characteristic temperature T* below the Curie temperature is found so that below T* the equilibrium magnetization shows modulations, which are strongly anharmonic. The wavelength and amplitude of the modulation rise for decreasing temperature, starting from zero at T*. Above T*, the equilibrium state is homogeneous, but the coupling between charge and magnetization leads to the appearance of an electrically charged layer in domain walls.


Confidentiality in end-of-life and after-death situations.
Confidentiality is one of the foundations on which psychotherapy is built. Limitations on confidentiality in the therapeutic process have been explained and explored by many authors and organizations. However, controversy and confusion continue to exist with regard to the limitations on confidentiality in situations where clients are considering their options at the end of life and after a client has died. This article review these 2 areas and provides some suggestions for future research.


Endoscopic diagnosis of Helicobacter pylori in patients with bleeding peptic ulcers.
Helicobacter pylori (H. pylori) is the main etiologic factor for peptic ulcers (PU), and it has been shown that H. pylori eradication therapy is effective in preventing recurrent bleeding from PU. The aim of this study was to establish the prevalence of H. pylori infection in patients with bleeding PU using two endoscopic-based methods--rapid urease test (RUT) and histology--and to compare their diagnostic accuracy. All patients underwent emergency endoscopy during which a biopsy specimen from the pre-pyloric antrum for RUT and two other specimens from the antrum and gastric corpus for histological assessment were taken. Ninety-one patients (52 men, 39 women, aged 18-78 years) were included; 69 patients had duodenal ulcer (DU), 18 had gastric ulcer (GU) and four had both duodenal and gastric ulcers. The most frequent presentation was melena (72.5%). Hemoglobin concentration ranged from 3.9 to 14.8 g/dL, and blood in the stomach was present in 59 (64.8%) of patients. Sixty-two patients (68.9%) were diagnosed by RUT as H. pylori-positive, while 81 patients (89.0%) were found to be positive by histology, the difference being statistically significant (p = 0.0048, 95% CI) The sensitivity and specificity of RUT were 76.5% and 100%, respectively. The presence of blood in the stomach did not influence the results of both RUT and histology. The study confirmed the high prevalence of H. pylori infection in patients with bleeding DU. RUT has a low sensitivity, and thus it is unreliable for the diagnosis of H. pylori infection in patients with bleeding PU; however, RUT has a high specificity and therefore, it should be used as the first choice test for the diagnosis of H. pylori in such patients undergoing emergency endoscopy. Additional biopsies should be taken during endoscopy and proceeded with histological examination when RUT is negative.


High-precision measurement of a fiber connector end face by use of a Mirau interferometer.
What we believe to be a new instrument for measuring the end-face geometrical parameters of fiber connectors is described. In this apparatus, a Mirau-type interferometric objective is employed to measure a small area of the connector end face and generate an interferogram corresponding to the surface profile. Various new technologies are used to ensure excellent performance and high measurement repeatability. A multipoint method is proposed to adjust the inclination of the physical contact sample stage. The physical contact angle of the sample stage is adjusted directly on the instrument by use of a special tool whose angle is calibrated with the reversal method. Measurement results of important parameters of the fiber connector end face are compared with those inspected by a commercial profiler or with a standard sample. Optical insertion losses of connectors inspected by the developed system are also evaluated.


Effect of chlortetracycline in a trace mineral salt mix on fertility traits in beef cattle females in Florida.
The study objective was to determine the effect of chlortetracycline in an ad libitum trace-mineralized salt mix given to heifers before and(or) during bull exposure on the proportion pregnant and the time to conception in a fixed breeding period. Heifers (n = 768), 13 to 15 mo of age, were individually identified, immunized (Leptospira, Campylobacter fetus), examined (body condition score, vaginal lesion score, BW), and randomly allocated within 2 x 2 factorial blocks of treatments where trace mineral salt with and without chlortetracycline medication was provided in similar but nonadjacent pastures either before and(or) during bull exposure. The chlortetracycline feeding period was about 30 d for each. In the 2 d immediately before bull exposure, heifers were examined (body condition score, vaginal lesion score, reproductive tract evaluation) and reallocated to treatment pastures. Pregnancy was determined by per rectal palpation at 45 d following bull removal. Mineral intake was below that expected for heifer groups and, as a result, chlortetracycline intake was estimated at less than one-third of that targeted. Many heifers were not cycling reproductively at the onset of bull exposure (n = 456, 60.3%, based on a reproductive tract score < 3). Despite these limitations, heifers receiving chlortetracycline treatment before breeding had a pregnancy percentage of 65% (chlortetracycline before and during breeding 67% and chlortetracycline before breeding 61.8%) compared to those receiving no treatment before breeding (53%, P < 0.03; no chlortetracycline before or during breeding 60.4% and chlortetracycline during breeding 47.4%). Heifers receiving chlortetracycline treatment before breeding were 57% more likely to become pregnant than those not treated before breeding. Change in vaginal lesion score was associated with the proportion pregnant, but neither body condition score nor average daily gain were.


Effect of heparin Na on the action of various bronchoconstrictors in guinea pig tracheal strips.
The effect of heparin Na on the actions of various bronchoconstrictors was examined. Guinea pig tracheal strips were suspended in bioassay glass chambers and superfused with Krebs-Henseleit solution, pH 7.4, at 37 degrees C saturated with oxygen and carbon dioxide gas (95:5, v/v). Contraction of the tissue was detected by an isotonic transducer and displayed on a polyrecorder. Heparin Na attenuated histamine-, prostaglandin F2 alpha-, acetylcholine-, serotonin-induced contractile responses dose-dependently, and shifted the dose-response curves of histamine, prostaglandin F2 alpha, acetylcholine, serotonin and bradykinin downward.


Human exposure to pulsed fields in the frequency range from 6 to 100 GHz.
Restrictions on human exposure to electromagnetic waves at frequencies higher than 3-10 GHz are defined in terms of the incident power density to prevent excessive temperature rise in superficial tissue. However, international standards and guidelines differ in their definitions of how the power density is interpreted for brief exposures. This study investigated how the temperature rise was affected by exposure duration at frequencies higher than 6 GHz. Far-field exposure of the human face to pulses shorter than 10 s at frequencies from 6 to 100 GHz was modelled using the finite-difference time-domain method. The bioheat transfer equation was used for thermal modelling. We investigated the effects of frequency, polarization, exposure duration, and depth below the skin surface on the temperature rise. The results indicated limitations in the current human exposure guidelines and showed that radiant exposure, i.e. energy absorption per unit area, can be used to limit temperature rise for pulsed exposure. The data are useful for the development of human exposure guidelines at frequencies higher than 6 GHz.


Effects of prenatal alcohol exposure on uncoupling protein in brown adipose tissue in neonatal rats.
Thermoregulatory deficits observed in neonatal rats exposed prenatally to alcohol may be due to peripheral and/or central dysfunction. One of the major mechanisms available to newborn mammals to generate heat is "nonshivering thermogenesis" in brown adipose tissue (BAT). In this study, the effects of prenatal alcohol exposure on the functional status of brown adipose tissue was assessed by immunoblot analysis of the content of mitochondrial uncoupling protein (UCP). BAT excised from 1- and 20-day-old male and female offspring from either alcohol-treated, pair-fed controls or standard control dams were analyzed. There were no effects of prenatal alcohol exposure on the UCP content. There was, however, a significant increase due to age. These results suggest that thermoregulatory deficits seen in alcohol-exposed offspring are not due to a deficiency in the concentration of mitochondrial UCP, and indicate a more central mechanism.


Chemoprevention of head and neck cancer with aspirin: a case-control study.
To evaluate the chemopreventive potential of aspirin against head and neck cancer. Hospital-based case-control study. National Cancer Institute-designated comprehensive cancer center. Patients Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (P(trend) = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to cigarette smoke or alcohol consumption.


Identification and characterization of AMPK gamma 3 mutations in the pig.
The RN(-) (rendement Napole, French for Napole yield) phenotype is common in Hampshire pigs and is characterized by a 70% increase in glycogen content in skeletal muscle and large effects on meat characteristics (pH, water content, technological yield and lean meat content). The phenotype is controlled by an autosomal dominant allele designated RN (-). The protein kinase AMP-activated gamma 3 subunit gene, PRKAG3, which encodes the gamma 3 isoform of AMP-activated protein kinase (AMPK), was identified as the causative gene for this phenotype by a pure positional cloning approach. There are now several lines of evidence supporting our interpretation that the RN(-) phenotype is caused by a missense mutation (Arg(200)-->Gln) in PRKAG3. Recent data from another group have revealed the presence of a third functional allele at the PRKAG3 locus, probably caused by a Val(199)-->Ile missense mutation. This allele has opposite effects compared with RN, as it is associated with a low glycogen content. We have confirmed the phenotypic effect of this third allele in a meat-quality study of a Hampshire/Landrace intercross. A physiological characterization of RN(-) carriers and normal pigs showed that the RN(-) pigs utilized glycogen during exercise to the same extent as normal pigs and they showed a significantly faster resynthesis of glycogen after exercise. The results strongly suggest that the Arg(200)-->Gln substitution is not associated with a defect in glycogen degradation, but rather with an increased glucose uptake in skeletal muscle.


Rheumatoid factor in acute bacterial endocarditis.
Sera from 55 parenteral drug abusers with endocarditis due to Staphylococcus aureus were assayed for the presence and titer of rheumatoid factor. Thirteen (24%) of the 55 patients with endocarditis had sera positive for rheumatoid factor at one point or another in their courses; only 2 (7%) of 30 noninfected drug users were found to be positive. It appeared that more severe cases, as evidenced by duration of fever after initiation of antibiotic therapy, were more likely to develop rheumatoid factor.


The ultrasound estimation of amniotic fluid volume in diamniotic twin pregnancies and prediction of peripartum outcomes.
To determine ultrasonic estimations of amniotic fluid in diamniotic twins across gestation using the single deepest pocket (SDP) technique and correlate volumes to intrapartum and neonatal outcomes. Prospective observational study using diamniotic dichorionic and diamniotic monochorionic pregnancies. Intrapartum and neonatal outcomes were evaluated. Between April 2004 and April 2006, 299 women were recruited. There was no significant relationship between SDP and gestational age. Statistically significant differences by SDP groups (for low, normal, and high volumes) include preterm delivery (P = .043; 56, 62, and 86%), abnormal labor tracing (P = .013; 5, 8, and 27%), fetal labor intolerance (P = .026; 6, 9, and 27%), Apgar scores at 5 minutes (P = .028; 17, 10, and 27%) and any neonatal complications (P = .002; 28, 21, and 55%). The SDP is constant between 17 and 37 weeks. Fetal labor intolerance and adverse neonatal outcomes are greater in a twin with hydramnios.


Ultra-compact broadband higher order-mode pass filter fabricated in a silicon waveguide for multimode photonics.
An ultra-compact and broadband higher order-mode pass filter in a 1D photonic crystal silicon waveguide is proposed and experimentally demonstrated. The photonic crystal is designed for the lower order mode to work in the photonic band gap, while the higher order mode is located in the air band. Consequently, light on the lower order mode is prohibited to pass through the filter, while light on a higher order mode can be converted to a Bloch mode in the photonic crystal and pass through the filter with low insertion loss. As an example, we fabricate a ∼15-μm-long first-order-mode pass filter that filters out the fundamental mode and provides a measured insertion loss of ∼1.8 dB for the first-order-mode pass signals. The extinction ratio is measured to be around 50 dB (with a variation of ±10 dB due to the detection limitation of the measurement setup) in the measured wavelength range from 1480 to 1580 nm. Additionally, calculations predict the extinction ratio to be larger than 50 dB in a 170 nm broad bandwidth.


Association of peripapillary scars with lesions characteristic of multiple evanescent white-dot syndrome.
Multiple evanescent white-dot syndrome, acute idiopathic blind-spot enlargement syndrome and multifocal choroiditis (pseudo-ocular histoplasmosis syndrome) are fundus diseases of unknown etiology. A single etiological agent or group of similar agents is thought to be responsible for these relatively rare manifestations. A 35-year-old male with associated symptoms of enlargement of the blind spot, evanescent white-dot syndrome and presumed ocular histoplasmosis is described. The association of these highly differentiated fundus abnormalities strengthens the hypothesis of an etiological or pathological linkage within phenotypically variable clinical forms.


Cultivating Resilience in Families Who Foster: Understanding How Families Cope and Adapt Over Time.
Families who foster offer essential care for children and youth when their own parents are unable to provide for their safety and well-being. Foster caregivers face many challenges including increased workload, emotional distress, and the difficulties associated with health and mental health problems that are more common in children in foster care. Despite these stressors, many families are able to sustain fostering while maintaining or enhancing functioning of their unit. This qualitative study applied an adaptational process model of family resilience that emerged in previous studies to examine narratives of persistent, long-term, and multiple fostering experiences. Data corroborated previous research in two ways. Family resilience was again described as a transactional process of coping and adaptation that evolves over time. This process was cultivated through the activation of 10 family strengths that are important in different ways, during varied phases.


[Autoimmune thyropathies in diabetics].
Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies. Authors examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/- 2.8). Diabetic patients were divided into three groups. 20 patients with type 1 diabetes mellitus - classical form were the first group, 12 patients with LADA were the second group and 47 patients with type 2 diabetes mellitus constituted the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %) patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes mellitus. They didn't find out statistically more frequent prevalence of chronic autoimmune thyroiditis in all groups of patients with diabetes (patients with type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes mellitus) in comparison with control group of non-diabetic subjects. They found out statistically significant more frequent prevalence of chronic autoimmune thyroiditis in diabetics of woman gender and in diabetics with positive family history of thyropathies. Results of paper confirm recommendation of examining once or twice a year autoantibodies against thyroid gland and level of thyrotropin (TSH) with the aim of early finding of laboratory manifestation of thyroidal autoimmunity or developing functional disorder.


Reduction of Defoliation in Citrus Caused by Mycosphaerella citri with a Novel Biocompatible Fungicide.
A novel, biocompatible fungicide, CD-2346, was evaluated for management of defoliation associated with greasy spot (Mycosphaerella citri Whiteside) in orange (Citrus sinensis (L.) Osbeck) and grapefruit (Citrus × paradisi Macfad.). This product contains potassium bicarbonate, potassium carbonate, urea, and a surfactant. CD-2346 (7.0 kg/ha) and a half-rate combination of CD-2346 + benomyl (0.55 kg/ha) were compared with a higher rate of benomyl (1.1 kg/ha) and commercial standards of oil (petroleum distillate FC-435-66 [70 to 93.5 liters/ha]) or oil (46.8 liters/ha) + copper sulfate (2.2 to 2.8 kg/ha). Fungicide efficacy was assessed using the area under the defoliation progress curve (AUDPC) and final defoliation in entire trees or final greasy spot severity in individual leaves. All fungicide treatments reduced the AUDPC, and all but benomyl reduced either final defoliation percentage or disease severity in individual leaves. CD-2346 and the reduced-rate combination of CD-2346 + benomyl were generally equal or superior to the full rate of benomyl in decreasing the AUDPC; CD-2346 + benomyl was equivalent to oil in reducing the AUDPC. Oil and CD-2346 treatments similarly reduced final defoliation, but oil + copper sulfate was superior to CD-2346 in reducing the AUDPC and final greasy spot defoliation or severity.


[Ultrasonographic examination of the liver and abdominal lymph nodes in patients with chronic lymphocytic leukemia].
Echography of the liver, gallbladder and abdominal lymph nodes was conducted in 85 patients with chronic lymphoid leukemia (CLL). An increased size of the liver, splenic vein, thickening of the gallbladder wall were recorded at the initial stage of the disease. Echogenicity of the liver was lowered. A growth in the size of the right and left lobes of the liver with simultaneous proportional distention of the splenic vein lumen were observed in CLL patients at the stage of extended clinical symptoms of the disease; the diameter of vena cava inferior was increased and lost its capacity to change during respiration; the margins of the liver became rounded, the common bile duct was expanded, the gallbladder wall was thickened. The detection of enlarged abdominal lymph nodes is important in the diagnosis of CLL. The data obtained are of great significance in the diagnosis of the disease for verification of CLL stages. The ultrasonic method of investigation of the liver and gallbladder in CLL patients is of high information content, it is noninvasive, safe, and therefore should be widely used in the clinical practice.


The implementation of a surgical antibiotic prophylaxis program: the pivotal contribution of the hospital pharmacy.
Although surgical site infection rates have decreased with the prophylactic use of antibiotics, the inappropriateness of surgical antibiotic prophylaxis is still a worldwide problem. Various strategies have been used to address this problem. This study describes the implementation of a perioperative antibiotic prophylaxis protocol that emphasizes the contribution of the pharmacist. A descriptive study design was used to evaluate the impact of the protocol on the appropriateness of prophylaxis in a private university hospital. The surgical antibiotic prophylaxis of all surgeries was evaluated for 1 month before and 1 month after the implementation of the protocol. The appropriateness of the indication for prophylaxis rose from 56.4% to 100% and that of the postoperative maintenance prophylactic antibiotics rose from 21.9% to 95.7%. The cost of the perioperative antibiotic prophylaxis per surgery decreased 40.5%. The implementation of a cost-effective perioperative antibiotic prophylaxis protocol was the result of a multidisciplinary effort. The hospital pharmacist participated in education activities as part of the discussion groups on the perioperative antibiotic prophylaxis protocol that involved all participants and in managerial actions that optimized the process of ordering, dispensing, administering, and documenting the perioperative antibiotic prophylaxis.


Investigation of red natural dyes used in historical objects by HPLC-DAD-MS.
High performance liquid chromatography (HPLC) with UV-Vis Diode Array Detection (DAD) and electrospray mass spectrometric (ESI-MS) method was utilized for the identification of coloring components of madder, Armenian and Mexican cochineal, lac dye, brazilwood, safflower and dragon blood--probably the most important red natural dyestuffs found in objects of the cultural heritage. UV-Vis detection limits in the range of 0.2-0.6 ng for carminic acid, alizarin and purpurin were achieved using a gradient elution of H2O-0.01% TFA and CH3CN-0.01% TFA. ESI mass spectrometer was also used, as a supportive detection method to the standard DAD, for further analysis of the tested materials, with the ability to analyze dyestuffs as small as one milligram. The presence of madder was revealed in two historical (Hellenistic and Roman period) samples, found in the Mediterranean area, by identifying purpurin in both of them. Munjistin was also identified in one of the samples (Hellenistic period) while alizarin was not detected, raising questions regarding the exact madder type, utilized in the historical samples.


[High-dose methylprednisolone in the treatment of terminal cancer patients].
High-dose corticoid therapy was assessed in 36 patients with end-stage cancer of various different types. These patients were compared with a control group of patients with terminal cancer on a conventional palliative regimen without corticoid therapy. Euphoria, a decrease in the required dose of analgetic and psychopharmacological drugs and an anti-inflammatory effect in cases with peritumorous oedema were observed in 27 patients.


Vulvar intraepithelial neoplasia of low grade: a challenging diagnosis.
The authors reviewed 21 cases of "mild vulvar atypia" diagnosed from 1981 to 1990. The first 16 cases were diagnosed as hyperplastic dystrophy with mild atypia according to the 1976 ISSVD Classification of Vulvar Disease, while the last five cases were diagnosed as vulvar intraepithelial neoplasia grade I (VIN I). The review of the specimens was made by the same pathologist who gave the initial diagnosis and by a dermatopathologist unaware of the initial diagnosis. Both reviewers used the 1986 and 1989 ISSVD terminologies. The presence of "mild atypia" was confirmed in only four of the 21 specimens, that is in 19% of the cases, and two of them were found in the context of patients suffering from a lichen planus. These findings show that the diagnosis of mild atypia in vulvar tissues is a challenge and that mild vulvar atypia cannot be automatically considered a VIN I.


Binge eating in bariatric surgery patients.
Eating behavior, attitudes toward eating and body weight and shape, and depression were assessed in a sample of 64 morbidly obese gastric bypass surgery candidates. The Beck Depression Inventory (BDI), the Three-Factor Eating Questionnaire (TFEQ), and the Eating Disorder Examination (EDE) were administered at the first preoperative visit. Twenty-five subjects (39%) reported at least one binge episode per week on average over the 3 months prior to seeking treatment. Binge eaters had significantly higher TFEQ Disinhibition and Hunger scores than nonbinge eaters. Binge eaters also differed from nonbinge eaters in terms of attitudes toward eating, shape, and weight. A significant number of gastric bypass surgery candidates report binge eating. The findings are consistent with other studies showing binge eaters to be a distinctive subgroup of the obese.


A psychophysical study of apparent rarefaction.
Five psychophysical functions for visual density are obtained with the use of the magnitude-estimation method. Because of apparent rarefaction, a different psychophysical function ensues for each size of square used. It is found that apparent rarefaction is barely barely detectable for sides longer than 10-15 cm (6-9 deg). It is also found that apparent rarefaction occurs to the greatest extent when short interlinear spacings are used.


A comparison of three methods of in vitro culture of human oesophageal mucosa.
Three methods of in vitro culture of human oesophageal epithelium were assessed which included the Bijou bottle, cell suspension and organ culture. The epithelium did not survive in the Bijou bottle and the cell suspension caused a growth of oesophageal fibroblasts. Organ culture proved to be the best method with survival up to ten days. Organ culture of human oesophageal epithelium provides an easy in vitro method of studying various cytotoxic factors which may play a role in reflux oesophagitis.


Neurological examination of newborn foals.
Behaviour and response to neurological testing of apparently healthy newborn foals differed significantly from the adult in several ways. Foals responded to external stimulation with exaggerated movements although they tended to sink into a relaxed state when restrained. They had a more angular head position and assumed a base wide stance. The menace reflex developed during the first two weeks post partum. In general, the foals' gait was choppy or dysmetric. In lateral recumbency the foals had increased extensor tone, hyperreflexive tendon reflexes, crossed extensor reflexes as well as recumbent extensor thrust reflexes in all four limbs.


Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit.
Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were prepared from brain cortex, hippocampus and striatum. Hepatic encephalopathy was induced by a two-stage liver devascularization procedure and acute hyperammonemia by a prolonged ammonium-acetate infusion; rabbits receiving a sodium-potassium-acetate infusion served as controls. In these animal models extracellular brain glutamate levels are known to be elevated. However no significant alterations in the number nor the affinity of the MK-801 binding sites of the NMDA receptors were found during acute liver failure and acute hyperammonemia. These findings suggest that the NMDA receptor population remains unaltered in experimental encephalopathy from acute liver failure and acute hyperammonemia, despite alterations in extracellular brain glutamate levels.


Diffusion and reaction pathways of water near fully hydrated TiO2 surfaces from ab initio molecular dynamics.
Ab initio molecular dynamics simulations are reported for water-embedded TiO2 surfaces to determine the diffusive and reactive behavior at full hydration. A three-domain model is developed for six surfaces [rutile (110), (100), and (001), and anatase (101), (100), and (001)] which describes waters as "hard" (irreversibly bound to the surface), "soft" (with reduced mobility but orientation freedom near the surface), or "bulk." The model explains previous experimental data and provides a detailed picture of water diffusion near TiO2 surfaces. Water reactivity is analyzed with a graph-theoretic approach that reveals a number of reaction pathways on TiO2 which occur at full hydration, in addition to direct water splitting. Hydronium (H3O+) is identified to be a key intermediate state, which facilitates water dissociation by proton hopping between intact and dissociated waters near the surfaces. These discoveries significantly improve the understanding of nanoscale water dynamics and reactivity at TiO2 interfaces under ambient conditions.


Content and biosynthesis of cortisol in aldosterone-producing adenomas.
The content and biosynthesis of aldosterone and cortisol were examined and compared in the aldosterone-producing adenomas and adjacent adrenal glands from patients with primary aldosteronism that resulted from solitary, benign adrenocortical tumors (0.8 to 32.3 gm). Histologic examination of the six aldosterone-producing adenomas studied confirmed a predominance of cells resembling zona fasciculata rather than zona glomerulosa, as reported in previous studies. Measurement by radioimmunoassay of the tissue content of steroids preformed in vivo demonstrated that aldosterone was present in concentrations 8 times higher in aldosterone-producing adenomas (1.5 +/- 0.5 micrograms/gm tissue; mean +/- SEM) than in adrenal glands (0.2 +/- 0.06 micrograms/gm tissue). Cortisol concentration in aldosterone-producing adenomas (5.4 +/- 1.4 micrograms/gm tissue) was approximately one third that in adrenal glands (15.8 +/- 6.3 micrograms/gm tissue), but cortisol was by far the major steroid in both types of tissue. In vitro, the most important metabolic product quantitatively from 4-carbon 14-labeled cholesterol incubated with mitochondria plus microsomes and from 4-14C-labeled pregnenolone incubated with tissue slices was cortisol, formed in a time-dependent manner in both types of preparations; cortisol synthesis greatly exceed that of aldosterone in adrenal glands, but even in aldosterone-producing adenomas the formation of cortisol was at least 5 times greater than that of aldosterone. The fasciculata structure and dual biosynthetic capacity of aldosterone producing adenomas for cortisol and aldosterone are interpreted in the light of developing concepts of the roles of adrenocorticotropic hormone and of alterations in the microenvironment of the cell in the zonal differentiation of the normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)


Distinct memory circuits composing the hippocampal region.
The very different anatomical designs of the adjacent circuitries of the cortico-hippocampal pathway, along with their somewhat different synaptic plasticity mechanisms, suggest a nearly serial pathway of distinct memory circuits each contributing its own specialized processing operation to overall hippocampal function. Modeling and formal theoretical analysis of the prominent anatomical design features of particular circuits (piriform/entorhinal cortex; hippocampal field CA3; hippocampal field CA1) are found to identify potential emergent function not readily arrived at in the absence of these formal models, and yet which once derived can be seen potentially to confer unique capabilities to an integrated hippocampal mechanism for processing memories during behavior.


A culture of compassion: How timeless principles of kindness and empathy become powerful tools for confronting today's most pressing healthcare challenges.
The role of compassion in healthcare is receiving increased attention as emerging research demonstrates how compassionate patient care can improve health outcomes and reduce workplace stress and burnout. To date, proposals to encourage empathy, kindness, and compassion in healthcare have focused primarily on training individual care providers. This article argues that increasing the awareness and skills of individuals is necessary but insufficient. Compassionate care becomes an organizational norm only when health leaders create and nurture a "culture of compassion" that actively supports, develops, and recognizes the role of compassion in day-to-day management and practice. The article profiles four organizations that have adopted compassionate healthcare as an explicit organizational priority and implemented practical measures for building and sustaining a culture of compassion. Common principles and practices are identified. These organizations demonstrate how compassion can lead directly to improved outcomes of primary importance to healthcare organizations, including quality and safety, patient experience, employee and physician engagement, and financial performance. They show how compassion can be a powerful yet often underappreciated tool for helping organizations successfully manage current challenges.


Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma.
Uterine smooth muscle tumors (USMTs) constitute a group of histologic, genetic, and clinical heterogeneous tumors that include at least 6 major histologically defined tumor types: leiomyoma (ULM), mitotically active leiomyoma (MALM), cellular leiomyoma (CLM), atypical leiomyoma (ALM), uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Apart from ULM and LMS, the nature of these variants is not well defined. A total of 167 cases of different USMT variants were collected, reviewed, and diagnostically confirmed based on the World Health Organization and Stanford schemes. These included 38 cases of LMS, 18 cases of STUMP, 42 cases of ALM, 22 cases of CLM, 7 cases of MALM, and 40 cases of ULM. Molecular analysis included selected microRNAs (miRNAs), oncogenes, and tumor suppressors that are highly relevant to USMT. Overall, 49% (17/35) of LMS cases and 7% (1/14) of STUMP cases died due to their USMT, but no deaths were attributed to ALM. miRNA profiling revealed that ALM and LMS shared similar miRNA signatures. P53 mutations and PTEN deletions were significantly higher in LMS, ALM, and STUMP compared with other USMT variants (P < .01). In contrast, MED12 mutations were extremely common in ULM and MALM (> 74%) but were significantly less common (< 15%) in CLM, ALM, STUMP, and LMS (P < .01). Six types of USMT have different gene mutation fingerprints. ALM shares many molecular alterations with LMS. Our findings suggest that ALM may be a precursor lesion of LMS or have similar genetic changes during its early stage.


[Cysticercosis of the cerebellopontine angle: treatment with single-dose praziquantel].
Praziquantel has not been considered useful for therapy of subarachnoid cysticercosis. However, recent studies suggest that the introduction of a new regimen of praziquantel therapy, that includes the administration of higher doses of the drug at shorter intervals, may improve pharmacokinetic properties of praziquantel and increase its efficacy in this form of the disease. A 28 year-old woman presented with a six month history of headache, vomiting, nystagmus, right peripheral facial palsy, and left hemiparesis. Computerized tomography (CT) scan of the head revealed a large cysticercus in the right cerebellopontine angle cistern compressing the brain-stem. She was treated with praziquantel 100 mg/kg in three divided doses at two hours apart. Thereafter, she received three 8 mg doses of intravenous dexamethasone given 6, 24 and 48 hours after the last dose of praziquantel. She improved after therapy, with total resolution of hemiparesis. Control CT showed progressive reduction and size and further disappearance of the cystic lesions three months later. This single-dose regimen of praziquantel seems to be effective for therapy of subarachnoid cysticercosis. Further studies with a large number of patients are needed to confirm the efficacy of the drug in this form of the disease.


Synovial sheath cell migratory response to flexor tendon injury: an experimental study in rats.
We aimed to investigate the degree of participation of synovial sheath cells in the process of tendon healing by selective cell labeling and direct observation of migrational pathways. We designed a novel rat animal model that employed vital dye staining of synovial sheath cells. The flexor digitorum profundus (FDP) tendon was removed from its sheath and vital dye was applied directly to the synovial sheath cells. A window was cut in the removed tendon before being returned to the sheath, thus placing a tendon injury adjacent to the labeled synovial sheath cells. The synovium remained intact at all times, and labeling was confirmed to be localized to the synovium. The migrational response of the synovial sheath cells to the tendon injury was observed by harvesting the tendons at 1, 3, 5, and 7 days (n = 6 for each time period) after injury and assessing tendon response with frozen sections under ultraviolet microscopy. Labeled synovial sheath cells were observed within the substance of the healing tendon 24 hours after injury, with numbers increasing with time for up to 5 days, but decreasing by day 7. This study confirms that in the rat model synovial sheath cells move into the healing tendon area and then migrate into the tendon core.


The evaluation of the mobile nylon bag technique for determining the apparent protein digestibility in a wide variety of feedstuffs for pigs.
Studies were conducted with four (50 to 70 kg) barrows to evaluate the mobile nylon bag technique (MNBT) for determining the apparent protein digestibility (AD) in a variety of feedstuffs. One-gram samples of each feedstuff, ground through a 1.0-mm mesh screen, were enclosed in nylon bags (25 X 40 mm; 48 microns mesh). Following predigestion (.01 N HCl; 4,000 Folin Intestinal Pepsin Units/liter), four bags of each sample were inserted into each pig via a duodenal T-cannula. The indigested contents were pooled within pig and feedstuff prior to crude protein analysis. The AD of each feedstuff was determined previously with four barrows according to the conventional method (CM), based on a 5-d total collection of feces following a 14-d adaptation period. The following results, AD (%), were obtained with the MNBT (n = 4) and CM (n = 4), respectively. Barley, 70.1 vs 81.2 (P less than .05); corn, 72.3 vs 82.1 (P less than .05); wheat, 79.6 vs 86.4 (P less than .05); corn gluten feed, 73.9 vs 70.9; rice bran, 57.3 vs 57.4; wheat middlings, 70.8 vs 79.4 (P less than .05); soybean meal, 89.9 vs 93.0; a mixture of soybean meal and hulls, 86.9 vs 88.8; coconut expeller, 65.0 vs 69.8; fababeans, 79.5 vs 78.5; peas, 87.6 vs 88.1; meat meal, 83.2 vs 84.0; complete diet (4.3% crude fiber), 76.3 vs 83.6 (P less than .05); and complete diet (13.6% crude fiber), 56.5 vs 55.0.(ABSTRACT TRUNCATED AT 250 WORDS)


Nano-particle assembled porous core-shell ZnMn2O4 microspheres with superb performance for lithium batteries.
Porous ZnMn2O4 microspheres were prepared via a facile co-precipitation method followed by calcination at various temperatures and evaluated as anode materials for lithium ion batteries. The sample prepared at 600 °C outperformed the other samples in terms of electrochemical performance with high reversible capacity, high-rate capability, and excellent cycling performance. The capacity of the sample remained as high as 999 mAh g-1 at a current rate of 100 mA g-1 after 50 cycles-one of the best ever reported for ZnMn2O4-based materials. A high reversible capacity of 400 mAh g-1 was retainable at a current density of 2000 mA g-1 after 2500 cycles. A novel electrochemical reaction mechanism of ZnMn2O4 anodes was established and investigated at length. The Mn3O4 observed during the charge process was largely responsible for the enhanced performance, as confirmed by x-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The relatively large surface area, abundant porosity, large ion exchange space, and strong mechanical stability of the porous connected 3D framework were responsible for the unique oxidation/reduction Mn2+ ↔ Mn3+ process we observed.


A mouse lethal dose assay for detection and titration of Cowdria ruminantium (Kwanyanga strain) in goats and ticks.
A mouse lethal dose assay was used to detect a mouse pathogenic strain (Kwanyanga) of Cowdria ruminantium, the etiological agent of heartwater in goats and ticks. The titer of the rickettsial organisms in goat blood was directly related to the febrile response of the goat and the rickettsia were undetectable after the fever subsided. The maximum rickettsial titer in goat blood was 10(3) mouse LD50 ml-1. Cowdria-infected goat blood was shown to retain infectivity when held on ice for up to 2 h, but when held at room temperature infectivity declined by greater than 50% in 2 h. The mouse assay detected Cowdria in feeding female Amblyomma variegatum only on the eighth day of feeding and in feeding males on the second and eleventh days of feeding. Cowdria was shown to persist in the hemolymph of the soft tick Ornithodoros coriaceus for a period of at least 2 years.


Cophylogenetics and biogeography reveal a coevolved relationship between sloths and their symbiont algae.
Specialized species, like arboreal folivores, often develop beneficial relationships with symbionts to exploit ecologically constrained lifestyles. Although coevolution can drive speciation by specialization of a symbiont to a host, a symbiotic relationship is not indicative of coevolution between host and symbiont. We tested for coevolved relationships between highly specialized two- and three-toed sloths (Choloepus spp. and Bradypus spp., respectively) and their symbiotic algae using cophylogenies and phylogeography. Our phylogeographic analysis showed a biogeographic pattern for the sloth distribution that was not found in the algal phylogeny. We found support for congruence between the sloth and algae phylogenies, implying cospeciation, only in the Bradypus lineage. Algae host-switching occurred from Bradypus spp. to Choloepus spp. Our results support a previously hypothesized symbiotic relationship between sloths and the algae in their fur and indicate that coevolution may have played a role in algae diversification. More broadly, convergent evolution may facilitate host switching between deeply diverged host lineages.


Cricoid pressure and the pressor response to tracheal intubation.
Forty healthy adults who underwent rapid sequence induction of anaesthesia were allocated randomly to receive either cricoid pressure or its stimulation. The anticipated increase in systolic arterial pressure and heart rate after laryngoscopy and tracheal intubation were not altered significantly by the application of cricoid pressure.


Synthesis and biological evaluation of novel anticancer bivalent colchicine-tubulizine hybrids.
A series of novel antimitotic hybrids were synthesized in good yields by linking of azide-containing colchicine congeners with acetylene-substituted tubulizine-type derivatives using copper-mediated 1,3-dipolar cycloaddition. Obtained compounds exhibit good cytotoxicity against HBL100 epithelial cell lines (IC(50)=0.599-2.93 μМ). Several newly synthesized compounds are the substoichiometric inhibitors of microtubule assembly (R=0.41-0.78). The results highlight the importance of the length of spacer linking the tubulin binding ligands in heterodimeric molecules.


Evidence for direct binding of vinculin to actin filaments.
The interaction of vinculin with actin filaments was investigated by methods which exclude interference by contaminating proteins which may occur in vinculin preparations. Vinculin which was blotted from SDS-polyacrylamide gels onto nitrocellulose, was stained specifically by fluorescently labeled polymeric actin (100 mM KCl, 2 mM MgCl2). Vinculin which was purified from alpha-actinin and an actin polymerization-inhibiting protein (HA1), was found to be cosedimented with polymeric actin. Maximally one vinculin molecule was cosedimented per one hundred actin filament subunits. Half maximal binding of vinculin was observed at about 0.25 microM free vinculin. Vinculin could be replaced from actin by the addition of tropomyosin.


Seasonal Allergic Rhinitis: A focused systematic review and practice parameter update.
The review compares and contrasts seven major United States and international allergic rhinitis guidelines from 2008 to 2017. Despite many treatment options for allergic rhinitis, patients often report lack of therapeutic control and a reduced quality of life. Guidelines intended to improve allergic rhinitis care have been evolving into evidence based, systematic reviews, with less reliance on consensus of expert opinion characteristic of more traditional guidelines. The first Grading of Recommendations Assessment, Development, and Evaluation-based guideline developed in the United States for seasonal allergic rhinitis was first published in 2017. When critically analyzing the allergic rhinitis guidelines that use the rigorous Grading of Recommendations Assessment, Development, and Evaluation methodology, different groups of expert authors, using the same reference articles, will, at times, reach different conclusions regarding the quality of the evidence and the strength of the recommendation. Factors potentially contributing to these divergent determinations include: lack of objective primary outcome measures in allergic rhinitis, poorly defined Minimal Clinically Important Difference, failure to include all interested parties in guideline development, for example, patients, and subjectivity inherent in the expert panel.


Interhemispheric changes in alpha rhythm related to time perception.
Each cerebral hemisphere processes environmental information in a different but complementary manner. Structures located in the left hemisphere are assumed to participate in symbolic-logic thinking. Time perception may be considered among such thinking processes. The present study evaluates bilateral occipito-central EEG activity in healthy, right-handed subjects which was produced while they performed a visuomotor monitoring task. The task consisted of two stages. The first stage involved the subject's learning a fixed time interval (10 sec) and the measurement of their reaction time. Subjects responded to an isolated light stimulus by pressing a button with the dominant hand. In the second stage, the subjects accuracy in estimating interval-length was evaluated. Two forms of EEG analysis were used, frequency and alpha ratio, each of which was measured both prior to and subsequent to the motor response. A reversal group was used to carry out a complementary test. Subjects responded in the first block of experiments with the non-dominant (left) hand and with the dominant hand in the second. Results showed that left hemisphere activity was continuous during the interval-learning stage and with optimal reaction times and remained continuous when estimation values approximated the real interval. In addition, in optimal reaction time and near to optimal time estimation responses, the left side showed lower frequency and alpha ratio than did the right. Finally a progressive enhancement in both parameters from the right hemisphere was related to deterioration in test performance. Results from the reversal group did not differ from those of the first group. As evaluated by gross measurements of the EEG, a predominant participation of the left hemisphere in time processing is concluded.


Non-HLA antibodies post-transplantation: clinical relevance and treatment in solid organ transplantation.
Antibodies and B cells are increasingly recognized as major modulators of allograft function and survival. Improved immunohistochemical and serologic diagnostic procedures have been developed to monitor antibody responses against HLA antigens during the last decade. Acute and chronic allograft rejection can occur in HLA-identical sibling transplants implicating the importance of immune response against non-HLA targets. Non-HLA anti-bodies may occur as alloantiboides, yet they seem to be predominantly autoantibodies. Antigenic targets of non-HLA antibodies described thus far include various minor histocompatibility antigens, vascular receptors, adhesion molecules, and intermediate filaments. Non-HLA antibodies may function as complement- and non-complement-fixing antibodies and they may induce a wide variety of allograft injuries, reflecting the complexity of their acute and chronic actions. Refined approaches considering the subtle mechanistic differences in the individual antibody responses directed against non-HLA antigens may help to define patients at particular risk for irreversible acute or chronic allograft injuries and improve over-all outcomes. We attempted to summarize the current state of research, development in diagnostic and therapeutic strategies, and to address some emerging problems in the area of humoral response against non-HLA antigens beyond ABO blood group and MHC class I chain-related gene A and B (MICA and MICB) antigens in solid organ transplantation.


[Death of neurons and glial cells, induced by a photodynamic injury: signaling processes and neurone-glial interactions].
The mechanisms of photodynamic (PD) injury of neurons and glial cells are reviewed. Neuron responses: firing stimulation at high photosensitizer concentrations and inhibition at low concentrations (< 10(-7) M) that were followed by necrosis, are described. Glial cells died from both necrosis and apoptosis. Local laser inactivation of a neuron enhanced PD-induced apoptosis of glial cells, thus indicating that neuron maintained the survival of glia. Inter- and intracellular signaling mediated photodamage of these cells. Using inhibitors or activators of signaling proteins, the involvement of Ca(2+)-, adenylate cyclase- and tyrosine kinase-mediated signaling pathways in responses of neurons and glial cells to photosensitization was shown. Their pharmacological modulation can change selectivity of PD injury of neuronal and glial cells and efficiency of PD therapy.


[Pathogenesis of MALT-type lymphoma].
Gastric marginal zone lymphoma, MALT-type (MZBCL) is thought to be derived from precursor lesions in follicular H. pylori-associated gastritis, that through accumulating genetic changes ultimately develop into an autonomously proliferating, monoclonal B-cell lymphoma. In the early phases of the disease, the proliferation is still at least partly dependent on the presence of H. pylori-induced T-cell help. Ongoing genetic alterations drive the process into an antigen independent phase. First of all, Fas mutations resulting in loss of function were found in a high frequency in MZBCL and gastric DLBCL and imply that Fas may act as a tumor suppressor gene. Therefore it is possible, that various Fas mutations may arise in mature B-cells during V(D)J recombination and other diversification processes in the course of immune responses as it was shown recently for the bcl-6 gene. Second, allelic imbalances suggest two different pathways of MZBCL development and progression. One group of tumors develops along the pathway determined by the dysregulation of the API2 and MALT1 genes brought about by the t(11;18). These tumors do not accumulate enough secondary genetic aberrations to transform into DLBCL and remain in the stage of MZBCL. Other MALT lymphomas characterized by the absence of the t(11;18) and increased accumulation of various clonal genetic aberrations, most frequently the 3q26.2-27 amplification, could be the source of tumors which eventually do transform into high-grade DLBCL.


Portopulmonary hypertension in a case of non-cirrhotic portal fibrosis.
Portopulmonary hypertension (PPHT) is the unusual association of portal hypertension (HT) with pulmonary HT. We report a case of noncirrhotic portal fibrosis (NCPF) leading to PPHT which is exceedingly rare with only very few cases reported in the literature. This is an autopsy report of a 30 years old man, a known case of portal HT who died suddenly due to a syncopal attack. Autopsy revealed massive pulmonary thromobembolism with pulmonary HT. Liver showed changes of NCPF. The rarity of NCPF causing PPHT prompted this case report.


Potassium antimonyl tartrate induces caspase- and reactive oxygen species-dependent apoptosis in lymphoid tumoral cells.
The metalloid salt potassium antimonyl tartrate (PAT), previously used as an antiparasitic agent, has recently been shown to exert cytotoxicity towards acute promyelocytic leukaemia cells like arsenical compounds. In this study, we have investigated its effects towards human lymphoid malignant cells and compared them with those of arsenic trioxide (As2O3). Like As2O3, PAT was found to inhibit cell growth of various lymphoid cell lines, deriving from either acute lymphoid leukaemias (Jurkat, Molt-4 and Nalm-6) or lymphomas (Daudi, Raji and Rec1). PAT toxicity was linked, at least in part, to induction of apoptosis in both Daudi and Jurkat cells, which was dependent on caspase activity. This apoptotic process was also associated, similarly to that triggered by As2O3, with loss of mitochondrial potential and enhanced cellular production of reactive oxygen-related species. It was enhanced by co-treatment with the pro-oxidant buthionine sulphoximine and abolished in response to the antioxidant N-acetylcysteine, thus underlining that PAT toxicity, similarly to that of As2O3, is probably modulated by the redox status of the cells. PAT, used at concentrations in the micromolar range that are thought to be clinically achievable, was also demonstrated to markedly decrease the viability of primary cultured tumoral B cells that originated from 18 patients suffering from chronic lymphoid leukaemia whereas normal lymphocytes were less sensitive. These data therefore suggest that PAT may deserve to be evaluated in the treatment of some lymphoid malignancies.


The cytotoxic effect of surgical glove powder particles on adult human vascular endothelial cell cultures: implications for clinical uses of tissue culture techniques.
Clinical use of autogenous endothelial cell (EC) seeding of vascular prostheses (VP) would require reliable methods for EC harvest for immediate seeding or primary culture in a hospital or operating room setting. Observation of glove powder particles (GPP) in failed primary adult human saphenous vein EC (AHSVEC) cultures led us to study the effect of surgical GPP on cultured AHSVEC. Addition of GPP to the culture medium of growing ASHVEC cultures reduced the cell counts in a dose-dependent fashion; the mean concentration of GPP required to produce a greater than 50% decrease in cell number was 1.5 +/- 0.8 (SD) X 10(4) GPP/ml (N = 10 experiments), equivalent to a mean dose of 36 micrograms glove powder per milliliter. The effect was seen within 24 hr of addition of GPP and was not due to interference with EC attachment and spreading or to changes in medium osmolality, pH, glucose, electrolyte, Ca2+, or Mg2+ content. Instead, the effect appeared to be due to a filterable toxin added during the final rubber-vulcanizing stage of glove manufacture, since pure cornstarch particles and epichlorhydrin-treated pure cornstarch did not prevent culture growth, whereas 0.2 micron filtrates of medium incubated with GPP taken directly from gloves were lethal. We conclude that filterable cytotoxic substances from GPP may be an avoidable cause of failure in EC seeding of VP, and may affect surgical wound healing as well.


Clinical implications of continued alcohol consumption after diagnosis of upper aerodigestive tract cancer.
To examine clinical implications of findings on the relationship between continued alcohol consumption in patients after diagnosis and treatment of upper aerodigestive tract cancer. Clinical research literature on the prevalence and effects of alcohol consumption after oral cancer diagnosis was reviewed. Since limited research is currently available on this important clinical topic, all published studies were considered regardless of size and methodology. Between 34 and 57% of oral cancer patients continue to drink alcohol after cancer diagnosis. Continued drinking increases complications from surgery, increases the likelihood of recurrent cancer, and reduces disease-specific survival. Older patients and those with a longer and heavier drinking pattern prior to diagnosis are more likely to continue drinking after diagnosis. Findings indicate that routine alcohol screening of newly diagnosed oral cancer patients as well as brief intervention and/or treatment referral is warranted. Monitoring of alcohol consumption for the first year after diagnosis and treatment is recommended.


Development of spatial orientation skills: an fMRI study.
The ability to orient and navigate in spatial surroundings is a cognitive process that undergoes a prolonged maturation with progression of skills, strategies and proficiency over much of childhood. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the neurological mechanisms underlying the ability to orient in a virtual interior environment in children aged 10 to 12 years of age, a developmental stage in which children start using effective spatial orientation strategies in large-scale surroundings. We found that, in comparison to young adults, children were not as proficient at the spatial orientation task, and revealed increased neural activity in areas of the brain associated with visuospatial processing and navigation (left cuneus and mid occipital area, left inferior parietal region and precuneus, right inferior parietal cortex, right precentral gyrus, cerebellar vermis and bilateral medial cerebellar lobes). When functional connectivity analyses of resting state fMRI data were performed, using seed areas that were associated with performance, increased connectivity was seen in the adults from the right hippocampal/parahippocampal gyrus to the contralateral caudate, the insular cortex, and the posterior supramarginal gyrus; children had increased connectivity from the right paracentral lobule to the right superior frontal gyrus as compared to adults. These findings support the hypothesis that, as children are maturing in their navigation abilities, they are refining and increasing the proficiency of visuospatial skills with a complimentary increase in connectivity of longer-range distributed networks allowing for flexible use of efficient and effective spatial orientation strategies.


A comprehensive analysis of renal DTPA studies. II. Renal transplant evaluation.
Renal transplant radionuclide studies, using DTPA, were analysed to produce flow and transit time measurements in both the initial arterial phase, and the later glomerular phase. Results are presented for transplanted kidneys which are normal, infarcted, obstructed, or suffering from rejection or acute tubular necrosis. Sequential studies of the vascular flow and transit time indices showed considerable promise in the detection of acute rejection, even in the presence of acute tubular necrosis. Of the six numerical indices to demonstrate acute rejection, five had accuracies of 74% or more, and all three of the indices which compared a study with a previous one had accuracies of 83% or more.


Comparison of direct-plating and broth-enrichment culture methods for detection of potential bacterial pathogens in respiratory secretions.
We compared the recovery of potential respiratory bacterial pathogens and normal flora from nasopharyngeal specimens collected from children during health and at the onset of acute otitis media (AOM) by selective direct-plating and overnight broth-enrichment. Overall, 3442 nasal wash (NW) samples collected from young children were analysed from a 10-year prospective study. NWs were cultured by (1) direct-plating to TSAII/5 % sheep blood agar and chocolate agar plates and (2) overnight broth-enrichment in BacT/ALERT SA-broth followed by plating. Standard microbiology techniques were applied to identify three dominant respiratory bacterial pathogens: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hflu) and Moraxella catarrhalis (Mcat) as well as two common nasal flora, Staphylococcus aureus (SA) and alpha-haemolytic Streptococci (AHS).Results/Key findings. Direct-plating of NW resulted in isolation of Spn from 37.8 %, Hflu from 13.6 % and Mcat from 33.2 % of samples. In comparison, overnight broth-enrichment isolated fewer Spn (30.1 %), Hflu (6.2 %) and Mcat (16.2 %) (P<0.001-0.0001). Broth-enrichment resulted in significant increased isolation of SA (6.0 %) and AHS (30.1 %) (P<0.0001). Competition between bacterial species in broth when both species were detected by direct-plating was assessed, and it was found that SA and AHS out-competed other species during broth-enrichment when samples were collected from healthy children but not during AOM. In middle ear fluids (MEF) at the onset of AOM, broth-enrichment resulted in higher recovery of Spn (+10.4 %, P<0.001), Hflu (+4.4 %, P=0.39) and Mcat (+13.5 %, <0.001). Broth-enrichment significantly reduces the accurate detection of bacterial respiratory pathogens and increases identification of SA and AHS in NW. Broth-enrichment improves detection of bacterial respiratory pathogens in MEF samples.


Outpatient management of esophageal cancer with endoscopic Nd:YAG laser.
In 50 inoperable patients with advanced malignant obstruction of the esophagus, endoscopic Nd:YAG laser treatment was used for palliation of dysphagia. In 30 of these patients, treatment was carried out entirely in an outpatient setting, providing more time at home and saving costs of hospitalization. Most patients had received prior radiation and chemotherapy. All were unable to swallow solid food; 16 had difficulty with liquids. Palliation was achieved in 69% allowing patients to eat a nearly normal diet. Therapy was least successful in cancers involving the cervical esophagus, in cancers more than 8 cm in length, and in cancers that were primarily infiltrating or extraluminal. Epidermoid carcinomas and adenocarcinomas were effectively treated, except for adenocarcinomas of the gastric cardia, which tended to be infiltrating. There were two serious but nonfatal complications, one perforation and one episode of bleeding, directly attributable to Nd:YAG laser therapy. An esophageal dilation prior to endoscopic Nd:YAG laser treatment facilitated outpatient management.


UV-embossed microchannel in biocompatible polymeric film: application to control of cell shape and orientation of muscle cells.
This article shows that ultra violet (UV) micro-embossing can be successfully used for fabricating biocompatible micropatterned films with microchannels separated by high aspect ratio microwalls. Eight series of micropatterns were investigated; the width of the microwall was either 10 or 25 microm and that of the microchannel either 40, 80, 120, or 160 microm. The material investigated was principally polyurethane diacrylate. The UV-embossed micropattern was extracted with methanol, converting the micropatterns from cytotoxic to biocompatible. The typical UV embossing method was modified by using a marginally adhesive polyester substrate, which facilitates demolding but is removable before methanol extraction to avoid fragmentation of the embossed micropatterns. The effect of the micropatterns on A7r5 smooth muscle cells and C2C12 skeletal muscle cells was investigated. The dimensions of both channel and wall have significant effects on the elongation of both muscle cells. In the narrower 40-microm channel, the C2C12 cells merged together to form myofibers. These results indicate that UV-embossed micropatterns may present a useful scaffold for in vitro cell shape and orientation control needed in vascular and muscle tissue engineering.


Transforming growth factor-beta: a growth factor inducing alpha B-crystallin expression in ciliary muscle cells.
In a recent study we showed that, in vitro, transforming growth factor-beta 2 (TGF-beta 2) induces alpha B-crystallin expression in cultured trabecular meshwork (TM) cells, but not in cultured fibroblasts. We assumed that alpha B-crystallin can be induced by TGF-beta 2 only if the cells are already expressing a basal level of the protein. In the present study we therefore treated cultured ciliary muscle (CM) cells constitutively expressing alpha B-crystallin and investigated the effect of TGF-beta on expression of alpha B-crystallin and the corresponding mRNA in these cells. Monolayer cultures of third-passage CM cells from eyes of five human donors (12-73 years), being confluent for 7 days, were treated with 1.0 ng/ml TGF-beta 1 or TGF-beta 2. Induction of alpha B-crystallin and the related mRNA was investigated by immunofluorescence and by western and northern blot analysis. An increase in alpha B-crystallin mRNA was observed following treatment with TGF-beta. Actinomycin blocked the induction of alpha B-crystallin by the cytokine TGF-beta. Using western blotting the increase in alpha B-crystallin expression in CM cells was only small. These results confirm our assumption that induction of alpha B-crystallin by the cytokine TGF-beta depends on basal levels of the protein and its mRNA constitutively present within the cells. Comparison of the increase in alpha B-crystallin mRNA and protein expression indicate that post-transcriptional regulation mechanisms are responsible for these findings in CM cells.


Development of a versatile and stable internal control system for RT-qPCR assays.
RT-qPCR, an established method for the detection of RNA viruses, requires internal RNA controls for the correct interpretation of PCR results. Robust and versatile RT-PCR controls can be achieved for example by packaging RNA into a virus-derived protein shell. In this study a MS2-based internal control system was developed, that allows stable and universal packing of different RNAs into non-infectious, non-lytic MS2-based viral like particles (VLPs). Two competitive internal controls for a hantavirus assay and a Crimean-Congo Hemorrhagic Fever Virus (CCHFV) assay were cloned for the expression of VLPs. The expression of VLPs containing the RNA of interest could be induced with arabinose in Escherichia coli. The VLPs proved to be temperature resistant and could be frozen and thawed several times without degradation. Distinction of IC RNA from the target RNA was facilitated by a clear shift in the melting temperature or by specific hybridization signals. Furthermore, target and IC PCR amplification could be easily distinguished by their size in gel-electrophoretic analyses. Limits of detection were determined, demonstrating that the application of the IC did not reduce the sensitivity of the target RT-qPCR reactions. The system can be adapted to nearly any required sequence, resulting in a highly flexible method with broad range applications.