Excited-state proton transfer based fluorescence in Kaempferol powder and solutions with different concentrations.

Kaempferol (KMP) is one of the most common flavonoids, currently being extensively studied for its numerous beneficial health effects. Here we study the fluorescence (FL) emission of KMP powder and of its solutions prepared using different types of solvents (polar and non-polar). In the spectra of KMP powder and KMP solutions with high concentration, the same FL peak with maximum at 1.9 eV is observed. Another FL peak, at higher energy of 2.45 eV, emerges in solutions, its relative intensity increases with decreasing solution concentration. The FL emission of solutions with lowest concentration displays only that peak. To calculate characteristic energies of absorption and emission of KMP molecule in vacuum and in solutions we use time-dependent density functional theory. Comparing the results of computations with measured FL spectra, we associate the FL band at 1.9 eV with the emission due to excited state intramolecular transfer of the proton of -OH5 hydroxyl group. The FL emission at 2.45 eV is related to the -OH3 proton transfer. We measure the FL spectra of KMP powder using two different excitation energies, 3.06 eV and 2.33 eV, and find that its FL spectrum depends on the excitation energy. To understand that dependence, we compare the FL spectra of KMP and Q monohydrate powders. We consider the excited state intermolecular transfer of the proton from -OH3' hydroxyl group to a neighboring molecule in Q crystal and calculate the energy corresponding to the emission of the resulted anion of Q molecule. The spectral feature at 1.69 eV observed only in the FL spectrum of Q hydrate is attributed to the Q anion FL emission.

Comparison of the histopathological characteristics of osteomyelitis, medication-related osteonecrosis of the jaw, and osteoradionecrosis.

The purpose of this study was to compare the histopathological parameters of chronic/suppurative osteomyelitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoradionecrosis (ORN), and to examine the hypothesis that distinct histological features can be related to a specific disease, allowing for diagnosis based on microscopic evaluation alone. One hundred and ten samples were reviewed by two examiners in a blinded fashion, and a semi-quantitative histomorphometric analysis was performed. The parameters evaluated included the presence or absence of necrotic bone, inflammation, reactive bone formation, bacteria, and osteoclasts. No statistically significant differences were found between groups for any parameter. Necrotic bone was common to all three diagnoses. Inflammation and reactive bone formation were present in all three diagnoses. The presence of bacteria was a prominent feature in all cases. Osteoclasts were scarce in MRONJ and osteomyelitis, and non-existent in ORN. The results of this study failed to identify distinctive microscopic characteristics in any of the three entities that could be used to differentiate between them. Therefore, it is impossible to reach a specific final diagnosis based on microscopic findings alone. The role of microscopic analysis is to serve as an aid to diagnosis that must be complemented by the patient's history and imaging.

Upregulation of RET induces perineurial invasion of pancreatic adenocarcinoma.

Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes. Immunolabeling of tumors in KPC mice of different ages and analysis of human cancer specimens revealed that RET expression is upregulated during PDAC tumorigenesis. BMT experiments revealed that BM-derived macrophages expressing the RET ligand GDNF are highly abundant around nerves invaded by cancer. Inhibition of perineurial macrophage recruitment, using the CSF-1R antagonist GW2580 or BMT from CCR2-deficient donors, reduced perineurial invasion. Deletion of GDNF expression by perineurial macrophages, or inhibition of RET with shRNA or a small-molecule inhibitor, reduced perineurial invasion in KPC mice with PDAC. Taken together, our findings show that RET is upregulated during pancreas tumorigenesis and its activation induces cancer perineurial invasion. Trafficking of BM-derived macrophages to the perineurial microenvironment and secretion of GDNF are essential for pancreatic cancer neural spread.

The effect of army vest design on the occurrence of stress fractures and overuse injuries in female military recruits.

INTRODUCTION: Stress fractures (SFs) occur when microdamage caused by repetitive mechanical load exceeds the biological load-bearing capacity of the bone. The study objective was to test whether a vest specifically designed and manufactured for female recruits, compared with the standard vest used on a regular basis by Border Police recruits, would reduce the incidence of SF in female Border Police recruits. Data based on reports of military personnel show that women are more likely to sustain SFs. METHODS: A follow-up of 240 female Border Police infantry recruits, divided into two trial groups, was conducted from 2007 to 2009. Two different vests were evaluated-the standard special unit fighting vest, which was conventionally used by both men and women during basic training, and the new fighting vest, specially design for female body shape. RESULTS: No significant difference was noted in the number of SFs between the two groups which may be attributed to increased weight of the new vest. There was a lower incidence of long bone SFs which may have been due to the superior vest design. The female Border Police Infantry recruits expressed great satisfaction with the new vest. CONCLUSIONS: Increased effort should be invested to further reduce the weight of female combat gear, alongside efforts to improve fit and comfort.

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results.

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

Comparison of early performance indicators for screening projects within the European Breast Cancer Network: 1989-2000.

In 1989 the European Breast Cancer Network (EBCN) was established by the first pilot projects for breast cancer screening, co-funded by the Europe Against Cancer programme. We report early performance indicators for these EBCN projects while taking into account their organizational setting. Out of 17 projects in the network, 10 projects from six European countries contributed aggregated data on number of invitations, screening examinations, and breast cancers detected over the period 1989-2000. Results were summarized separately for projects in centralized versus decentralized health care environments. The European Guidelines for quality assurance in mammography screening provided reference values for the performance indicators. The most prominent finding in this study was the higher participation rate in centralized versus decentralized projects (average participation in 1998: 74 versus 33%; P<0.001), whereas the invitation system and screening policy in these projects were similar. Detection rates and characteristics of cancers detected at initial and subsequent screening examinations showed no significant differences between centralized and decentralized projects. Even though early performance indicators for centralized versus decentralized projects were similar, the impact of breast screening on mortality from this disease at the population level will differ since the decentralized projects reach only part of the target population.

Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks.

Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.

Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer.

Antiphospholipid antibodies (aPL) have been suggested to play a role in causing cognitive and behavioral impairments. In the present study we investigated the pathogenic potential of aPL by intracerebro-ventricular (ICV) administration of immunoglobulins (IgG) from patients with antiphospholipid syndrome (APS). IgG, purified from the sera of four APS patients, was tested for binding to normal mouse brain by immunohistological staining. These IgG (7.5 microg) were injected ICV unilaterally to male C3H mice. Mice injected with IgG purified from pooled sera derived from healthy subjects served as controls. The mice were examined neurologically for motor function and coordination, and cognitively in a Morris water maze. The cognitive tests were performed with the experimenter blinded to the treatment. The performance of the mice in four separate experiments was compared by analysis of variance with repeated measures. IgG from one APS patient was found to bind best to neuronal structures in the hippocampus and cerebral cortex. Mice (n = 43) injected with this IgG performed worse in the water maze compared to the controls (n = 45) with significant effects of the aPL IgG on the overall performance of the mice (treatment, P < 0.03), on learning throughout the experiment (treatment x day, P < 0.02) and on short term memory (treatment x day xtrial, P < 0.002). IgG injected from two of the three other patients also bound specifically to mouse brain neurons and produced an impairment in performance of the water maze. These results support the hypothesis that aPL that gain access to the central nervous system may play a direct role in the pathogenesis of neurological manifestations of APS.

Intratubular germ cell neoplasia: associated infertility and review of the diagnostic modalities.

The incidence of testicular neoplasia has increased, and its early detection has become a pressing clinical issue. The strong association between male subfertility and risk of testicular neoplasia is consistent with the existence of common pathogenetic factors. Most forms of testicular germ tumors are believed to stem from a common precursor, intratubular germ cell neoplasia (ITGCN), also known as testicular carcinoma in situ. Identification of ITGCN cells in testicular biopsies, however, is a diagnostic challenge and markers are sorely needed to assist in the accurate identification of the lesion.

Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study.

Protein phosphatase (PP2Calpha) is a member of the mammalian serine threonine-specific protein phosphatases family. We produced monoclonal antibodies against the recombinant PP2Calpha and evaluated the immunoreactivity of normal human tissues. The reactivity was strong in normal skin, the digestive tract, lung, kidney, breast, prostate, endocrine glands, and brain, while it was moderate in the ovary, testis, and liver. Epithelial cells revealed high levels of PP2Calpha expression, but stromal cells, including fibroblasts and endothelial cells, showed no or little PP2Calpha expression. Given the broad reactivity in endocrine and secreting epithelial cells, we propose that PP2Calpha expression might contribute to secretory cell function.

Primary papillary serous carcinoma of the peritoneum in a man.

BACKGROUND: Primary papillary serous carcinoma of the peritoneum is a well-known entity in women. The tumour is derived from the extraovarian mesothelium and the pelvis and lower abdomen mesothelia. The treatment strategies are similar to ovarian serous papillary carcinoma. PATIENTS AND METHODS: A case of primary serous papillary carcinoma of the peritoneum in a man is presented. The patient, 53 years old, died 2 months after diagnosis. RESULTS: The histologic and immunohistochemical studies of the tumour will be presented. These studies, made during lifetime and at autopsy of the patient, confirm a diagnosis of primary serous papillary carcinoma of the peritoneum. CONCLUSIONS: primary serous papillary carcinoma of the peritoneum can occur in men, and should be considered in the differential diagnosis in cases of abdominal carcinomatosis of unknown origin. Treatment options remain to be determined.

The hormonal milieu in early stages of bone cell differentiation modifies the subsequent sex-specific responsiveness of the developing bone to gonadal steroids.

We have established previously that rat bone tissue, as well as rat and human-derived bone cells in culture, show a sex-specific response to gonadal steroids in stimulation of the specific activity of the BB isozyme of creatine kinase (CK) and DNA synthesis. This response could be modified by manipulation of the endocrine environment during early stages in rat development. To further examine the influence of changing hormonal steroid milieu and vitamin D status on the action of gonadal steroids in developing bone tissue, we used two models of ectopic bone formation: demineralized tooth matrix (DTM) implanted under the skin, and femoral bone marrow (BM) transplanted under the kidney capsule of a syngeneic recipient mouse. The response to gonadal steroids in ossicles developed from implanted DTM depended on the recipient's gender; injection of estradiol 17beta (E2; 5 microg) into young female mice 21 days after DTM implantation increased, 24 h later, CK activity in the newly formed ossicles by approximately 60%, whereas injection of dihydrotestosterone (DHT; 50 microg) had no effect on CK activity. In contrast, in male mice, DHT but not E2 increased CK activity in the ossicles by approximately 50%. This sex-specific response was abolished in gonadectomized mice resulting in a similar response of the ossicles to both E2 and DHT. When DTM was implanted into vitamin D- deficient female mice, there was a lower basal CK activity and a significantly diminished response to E2 in the newly formed bone tissues. When BM, which contains mesenchymal and stromal cells and committed osteoprogenitor cells, was transplanted into 6-week-old intact or gonadectomized female or male mice, the response of the newly formed bone ossicles, 21 days after transplantation, to E2 or to DHT was according to the gender of the donor. Bone formed from BM obtained from female mice responded to E2 only and those formed from male BM responded to DHT only. Ossicles developed from BM obtained from gonadectomized mice showed lack of response to either gonadal steroid. Furthermore, only approximately 25% of the BM transplants obtained from castrated (CAST) male donors developed into ossicles. Ossicles formed from BM obtained from vitamin D-deficient female donors showed lack of response to gonadal steroids. These findings suggest that the manipulation of the hormonal milieu in early stages of the differentiation sequence of bone cells modifies the subsequent selective responsiveness of the developing bone tissue to gonadal steroids.

Nuclear localization of beta-catenin and plakoglobin in primary and metastatic human colonic carcinomas, colonic adenomas, and normal colon.

Beta-catenin is a cytoskeleton-associated signaling molecule shown to be elevated in various carcinomas but mostly in colon cancer owing to its impaired degradation. In contrast, its close homologue plakoglobin was shown to suppress the tumorigenicity of certain tumor cells. In the present study, we have used a semiquantitative immunohistochemical approach to evaluate the extent of nuclear localization of beta-catenin in human colonic adenocarcinomas and adenomas and compared it to the distribution of plakoglobin in the same tissues. We show that beta-catenin accumulates in the nuclei of the epithelium of primary and metastatic colonic adenocarcinoma as well as in colonic adenomas. In contrast, nuclear plakoglobin levels in these tissues were low, even compared to those found in epithelial cells of normal colon. These results support the view that the increase in beta-catenin levels in colon cancer cells occurs early in the tumorigenic process, leading to its nuclear localization, not only in invasive adenocarcinoma, but also in colonic adenoma with mild dysplasia.

Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis.

RBM (RNA-binding motif) protein is a marker of male germ cells. This protein is encoded by the Azoospermia factor region-b (AZF-b) of the human Y chromosome and is expressed exclusively in the male germ cell line, that is, spermatogonia, spermatocytes, and round spermatids. The authors analyzed the expression of the RBM gene in germ cell tumors and in the seminiferous tubules in the vicinity of these tumors to identify the presence of IGCN. Sections from testicular germ cell tumors of 21 patients were stained with anti-RBM antibody by using an immunohistochemical method. Distal tubules showing spermatogenesis were immunopositive for RBM protein. All of the germ cell tumors studied were completely immunonegative for RBM. Defined areas of IGCN also showed an absence of RBM expression. Tubules with spermatocyte-like cells, which were expected to express RBM, did not express this protein. This result enabled the identification of tubules as being IGCN. RBM is a novel marker consistently expressed in normal male germ cells but not in malignant germ cell tumors or IGCN. Thus, the absence of RBM expression in germ cells provides a new diagnostic tool of preinvasive malignancy of the testis.

Experimental intrauterine growth retardation alters renal development.

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation (IUGR), resulting in small-for-gestational-age, asymmetric newborns. IUGR neonates experience higher morbidity and mortality rates, as well as a possible contribution towards late sequelae, such as hypertension, and cardiovascular disease in adulthood. To simulate vascular placental insufficiency, an experimental rabbit IUGR model was used. Intrauterine growth retardation was achieved by ligation of 25-30% uteroplacental vessels of half of the fetuses during the last third of gestation. Ischemic fetuses were significantly small, asymmetric, and had a disproportionately small body with a relatively large head. The kidneys from all groups were analyzed for relative estimated glomeruli number (REGN) using an unbiased blind design. The glomeruli number was significantly reduced in the asymmetric IUGR rabbit fetuses, probably due to decreased renal vascular supply. Our results support the concept that the reduced number of glomeruli may contribute to impaired renal function, thus predisposing to neonatal renal dysfunction and late sequelae, such as adult hypertension. This study emphasizes the clinical importance of early IUGR diagnosis and prevention.

Redundant basal forebrain modulation in taste aversion memory formation.

Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. It has been demonstrated that in spite of the strong cholinergic depletion after injections into the basal forebrain of the immunotoxin 192IgG-saporin, no detectable deficit can be found in the acquisition of several learning tasks, including conditioned taste aversion. Conversely, NMDA-induced lesions of the basal forebrain strongly impair taste aversion learning. In this study we show that 192IgG-saporin produces an efficient and selective cholinergic deafferentation of the rat neocortex but not the amygdala. Furthermore, a stronger relationship between severity of memory impairment after NMDA lesions and basoamygdaloid cholinergic deafferentation was found. Therefore, in a second experiment, we show that combining NMDA-induced lesions into the basolateral amygdala with 192IgG-saporin injections into the basal forebrain results in a strong disruption of taste aversion learning, whereas none of these treatments were by themselves capable of producing any detectable impairment in this learning task. The double lesion effect was only paralleled by simple NMDA lesions into the basal forebrain, suggesting that the learning deficits associated to excitotoxic lesions of the basal forebrain are the result of the simultaneous destruction of the corticopetal and basoamygdaloid interaction. A model is proposed, according to which the modulation of learning processes exerted by the basal forebrain can be redundantly performed by both the basocortical and basoamygdaloid pathway.

Exposure of human peripheral blood mononuclear cells (PBMC) to hydrostatic pressure increases their proliferative response to phytohemagglutinin A (PHA) and anti-CD3 antibody.

In the present study we show that a brief exposure of human PBMC to hydrostatic pressure (HyP) increased their proliferative response to PHA and anti-CD3 antibody, assessed by DNA synthesis. The effect of HyP was most prominent at 400 atmospheres of HyP followed by 600 and 200 atmospheres. At any pressure level, the highest effect of HyP was noted when employing PHA and anti-CD3 antibody at 10(-2) dilution. When PBMC were exposed to 400 atmospheres HyP, maximal effect was achieved at 20 minutes of exposure. The highest effect of HyP on DNA synthesis was noted at 48 and 72 hours of incubation with PHA, when exposing cells to pressure for 20 minutes at 400 atmospheres. Exposure of PBMC under similar conditions for 40 minutes, caused an increase in DNA synthesis only at 48 hours incubation with PHA. These results demonstrate that exposure of human PBMC to HyP increases their proliferative response to different polyclonal activators. The possible mechanisms involved in this phenomenon are discussed.

Feature extraction of event-related potentials using wavelets: an application to human performance monitoring.

This report describes the development and evaluation of mathematical models for predicting human performance from discrete wavelet transforms (DWT) of event-related potentials (ERP) elicited by task-relevant stimuli. The DWT was compared to principal components analysis (PCA) for representation of ERPs in linear regression and neural network models developed to predict a composite measure of human signal detection performance. Linear regression models based on coefficients of the decimated DWT predicted signal detection performance with half as many free parameters as comparable models based on PCA scores. In addition, the DWT-based models were more resistant to model degradation due to over-fitting than PCA-based models. Feed-forward neural networks were trained using the backpropagation algorithm to predict signal detection performance based on raw ERPs, PCA scores, or high-power coefficients of the DWT. Neural networks based on high-power DWT coefficients trained with fewer iterations, generalized to new data better, and were more resistant to overfitting than networks based on raw ERPs. Networks based on PCA scores did not generalize to new data as well as either the DWT network or the raw ERP network. The results show that wavelet expansions represent the ERP efficiently and extract behaviorally important features for use in linear regression or neural network models of human performance. The efficiency of the DWT is discussed in terms of its decorrelation and energy compaction properties. In addition, the DWT models provided evidence that a pattern of low-frequency activity (1 to 3.5 Hz) occurring at specific times and scalp locations is a reliable correlate of human signal detection performance.