Facial reanimation surgery restores affect display.
Assess the ability of facial reanimation surgery to restore affect display in patients with severe facial paralysis. Survey of healthy observers' perception of change in facial visage from preoperative to postoperative state. Academic tertiary referral center. Observer graded affect display. Ninety naive observers completed a survey with pictures of paralyzed faces, smiling and in repose, before and after surgery, as well as normal comparison faces. Observers characterized affect display of each face coded in primary affects from the Derogatis Affects Balance Scale. Results were analyzed with latent class analysis and regression using a three-class model. Preoperatively, paralyzed faces in repose were most likely to be considered negative (56.0%), then neutral (41.3%) and positive (2.7%). In this same cohort of patients in repose, reanimation surgery restored affect display to normal levels: decreasing negative classification (18.9%) and increasing neutral (53.4%) and positive (27.7%) classification. Hypothesis testing revealed no statistically significant differences in the mean classification probabilities for postoperative faces in repose versus normal faces in repose. The same analysis was performed for smiling faces, which showed marked improvement with reanimation surgery: decreasing negative (45.6%-11.7%) and increasing positive (26.2%-60.0%) classification. Despite this improvement, there were statistically significant differences in classification of postoperative smiling faces versus normal smiling faces. Facial reanimation surgery was associated with normalized affect display for faces in repose and improved affect display for smiling faces. These results provide evidence that facial reanimation improves the facial expression of emotion. Further assessment in additional contexts will help better characterize the ability of facial reanimation to mitigate the psychosocial burden associated with facial paralysis.


Roles and responsibilities of chief medical officers in member organizations of the Association of American Medical Colleges.
To explore the roles of physician leaders who hold titles such as chief medical officer (CMO), vice president for medical affairs, and vice dean for clinical affairs in Association of American Medical Colleges (AAMC) member organizations, and to identify critical success factors for these positions. An Internet-based survey was submitted to 340 physician leaders in 281 AAMC member institutions. The survey posed questions regarding demographics, titles, reporting relationships, time commitments, scope of responsibility, accomplishments, and challenges related to recipients' positions, among other questions. Responses were received from 154 physicians representing 139 institutions (response rates 45% and 49%, respectively). Forty-nine percent of these positions had existed for 10 years or less. The most common administrative title was CMO (48%). Eighty-five percent of these individuals reported directly to the dean or CEO of their organization. The majority of administrative effort involved quality and safety (31%), coordination of clinical care (21%), and graduate medical education (9%). The remainder (39%) encompassed a broad portfolio of responsibilities ranging from information technology (6%) to nursing services (2%). Keys to job success included personal stature and relationships, clear definition of responsibilities, and the commitments of the senior administration to the position. Teaching hospitals and medical schools are creating or strengthening positions for physician leaders, most commonly called CMOs. CMOs' work involves numerous activities beyond the traditional areas of quality and safety. The effectiveness of these positions requires clear definition of the role throughout the organization and strong, evident support from senior executives in the organization.


Field evidence for leech-borne transmission of amphibian Ichthyophonus sp.
Parasites have been implicated in mass mortality events and population declines of amphibians around the world. One pathogen associated with mortality events in North America is an Ichthyophonus sp.-like organism that affects red-spotted newts (Notophthalmus viridescens) and several frog species, yet little is known about the distribution of this pathogen in wild populations or the mechanism of transmission. In an effort to identify factors influencing the distribution and abundance of this pathogen, we measured Ichthyophonus sp. prevalence and a series of factors that could contribute to transmission in 16 newt populations during spring 2004. In contrast to our initial hypotheses of trophic transmission, several lines of evidence suggested a role for the amphibian leech (Placobdella picta) in Ichthyophonus sp. transmission. We propose the mechanistic hypothesis that a leech acquires Ichthyophonus sp. infection when inserting its proboscis into the muscles beneath the skin of infected newts and transmits the infection to other newts in subsequent feeding bouts. We also found effects of host sex, body mass, and breeding condition on Ichthyophonus sp. prevalence and the number of attached leeches. The number of leeches attached to newts was strongly related to the proportion of newt habitat containing emergent vegetation, suggesting that anthropogenic eutrophication might lead to more frequent or severe outbreaks of Ichthyophonus sp. infection in amphibians.


Oral consumption of cranberry juice cocktail inhibits molecular-scale adhesion of clinical uropathogenic Escherichia coli.
Cranberry juice cocktail (CJC) has been shown to inhibit the formation of biofilm by uropathogenic Escherichia coli. In order to investigate whether the anti-adhesive components could reach the urinary tract after oral consumption of CJC, a volunteer was given 16 oz of either water or CJC. Urine samples were collected at 0, 2, 4, 6, and 8 hours after consumption of a single dose. The ability of compounds in the urine to influence bacterial adhesion was tested for six clinical uropathogenic E. coli strains, including four P-fimbriated strains (B37, CFT073, BF1023, and J96) and two strains not expressing P-fimbriae but exhibiting mannose-resistant hemagglutination (B73 and B78). A non-fimbriated strain, HB101, was used as a control. Atomic force microscopy (AFM) was used to measure the adhesion force between a silicon nitride probe and bacteria treated with urine samples. Within 2 hours after CJC consumption, bacteria of the clinical strains treated with the corresponding urine sample demonstrated lower adhesion forces than those treated with urine collected before CJC consumption. The adhesion forces continued decreasing with time after CJC consumption over the 8-hour measurement period. The adhesion forces of bacteria after exposure to urine collected following water consumption did not change. HB101 showed low adhesion forces following both water and CJC consumption, and these did not change over time. The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.


Lead levels determined in Swedish permanent teeth by particle-induced X-ray emission.
The determination of lead in permanent teeth is a useful measure of past exposure in early childhood since these teeth are mineralized in early childhood. Particle-induced X-ray emission (PIXE) analysis has been shown to be a method with good applicability for the contamination-free analysis of elements heavier than calcium in dental hard tissues. The method is rapid and nondestructive. The purpose of this study, which used the PIXE technique, was to survey the average level of lead in the coronal dentin of permanent bicuspid teeth collected in three places representing Swedish urban and rural areas. In addition teeth from the New York City area were analyzed. The material comprised 165 teeth from Sweden and, for comparison, 14 teeth from New York City. The median value of lead in the Swedish teeth was 2.9 micrograms/g, a value indicating an insignificant influence from the environment in comparison to the New York teeth, for which the median value was 9.2 micrograms/g. There was however a statistically significant difference in the lead concentration of teeth from large and small Swedish cities; this finding may reflect different automobile traffic intensity.


Multiparametric Approach to Breast Cancer With Emphasis on Magnetic Resonance Imaging in the Era of Personalized Breast Cancer Treatment.
A multiparametric approach to breast cancer imaging offers the advantage of integrating the diverse contributions of various parameters. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the most important MRI sequence for breast imaging. The vascularity and permeability of lesions can be estimated through the use of semiquantitative and quantitative parameters. The increased use of ultrafast DCE-MRI has facilitated the introduction of novel kinetic parameters. In addition to DCE-MRI, diffusion-weighted imaging provides information associated with tumor cell density, with advanced diffusion-weighted imaging techniques such as intravoxel incoherent motion, diffusion kurtosis imaging, and time-dependent diffusion MRI opening up new horizons in microscale tissue evaluation. Furthermore, T2-weighted imaging plays a key role in measuring the degree of tumor aggressiveness, which may be related to the tumor microenvironment. Magnetic resonance imaging is, however, not the only imaging modality providing semiquantitative and quantitative parameters from breast tumors. Breast positron emission tomography demonstrates superior spatial resolution to whole-body positron emission tomography and allows comparable delineation of breast cancer to MRI, as well as providing metabolic information, which often precedes vascular and morphological changes occurring in response to treatment. The integration of these imaging-derived factors is accomplished through multiparametric imaging. In this article, we explore the relationship among the key imaging parameters, breast cancer diagnosis, and histological characteristics, providing a technical and theoretical background for these parameters. Furthermore, we review the recent studies on the application of multiparametric imaging to breast cancer and the significance of the key imaging parameters.


How to build a multi-arterial coronary artery bypass programme: a stepwise approach.
Observational evidence shows that the use of multiple arterial grafts (MAG) is associated with longer postoperative survival and improved clinical outcomes. The current European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines on myocardial revascularization recommend the use of MAG in appropriate patients. However, a significant volume-to-outcome relationship exists for MAG, and lack of sufficient experience is associated with increased operative risk. A stepwise approach to building experience with MAG allows successful implementation of this technique into routine coronary surgery practice.


Combined atelectasis of right upper and middle lobes: a clinical study of 15 cases.
Because of the independent and remote origin of the right upper and middle lobe bronchi, combined collapse of right upper and middle lobes is thought to be uncommon. We report 15 cases of combined right upper and middle lobe collapse found by plain chest radiograph in the past 8 years. Malignancies were confirmed in 13 cases. The other 2 cases with benign etiology included one case of endobronchial TB and one of pneumonia. These cases of combined bilobar collapse were possibly due to (1) the intraluminary infiltration of the primary tumor of the upper lobe to the middle lobe bronchus, (2) separated area of collapse produced by the primary tumor and its metastatic lymphadenopathy, (3) upper lobe tumor with external compression to intermediate bronchus that obstructed both the upper and middle bronchi, (4) multi-centric neoplasm, (5) tumor obstruction and sputum impaction at different bronchi, or (6) benign lesions operated at two different locations. The more frequent occurrence of bronchogenic carcinoma than that of benign lesions in our study revealed the invalidity of the "double lesion sign". Bronchoscopy or CT scan should be used to search for the etiology. If malignancy is confirmed in such condition, the prognosis is usually poor due to its advanced invasion.


Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia.
Interleukin (IL)-18 can induce Th2 cytokine production particularly in collaboration with IL-2. Accumulation of Th2 cells and increased levels of Th2 cytokines are found in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia (EP). To evaluate the role of IL-18 in the pathogenesis of EP, we measured the concentration of IL-2, IL-12, IL-18, and Th2 cytokines in BALF from patients with EP. The concentrations of interferon (IFN)-gamma, IL-2, IL-5, IL-10, IL-12, IL-13, and IL-18 in BALF were measured in patients with idiopathic acute eosinophilic pneumonia (AEP), with idiopathic chronic eosinophilic pneumonia (CEP), with sarcoidosis and healthy volunteers (HV). The BALF concentrations of Th2 cytokines, IL-5, IL-10, and IL-13, were higher in patients with EP than in sarcoidosis and control. The IL-2 level in BALF was higher in EP than in sarcoidosis and control. The IL-18 and IL-12 (p40 + p70) levels were higher in patients with EP than sarcoidosis, while the level of IL-12 (p70) was below the detection limit in patients with EP. There was a significant correlation between IL-2 level and both IL-5 and IL-13 in BALF of patients with EP. Our findings suggest that IL-18 may contribute to Th2 cytokine-dominant responses in patients with EP in collaboration with IL-2.


[Advantages of using swine serum in culturing animal and human cell lines].
Using the culture of lymphoid human cells, mice myeloma cells and hybridoma (the latter was obtained by fusion of myeloma cells with those of mice spleen immunized with phage lambda), the fetal serum was shown to be surpassed in growth activity by that from adult swines. This fact is especially pronounced at small serum concentrations. When hybridoma cells were cultured there were no differences in titre of monoclonal antibodies specific to phage lambda with the use of both sera. The possibility of substitution of swine serum for human one was demonstrated using the culture of lymphocytes from human peripheral blood.


Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation.
Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S', fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S' (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87-0.99]|0.91[0.84-0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR.


Effects of noncavity-distorting fibroids on endometrial gene expression and function.
Uterine fibroids are a common finding in infertility patients. Impaired implantation and decidualization have been proposed to contribute to compromised fertility. Data are limited on the endometrial transcriptome from subjects with uterine fibroids, as well as endometrial receptivity and decidualization potential of endometrial stromal fibroblasts (eSF) from women with fibroids. Our objective was to investigate the endometrial transcriptome of women with noncavity-distorting intramural fibroids and compare them to control subjects with no uterine pathology throughout the menstrual cycle. We also evaluated endometrial receptivity gene expression and basic endometrial functions such as decidualization, proliferation, and apoptosis in women with fibroid uterus. Results showed that large numbers of transcripts were significantly dysregulated throughout the menstrual cycle in fibroid subjects compared to controls. However, there were essentially no differences in the expression of receptivity markers at the tissue level, as well as decidualization markers in tissue and eSF in subjects with fibroids compared to controls. However, eSF from women with a fibroid uterus exhibited decreased proliferation potential and increased apoptosis upon decidualization. These data indicate preserved implantation and decidualization potential despite observed gene expression changes in endometrium from women with noncavity-distorting fibroids compared to controls. How this phenomenon and altered proliferation/apoptosis may contribute to impairment of endometrial function in subfertile patients warrants further investigation.


Analytical study of the degradation of nucleohistone during calf thymus chromatin autolysis.
The mechanism of nucleohistone degradation in calf thymus chromatin during autolysis of the latter involves a release of lysine-rich histone fractions, followed by degradation of the thus-exposed DNA portions; the latter portions are richest in adenine-thymine sequences. After this degradation process, residual nucleohistone fragments of low molecular weight (10(5)) remain. Their chemical composition is special, in that the DNA contains a larger proportion of guanine-cytosine sequences than does the initial DNA and it is combined with arginine-rich histones.


Hepatocellular carcinoma incidence in Florida. Ethnic and racial distribution.
Hepatocellular carcinoma (HCC), the primary form of liver carcinoma, is increasing in incidence worldwide. The increasing numbers of Hispanic immigrants in Florida suggest that the rate of HCC in the Hispanic population should be of special concern. This study describes racial and ethnic distribution and trends of incident HCC in Florida from 1985 to 1995. A total of 2837 cases of incident HCC from 1985 to 1995 were examined from Florida's incident cancer registry, the Florida Cancer Data System. Age standardized and age specific average annual incidence rates were calculated for the state of Florida by gender and by racial and ethnic group. Over the study period, the average annual incidence HCC rates in Florida among male and female Hispanics and blacks were consistently and significantly twice the rate of white males and females as standardized rate ratios. Males were at least twice as likely to have HCC compared with females in all three racial and ethnic subpopulations. The incidence of HCC in Florida was comparable to the overall U.S. incidence with respect to average annual incidence and gender distribution. Florida blacks and Hispanics are at significantly increased risk for HCC incidence compared with Florida whites. These results have implications for preventive HCC recommendations in growing racial and ethnic subpopulations in the United States.


Uterine size measured by ultrasound during the menstrual cycle.
In the following study changes in the size of non-pregnant uterus were measured by B-scan ultrasonography. Uterine size in different stages of the menstrual cycle was measured ultrasonically in 16 women, whose periods were confirmed to be ovulatory, both by basal body temperature (BBT) and by the radioimmunological measurement of plasma estradiol and progesterone. It was established that the size of the uterus grows significantly towards the end of the menstrual cycle. In addition to the above mentioned, the examination was performed on a woman of child-bearing age with disturbances in her menstrual cycle. Hormone measurements indicated that her period was anovulatory. No typical uterine growth characteristic of ovulatory cycles could be observed.


Purines and Pyrimidines: Metabolism, Function and Potential as Therapeutic Options in Neurodegenerative Diseases.
Various neurodegenerative disorders have various molecular origins but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.


Determination of the biological activity and structure activity relationships of drugs based on the highly cytotoxic duocarmycins and CC-1065.
The natural antibiotics CC‑1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electro-spray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given.


[Specific features of the development of Siberian stone pine megagametophytes and embryos in vitro].
Seedlings were grown in vitro from fertilized eggs and immature embryos of the Siberian stone pine. Cultivation of megagametophytes on a hormone-containing Murashige-Skoog medium from the egg formation until the globular embryo stage made it possible to manipulate fertilization and embryogenesis. Immature embryos are the most promising for in vitro cultivation. Their maturation and germination proceed within seven days of cultivation. When zygotic embryos were cultivated, adventitious buds were formed from cells at the cotyledon base and tips. When adventitious buds were subcultivated on a medium containing benzylaminopurine and naphthylacetic acid, organogenic callus and shoots were formed. Thus, cultivation of megagametophytes and embryos of the Siberian stone pine led to the completion of embryogenesis and formation of viable of seedlings.