Analysis of temperature/pressure sensitivity of the resonant wavelength of long-period channel waveguide gratings.
A theoretical study on the sensitivity of the resonant wavelength of long-period waveguide gratings (LPWGs) to temperature and pressure is reported. Starting with the phase-matching condition of the LPWG, general expressions for the temperature and pressure sensitivities are derived. The temperature sensitivity considers the thermo-optic and thermal expansion effects, and the pressure sensitivity takes into account the elasto-optic and elastic deformation effects of the materials involved, as well as the modal dispersion effect. Focusing on the extensively studied glass and polymer waveguides, the contributions of these effects to the temperature or pressure sensitivity were roughly evaluated and illustrated in the form of histograms in order to show the roles of these effects straightforwardly. The results show that a LPWG based on a polymer waveguide is preferred to that based on a glass waveguide for obtaining high temperature or pressure sensitivity. The temperature sensitivity is dominated by the modal dispersion effect and the difference between the thermo-optic coefficients of the waveguide and the cover layer materials, while the thermal expansion effects make only a minor contribution to the sensitivity for the cases of both glass and polymer waveguides. The pressure sensitivity is dominated by the modal dispersion effect and the difference between the elasto-optic coefficients of the channel waveguide and the cover layer materials. In particular, in the case of the polymer LPWG the elastic deformation effects of the waveguide and grating materials make a moderate contribution to the pressure sensitivity and cannot be ignored. The minor contributions from the thermal expansion effects or the elastic effects may play a role in designing a temperature- or a pressure-insensitive LPWG device. Finally, the possibility that the waveguide loss affects the LPWG temperature/pressure sensitivity is discussed.


Phase-locking factor in a motor imagery Brain-Computer Interface.
A Brain-Computer Interface (BCI) attempts to create a direct channel of communication between the brain and a computer. This is especially important for patients that are "locked in", as they have limited motor function and thus require an alternative means of communication. In this scope, a BCI can be controlled through the imagination of motor tasks, i.e. Motor Imagery. This thinking of actions produce changes on the ongoing Electroencephalogram (EEG), such as the so called Event-Related Desynchronization (ERD), that can be detected and measured. Traditionally, ERD is measured through the estimation of EEG signal power in specific frequency bands. In this work, a new method based on the phase information from the EEG channels, through the Phase-Locking Factor (PLF), is proposed. Both feature types were tested in real data obtained from 6 voluntary subjects, who performed 7 motor tasks in an EEG session. The features were classified using Support Vector Machine (SVM) classifiers organized in a hierarchical structure. The results show that the PLF features are better, with an average accuracy of ≈ 86%, against an accuracy of ≈ 70% for the band power features. Although more research is still needed, the PLF measure shows promising results for use in a BCI system.


ProTaper rotary root canal preparation: effects of canal anatomy on final shape analysed by micro CT.
To evaluate the relative performance of ProTaper nickel-titanium (Ni-Ti) instruments shaping root canals of varying preoperative canal geometry. Extracted human maxillary molars were scanned, before and after shaping with ProTaper, employing micro computed tomography (muCT) at a resolution of 36 mum. Canals were three-dimensionally reconstructed and evaluated for volume, surface area, 'thickness' (diameter), canal transportation and prepared surface. Based on median canal volume, canals were divided into 'wide' and 'constricted' groups. Comparisons were made between mesiobuccal (mb), distobuccal (db) and palatal (p), as well as 'wide' and 'constricted' canals, using repeated-measures anova and Scheffé posthoc tests. Volume and surface area increased significantly and similarly in mb, db and p canals, and gross preparation errors were found infrequently. Root canal diameters, 5-mm coronal to the apex, increased from 0.38 to 0.65 mm, 0.42 to 0.66 mm and 0.57 to 0.79 mm for mb, db and p canals, respectively. Apical canal transportation ranged from 0.02 to 0.40 mm and was independent of canal type; 'wide' canals had a significantly higher (P < 0.05) proportion of unprepared surfaces than 'constricted' canals. Canals in maxillary molars were prepared in vitro using ProTaper instruments without major procedural errors. These instruments may be more effective in shaping narrow canals than wider, immature ones.


Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function.
An Icelandic family with two cases of benign monoclonal gammopathy and one case each of Waldenström's macroglobulinaemia, histiocytic lymphoma and multiple myeloma was first described in 1978. Nine family members had then shown raised values for se-IgM. Of these one has since died and another was not available for testing. In four of the remaining seven se-IgM had returned to normal; the three subjects who still showed raised se-IgM included the case of multiple myeloma diagnosed in 1985. Baseline production of IgM, IgG and Ig in vitro was normal in the 35 family members studied compared with 13 healthy control subjects, but the mean production of all immunoglobulin classes in response to minimal stimulation with PWM (1 microgram/ml) was significantly increased (P < 0.05). Ten family members showed markedly increased production of all three immunoglobulin classes (> 3 x SD above mean for controls). Raised production of IgM never occurred alone, indicating intact class switching. One family member showed extremely high values: IgA: 5.15 micrograms/ml, IgG: 16.3 micrograms/ml, IgM: 24.8 micrograms/ml (means for controls: 0.066, 0.123, 0.185 respectively). These 10 family members were of both sexes, ranged in age from 16 to 84 years and were clustered mainly in three distinct groups within the pedigree suggesting heredity. Proliferative responses to PWM were not significantly increased. Serum levels of interleukin-4 were tested in the patient with multiple myeloma and the family member with highest Ig production and found to be normal. We found no evidence for depressed NK function. Thus, in this family with a tendency for macroglobulinaemia and B cell derived malignancies B cell hyperreactivity was detectable by in vitro testing in several asymptomatic family members, of both sexes and all ages. No evidence was obtained for defects in regulatory mechanisms.


Child care practices of mexican-american working mothers: a pilot study.
There is scarce information on child care strategies among Hispanics in the United States. The purpose of this pilot study was to identify and understand child care practices in a sample of forty-five Mexican-American working mothers living in northern California by means of conducting six focus groups. Results included data on child care selection, problems, and preferences. Results also expose myths based on ethnic stereotyping that have obscured the understanding of this issue. Suggestions for further research are discussed as well as child care policy considerations.


Resistance to NMDA toxicity correlates with appearance of nuclear inclusions, behavioural deficits and changes in calcium homeostasis in mice transgenic for exon 1 of the huntington gene.
Transgenic Huntington's disease (HD) mice, expressing exon 1 of the human HD gene (lines R6/1 and R6/2), are totally resistant to striatal lesions caused by the NMDA receptor agonist quinolinic acid (QA). Here we show that this resistance develops gradually over time in both R6/1 and R6/2 mice, and that it occurred earlier in R6/2 (CAG-155) than in R6/1 (CAG-115) mice. The development of the resistance coincided with the appearance of nuclear inclusions and with the onset of motor deficits. In the HD mice, hippocampal neurons were also resistant to QA, especially in the CA1 region. Importantly, there was no change in susceptibility to QA in transgenic mice with a normal CAG repeat (CAG-18). R6/1 mice were also resistant to NMDA-, but not to AMPA-induced striatal damage. Interestingly, QA-induced current and calcium influx in striatal R6/2 neurons were not decreased. However, R6/2 neurons had a better capacity to handle cytoplasmic calcium ([Ca2+]c) overload following QA and could avoid [Ca2+]c deregulation and cell lysis. In addition, basal [Ca2+]c levels were increased five-fold in striatal R6/2 neurons. This might cause an adaptation of R6 neurons to excitotoxic stress resulting in an up-regulation of defense mechanisms, including an increased capacity to handle [Ca2+]c overload. However, the increased level of basal [Ca2+]c in the HD mice might also disturb intracellular signalling in striatal neurons and thereby cause neuronal dysfunction and behavioural deficits.


[Dipeptidyl peptidase IV of peripheral blood lymphocytes in patients with primary biliary cirrhosis].
Investigations concerning changes of dipeptidyl-peptidase IV-positive (DP IV+) lymphocytes in the peripheral blood (PBL) were undertaken in 22 patients with primary biliary cirrhosis (PBC) under therapy with ursodeoxycholic acid (750 mg/day). We found that after 4-8 weeks of therapy the number of DP IV+ PBL was raised from an initially low, suppressed level of 5-12% to 18-33% corresponding to the range observed in healthy subjects. Concurrently liver function parameters of the patients were significantly improved. The identity of DP IV+ CD 26+ peripheral T-cells could be shown by the combination of cytochemical DP IV-staining with the indirect immuno-fluorescence of the lymphocyte marker CD 26. These results show that the UDCA-therapy in patients with PBC has a direct effect on the immune system and a positive influence on the immuno-regulative capacity.


Transient expression of a ventricular myosin heavy chain isoform in developing chicken intrafusal muscle fibers.
Sections of chicken tibialis anterior and extensor digitorium longus muscles were incubated with monoclonal antibodies against myosin heavy chains (MHC). Ventricular myosin was present in developing secondary intrafusal myotubes when they were first recognized at embryonic days (E) 13-14, and in developing extrafusal fibers prior to that date. The reaction in intrafusal fibers began to fade at E17, and in 2-week-old postnatal and older muscles the isoform was no longer recognized. Only those intrafusal fibers which also reacted with a monoclonal antibody against atrial and slow myosin contained ventricular MHC. Intrafusal myotubes which developed into fast fibers did not express the isoform. Hence, based on the presence or absence of ventricular MHC, two lineages of intrafusal fiber are evident early in development. Strong immunostaining for ventricular MHC was observed in primary extrafusal myotubes at E10, but the isoform was already downregulated at E14, when secondary intrafusal myotubes were still forming and expressed ventricular MHC. Only light to moderate and transient immunostaining was observed in coexisting secondary extrafusal myotubes, most of which developed into fast fibers. Thus at the time when nascent muscle spindles are first recognized, differences in MHC profiles already exist between prospective intrafusal and extrafusal fibers. If intrafusal fibers stem from a pool of primordial muscle cells, which is common to intrafusal and extrafusal myotubes, they diverged from it some time prior to E13.


Summated circulatory responses of thermal and baroreflexes in humans.
Baroreceptor and thermal receptor mediated reflexes are important neural control systems that can markedly alter blood pressure in humans. These two systems have different afferent limbs and are integrated at different central sites. Although the circulatory effects of activating these individual reflexes have been examined, the effects of simultaneous activation of two or more separate reflexes have received relatively little attention. We used noninvasive methods in 13 normal men (20-27 yr) to examine the responses mediated by cardiopulmonary and arterial baroreceptors; the reflexes were elicited by alterations in central blood volume [lower body negative pressure (LBNP) and leg elevation (LE)] in the presence or absence of local thermal receptor stimulation induced by hand immersion (HI) in 10 degree C water. During all levels (-10, -25, and -40 Torr) of LBNP and during LE, forearm vascular resistance (FVR) was altered. At the two higher levels of LBNP, stroke volume, cardiac index, and blood pressure (BP) decreased, and heart rate (HR) and total peripheral resistance (TPR) increased. TPR, FVR, and BP increased during HI. Our analyses indicated that responses to combined stimuli, i.e., local cold during LBNP or LE, resulted in simple additive responses in all variables except HR. A central interaction between thermal and baroreflex control of HR is possible.


Neuroblastoma associated with seizures and arrested development.
Two unrelated cases of childhood peripheral neuroblastoma associated with infantile seizures and developmental problems (but without opsoclonus-myoclonus) are presented. The considerable body of evidence supporting the view that the opsoclonus-myoclonus syndrome associated with neuroblastoma has an immunologic basis is reviewed. Patients with neuroblastoma and opsoclonus-myoclonus syndrome commonly have subsequent developmental problems and, rarely, may have seizures. The authors postulate that the seizures and developmental problems in their two patients may result from an immunologic mechanism similar to that suggested for the opsoclonus-myoclonus syndrome of neuroblastoma. The only laboratory evidence to support an immunologic mechanism in these two patients was the presence of raised cerebrospinal fluid immunoglobulins in Patient 2. Specific antineuronal antibody tests in Patient 2 were negative. It is therefore possible that the association reported in these two unrelated cases is coincidental. However, reasonably extensive investigations did not uncover an alternative etiology for the presence of the seizures and developmental delay.


Peripheral or axial bone density measurements to identify osteoporosis in prostate cancer patients undergoing androgen deprivation therapy?
To compare aDEXA and pDEXA in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). A significant proportion of patients presenting with advanced PCa are osteoporotic, and many will become so because of ADT. Guidelines have recommended bone densitometry assessment before beginning ADT, with subsequent monitoring. However, axial dual energy x-ray absorptiometry (aDEXA) scanners, being large, expensive, and hospital-based, are not always widely available. Peripheral DEXA (pDEXA), with portable, office-based machines can be used, but the results have mostly been compared with aDEXA in women without cancer. A total of 73 men (mean age 76 years) with advanced PCa, who were receiving ADT and found to be osteoporotic (T score <or=-2.5) on pDEXA (Osteometer-DTX200) were also scanned by aDEXA (Hologic-QDR 4500 DEXA). Comparisons were made between the bone mineral density measurements of the ultradistal forearm and axial sites. The mean +/- SD T score of the forearm, femoral neck, total hip, and lumbar spine was -3.4 +/- 0.8, -2.6 +/- 1.0, -1.8 +/- 0.9, and -0.8 +/- 1.3, respectively. Of the 73 men, 67, 61, and 39 were found to be osteoporotic or osteopenic at the femoral neck, total hip, and lumbar spine, respectively. The correlation coefficients between the forearm and axial T scores were all significant (P < .05): femoral neck, r = 0.32, total hip, r = 0.34, lumbar spine, r = 0.24. When osteoporosis is diagnosed on pDEXA, most patients with PCa will be either osteoporotic or osteopenic at the hip, but a large proportion will be normal at the lumbar spine. In this setting, lumbar DEXA might be less reliable at predicting the fracture risk probably owing to calcification and degenerative changes.


Single-dose pharmacokinetics and effect of food on the bioavailability of topiramate, a novel antiepileptic drug.
Topiramate, a new antiepileptic drug effective in controlling partial-onset seizures, was administered to humans for the first time as single oral doses of 100 mg, 200 mg, 400 mg, 800 mg, and 1,200 mg in a phase I safety and pharmacokinetic study. Model-independent pharmacokinetic data analysis was performed on plasma concentration and renal excretion data for topiramate. Maximum plasma concentrations (Cmax) were observed between 1.4 and 4.3 hours after administration. Mean values for plasma Cmax and area under the concentration-time curve (AUC) increased linearly with dose; however, a greater-than-proportional increase in both parameters was observed, probably due to saturable binding of the drug to erythrocytes. Mean oral clearance (Cl/F) was 22.5 to 36.1 mL/min and mean volume of distribution (Vd/F) was 38.5 to 58.0 L. Approximately 50% of the dose was excreted renally and cumulative urinary excretion increased linearly and proportionally over the 200 mg to 1,200 mg dose range. Elimination half-life (t1/2) values calculated from plasma (21.5 hrs) and urinary data (18.5 hrs) were consistent and independent of dose. Intersubject variability was low for all parameters. Renal clearance was 13.9 mL/min, suggesting that renal tubular reabsorption may be prominently involved in the renal handling of topiramate. The elimination profile of topiramate indicated that longer sampling times are necessary in future studies to more accurately determine the t1/2. Food effect studies indicated a slight reduction in the rate (approximately 10% decrease in mean Cmax and mean tmax approximately 2 hours later) but not the extent of absorption when topiramate was given with food. Topiramate demonstrates a number of favorable pharmacokinetic features, including linear and predictable dose-concentration relationships, excretion mainly as unchanged drug by the kidney, a dose-independent t1/2, low intersubject variability in pharmacokinetic parameters, and lack of clinically significant effect of food on bioavailability.


Isolation of Inoue-Melnick virus from colorectal carcinoma tissues.
Isolation of Inoue-Melnick virus (IMV) Type 1 from tumor tissues of patients with colorectal carcinoma in Japan was reported. A high prevalence of IMV antibodies has been found among patients with colorectal carcinoma in Buffalo, New York. IMV was isolated from homogenates of colorectal carcinoma and other tissues, inoculated into MRC-5 human fibroblast cultures. IMV-specific cytopathic effects were detected and titrated following 7 days of incubation in a roller-tube apparatus. IMV was isolated from all nine (100%) colorectal carcinoma tissues tested and all four (100%) normal parts of colon mucosa tissues obtained from patients with cancer. Biopsy specimens of normal colon mucosa from 10 patients without colon carcinoma were negative for IMV (0%). Average infectious titers of IMV in these tissue homogenates were 4.41 for tumor tissue and 2.55 log10 tissue culture infectious dose by 50% (TCID50)/0.1 ml for colon mucosa, respectively. Most of the isolates were the IMV intermediate type. Our results confirmed the production of infectious IMV in colorectal carcinoma tissues, as reported recently in Japan. The role of IMV in colorectal carcinogenesis is currently unknown.


Investigation of factor VIII:C gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria.
The frequency of alleles for intragenic (intron 17 and intron 25) and extragenic (DXS15 and DXS52) F8C RFLPs was investigated in the Algerian population. Altogether 287 X chromosomes (97 males and 95 females) were studied. The allele frequencies found with the two intragenic F8C RFLPs were not substantially different from those reported in a Mediterranean population. At the highly polymorphic extragenic DXS52 locus the distribution in Algeria differed from that found in France. A new allele (14 kb), called 1 DZ, was found in 3.1% of the chromosomes. Fifty-one families with hemophilia A were studied with the same probes (374 subjects). Of the females, 94% were informative for at least one intra- or extragenic RFLP. Two recombinations were found between DXS52 and F8C, of which one occurred between the DXS15, DXS52 block and F8C, indicating that the two anonymous loci are on the same side of the F8C gene. Only two obvious gene deletions were observed in 73 unrelated hemophiliacs: one encompassed exons 14-22 (about 4.3 kb of cDNA and 36 kb of genomic DNA); the other removed the last exon (exon 26, representing 2 kb of cDNA).


Spatial distribution and population genetics of Leishmania infantum genotypes in São Paulo State, Brazil, employing multilocus microsatellite typing directly in dog infected tissues.
This study investigated the genetic characteristics of Leishmania infantum samples from São Paulo (SP) State, Brazil in order to collaborate with information about the possible origins of the parasites, as well as, the introduction and spread of visceral leishmaniasis in this Brazilian State. Multilocus microsatellite typing (MLMT) was performed using a set of 17 microsatellite markers. DNA was extracted from 250 samples collected from dogs diagnosed with visceral leishmaniasis and 112 (45%) were genotyped: 67 from the northwest region (NWSP), and 29 from the southeast region (SESP) of SP. The results were correlated with other 16 samples from Mato Grosso do Sul State (MS) (which borders NWSP). Although, a small portion of samples was genotyped, it was possible to genotype multiple loci using small amounts of Leishmania DNA extracted directly from dog tissues. Despite the fact that MLMT analysis defined 33 different genotypes, a low polymorphism was detected within the parasites studied with 10 polymorphic loci. There are two main genetic clusters circulating in SP with strong genetic differentiation, one (POP-A) is composed by samples from SESP and NWSP and presented a weak signal of geographical substructure. The other, belongs to the same cluster found in the state of MS (POP-B), which was the main one. The majority (93.75%) of MS parasite genotypes belonged to POP-B, with just one sample (6.25%) grouped in POP-A. POP-B also comprised 10.34% of SESP and 26.87% of NWSP samples. Besides one sample from MS, POP-A is composed by 73.13% of NWSP and 89.66% of SESP samples. The MLMT analysis supported the idea of canine visceral leishmaniasis being introduced in the Northwest region of SP State by the traffic of humans and dogs from MS. In the southeast region of SP occurred an introduction of a new L. infantum genetic cluster. Probably the transmission was spread by traffic of infected dogs from other Brazilian regions, or by introduction of imported dogs from other countries. All these data together contributed to the detection of the genetic profile of L. infantum population in SP State.


Variations in self-reported nausea, vomiting, and well-being during the first 10 days postchemotherapy in women with breast cancer.
Women with breast cancer undergoing chemotherapy experience nausea and vomiting, both common symptoms affecting quality of life. The aim of the current study was to describe how nausea, vomiting, and well-being vary during the first 10 days after chemotherapy in women with breast cancer. A pilot study with a repeated-measurements design was conducted at a Swedish county hospital where 39 women with breast cancer treated with adjuvant chemotherapy were observed. A structured 10-day diary was used for data collection. Of the 39 women in the study, 33 experienced nausea and 6 also experienced vomiting after chemotherapy. Changes in well-being as a result of nausea or vomiting during any part of the day, as well as distress for other reasons, were reported. Well-being also varied among the individuals. The pattern of change in experienced levels of well-being was not homogeneous, nor did it move in any certain direction. The results of this study show that an individualized treatment approach is required to better meet individual women's needs.


[Strain-specific antigens detected on murine tumour cells by means of rabbit heteroantisera (author's transl)].
The rabbit heteroantisera anti-Meth A sarcoma (H-2d) (RAMA) and rabbit anti-RBL-5 leukemia (H-2b) (RAR-5) have been used to study the presence of normal strain antigens on the surface of different murine tumour cells. RAR-5 detected H-2-like structures on TLX9 (H-bb) lymphoma, however RAMA did not on LSTRA leukemia (H-2d) mastocytoma. Neither RAR-5 nor RAMA contained antibodies against non-H-2 and differentiation antigens.


Absence of evidence that the pro re nata regimen confers benefit: a review of the studies.
Studies were sought that evaluated the prevalence, effectiveness, and safety of pro re nata (p.r.n.) medications in psychiatric practice for which evidence has been scarce despite their wide application. To this end, a systematic literature search was performed using various search engines (last search: October 2012) with cross-referencing. A total of 34 studies were identified: 16 studies on epidemiological usage, 16 retrospective studies on effectiveness/safety as well as reasons, and only two prospective studies on the effectiveness/safety of p.r.n. medications. All the patients studied were inpatients, and the reasons for p.r.n. were acute behavioral dyscontrol in 29 studies. Psychiatric diagnoses and outcome measures to assess effectiveness/safety varied and were described in 27 and 20 studies, respectively. Medications under study included antipsychotics (mainly chlorpromazine, haloperidol, olanzapine, risperidone, or quetiapine), benzodiazepines (mainly diazepam and lorazepam), and antihistamines (mainly diphenhydramine). Altogether, 17 studies reported that p.r.n. medications were effective in psychiatric inpatients. Those two prospective studies targeted solely a child/adolescent population with small sample sizes. Currently available data are limited in number, quality, and scope; there has been only equivocal evidence to guide the choice of p.r.n. medications for psychiatric patients, hence there is a need for more investigations on this important clinical topic.


The relationship between the GJB3 c.538C>T variant and hearing phenotype in the Chinese population.
Mutations in GJB3 were originally shown to underlie an autosomal dominant form of non-syndromic deafness in Chinese patients and the c.538C>T (p.R180*) variants caused high-frequency hearing loss. But after that, few reports have reported this mutation. This study investigated the relationship between the GJB3 c.538C>T variant and hearing phenotype in Chinese to assist with risk assessment and genetic counseling for hearing loss patients and their families. The study enrolled 5700 patients with hearing loss and 4600 normal subjects. Deafness gene mutations were distinguished using a gene chip. The GJB3 c.538C>T variant rate was calculated from the results. Of the 5700 patients, 23 (0.40%) carried a GJB3 c.538C>T heterozygous variant; of these, 11 patients had other gene (GJB2/SLC26A4) mutations simultaneously. Most patients had moderate to profound hearing loss. All 23 patients were sporadic cases and had no family history of deafness. Of the 4600 normal individuals, 11 (0.24%) had GJB3 c.538C>T heterozygous variant. There was no statistical difference in incidence between the two groups. Our results showed that the GJB3 c.538C>T variant has a very low incidence in the Chinese population, and there was no clear evidence to support a role of the GJB3 c.538C>T variant in the autosomal dominant form of non-syndromic deafness. Our findings suggested that GJB3 c.538C>T does not contribute to hearing loss, and this conclusion will assist with genetic counseling and risk prediction for deafness related to the GJB3 c.538C>T variant.


Association of Sympathovagal Imbalance With Cognitive Impairment in Type 2 Diabetes in Adults.
Sympathovagal imbalance (SVI) has been reported to be associated with metabolic derangements in type 2 diabetes. We investigated the association of SVI with cognitive impairment in patients with type 2 diabetes. Patients with a new diagnosis of type 2 diabetes (n=43) and age-matched healthy control subjects (n=43) were recruited for the study. Body mass index and blood pressure measurements were recorded. SVI was assessed by spectral analysis of heart rate variability (HRV), and cognitive function was assessed by recording the positive wave that appears in 300 milliseconds from application of stimulus in event-related potential tracing (P300). Insulin resistance was determined by the homeostatic model assessment of insulin resistance (HOMA-IR) formula using blood glucose and insulin data, and oxidative stress was assessed by estimation of malondialdehyde. Association of various factors with cognitive impairment was evaluated by Pearson correlation analysis, and independent contributions of these factors to cognitive impairment were assessed by multiple regression analysis. P300 latency was significantly prolonged in the diabetes group compared with the control group. Ratio of low-frequency to high-frequency power (LF-HF ratio) of HRV, the marker of SVI was found to be significantly correlated and linked with P300. Malondialdehyde and HOMA-IR were correlated with LF-HF ratio. Treatment-naïve patients with type 2 diabetes have SVI and considerable cognitive impairment. Insulin resistance and oxidative stress contribute to cognitive impairment, and SVI could be the physiologic link to cognitive impairment in treatment-naïve patients with type 2 diabetes.


Fluorescence microscopy and 3D image reconstruction of cytokine initiated disruption of the Parkinson disease associated proteins alpha-synuclein, tau and ubiquitin in cultured glial cells.
Human derived glioblastoma cells were cultured and treated with cytokines interleukin-6 (IL6), tumor necrosis factor alpha (TNF) and interferon-gamma (IFN) and imaged by fluorescence deconvolution microscopy to localize alpha-synuclein, tau and ubiquitin. Exposures were for short (2 h) and prolonged times (up to 96 h), with doses at both low (10 ng/ml), and high (100 ng/ml) concentrations. Further experiments used additive doses up to 200 ng/ml (2 x 100 ng), mimicking a super-infection state. Single, low doses of the cytokines initiated changes in levels of intracellular proteins, but these changes, be they increases or decreases, were not sustained, so we added higher doses of cytokine to the culture medium or fresh aliquots of cytokines over time. Finally, we treated cells with high, single doses of cytokine (200 ng/ml), to try to sustain perturbations of the proteins with cytokines. IFN caused a disruption and reduction of peripheral synuclein, TNF treatment resulted in increased levels of ubiquitin and IL6 disrupted and appeared to fragment tau. Of note, each of the proteins was found in a specific locale, tau being perinuclear, ubiquitin residing in the cytoplasm, and alpha-synuclein occupying the tips of cellular processes, exhibiting the characteristics of an adhesion protein/molecule [Word count=198].


Response of preschool children with asthma symptoms to fluticasone propionate.
Many uncertainties remain in the diagnosis and treatment of preschool children with asthma symptoms. We sought to determine the subgroups of preschool children (aged 12-47 months) with recurrent asthma symptoms most likely to respond to inhaled fluticasone propionate (200 microg/d). Subgroups of pooled data from 2 similar 12-week multicenter studies were analyzed. Children with frequent symptoms (symptoms on > or =3 days per week and a total of > or =75% days with symptoms during the 4-week run-in period; n = 169) showed a significantly greater increase in days without symptoms after fluticasone propionate treatment (0% to 45%) compared with after placebo treatment (0% to 25%, P =.005). Children with a family history of asthma (n = 213) also had a significantly greater increase in days without symptoms after fluticasone propionate (11% to 54%) compared with after placebo (7% to 35%, P =.002) and a significantly higher proportion of exacerbation-free patients (61% to 76%, P =.02). Children with less frequent symptoms, no family history of asthma, or both showed no significant treatment effect. There seemed to be no association between response to fluticasone propionate and history of rhinitis or eczema or the number of previous exacerbations. Children with frequent symptoms, a family history of asthma, or both showed the greatest response to fluticasone propionate treatment. These findings may help to predict treatment outcome and guide the management of preschool children with recurrent asthma symptoms.


A novel ascorbic acid sensor based on the Fe3+/Fe2+ modulated photoluminescence of CdTe quantum dots@SiO2 nanobeads.
In this paper, CdTe quantum dot (QD)@silica nanobeads were used as modulated photoluminescence (PL) sensors for the sensing of ascorbic acid in aqueous solution for the first time. The sensor was developed based on the different quenching effects of Fe(2+) and Fe(3+) on the PL intensity of the CdTe QD@ silica nanobeads. Firstly, the PL intensity of the CdTe QDs was quenched in the presence of Fe(3+). Although both Fe(2+) and Fe(3+) could quench the PL intensity of the CdTe QDs, the quenching efficiency were quite different for Fe(2+) and Fe(3+). The PL intensity of the CdTe QD@silica nanobeads can be quenched by about 15% after the addition of Fe(3+) (60 μmol L(-1)), while the PL intensity of the CdTe QD@silica nanobeads can be quenched about 49% after the addition of Fe(2+) (60 μmol L(-1)). Therefore, the PL intensity of the CdTe QD@silica nanobeads decreased significantly when Fe(3+) was reduced to Fe(2+) by ascorbic acid. To confirm the strategy of PL modulation in this sensing system, trace H2O2 was introduced to oxidize Fe(2+) to Fe(3+). As a result, the PL intensity of the CdTe QD@silica nanobeads was partly recovered. The proposed sensor could be used for ascorbic acid sensing in the concentration range of 3.33-400 μmol L(-1), with a detection limit (3σ) of 1.25 μmol L(-1) The feasibility of the proposed sensor for ascorbic acid determination in tablet samples was also studied, and satisfactory results were obtained.


Rapid, proteomic urine assay for monitoring progressive organ disease in Fabry disease.
Fabry disease is a progressive multisystemic disease, which affects the kidney and cardiovascular systems. Various treatments exist but decisions on how and when to treat are contentious. The current marker for monitoring treatment is plasma globotriaosylsphingosine (lyso-Gb3), but it is not informative about the underlying and developing disease pathology. We have created a urine proteomic assay containing a panel of biomarkers designed to measure disease-related pathology which include the inflammatory system, lysosome, heart, kidney, endothelium and cardiovascular system. Using a targeted proteomic-based approach, a series of 40 proteins for organ systems affected in Fabry disease were multiplexed into a single 10 min multiple reaction monitoring Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) assay and using only 1 mL of urine. Six urinary proteins were elevated in the early-stage/asymptomatic Fabry group compared with controls including albumin, uromodulin, α1-antitrypsin, glycogen phosphorylase brain form, endothelial protein receptor C and intracellular adhesion molecule 1. Albumin demonstrated an increase in urine and could indicate presymptomatic disease. The only protein elevated in the early-stage/asymptomatic patients that continued to increase with progressive multiorgan involvement was glycogen phosphorylase brain form. Podocalyxin, fibroblast growth factor 23, cubulin and Alpha-1-Microglobulin/Bikunin Precursor (AMBP) were elevated only in disease groups involving kidney disease. Nephrin, a podocyte-specific protein, was elevated in all symptomatic groups. Prosaposin was increased in all symptomatic groups and showed greater specificity (p<0.025-0.0002) according to disease severity. This work indicates that protein biomarkers could be helpful and used in conjunction with plasma lyso-Gb3 for monitoring of therapy or disease progression in patients with Fabry disease.


Efferent innervation of the cervical segment of the trachea in early postnatal ontogenesis.
A method based on retrograde axonal transport of horseradish peroxidase was used to study the efferent innervation of the cervical segment of the trachea in neonatal kittens and kittens aged 10, 20, and 30 days and two months. Labeled neurons in all animals were located in the cranial cervical, middle cervical, and cervicothoracic sympathetic ganglia on the right and left sides, at the level of the medulla oblongata, and in the dorsal and ambiguus nuclei of the vagus nerves. Up to age 30 days, neurons were also seen in the ventral horns of the spinal cord in segments C1 to C5. The number of sympathetic neurons innervating the trachea increased from the moment of birth, reaching a maximum by 10-20 days and then decreasing to age two months. The number of parasympathetic neurons gradually decreased during ontogenesis.


Quantifying segregation in an integrated urban physical-social space.
Our knowledge of how cities bring together different social classes is still limited. Much effort has been devoted to investigating residential segregation, mostly over well-defined social groups (e.g. race). Little is known of how mobility and human communications affect urban social integration. The dynamics of spatial and social-network segregation and individual variations along these two dimensions are largely untapped. In this article, we put forward a computational framework based on coupling large-scale information on human mobility, social-network connections and people's socio-economic status (SES), to provide a breakthrough in our understanding of the dynamics of spatio-temporal and social-network segregation in cities. Building on top of a social similarity measure, the framework can be used to depict segregation dynamics down to the individual level, and also provide aggregate measurements at the scale of places and cities, and their evolution over time. By applying the methodology in Singapore using large-scale mobile phone and socio-economic datasets, we find a relatively higher level of segregation among relatively wealthier classes, a finding that holds for both social and physical space. We also highlight the interplay between the effect of distance decay and homophily as forces that determine communication intensity, defining a notion of characteristic 'homophily distance' that can be used to measure social segregation across cities. The time-resolved analysis reveals the changing landscape of urban segregation and the time-varying roles of places. Segregations in physical and social space are weakly correlated at the individual level but highly correlated when grouped across at least hundreds of individuals. The methodology and analysis presented in this paper enable a deeper understanding of the dynamics of human segregation in social and physical space, which can assist social scientists, planners and city authorities in the design of more integrated cities.


Isolation of remnant particles by immunoseparation: a new approach for investigation of postprandial lipoprotein metabolism in normolipidemic subjects.
Abnormal postprandial lipoproteins are associated with an increased risk for cardiovascular disease. Postprandial remnant lipoproteins were usually analyzed indirectly using retinyl esters (RE) as a chylomicron core label during an oral fat loading test. Apo B-100 containing VLDL remnants in addition to apo B-48 containing chylomicron remnants can also be directly quantified using the RLP-Cholesterol Immunoseparation Assay. This recently available method uses monoclonal antibodies to apo A-I and apo B-100 to remove non-remnant lipoproteins and quantifies cholesterol in the remaining apo E-rich remnant fraction. In the present study we compared the analysis of retinyl ester with the immuno-based RLP-Cholesterol (RLP-C) analysis in measuring postprandial remnant lipoproteins in healthy normolipidemic subjects. Sixteen healthy normolipidemic subjects were selected for this study. Postprandial plasma retinyl esters peaked at 5.0+/-1.2 h, whereas plasma RLP-C showed a peak significantly earlier (P<0.001) at 3.5+/-0.6 h. In comparison, postprandial plasma TG and FFA peaked at 3.3+/-1.1 h (P<0.005 compared to retinyl esters). In conclusion, levels of RLP-C changed, during the postprandial phase, in parallel with plasma TG and FFA concentrations and peaked significantly earlier than retinyl esters. Postprandial measurements of RLP-C can be considered as a fast alternative method for the more laborious retinyl-ester analysis in clinical studies.


The compensatory antioxidant response system with a focus on neuroprogressive disorders.
Major antioxidant responses to increased levels of inflammatory, oxidative and nitrosative stress (ONS) are detailed. In response to increasing levels of nitric oxide, S-nitrosylation of cysteine thiol groups leads to post-transcriptional modification of many cellular proteins and thereby regulates their activity and allows cellular adaptation to increased levels of ONS. S-nitrosylation inhibits the function of nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor-mediated signalling and the activity of several mitogen-activated protein kinases, while activating nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2); in turn, the redox-regulated activation of Nrf2 leads to increased levels and/or activity of key enzymes and transporter systems involved in the glutathione system. The Nrf2/Kelch-like ECH-associated protein-1 axis is associated with upregulation of NAD(P)H:quinone oxidoreductase 1, which in turn has anti-inflammatory effects. Increased Nrf2 transcriptional activity also leads to activation of haem oxygenase-1, which is associated with upregulation of bilirubin, biliverdin and biliverdin reductase as well as increased carbon monoxide signalling, anti-inflammatory and antioxidant activity. Associated transcriptional responses, which may be mediated by retrograde signalling owing to elevated hydrogen peroxide, include the unfolded protein response (UPR), mitohormesis and the mitochondrial UPR; the UPR also results from increasing levels of mitochondrial and cytosolic reactive oxygen species and reactive nitrogen species leading to nitrosylation, glutathionylation, oxidation and nitration of crucial cysteine and tyrosine causing protein misfolding and the development of endoplasmic reticulum stress. It is shown how these mechanisms co-operate in forming a co-ordinated rapid and prolonged compensatory antioxidant response system.


Alprostadil plus Vacuum (VITARUM) in severe erectile dysfunction (ED).
Severe erectile dysfunction (ED) is not uncommon, as can be seen from the epidemiological literature, and there are several possible causes, which are not always known, or leastways evident. Having ascertained the ineffectiveness, intolerance to or rejection of pharmacological aids, the option of prosthetic surgery remains, but before this, it may be wise when feasible to use Alprostadil cream in association with Vacuum device. 12 patients, aged between 55 and 65 years, with severe erectile dysfunction without palpable cavernous fibrosis, were instructed to self-insert into the urethral meatus, 3 mg of Alprostadil cream, sufficient to make it easy to place the Vacuum device over the penis. In the cases observed, the preliminary use of Alprostadil cream fast produced an erection with enough rigidity to place the Vacuum. A sufficient erection was maintained, obviously using an elastic ring at the base of the penis, to achieve penetration. The reproducibility of the use of Alprostadil cream with Vacuum device was then confirmed at home, to the satisfaction of the patients.


[Potassium cyanate modification of the toxic and mutagenic effects of gamma radiation and benzo(a)pyrene].
In experiments with CHO-AT3-2 cell culture, a study was made of the effect of potassium cyanate (KNCO) on the effect of gamma radiation and benzo(a)pyrene (BP) by the following tests: cell viability, induction of cells with micronuclei and fragmented nuclei and mutations by thymidine kinase (TK) and Na+/K+-ATPase loci. Some tests have revealed the increase in the effect of gamma radiation and BP produced by potassium cyanate. It is suggested that the sensitizing effects are related to repair system inhibition and/or changes in the cell chromatin structure produced by KNCO.


Variability in glycosylated hemoglobin values in diabetic patients living in long-term care facilities.
The objectives of this study were to determine the prevalence of diabetes and mean A1C of patients in long-term care facilities (LTCFs); to determine differences in A1C values based on patient characteristics; and to examine the self-reported practices of providers regarding diabetes management goals. Twelve-month retrospective review of patient charts; survey of physicians and nurse practitioners providing care to these patients. Nursing facility practice of an urban teaching hospital. Participants included 168 diabetic patients living in 20 nursing facilities and 18 physician and nurse practitioners in one practice providing care to these patients. The prevalence of diabetes was 21.6% (168 of 778 patients). Mean A1C was 7.1% +/- 1.2%for 135 patients who had AIC values measured during the study interval. A1C varied by age, with patients younger than 65 having higher A1C values than patients older than 65. Higher A1C values were associated with insulin use, frequent glucose monitoring, and attending a diabetes clinic. Although a survey of providers identified modifying A1C target ranges for LTCF compared with ambulatory patients, they did not reach consensus on the actual target A1C. No association between provider perception of either patient health status or patient life expectancy and A1C values was found. Relatively low A1C values were obtainable in LTCF patients without diabetes specialty clinic use. Providers identified modifying target A1C values for LTCF patients, but achieved relatively low A1C values and did not agree on a target A1C value for LTCF patients.


Perceptions of clinical utility of an Augmented Reality musical software among health care professionals.
Augmented Reality musical software (GenVirtual) is a technology, which primarily allows users to develop music activities for rehabilitation. This study aimed to analyse the perceptions of health care professionals regarding the clinical utility of GenVirtual. A second objective was to identify improvements to GenVirtual software and similar technologies. Music therapists, occupational therapists, physiotherapists and speech and language therapist who assist people with physical and cognitive disabilities were enrolled in three focus groups. The quantitative and qualitative data were collected through inductive thematic analysis. Three main themes were identified: the use of GenVirtual in health care areas; opportunities for realistic application of GenVirtual; and limitations in the use of GenVirtual. The registration units identified were: motor stimulation, cognitive stimulation, verbal learning, recreation activity, musicality, accessibility, motivation, sonic accuracy, interference of lighting, poor sound, children and adults. This research suggested that the GenVirtual is a complementary tool to conventional clinical practice and has great potential to motor and cognitive rehabilitation of children and adults. Implications for Rehabilitation Gaining health professional' perceptions of the Augmented Reality musical game (GenVirtual) give valuable information as to the clinical utility of the software. GenVirtual was perceived as a tool that could be used as enhancing the motor and cognitive rehabilitation process. GenVirtual was viewed as a tool that could enhance clinical practice and communication among various agencies, but it was suggested that it should be used with caution to avoid confusion and replacement of important services.


Granulomatous angiopanniculitis of the breast. A case report.
Granulomatous angiopanniculitis (GAP) is a rare benign condition of the breast of unknown etiology. Clinically and by fine needle examination, GAP may simulate breast carcinoma. The cytologic characteristics have not been described before. A 63-year-old female exhibited a palpable mass in her left breast. The fine needle aspirate contained both epithelioid and stromal elements. The epithelioid component consisted of dissociated individual cells and small groups and clusters of atypical cells. The stromal component showed a uniform, not-atypical pattern. The lumpectomy specimen showed nonnecrotizing granulomatous panniculitis and lymphoid angiitis without involvement of ducts or lobules. Granulomatous lesions should be borne in mind in the differential diagnosis of breast cancer in fine needle aspiration cytology. GAP must be histopathologically distinguished from granulomatous inflammation in the breast of autoimmune or infectious origin as specific medical therapy may be available for these latter diseases.


Phylogeography of the Qinghai-Tibetan Plateau endemic Juniperus przewalskii (Cupressaceae) inferred from chloroplast DNA sequence variation.
The vegetation of the northeast Qinghai-Tibetan Plateau is dominated by alpine meadow and desert-steppe with sparse forests scattered within it. To obtain a better understanding of the phylogeography of one constituent species of the forests in this region, we examined chloroplast trnT-trnF and trnS-trnG sequence variation within Juniperus przewalskii, a key endemic tree species. Sequence data were obtained from 392 trees in 20 populations covering the entire distribution range of the species. Six cpDNA haplotypes were identified. Significant population subdivision was detected (G(ST) = 0.772, N(ST) = 0.834), suggesting low levels of recurrent gene flow among populations and significant phylogeographic structure (N(ST) > G(ST), P < 0.05). Eight of the nine disjunct populations surveyed on the high-elevation northeast plateau were fixed for a single haplotype (A), while the remaining, more westerly population, contained the same haplotype at high frequency together with two low frequency haplotypes (C and F). In contrast, most populations that occurred at lower altitudes at the plateau edge were fixed or nearly fixed for one of two haplotypes, A or E. However, two plateau edge populations had haplotype compositions different from the rest. In one, four haplotypes (A, B, D and E) were present at approximately equivalent frequencies, which might reflect a larger refugium in the area of this population during the last glacial period. Phylogenetic analysis indicated that the most widely distributed haplotype A is not ancestral to other haplotypes. The contrasting phylogeographic structures of the haplotype-rich plateau edge area and the almost haplotype-uniform plateau platform region indicate that the plateau platform was recolonized by J. przewalskii during the most recent postglacial period. This is supported by the findings of a nested clade analysis, which inferred that postglacial range expansion from the plateau edge followed by recent fragmentation is largely responsible for the present-day spatial distribution of cpDNA haplotypes within the species.


The hyperoxic test in infants reinvestigated.
The hyperoxic test (HT) examines peripheral chemoreceptor function (PCF) by measuring the decrease in ventilation (V E) after 100% O(2) inhalation. A 30-s HT has been previously used in infants with calculation of the ventilatory response (VR) as the mean percentage change in V E during HT as compared with normoxia. However, it has been shown that during hyperoxia V E rises secondarily after the initial drop because of loss of PCF. We hypothesized that the mean V E change over a 30-s HT may underestimate the strength of PCF and may be poorly reproducible. We performed breath-by-breath analysis during 30-s HTs, calculating VR at the response time (RT) defined as the time from HT onset to the first significant HT-related change in V E. Eighteen infants (postnatal age, 21 +/- 4 d) underwent two HTs (quiet sleep, face mask attached to a pneumotachograph, and inspired and expired O(2) and CO(2) fractions measured using mass spectrometry). V E, VT, and VT/TI decreases at the RT were significantly greater than the corresponding means (-21 +/- 7 versus -15 +/- 7%, -21 +/- 8 versus -13 +/- 8%, and -22 +/- 11 versus -17 +/- 11%, respectively). Intra-individual coefficients of variation of V E, VT and VT/TI were significantly smaller when RT values were considered rather than means. We conclude that calculation of the VR to HT at RT improves assessment of PCF and enhances HT reproducibility in infants.


Imaging of parasitic infections of the central nervous system.
Parasitic infections of the central nervous system (CNS) have increased over the last couple of decades, partly due to a drop in the living conditions of large populations in the world and the AIDS epidemic. Parasitic infections of the CNS are indolent and often life threatening, hence, an early diagnosis is imperative. While brain biopsy and laboratory analysis remain the gold standard for diagnosis, neuroimaging contributes significantly to diagnosis and follow-up. Imaging can demonstrate the extent of infection and complications and possibly, the type of parasitic infection when characteristic features are evident. The disappearance of the parasite or inflammation, gliosis, and/or calcification suggest a therapeutic response. The initial experience of the CT scan has been greatly enhanced by MRI which is currently the imaging modality of choice. This has been due to the greater tissue contrast resolution of MRI and its ability to detect subtle changes in the tissue parenchyma. Advanced techniques such as diffusion-weighted imaging (DWI), perfusion imaging (PI), MR angiography (MRA), and MR spectroscopy (MRS) have been used to improve the sensitivity for characterizing the type, viability, and burden of the parasites and the host tissue response. Additionally, it is possible to demonstrate the complications of the primary infection and those secondary to treatment, in some cases.


Relation between EPS adherence, viscoelastic properties, and MBR operation: Biofouling study with QCM-D.
Membrane fouling is one of the main constraints of the wide use of membrane bioreactor (MBR) technology. The biomass in MBR systems includes extracellular polymeric substances (EPS), metabolic products of active microbial secretion that adversely affect the membrane performance. Solids retention time (SRT) in the MBR is one of the most important parameters affecting membrane fouling in MBR systems, where fouling is minimized at optimal SRT. Among the operating parameters in MBR systems, SRT is known to strongly influence the ratio of proteins to polysaccharides in the EPS matrix. In this study, we have direct evidence for changes in EPS adherence and viscoelastic properties due to changes in the sludge removal rate that strongly correlate with the membrane fouling rate and EPS composition. EPS were extracted from a UF membrane in a hybrid growth MBR operated at sludge removal rates of 59, 35.4, 17.7, and 5.9 L day(-1) (corresponding SRT of 3, 5, 10, and 30 days, respectively). The EPS adherence and adsorption kinetics were carried out in a quartz crystal microbalance with dissipation monitoring (QCM-D) technology in several adsorption measurements to a gold sensor coated with Polyvinylidene Fluoride (PVDF). EPS adsorption to the sensor surface is characterized by a decrease of the oscillation frequency and an increase in the dissipation energy of the sensor during parallel flow of aqueous media, supplemented with EPS, above the sensor surface. The results from these experiments were further modeled using the Voigt based model, in which the thickness, shear modulus, and shear viscosity values of the adsorbed EPS layers on the PVDF crystal were calculated. The observations in the QCM-D suggested that the elevated fouling of the UF membrane is due to higher adherence of the EPS as well as reduction in viscosity and elasticity of the EPS adsorbed layer and elevation of the EPS fluidity. These results corroborate with confocal laser scanning microscopy (CLSM) image analysis showing thicker EPS in close proximity to the membrane surface operated at reactor conditions which induced more fouling at elevated sludge removal rates.


Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.
Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established.


Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants.
Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1.57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan-unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in fat mass influence SREBP-1c and UCP-2 gene expression in formerly obese subjects.
To investigate the effect of fat mass (FM) reduction on adipose tissue gene expression in terms of lipid synthesis [sterol regulatory binding protein 1c (SREBP-1c)] and lipid oxidation [uncoupling protein 2 (UCP-2)] 2 years after lipid malabsorption and to assess the influence of lipid malabsorption on fat-free mass (FFM) maintenance evaluating the expression of genes related to glycolysis [hexokinase (HKII)] and glucose storage [glycogen synthase (GS)]. SREBP-1c, UCP-2, HKII, and GS mRNA expression were studied by reverse transcriptase-competitive polymerase chain reaction in 10 massively obese subjects before and 2 years after bilio-pancreatic diversion (BPD). Body composition was assessed by isotopic dilution method and insulin sensitivity by euglycemic-hyperinsulinemic clamp. FM decrease was approximately 60%, whereas FFM remained at normal physiological levels. In adipose tissue, SREBP-1c mRNA reduction (-39%, p < 0.005) was related only to FM changes after BPD, and UCP-2 decrease (-37%, p < 0.05) was dependent on free fatty acid (FFA) changes. No significant variations were observed in HKII and GS gene expression in skeletal muscle. Lipid malabsorption induced by BPD altered the expression of genes involved in glucose and lipid metabolism, with different consequences on FM and FFM. The degree of FM loss seems to interfere with SREBP-1c gene suppression to preserve an adequate amount of fat storage, in accordance with the thrifty genotype hypothesis. The reduction of FFAs induced by BPD acts in inhibiting FFA transportation to the mitochondria (UCP-2), contributing to the decreased lipid oxidation inside the adipose tissue.


Quantitative clinical adjustment analysis of posterior single implant crown in a chairside digital workflow: A randomized controlled trial.
To compare the three-dimensional changes in quantity and morphology following clinical adjustment of a posterior single implant crown between chairside digital workflow (test) and hybrid digital workflow (control). A total of 33 participants were included for single-tooth replacement with screw-retained crowns in posterior sites of either the maxillary or mandible. A total of 17 participants were carried to a chairside digital workflow, receiving monolithic lithium disilicate (LS2)-crowns (test), while the remaining 16 participants were fitted with CAD/CAM-fabricated zirconia superstructures and hand-layered ceramic veneering crowns (control). As each crown underwent intraoral scanning (3Shape TRIOS Color, 3Shape), 3D digital models were rendered. These scans were taken both before and after try-in. Clinical adjustment dimensional changes were measured by superimposing the optical scans of models within a reverse software (Geomagic Control 2014). Adjustment counts and amounts (from vertical dimension) between two workflows were assessed and compared. Time consumption was recorded for efficiency analysis. All patients were successfully treated in both groups. The median maximum vertical adjustment (taking both occlusal and interproximal surfaces into consideration) was 237 μm ± 112 in the test group and 485 μm ± 195 in the control group (p < .0001), respectively. The median adjustment count was 2.00 ± 1.09 in test group and 3.00 ± 1.05 in control group (p = .001), respectively. The total active working time/ total time for two workflows was 92.3/113.7 min for the test group and 146.3/676.3 min for the control group, respectively. The test group showed fewer adjustments and apparent precision on the occlusal surface compared with the control group with only a fifth of the consumption of a hybrid workflow.


Differential GABAA receptor clustering determines GABA synapse plasticity in rat oxytocin neurons around parturition and the onset of lactation.
Expression, functional properties, and clustering of alpha 1-, alpha 2-, and alpha 3-subunit containing GABA(A) receptors (GABA(A)Rs) were studied in dorsomedial SON neurons of the adult female rat supraoptic nucleus (SON) around parturition. We show that, although the decay time constant (tau(decay)) of GABAergic postsynaptic currents between and within individual recordings was very diverse, ranging from fast (i.e., alpha 1-like) to significantly slower (i.e., non-alpha 1-like), there was an overall shift towards slower decaying synaptic currents during the onset of lactation. This shift is not due to changes in mRNA expression levels, because real-time quantitative PCR assays indicated that the relative contribution of alpha 1, alpha 2, and alpha 3 remained the same before and after parturition. Also, changes in phosphorylation levels are not likely to affect the tau(decay) of postsynaptic currents. In alpha-latrotoxin (alpha-LTX)-induced bursts of synaptic currents from individual synapses, the tau(decay) of consecutive synaptic events within bursts was very similar, but between bursts there were large differences in tau(decay). This suggested that different synapses within individual SON neurons contain distinct GABA(A)R subtypes. Using multilabeling confocal microscopy, we examined the distribution of postsynaptic alpha 1-, alpha 2-, and alpha 3-GABA(A)Rs, based on colocalization with gephyrin. We show that the three GABA(A)R subtypes occurred either in segregated clusters of one subtype as well as in mixed clusters of two or possibly even three receptor subtypes. After parturition, the density and proportion of clusters containing alpha 2- (or alpha 3-), but not alpha1-GABA(A)Rs, was significantly increased. Thus, the functional synaptic diversity at the postsynaptic level in dorsomedial SON neurons is correlated with a differential clustering of distinct GABA(A)R subtypes at individual synapses.


Blood inflammatory markers and risk of dementia: The Conselice Study of Brain Aging.
Incidence studies of blood inflammatory markers as predictors of dementia in older age are few and did not take into account hyperhomocysteinemia, although this condition is associated with both inflammation and increased risk of dementia. We investigated the relationships of baseline serum C-reactive protein (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and hyperhomocysteinemia (defined as plasma total homocysteine>15 micromol/L) with risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a dementia-free Italian population-based elderly cohort (n=804, 53.2% women, mean age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in combination, predicted AD risk whereas the combination of high CRP and high IL6 was associated with risk of VaD (HR, 2.56; 95%CI, 1.21-5.50) independently of socio-demographic confounders, traditional risk factors and hyperhomocysteinemia. By contrast, in the same model, hyperhomocysteinemia was independently associated with AD (HR, 1.91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia.


[Localized pleural mesotheliomas. Clinicopathological considerations on a case report].
Pleural mesotheliomas are rare, and their diagnosis and treatment not clear. The case observed in our Department leads us to an analysis of the literature. This showed that differential diagnosis with pulmonary carcinoma is very difficult, even in cases of parietal mesothelioma; however local treatment may be performed even in malignant mesothelioma.


Bilateral papillary renal cell carcinoma and angiomyolipoma in the patients with autosomal dominant polycystic kidney disease: case report of two cases and literature review.
We herein report two rare cases of bilateral renal neoplasms associated with autosomal dominant polycystic kidney disease (ADPKD). Case 1: Bilateral nephrectomy was performed on bilateral renal masses in a 58-year-old man with ADPKD. Case 2: Bilateral nephrectomy was performed on bilateral renal masses in a 32-year-old man with clinically suspected ADPKD. In case 1, angiomyolipoma (AML) and papillary renal cell carcinoma (PRCC) (type 1) were detected in the bilateral kidneys. In case 2, PRCC (type 1) was detected in the bilateral kidneys.


Immunological studies in neonates with spina bifida.
Fifteen neonates with spina bifida were investigated prior to surgery for T and B lymphocytes subpopulations and mitogen responsiveness to PHA. Results were compared to similar studies in 30 normal healthy neonates. The mean percentage of T-lymphocyes in spina bifida patients was 44.6% compared to 48.9% in normal neonates. A normal dose response to PHA was obtained in all patients. These results suggest no impairment of lymphocyte function in neonates born with spina bifida.


[Evaluation of chromatographic performance of polymerized ionic liquid stationary phase for capillary gas chromatography].
The selectivity and thermal stability of ionic liquids as the stationary phases for capillary gas chromatography (CGC) have attracted much attention of researchers in recent years. In this study, 1-vinyl-3-benzyl imidazolium-bis(trifluoromethane-sulphonyl)imidate (VBIm-NTf2) was synthesized and polymerized (PVBIm-NTf2) in a CGC column. In comparison with VBIm-NTf2, PVBIm-NTf2 exhibits much better thermal stability and chromatographic selectivity, and achieves satisfactory resolution for Grob test mixture, alcohols mixture, esters mixture and aromatics mixture with narrow and symmetric peak shapes. The satisfactory resolution and selectivity of the polymerized column still remain after conditioned at 250 degrees C for 6 h. Additionally, the Abraham solvation parameters of PVBIm-NTf2 were determined and the interactions between the stationary phase and solutes were elucidated. The present work demonstrates that the polymerization is an effective way to improve the selectivity and thermal stability of common ionic liquids as CGC stationary phases.


Early cortical orientation selectivity: how fast inhibition decodes the order of spike latencies.
Following a flashed stimulus, I show that a simple neurophysiological mechanism in the primary visual system can generate orientation selectivity based on the first incoming spikes. A biological model of the lateral geniculate nucleus generates an asynchronous wave of spikes, with the most strongly activated neurons firing first. Geniculate activation leads to both the direct excitation of a cortical pyramidal cell and disynaptic feed-forward inhibition. The mechanism provides automatic gain control, so the cortical neurons respond over a wide range of stimulus contrasts. It also demonstrates the biological plausibility of a new computationally efficient neural code: latency rank order coding.


Immunohistochemical study of oestrogen receptors in 351 human thyroid glands.
It is well recognised that the pathogenesis of thyroid diseases is complex and different factors such as genetic factors, iodine deficiency, sex, age, radiation therapy in childhood, growth stimulating antibodies, and other epithelial growth factors can influence them. Epidemiological features of thyroid tumours and experimental evidence suggest that female sex hormones may exert effects on the thyroid gland and its neoplasms. This possibility was addressed by investigating the expression of oestrogen receptor protein in 351 thyroid lesions. The tissues from 351 human thyroid glands comprising 130 nodular goitres and 221 neoplastic lesions were used for the present immunohistochemical assessment of oestrogen receptor expression. Incidence of oestrogen receptor positive cases were 24 percent (31/130) for nodular goitres, 22 percent (8/37) for follicular adenomas, 11 percent (2/18) for follicular carcinomas, 31 percent (37/119) for papillary carcinomas, zero percent (0/35) for medullary carcinomas and zero percent (0/12) for undifferentiated carcinomas. The incidence of oestrogen receptor positivity, which is compatible with other studies, is higher in well-differentiated thyroid lesions. The incidence of oestrogen receptor reactivity does not significantly differ between females and males of different age groups and it does not correlate with lymph node status, and vascular and capsular invasions. The relatively high proportion of oestrogen receptor positivity in goitres, follicular adenomas and papillary carcinomas, compared with its reactivity in other thyroid neoplasms, and contrasted against normal thyroid tissue, suggests that the incidence of oestrogen receptor reactivity tends to increase with better differentiation of thyroid lesions. This finding may have clinical relevance.


Probing the folding landscape of the Tetrahymena ribozyme: commitment to form the native conformation is late in the folding pathway.
Large, structured RNAs traverse folding landscapes in which intermediates and long-lived misfolded states are common. To obtain a comprehensive description of the folding landscape for a structured RNA, it is necessary to understand the connections between productive folding pathways and pathways to these misfolded states. The Tetrahymena group I ribozyme partitions between folding to the native state and to a long-lived misfolded conformation. Here, we show that the observed rate constant for commitment to fold to the native or misfolded states is 1.9 min(-1) (37 degrees C, 10 mM Mg(2+)), the same within error as the rate constant for overall folding to the native state. Thus, the commitment to alternative folding pathways is made late in the folding process, concomitant with or after the rate-limiting step for overall folding. The ribozyme forms much of its tertiary structure significantly faster than it reaches this commitment point and the tertiary structure is expected to be stable, suggesting that the commitment to fold along pathways to the native or misfolded states is made from a partially structured intermediate. These results allow the misfolded conformation to be incorporated into a folding framework that reconciles previous data and gives quantitative information about the energetic topology of the folding landscape for this RNA.


Exercise intensity and postprandial health outcomes in adolescents.
The effect of exercise intensity and sex on postprandial risk factors for cardiovascular disease in adolescents is unknown. We examined the effect of a single bout of work-matched high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on postprandial triacylglycerol (TAG) and systolic blood pressure (SBP) in adolescents. Twenty adolescents (10 male, 14.3 ± 0.3 years) completed three 1-day trials: (1) rest (CON); (2) 8 × 1 min cycling at 90 % peak power with 75 s recovery (HIIE); (3) cycling at 90 % of the gas exchange threshold (MIE), 1 h before consuming a high-fat milkshake (1.50 g fat and 80 kJ kg(-1)). Postprandial TAG, SBP and fat oxidation were assessed over 4 h Compared to CON, the incremental area under the curve for TAG (IAUC-TAG) was not significantly lowered in HIIE [P = 0.22, effect size (ES) = 0.24] or MIE (P = 0.65, ES = 0.04) for boys. For girls, HIIE and MIE lowered IAUC-TAG by 34 % (P = 0.02, ES = 0.58) and 38 % (P = 0.09, ES = 0.73), respectively, with no difference between HIIE and MIE (P = 0.74, ES = 0.14). Changes in TAG were not related to energy expenditure during exercise or postprandial fat oxidation. Postprandial SBP (total-AUC pooled for both sexes) was lower in HIIE compared to CON (P = 0.01, ES = 0.68) and MIE (P = 0.02, ES = 0.60), with no difference between MIE and CON (P = 0.45, ES = 0.14). A single bout of HIIE and MIE, performed 1 h before an HFM, can meaningfully attenuate IAUC-TAG in girls but not boys. Additionally, HIIE, but not MIE, may lower postprandial SBP in normotensive adolescents.


Chicken egg yolk antibodies specific for the gamma chain of human hemoglobin for diagnosis of thalassemia.
Immunoglobulin Y (IgY) technology was used to generate anti-hemoglobin Bart's (Hb Bart's) IgY antibodies (Abs) for development into an enzyme-linked immunosorbent assay (ELISA) test for thalassemia diagnosis. Hb Bart's purified from the hemolysate of a patient with Hb Bart's hydrops fetalis (homozygous alpha-thalassemia) was used to immunize a chicken via the pectoralis muscle. After water dilution and sodium sulfate precipitation, 40 to 70 mg of IgY could be extracted from an egg. IgY, first detected in sera 2 weeks after immunization, reached the highest titer at week 4, and the titer remained stable for at least 2 weeks before declining. The pattern of Ab response in the yolk was the same as in the serum but was somewhat delayed. The IgY Abs produced reacted with gamma globin, Hb Bart's, Hb F, normal cord hemolysate (Hbs F plus A), and Hb Bart's hydrops fetalis (Hbs Bart's plus Portland) and to a lesser degree with beta globin, Hb A, Hb A2 and adult hemolysate (Hbs A plus A2), but the Abs did not react with alpha globin. Immunoaffinity purification with Hb A coupled to Sepharose was used to isolate an unbound IgY that reacted with Hb F, Hb Bart's, and gamma globin, and this IgY was used to develop an ELISA test for thalassemia diagnosis. The results of direct ELISA analyses of 336 hemolysate samples from individuals with various known thalassemia genotypes and phenotypes and from healthy individuals confirmed the specificity of the polyclonal Abs for Hbs containing Hb F and Hb Bart's. This specificity, which was due to the Abs' strong reactivity in cases of pathologic thalassemic diseases and weak reactivity in cases of nonpathologic thalassemic diseases, depended on the levels of Hb Bart's and Hb F.


Wishful Thinking: The Surprisingly Sparse Evidence for a Relationship between Oxidative Stress and Cardiovascular Disease in Hemodialysis Patients.
The increased frequency of cardiovascular disease observed in hemodialysis patients is secondary to the combination of many traditional (age, male sex, hypertension, smoking, diabetes mellitus, and dyslipidemia) and novel and uremia-related (inflammation, uremic toxins, adipokine imbalance, coagulation disorders, protein-energy wasting, volume overload, endothelial dysfunction, hyperparathyroidism, and subclinical hypothyroidism) risk factors. Usually, in the latter group, oxidative stress is included. However, after decades of research, it remains essentially unknown if oxidative stress has a causative role in the development of cardiovascular disease in long-term hemodialysis patients because adequate longitudinal studies are lacking. Data deriving from cross-sectional studies suggest that biomarkers of oxidative stress are associated with cardiovascular disease prevalence. Conversely, conflicting and inconclusive results have been obtained on the association between oxidative stress and coronary artery calcification, atherosclerosis, and all-cause and cardiovascular disease-related outcome. It is desirable that further studies are conducted on this topic in the near future.


Characterization of key aroma-active sulfur-containing compounds in Chinese Laobaigan Baijiu by gas chromatography-olfactometry and comprehensive two-dimensional gas chromatography coupled with sulfur chemiluminescence detection.
Volatile sulfur-containing compounds (VSCs) often exist at extremely low concentrations, making them difficult to be determined. The VSCs in Laobaigan (LBG) Baijiu were analyzed by headspace solid-phase microextraction (HS-SPME) coupled with GC × GC-SCD, by which 12 VSCs were identified. Among the 65 odor-active compounds that were determined by GC-O with the aid of aroma extract dilution analysis (AEDA), benzenemethanethiol and 2-methyl-3-furanthiol were found to possess the highest FD values of 6561. The limits of detection (LODs) of the identified VSCs determined by GC × GC-SCD were found to be extremely low at 0.05-1.53 ng/L, with their analytical recoveries from 85% to 116%. The VSCs in the LBG samples were determined in a range of concentrations from 0.77 ± 0.02 µg/L to 60.04 ± 2.32 µg/L. Benzenemethanethiol, dimethyl trisulfide, 2-methyl-3-furanthiol and 2-furfurylthiol exhibited odor activity values (OAVs) > 100 and significantly contributed to the overall aroma of LBG Baijiu.


Mechanistic DNA damage simulations in Geant4-DNA Part 2: Electron and proton damage in a bacterial cell.
We extended a generic Geant4 application for mechanistic DNA damage simulations to an Escherichia coli cell geometry, finding electron damage yields and proton damage yields largely in line with experimental results. Depending on the simulation of radical scavenging, electrons double strand breaks (DSBs) yields range from 0.004 to 0.010 DSB Gy-1 Mbp-1, while protons have yields ranging from 0.004 DSB Gy-1 Mbp-1 at low LETs and with strict assumptions concerning scavenging, up to 0.020 DSB Gy-1 Mbp-1 at high LETs and when scavenging is weakest. Mechanistic DNA damage simulations can provide important limits on the extent to which physical processes can impact biology in low background experiments. We demonstrate the utility of these studies for low dose radiation biology calculating that in E. coli, the median rate at which the radiation background induces double strand breaks is 2.8 × 10-8 DSB day-1, significantly less than the mutation rate per generation measured in E. coli, which is on the order of 10-3.


Calpain regulation of integrin alpha IIb beta 3 signaling in human platelets.
Efficient platelet adhesion and aggregation at sites of vascular injury requires the synergistic contribution of multiple adhesion receptors. The initial adhesion of platelets to subendothelial matrix proteins involves GPIb/V/IX and one or more platelet integrins, including integrin alpha IIb beta 3, alpha 2 beta 1, alpha 5 beta 1 and possibly alpha 6 beta 1. In contrast, platelet-platelet adhesion (platelet cohesion or aggregation) is mediated exclusively by GPIb/V/IX and integrin alpha IIb beta 3. Integrin alpha IIb beta 3 is a remarkable receptor that not only stabilizes platelet-vessel wall and platelet-platelet adhesion contacts, but also transduces signals necessary for a range of other functional responses. These signals are linked to cytoskeletal reorganization and platelet spreading, membrane vesiculation and fibrin clot formation, and tension development on a fibrin clot leading to clot retraction. This diverse functional role of integrin alpha IIb beta 3 is reflected by its ability to induce the activation of a broad range of signaling enzymes that are involved in membrane phospholipid metabolism, protein phosphorylation, calcium mobilization and activation of small GTPases. An important calcium-dependent signaling enzyme involved in integrin alpha IIb beta 3 outside-in signaling is the thiol protease, calpain. This enzyme proteolyses a number of key structural and signaling proteins involved in cytoskeletal remodeling and platelet activation. These proteolytic events appear to play a potentially important role in modulating the adhesive and signaling function of integrin alpha IIb beta 3.


Primary, secondary, tertiary, and quaternary treatment with troglitazone in type 2 diabetes mellitus in an outpatient clinical practice.
To assess the value of troglitazone in various combinations of therapy with sulfonylureas, biguanides, and insulin, including triple oral agent therapy with and without insulin, in an outpatient clinical practice. We compiled results in our first 207 patients with type 2 diabetes treated for 1 year with troglitazone. In eight study groups, troglitazone was added to the following prior regimens: (1) diet alone, (2) sulfonylurea, (3) metformin, (4) sulfonylurea and metformin, (5) insulin, (6) insulin and sulfonylurea, (7) insulin and metformin, and (8) insulin, sulfonylurea, and metformin. Glycosylated hemoglobin, fasting plasma glucose, hemoglobin, weight, and insulin dose were recorded every 3 months for 1 year and are reported. The glycosylated hemoglobin decreased in all study groups during the 1-year period. With the addition of troglitazone, it declined from 8.0% to 6.0% in the diet-only treatment group, from 8.9% to 7.3% in the sulfonylurea group, from 8.4% to 7.2% in the metformin group, and from 8.6% to 7.5% in the group treated with sulfonylurea and metformin. For the groups receiving insulin, glycosylated hemoglobin decreased in conjunction with a significant decline in insulin dose. The dose of insulin was reduced from a baseline of 62 to 41 U per patient in the insulin-only treatment group, from 36 to 12 U per patient in the group treated with insulin and sulfonylurea, and from 28 to 11 U per patient in the group treated with insulin and metformin. In the group treated with insulin, sulfonylurea, and metformin, the dose of insulin was decreased from 36 to 13 U. From our data in more than 200 patients with type 2 diabetes, who participated in a 1-year follow-up in an outpatient clinical practice, we found that troglitazone improved glycemic control in each study group and also decreased the insulin dose in the insulin-requiring patients. Troglitazone improves glycemic control as a primary, secondary, tertiary, or even quaternary therapy in patients with type 2 diabetes.


How prevalent are hospital-based palliative care programs? Status report and future directions.
In the United States, the majority of deaths occur in the hospital but the dying process there is at best unsatisfactory and more likely inadequate for both patients and caregivers. The development of hospital-based palliative care programs (HBPCPs) can vastly improve inpatient end-of-life care. This study is the first to examine the prevalence and characteristics of HBPCPs in the United States, thus providing a snapshot of the characteristics of these HBPCPs. It also serves as a baseline and benchmark against which future development and patterns of HBPCPs can be compared. Phase 1: Data were obtained from the American Hospital Association (AHA) 1998 Annual Survey, on the existence of end-of-life care (EOLC) and pain management (PM) services in U.S. hospitals. Phase 2: A focused survey further assessed programs in Phase 1 and was sent to all registered hospitals that responded affirmatively to the AHA survey questions as having either a PM service, an EOLC service, or both. In phase 1, 1,751 (36%) hospitals reported having a PM service and 719 (15%) had an EOLC service, for a total of 2,015 unique hospitals that had one or both. For Phase 2, 1,120 of 2,015 responded (56%). Of these, 337 (30%) hospitals reported having an HBPCP, and another 228 (20.4%) had plans to establish one. HBPCPs are most commonly structured as inpatient consultation service and hospital-based hospice. They tend to be based in oncology, general medicine, and geriatrics. We also assessed reasons for consultation, patient characteristics, and future development needs. These findings can help guide future funding, educational, and programming efforts in hospital-based palliative care.


Anatomic and morphometric analysis of manubrium sterni as a source of autograft for anterior cervical fusion surgery using quantitative 3-dimensional computed tomographic scans.
A morphologic study of manubrium sterni using 3-dimensional computed tomography (3D-CT). To investigate the anatomic features of adult manubrium as a source of bone graft and to measure the sizes and available cancellous bone volume of manubrium. Manubrium bone graft has been reported as a potential ideal material in anterior cervical fusion surgery, whereas the related applied anatomy is lacking in the literature. One hundred twenty adult manubria from 68 male and 52 female patients were scanned and reformatted with 3D-CT. Configurations of manubrium was observed on 3D volume-rendered images. The breadths, height, medullar thickness, and thickness distribution of manubrium were evaluated. A safe area for procurement of graft was proposed and the available cancellous bone volume of manubrium was measured. Frontal manubrium bears a prominent pentagonal area, which was a bare area without muscle attachments. The breadths, height, and thickness of male manubrium were significantly larger than those of female manubrium. Maximal medullar thickness for male patient was 10.4 ± 1.1 (range, 8.8-12.8) mm, and for female patient it was 9.4 ± 1.4 (range, 6.6-11.9) mm. Minimal medullar thickness for male was 6.8 ± 1.1 (range, 4.9-9.4) mm, and for female it was 5.8 ± 0.9 (range, 4.2-7.4) mm. The thickest region of manubrium located at the level of lower clavicular notches, whereas the thinnest region located at the junction between upper two-thirds and lower third of manubrium. Available volume of cancellous bone was 10.1 ± 2.2 (range, 6.6-15.6) cm(3) in male and 7.7 ± 2.5 (range, 3.6-12) cm(3) in female. The size of male manubrium is significantly larger than that of female manubrium. Manubrium bone is far more sufficient for most adult anterior cervical fusion surgeries. Safe area for procurement of graft is defined as the upper two-thirds of manubrium, and the optimal site to access medullar cavity is suggested at bare area. However, because considerable variability of manubrium size exists, preoperative evaluation of manubrium is suggested to avoid pitfalls, especially when manubrium graft is intended in a female patient.


β-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria.
To describe the antimicrobial activity of β-defensin-2 produced in the mammary gland and secreted in human breast milk. The peptide production was performed by DNA cloning. β-defensin-2 levels were quantified in 61 colostrum samples and 39 mature milk samples from healthy donors, by an indirect enzyme-linked immunosorbent assay (ELISA). Using halo inhibition assay, this study assessed activity against seven clinical isolates from diarrheal feces of children between 0 and 2 years of age. The activity of β-defensin-2 against three opportunistic pathogens that can cause nosocomial infections was determined by microdilution test. The peptide levels were higher in colostrum (n=61) than in mature milk samples (n=39), as follows: median and range, 8.52 (2.6-16.3) μg/ml versus 0.97 (0.22-3.78), p<0.0001; Mann-Whitney test. The recombinant peptide obtained showed high antimicrobial activity against a broad range of pathogenic bacteria. Its antibacterial activity was demonstrated in a disk containing between 1-4 μg, which produced inhibition zones ranging from 18 to 30 mm against three isolates of Salmonella spp. and four of E. coli. β-defensin-2 showed minimum inhibitory concentrations (MICs) of 0.25 μg/mL and 0.5 μg/mL for S. marcescen and P. aeruginosa, respectively, while a higher MIC (4 μg/mL) was obtained against an isolated of multidrug-resistant strain of A. baumannii. To the authors' knowledge, this study is the first to report β-defensin-2 levels in Latin American women. The production and the activity of β-defensin-2 in breast milk prove its importance as a defense molecule for intestinal health in pediatric patients.


Human endothelial cells inhibit granulocyte aggregation in vitro.
Granulocyte aggregation in response to circulating or locally released inflammatory mediators may cause vascular injury. The factors that regulate the granulocyte aggregation response and prevent its occurrence are not defined. We found that primary monolayers of human endothelial cells (EC) derived from umbilical veins released products that inhibited granulocyte aggregation. When polymorphonuclear leukocytes (PMN) and EC were incubated together, the subsequent aggregation response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was inhibited by 40 to 60%, depending in part on the duration of incubation and the concentration of the agonist. Suspension of the granulocytes in albumin-containing buffer that had been rocked with EC monolayers had a similar effect, demonstrating that the EC release a soluble product that modulates the aggregation response. The fMLP concentration-response curve was shifted downward and to the right by EC. Incubation of the granulocytes with endothelial monolayers for various times indicated that the inhibition was maximal at 2 to 3 min, and the PMN responsiveness returned to control over the next 15 min. The inhibiting effect was not selectively directed against fMLP, because incubation of PMN with EC or suspending the PMN in supernatants from endothelial monolayers also inhibited aggregation stimulated by platelet-activating factor, leukotriene B4, and C5a desarg. Release of the inhibitory activity by EC was attenuated by indomethacin, suggesting that the activity is in part due to a cyclooxygenase pathway product. Prostacyclin (PGI2), an eicosanoid produced by EC via the cyclooxygenase pathway, inhibited granulocyte aggregation; however, PGI2 was much less potent as an inhibitor of PMN aggregation than of platelet aggregation. Furthermore, the concentration of PGI2 in buffer that had been incubated with EC was not sufficient to account for the magnitude of the PMN inhibition. The concentration of prostaglandin E2 (PGE2) was also insufficient to completely account for the inhibition. EC that had been treated with indomethacin or aspirin, which blocked the release of PGI2 and PGE2, retained the partial ability to release an activity that blunted granulocyte aggregation; this inhibiting activity was stable at 37 degrees C for 60 min. The results indicate that human EC have the biologic potential to modulate granulocyte aggregation stimulated by inflammatory mediators, and the activity is only partly due to PGI2 and other cyclooxygenase products of arachidonic acid.(ABSTRACT TRUNCATED AT 400 WORDS)


Metabolic activity in bone metastases of breast and prostate cancer were similar as studied by 18F-FDG PET/CT. The role of 99mTc-MDP.
The aim of this study was to compare the metabolic activity of metastatic foci from breast and prostate cancer patients as scanned by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and by technetium-99m methyl diphosphonate (99mTc-MDP) bone scan (BS). Forty one patients were studied, divided into 2 groups based on histologically confirmed diagnosis: a) Breast cancer group, 23 women, mean age: 61±12 years, range: 37-79 years and, b) Prostate cancer group, 18 men, mean age 68±8 years, range: 52-82 years. Another group of 17 non cancer atherosclerotic subjects 9 women and 8 men, of mean age and age range similar to the above were also studied for comparison. The R index (the total count rate in bone metastases divided by the total count rate in a contralateral area), the maximum semi-quantitative standardized uptake value (SUVmax) of BS lesions and the mean number of metastases were evaluated. For the metastatic findings in the PET/CT scans the automatic method of contouring with 50% background cut-off was used, while for the 99mTc-MDP BS metastases were delineated manually. The mean R index of the bone metastatic foci studied by 18F-FDG PET/CT was 1.89±0.69 for Groups I and II patients. There was no significant difference of the R index between prostate cancer and breast cancer metastases (1.95±0.86 vs 1.83±0.52). The average SUVmax value was significantly higher in breast cancer patients than in prostate cancer patients (5.15±2.54 vs 4.01±1.71; P<0.05). There was no significant correlation in both cancer groups between R index and SUVmax values. The number of metastatic foci diagnosed by the 99mTc-MDP BS scan was much less than by the 18F-FDG PET/CT. No significant correlation was noticed in the metabolic activity-glucose utilization of metastatic bone foci between breast and prostate cancer cases. This observation validates the independent value of analyzed diagnostic methods and suggests negligible influence of glucose utilization in bone re-modeling in the above metastatic cancer cells. The 18F-FDG PET/CT bone scan was much better in diagnosing metastases compared to the 99mTc-MDP scan.


Applications of integrated human error identification techniques on the chemical cylinder change task.
This paper outlines the human error identification (HEI) techniques that currently exist to assess latent human errors. Many formal error identification techniques have existed for years, but few have been validated to cover latent human error analysis in different domains. This study considers many possible error modes and influential factors, including external error modes, internal error modes, psychological error mechanisms, and performance shaping factors, and integrates several execution procedures and frameworks of HEI techniques. The case study in this research was the operational process of changing chemical cylinders in a factory. In addition, the integrated HEI method was used to assess the operational processes and the system's reliability. It was concluded that the integrated method is a valuable aid to develop much safer operational processes and can be used to predict human error rates on critical tasks in the plant.


Ambulatory Monitoring of Heart Sounds via an Implanted Device Is Superior to Auscultation for Prediction of Heart Failure Events.
We compared the relationship between the third heart sound (S3) measured by an implantable cardiac device (devS3) and auscultation (ausS3) and evaluated their prognostic powers for predicting heart failure events (HFEs). In the MultiSENSE study, devS3 was measured daily with continuous values, whereas ausS3 was assessed at study visits with discrete grades. They were compared among patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits and over the whole study. Simulations were performed on devS3 to match the limitations of auscultation. We studied 900 patients, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other, but at baseline, only devS3 differentiated patients with or without HFEs (P < 0.0001). The prognostic power of devS3 was superior to that of ausS3 both between follow-up visits (HR = 5.7, P < 0.0001, and 1.7, P = 0.047, respectively) and over the whole study (HR = 2.9, P < 0.0001, and 1.4, P = 0.216, respectively). Simulation results suggested this superiority may be attributed to continuous monitoring and to subaudible measuring capability. S3 measured by implantable cardiac devices has stronger prognostic power to predict episodes of future HFEs than that of auscultation.