Gender Differences in Processing Fearful and Angry Body Expressions.
Previous studies have demonstrated differential perception of body expressions between males and females. However, only two recent studies (Kret et al., 2011; Krüger et al., 2013) explored the interaction effect between observer gender and subject gender, and it remains unclear whether this interaction between the two gender factors is gender-congruent (i.e., better recognition of emotions expressed by subjects of the same gender) or gender-incongruent (i.e., better recognition of emotions expressed by subjects of the opposite gender). Here, we used event-related potentials (ERPs) to investigate the recognition of fearful and angry body expressions posed by males and females. Male and female observers also completed an affective rating task (including valence, intensity, and arousal ratings). Behavioral results showed that male observers reported higher arousal rating scores for angry body expressions posed by females than males. ERP data showed that when recognizing angry body expressions, female observers had larger P1 for male than female bodies, while male observers had larger P3 for female than male bodies. These results indicate gender-incongruent effects in early and later stages of body expression processing, which fits well with the evolutionary theory that females mainly play a role in care of offspring while males mainly play a role in family guarding and protection. Furthermore, it is found that in both angry and fearful conditions male observers exhibited a larger N170 for male than female bodies, and female observers showed a larger N170 for female than male bodies. This gender-incongruent effect in the structural encoding stage of processing may be due to the familiarity of the body configural features of the same gender. The current results provide insights into the significant role of gender in body expression processing, helping us understand the issue of gender vulnerability associated with psychiatric disorders characterized by deficits of body language reading.


Correlation between vaccine coverage against polio and circulation and genetic evolution of the poliovirus strains isolated in Romania in the framework of the global polio eradication strategy.
Until 2008 in Romania poliomyelitis has been controlled by predominantly using trivalent oral poliovirus vaccine (TOPV). The alternative vaccination schedule (formalin inactivated poliovirus vaccine IPV/OPV) has been implemented starting September 2008 and at the begining of 2009 was decided only vaccination with IPV. Between 1995-2006 the risk of the vaccine-associated paralytic poliomyelitis (VAPP) decreased with an average of less than 2 VAPP cases/year and no VAPP case between 2007 - September 2009. Begining with 2007 the number of the poliovirus strains isolated was less. All 9 poliovirus strains (PV) isolated between 2007-2009 and investigated by RT-PCR-RFLP in VP1-2A and VP3-VP1 coding regions showed Sabin-like profiles, and only one strain poliovirus type 3 showed Sabin 2-like profile by RFLP in 3D coding ARN polymerase region. The study about the seroprevalence of antibodies against poliovirus types in serum samples from the acute flaccid paralysis (AFP), facial paralysis (FP) cases showed that the seroprevalence of antibodies against types 1 and 2 Sabin strains was higher (>90%) than for type 3 Sabin strains (average 85%). It was confirmed the necessity of maintaining a proper vaccine coverage in population, after the switch in the vaccination strategy in Romania until all threats of poliovirus are eliminated globally.


Acute dissection of the descending thoracic aorta: repair in an unusual case.
Acute tamponade, although a rare manifestation of a descending thoracic aneurysm, was the dominant clinical feature of a classic type III dissecting aneurysm (arising distal to the left subclavian artery) in a 52-year-old man. High-quality aortography confirmed the diagnosis, ruling out any anomaly of the ascending aorta and the aortic arch. Surgical treatment was carried out 24 hours after the initial episode without cardiopulmonary bypass. Through a left thoracotomy, a Gott shunt was inserted proximally at the apex of the left ventricle and distally in the left femoral artery. Aortic repair with the interposition of a 30-mm woven Dacron prosthesis was successful. Postoperative aortography showed complete restoration of aortic integrity.


Study on Adhesion Performance and Aging Strength Degradation Mechanism of SBS Modified Asphalt with Different Anti-Aging Additive.
After aging, the adhesiveness of asphalt deteriorates, leading to a reduction in the durability of asphalt mixtures and affecting the service life of asphalt pavements. To enhance the anti-aging performance of asphalt, this study employed the method of melt blending to prepare three types of modified asphalt: graphene/SBS modified asphalt (G/SBSMA), crumb rubber/SBS modified asphalt (CR/SBSMA), and petroleum resin/SBS modified asphalt (PR/SBSMA). Different dosages of the three types of modified asphalt were tested for changes in conventional performance indicators. The optimal dosages of graphene, crumb rubber, and C9 petroleum resin were determined to be 2%, 15%, and 5%, respectively. Based on the theory of surface free energy, the effects of anti-aging agents on the microscopic properties of SBS modified asphalt before and after aging were analyzed using the three-liquid method. The mechanisms of strength attenuation at the asphalt-aggregate interface under water exposure and aging were revealed. The results showed that with the increase of aging gradient, the asphalt-aggregate biphasic system became more active. The cohesive energy and peel energy of SBS modified asphalt increased continuously, while the adhesive energy decreased continuously, leading to a decrease in the energy ratio parameter. Resin-based anti-aging agents exhibited the most significant improvement in asphalt adhesion performance, while graphene demonstrated a more stable enhancement in asphalt's water stability during the aging stage.


Papaverine selectively inhibits human prostate cancer cell (PC-3) growth by inducing mitochondrial mediated apoptosis, cell cycle arrest and downregulation of NF-κB/PI3K/Akt signalling pathway.
The main objective of the current research work was to investigate the antitumor effects of papaverine in PC-3 human prostate cancer cells along with testing its toxicity in the normal human fibroblast (NHF) cells. The cytotoxic effects of papaverine were examined by the MTT cell viability assay. Flow cytometry using annexin V-FITC/PI was used to study the effects on apoptosis, including its quantification. Effects on cell cycle progression were analyzed by flow cytometry while as effects on apoptosis-related proteins, NF-kB and PI3K/Akt pathways were estimated by Western blot assay. The results indicated that papaverine could induce significant, highly selective and dose-dependent cytotoxic effects in PC-3 cells without causing too much toxicity in normal cells. Papaverine also led to induction of early and late apoptosis along with inducing sub-G1 cell cycle arrest in a dose-dependent manner. Papaverine induced a dose-dependent reduction in the expression levels of Blc-2 proteins and a dose-dependent increase in the expression levels of Bax protein. The expression levels of NF-kB were decreased markedly in comparison to the untreated control. Papaverine treatment also led to a dose-dependent downregulation of PI3K and phospho-Akt expression. Papaverine showed selective antitumor properties against PC-3 human prostate cancer cells by inducing early and late apoptosis, sub-G1 cell cycle arrest, modulation of apoptosis-related proteins like Bcl-2, Bax, Bid, XIAP and cytochrome C along with downregulation of NFkB, PI3K/Akt signalling pathway.


Leptin, adiposity, and testosterone in captive male macaques.
Leptin is considered to act as a signal relating somatic energetic status to the reproductive system. However, the nature of that signal and its relationship with male reproductive function across nonhuman primate species are unclear. We suggest that species-specific differences in leptin physiology may be related to the degree of environmental variation and variation in the importance of energy stores for male reproduction. In order to test the role of seasonality in species differences among nonhuman primates, we compared leptin, testosterone, and body composition in male rhesus (n = 69) and pig-tailed (n = 43) macaques. Despite having larger abdominal fat deposits, the rhesus macaques did not exhibit significantly higher leptin levels (rhesus, 2.21 +/- 0.43 ng/ml; pig-tailed, 2.12 +/- 0.39 ng/ml). Both species showed increases in leptin across adolescent, subadult, and adult age-groups (P = 0.036 for rhesus; P = 0.0003 for pig-tailed by ANCOVA). Testosterone was not significantly associated with leptin in either the rhesus (r = 0.039; P = 0.754) or pig-tailed (r = 0.2862; P = 0.066) samples. Comparison of leptin levels across the two species using univariate modeling procedures showed no significant age-group by abdominal fat interaction. These findings suggest little difference in leptin production between these two closely related species, despite the difference in breeding seasonality.


Transcriptome fingerprints distinguish hallucinogenic and nonhallucinogenic 5-hydroxytryptamine 2A receptor agonist effects in mouse somatosensory cortex.
Most neuropharmacological agents and many drugs of abuse modulate the activity of heptahelical G-protein-coupled receptors. Although the effects of these ligands result from changes in cellular signaling, their neurobehavioral activity may not correlate with results of in vitro signal transduction assays. 5-Hydroxytryptamine 2A receptor (5-HT2AR) partial agonists that have similar pharmacological profiles differ in the behavioral responses they elicit. In vitro studies suggest that different agonists acting at the same receptor may establish distinct patterns of signal transduction. Testing this hypothesis in the brain requires a global signal transduction assay that is applicable in vivo. To distinguish the cellular effects of the different 5-HT2AR agonists, we developed an assay for global signal transduction on the basis of high throughput quantification of rapidly modulated transcripts. Study of the responses to agonists in human embryonic kidney 293 cells stably expressing 5-HT2ARs demonstrated that each agonist elicits a distinct transcriptome fingerprint. We therefore studied behavioral and cortical signal transduction responses in wild-type and 5-HT2AR null-mutant mice. The hallucinogenic chemicals (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) and lysergic acid diethylamide (LSD) stimulated a head-twitch behavioral response that was not observed with the nonhallucinogenic lisuride hydrogen maleate (LHM) and was absent in receptor null-mutant mice. We also found that DOI, LSD, and LHM each induced distinct transcriptome fingerprints in somatosensory cortex that were absent in 5-HT2AR null-mutants. Moreover, DOI and LSD showed similarities in the transcriptome fingerprints obtained that were not observed with the behaviorally inactive drug LHM. Our results demonstrate that chemicals acting at the 5-HT2AR induce specific cellular response patterns in vivo that are reflected in unique changes in the somatosensory cortex transcriptome.


Transverse testicular ectopia: a rare association with inguinal hernia.
Transverse testicular ectopia (TTE) is a rare anomaly that is commonly associated with inguinal hernia. Most of the reported cases are in children with very few reported cases in adults. We report a case of 42 years, fertile male, who presented with left reducible inguinal hernia. During surgery, he was found to have a left indirect inguinal hernia with TTE with both testes on the left side. Hernioplasty and bilateral orchidopexy were performed. He had an uneventful recovery. Most of these cases are diagnosed intraoperatively, but imaging (ultrasonography and magnetic resonance imaging) has emerged as a promising tool for preoperative diagnosis although ultrasound missed it in this case.


Influencing behaviour change in general practice - Part 2 - motivational interviewing approaches.
Behaviour change toward achieving a healthy lifestyle is important for all Australians, and general practitioners have a key role to play in assisting patients to make these changes. This is the second of two articles on influencing behaviour change in general practice. This article deals with the 'how to' of motivational interviewing in the general practice setting. Motivational interviewing can help build motivation, commitment and confidence to change. General practitioners can use motivational interviewing to help their patients achieve their health goals. Motivational interviewing is not about a set of techniques and questions; it is about creating a climate that facilitates change; it is more about listening than telling, evoking rather than instilling. Motivational interviewing can be done in the brief periods available in consultations over time.


Sex-specific moderation by lifestyle and psychosocial factors on the genetic contributions to adiposity in 112,151 individuals from UK Biobank.
Evidence suggests that lifestyle factors, e.g. physical activity, moderate the manifestation of genetic susceptibility to obesity. The present study uses UK Biobank data to investigate interaction between polygenic scores (PGS) for two obesity indicators, and lifestyle and psychosocial factors in the prediction of the two indicators, with attention to sex-specific effects. Analyses were of 112 151 participants (58 914 females; 40 to 73 years) whose genetic data passed quality control. Moderation effects were analysed in linear regression models predicting body mass index (BMI) and waist-to-hip ratio (WHR), including interaction terms for PGS and each exposure. Greater physical activity, more education, higher income, moderate vs low alcohol consumption, and low material deprivation were each associated with a relatively lower risk for manifestation of genetic susceptibility to obesity (p < 0.001); the moderating effects of physical activity and alcohol consumption were greater in women than men (three-way interaction: p = 0.009 and p = 0.008, respectively). More income and less neuroticism were related to reduced manifestation of genetic susceptibility to high WHR (p = 0.007; p = 0.003); the effect of income was greater in women (three-way interaction: p = 0.001). Lifestyle and psychosocial factors appear to offset genetic risk for adiposity in mid to late adulthood, with some sex-specific associations.


Two-photon multiplexing bio-imaging using a combination of Eu- and Tb-bioprobes.
During the course of our research studies aiming to combine the unique photophysical properties of lanthanide complexes and the intrinsic advantage of a nonlinear two-photon excitation, we described the proof-of-concept of a biphotonic multiplexing bio-imaging experiment. To that end, a new Tb-luminescent bioprobe [TbL(2)] was designed using the TACN-trispicolinate platform. The biphotonic imaging of T24 fixed cells stained either with [TbL(2)] or with the already described [EuL(1)] complexes is reported. Finally the biphotonic multiplexing experiment was performed using a combination of both probes using the spectral mode of the two-photon microscope.


Inhibitory effect of stannous fluoride and other commonly used antimicrobial agents on oral bacteria.
The purposes of this investigation were to evaluate and compare the antimicrobial effect of stannous fluoride (SnF2) gel and other commonly used oral antimicrobial agents/products. The antibacterial inhibitory effect of the various agents was evaluated by their effect against oral plaque bacteria including strains of Streptococcus sanguis, Streptococcus sobrinus, Actinomyces viscosus, Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius. A lawn of the specific bacteria to be tested was placed onto blood agar plates. Wells were then punched into the agar and each well was filled with 75 microliters of one of the antimicrobial products or control solutions. A positive control was a 0.12% chlorhexidine solution and a negative control was physiological saline. Agar plates were incubated in an anaerobic chamber at 37 degrees C for 5-7 days. Zones of inhibition in the lawn of bacteria were measured by a boley gauge. Each experiment was performed in duplicate and mean zones of bacterial inhibition were determined. Only 0.4% SnF2 and 0.12% chlorhexidine were consistently more effective in inhibiting oral bacteria when compared with other commercial mouth rinses/agents which had any one of a variety of antimicrobial agents as ingredients (alpha = 0.05). This in vitro study demonstrates that stannous fluoride gel is as effective as chlorhexidine in inhibiting the growth of bacteria often found in dental plaque.


A Survey of Treatment Trends for Acute Quadriceps Tendon Ruptures Among North American Surgeons.
To date, little clinical evidence exists to support a specific surgical technique or postoperative rehabilitation protocol for quadriceps tendon ruptures. With a lack of evidence-based superiority, assessment of clinical practices and surgeon preferences is pertinent. To describe the current surgical technique and rehabilitation preferences among members of the Canadian Orthopaedic Association and American Orthopaedic Society for Sports Medicine pertaining to acute quadriceps tendon rupture. Cross-sectional study. Orthopaedic staff members of the Canadian Orthopaedic Association and American Orthopaedic Society for Sports Medicine were invited to complete an internet-based survey composed of 26 questions assessing current trends in the management and rehabilitation of acute quadriceps tendon rupture. Survey questions were developed after a thorough review of current literature. Survey responses were analyzed and reported using descriptive statistics (absolute values, frequencies, and percentages) where appropriate. Statistical comparisons and contrasts between Canadian and American surgeons were made using chi-square analyses and Student t tests. A total of 264 surgeons participated in the survey (136 Canadians; 128 Americans). Canadian surgeons were more likely to obtain a preoperative ultrasound as compared with Americans (43.0% vs 6.7%; P < .00001), while American respondents were more likely to obtain magnetic resonance imaging scans (65.8% vs 10.2%; P < .00001). The transosseous drill hole technique was the most commonly utilized (70.2%); the suture anchor technique was used 20.6% of the time. Canadian respondents trended toward a higher use of transosseous tunnels; however, this was not statistically significant (75.8% vs 64.2%; P = .068). American respondents were more likely to utilize suture anchors (27.5% vs 14.1%; P = .0096). Most respondents advanced range of motion goals stepwise in 2-week intervals of 30° (Canadians, 54.0% vs Americans, 58.5%; P = .3091); timing of range of motion initiation varied. Among North American surgeons who responded to this study, the transosseous technique was the most commonly used, and range of motion was generally advanced in a 2-week stepwise fashion. We found several differences in practice between Canadian and American respondents, including the type of preoperative imaging and the frequency of using the suture anchor technique.


Community-equipoise and the ethics of randomized clinical trials.
This paper critically examines a particular strategy for resolving the central ethical dilemma associated with randomized clincial trials (RCTs) -- the "community equipoise" strategy (CE). The dilemma is that RCTs appear to violate a physician's duty to choose that therapy which there is most reason to believe is in the patient's best interest, randomizing patients even once evidence begins to favor one treatment. The community equipose strategy involves the suggestion that our judgment that neither treatment is to be preferred (that there obtains a state of "equipoise") is to be assessed according to a community rather than an individual standard. Thus, though a physician may personally believe that there is some reason to prefer one treatment, patients can legitimately be randomized if there remains disagreement in the community of medical professionals. Rationales in favor of this conception include the following: (i) medical knowledge is best understood as residing in the community, (ii) the judgments of others count as evidence, and so should change one's own opinion, (iii) subjects would not be better off outside the trial, and (iv) the point of any trial is the resolution of dispute in the medical community. I critically examine these rationales and argue that they are insufficient. Amongst the problems are tensions between various of these underlying rationales, and important ambiguities in just what the CE criterion is to amount to. Finally, I argue that even if use of CE was justified, it would not justify carrying out RCTs anywhere near long enough to discharge our duty to gain reliable knowledge on which to base safe and effective medical practice. Hence, we need some different justification for carrying out RCTs.


Cytokine production in patients with tuberculous pericarditis.
An academic hospital in the Western Cape, South Africa. To evaluate cytokine production (interferon-gamma [IFN-gamma], interleukin-1 [IL-1], interleukin-2 [IL-2], interleukin-6 [IL-6], interleukin-10 [IL-10], interleukin-4 [IL-4] and tumour necrosis factor-alpha [TNF-alpha]) in patients with tuberculous pericarditis. Subpopulation of a consecutive prospective case series. Thirty patients presenting with pericardial effusions due to tuberculosis (n = 19), malignancy (n = 6) and non-tuberculous infections (n = 5), and five control subjects who had undergone open heart surgery. The concentration of IFN-gamma was significantly higher in tuberculous pericardial effusions than in the other diagnostic classes (P < 0.0005). The concentration of TNF-alpha was similar in both infective and tuberculous effusions, but was significantly higher than that of malignant effusions. IL-1 and IL-2 were undetectable in malignant effusions, but elevated in both infective and tuberculous pericardial effusions. The levels of IL-1 and IL-2 were furthermore significantly higher in pericardial effusions due to infective compared to tuberculous causes. The concentration of IL-6, while elevated in all diagnostic classes, was significantly higher in the malignant group. Elevated levels of IL-10 and undetectable levels of IL-4 were observed in all three diagnostic groups. These findings suggest that tuberculous pericardial effusions arise due to a hypersensitivity reaction that is orchestrated by the TH-1 lymphocytes.


Analysis of neuronal networks: a review of techniques for labeling axonal projections.
In order to analyze connections between neurons in the vertebrate central nervous system, methods have been developed to label a given population of axons of known origin so that they can be differentiated from other, non-labeled structures. Three such methods are reviewed here: experimentally induced orthograde (Wallerian) degeneration, axon transport of radioactive proteins demonstrated by autoradiography, and axon transport of macromolecules that can be reacted histochemically to yield a visible reaction product. Each of the methods has particular strengths and weaknesses. Degeneration methods may differentiate between different functional classes of axons which have different fiber diameters. However, degeneration distorts the morphology of axon terminals, making them more difficult to interpret, and degenerating terminals may be removed rapidly by phagocytosis. Autoradiography of radioactive terminals preserves normal fine structure, but the necessary exposure times extend the method by weeks or months, and care must be exercised to distinguish labeled axons from other structures exhibiting background or transneuronal radioactivity. Histochemical methods, such as those used to demonstrate horseradish peroxidase conjugated to wheat germ lectin (WGA-HRP), are sensitive and rapid, but the injection site must be carefully characterized, and the presence of transneuronal label may make interpretation of the results difficult. Experimental methods of axonal labeling have been invaluable in studying neuronal networks. Each of the methods described here may be of particular value, given the nature of the system to be analyzed.


Fibrolipomatous hamartoma and its ultrasound diagnosis: case series and review of the literature.
Fibrolipomatous hamartoma is a benign tumor mainly affecting peripheral nerves. It is characterized by abnormal growth of fibroadipose tissue within the nerve, leading to progressive compressive neuropathies. Carpal tunnel syndrome is the most frequent among them. Although it is considered an infrequent tumor, magnetic resonance imaging use has led to an increase in case reports. We present 3 clinical cases of fibrolipomatous hamartoma consulting due to soft tissue mass, which were diagnosed by ultrasound.


A systematic review on Chinese herbal treatment for radiotherapy-induced xerostomia in head and neck cancer patients.
Over 80% of head and neck cancer patients suffer from radiotherapy-induced xerostomia (dry mouth). Xerostomia affects cancer patients' quality of life, and xerostomia sometimes persists throughout the patients' lifetime. This review aimed to evaluate the effectiveness and safety of Chinese herbs in relieving radiotherapy induced xerostomia. Systematic searches were conducted on 6 databases (English and Chinese). Studies published up till May 2017 were considered for inclusion. A final 14 RCTs (total 994 head and neck cancer patients undergoing radiotherapy) compared Chinese herbs with no herbs, were included in analysis. Very low to moderate quality of evidence found Chinese herbal treatment may relief radiotherapy-induced xerostomia and other related complications (such as oral mucositis and loss of appetite) in head and neck cancer patients. There is limited evidence that Chinese herbal treatment may relief radiotherapy-induced xerostomia and other related complications in head and neck cancer patients.


The role of the biopsy in diagnosis of early gastric cancer.
In order to determine the reliability of endoscopic biopsy in diagnosis of early gastric cancer, and to clarify the problems with biopsies, preoperative endoscopic biopsies from 771 early gastric cancer cases were reviewed and analyzed clinicopathologically in comparison with surgically resected specimens. The 771 cancers were surgically resected at the National Cancer Center Hospital during the period from 1972 to 1982. Definite histological diagnosis was obtained in 87.4% of the carcinomas at the initial biopsies. Repeated biopsy raised the percentage of correct definite diagnoses to 96.1%. False-negative (including suspicion of cancer) diagnosis was most frequent in the case of depressed lesions (50 lesions). Half of the false negatives were found to be due to sampling errors by the endoscopists. The other half of these 50 lesions were diagnosed as "suspicious of malignancy" because of the histological difficulty in differentiating early gastric cancer from regenerative atypia with intestinal metaplasia, or because there was not enough information, or for the other reasons. Most of the 31 false-negative diagnoses at the initial biopsy from elevated lesions were reported as adenoma (group III) or suspicious of carcinoma (group IV), indicating that differential diagnosis between well-differentiated adenocarcinoma and adenoma is very difficult. The result of the present study suggests that repeated biopsy from correct sites and discussion of the lesions between clinicians and pathologists are very important.


A Review of the Impact of Obstetric Anesthesia on Maternal and Neonatal Outcomes.
Obstetric anesthesia has evolved over the course of its history to encompass comprehensive aspects of maternal care, ranging from cesarean delivery anesthesia and labor analgesia to maternal resuscitation and patient safety. Anesthesiologists are concerned with maternal and neonatal outcomes, and with preventing and managing complications that may present during childbirth. The current review will focus on recent advances in obstetric anesthesia, including labor anesthesia and analgesia, cesarean delivery anesthesia and analgesia, the effects of maternal anesthesia on breastfeeding and fever, and maternal safety. The impact of these advances on maternal and neonatal outcomes is discussed. Past and future progress in this field will continue to have significant implications on the health of women and children.


Update on the Diagnosis and Treatment of Idiopathic Intracranial Hypertension.
Idiopathic intracranial hypertension (IIH) is a rare disorder occurring more frequently in obese women of childbearing age, resulting in increased intracranial pressure (ICP) from an unknown cause. Recent advances in epidemiology, imaging, and treatment have provided a better understanding of IIH in recent years, with better identification of visual risk factors and atypical forms of IIH, including fulminant IIH and spontaneous cerebrospinal fluid leaks, and a randomized clinical trial providing the rationale for the use of acetazolamide. In addition, a revised version of the modified Dandy criteria for the diagnosis of IIH was suggested in 2013, with better definition of IIH in adults and children; however, controversy regarding nomenclature has precluded its acceptance among IIH experts. Finally, questions regarding the best surgical strategy, the indications for venous sinus stenting, and the diagnostic role of the radiologic findings commonly seen in IIH have remained unanswered.


Effect of CdSe/ZnS quantum dot dispersion on phase transitional behavior of 8OCB liquid crystal.
We report the effect on the phase transitional behavior of 8OCB liquid crystal (LC) doped with functionalized CdSe/ZnS quantum dots (QDs) in different concentrations. The temperature-dependent data of high-resolution optical birefringence and dielectric anisotropy are utilized to characterize the critical anomaly for both the isotropic-to-nematic (I-N) and nematic-to-smectic-A (N-SmA) phase transitions. The obtained results reveal that the order parameter exponent (β) for the pure LC is found to be β=0.249 and does not vary upon the inclusion of QDs in the pure matrix. It describes the weakly first-order characteristic of the I-N phase transition for all the studied samples, which falls within the limit of the tricritical hypothesis. Conversely, depending on the range of the N phase, we observed a nonuniversal nature of the specific heat capacity critical exponent (α^{'}) linked with the N-SmA phase transition for all the studied samples. A relative comparison was made amongst the α^{'} values extracted from both the anisotropy data, and further, a theoretical relationship is established with these exponent values. The coupling strength among the N and SmA order parameters is determined using the optical birefringence data and discussed from the perspective of mutual interaction between the LC-QDs ligands. The results signify that a strong ligand-ligand interaction between neighboring QDs effectively reduces the N range and slightly influences the N-SmA phase transition.


Cytotoxic Necrotizing Factors: Rho-Activating Toxins from Escherichia coli.
This article reviews the Escherichia coli toxins called cytotoxic necrotizing factors (CNFs), which cause activation of Rho GTPases. It describes their modes of action, structure-function relationships, and roles in disease. Rho GTPases, the targets of CNFs, belong to the Ras superfamily of low molecular mass GTPases and act as molecular switches in various signaling pathways. Low molecular mass GTPases of the Rho family are known as master regulators of the actin cytoskeleton. Moreover, they are involved in various signal transduction processes, from transcriptional activation, cell cycle progression, and cell transformation to apoptosis. CNFs are cytotoxic for a wide variety of cells, including 3T3 fibroblasts, Chinese hamster ovary cells, Vero cells, HeLa cells, and cell lines of neuronal origin. This implies that a commonly expressed receptor is responsible for the uptake of CNF1. Cultured mammalian cells treated with CNFs are characterized by dramatic changes in actin-containing structures, including stress fibers, lamellipodia, and filopodia. Most striking is the formation of multinucleation in these cells. Rho GTPases are increasingly recognized as essential factors in the development of cancer and metastasis. This fact has initiated a discussion as to whether activation of Rho proteins by CNFs might be involved in tumorigenesis. Moreover, CNF1 increases the expression of the cyclooxygenase 2 (Cox2) gene in fibroblasts. Increased expression of Cox2 is observed in some types of tumors, e.g., colon carcinoma. Lipid-mediators produced by the enzyme are suggested to be responsible for tumor progression.


Molecular biology and transgenetics of prion diseases.
Considerable progress has been made deciphering the role of an abnormal isoform of the prion protein (PrP) in scrapie of animals and Gerstmann-Sträussler syndrome (GSS) of humans. Some transgenic (Tg) mouse (Mo) lines that carry and express a Syrian hamster (Ha) PrP gene developed scrapie 75 d after inoculation with Ha prions; non-Tg mice failed to show symptoms after greater than 500 d. Brains of these infected Tg(HaPrP) mice featured protease-resistant HaPrPSc, amyloid plaques characteristic for Ha scrapie, and 10(9) ID50 units of Ha-specific prions upon bioassay. Studies on Syrian, Armenian, and Chinese hamsters suggest that the domain of the PrP molecule between codons 100 and 120 controls both the length of the incubation time and the deposition of PrP in amyloid plaques. Ataxic GSS in families shows genetic linkage to a mutation in the PrP gene, leading to the substitution of Leu for Pro at codon 102. Discovery of a point mutation in the Prp gene from humans with GSS established that GSS is unique among human diseases--it is both genetic and infectious. These results have revised thinking about sporadic Creutzfeldt-Jakob disease, suggesting it may arise from a somatic mutation. These findings combined with those from many other studies assert that PrPSc is a component of the transmissible particle, and the PrP amino acid sequence controls the neuropathology and species specificity of prion infectivity. The precise mechanism of PrPSc formation remains to be established. Attempts to demonstrate a scrapie-specific nucleic acid within highly purified preparations of prions have been unrewarding to date. Whether transmissible prions are composed only of PrPSc molecules or do they also contain a second component such as small polynucleotide remains uncertain.


[Gastrointestinal hemorrhage in children against a background of viral and bacterial infections].
In the process of intensive therapy, 22 of 32 patients developed gastrointestinal bleeding against the background of acute virobacterial pneumonia. The degree of intoxication, hypoxia, impairment in the coagulative blood system, and the level of circulating immune complexes were the main factors, which defined severity of the state of a patient, massiveness of bleeding and outcome of the treatment. The bleeding developed, if the DIC-syndrome achieved the stage of consumptive coagulopathy, and the content of the middle molecular mass substances and circulating immune complexes exceeded 1.5-2-fold the age indices.


Purification and characterization of a mutant tRNA nucleotidyltransferase.
tRNA nucleotidyltransferase has been extensively purified from a mutant strain of Escherichia coli which displays greatly decreased AMP incorporation, but normal CMP incorporation. The defect in AMP incorporation is retained throughout the purification of the mutant protein. The mutant protein behaves identically to the wild-type protein with regard to elution position on various chromatographic columns, and both have similar molecular weights of about 50000. The defect in the mutant protein is accentuated by the use of yeast tRNA rather than E. coli tRNA-C--C as substrate, by decreased pH, by increased ionic strength and by decreased divalent cation concentration. Substitution of MN2+ for Mg2+ greatly increases the relative activity of the mutant enzyme. In all these cases, CMP incorporation by the mutant enzyme remains the same as the wild-type enzyme. The Km values of the mutant enzyme for its tRNA and triphosphate substrates are unchanged, and the mutant protein is as stable as the wild type with respect to temperature inactivation. These results strongly suggest that the mutation is in the structural gene for tRNA nucleotidyltransferase, and that the mutation probably does not affect the overall structure of the mutant protein, but only a localized region near the AMP-incorporating site.


[Cerebrospinal fluid eosinophils in inflammatory processes of the central nervous system and its coverings].
Eosinophil cells play an important role in the signalization of cerebrospinal fluid (CSF) by inflammatory diseases of central nervous system and its leptomeningeal coverings (CNS), according to present data on neuroimmunology. The extent of their participation in local immunological phenomena is evaluated, and data on other changes in the CSF cytoprotein dual were considered for comparative purposes. CSF of two types of inflammatory diseases of the CNS were studied for this purpose: samples of 35 patients in early stages of acute eosinophilic leptomeningites possibly of viral origin (first group) and 20 samples of 10 patients with neurocysticercosis (second group). Samples of the second group were collected in the early stages of each one of two episodes of exhacerbation in the inflammatory reaction observed at each one of the two series of administration of Praziquantel, a pirazino-isochinoleinic derivate which action upon cysticerci has been reported. Statistical analysis shows that participation of eosinophil cells in the inflammatory response does not differ in the two groups. Their participation is related to changes observed in the CSF cytoprotein dual rather than to the type of the inflammatory model: acute and monophasic in the first group, and chronic an repetitive in the second. Gamma globulins participe in the exhacerbation of CSF inflammatory reaction in neurocysticercosis but their behaviour not always is similar. In some instances it is similar to that found in other chronic and repetitive inflammatory models, as multiple sclerosis for instance.


Occlusal forces in prosthetically restored dentitions: a methodological study.
The present paper describes a method developed to study occlusal forces in prosthetically restored dentitions. Using this method the magnitude, duration and frequency of the forces can be measured in various parts of the dentition simultaneously. The measurements are based on the use of strain gauge transducers of such dimensions that they can be mounted into artificial crowns, bridge-pontics or removable dentures, without interfering with the occlusion. The output signal of each transducer is linear for forces up to 300 N which corresponds to an amplitude (elastic deformation) of 20 microns. At least four transducers are used distributed over the tooth-arch to create bilateral and simultaneous contacts. They are mounted in a supraoccluding position of 20 microns in relation to non-transducer areas. This means that on jaw closure each transducer registers all the force transmitted to that part of the prosthetic construction represented by the transducer, provided there is no force leakage to non-transducer areas. The sum of these local forces constitutes the total force acting on the entire dentition at any given moment.


Facile synthesis of 1,5-disubstituted 1,2,3-triazoles by the regiospecific alkylation of a ruthenium triazolato complex.
The alkylation of the N(2)-bound ruthenium triazolate [Ru]N3C2HCO2Et (2, [Ru] = (η5-C5H5)(dppe)Ru, dppe = Ph2PCH2CH2PPh2) with benzylbromides is reported. The regiospecific alkylation of 2, which results from the [3 + 2] cycloaddition of ethyl propiolate with [Ru]-N3 (1), gives a series of cationic N(1)-bound N(3)-alkylated-4-ethoxycarbonyl triazolato complexes {[Ru]N3(CH2R)C2HCO2Et}[Br] (3a, R = 4-CH2Br-C6H4; 3b, R = 3,5-(CH2Br)2-C6H3; 3c, R = 2,6-F2-C6H3; 3d, R = 4-CN-C6H4) and the subsequent cleavage of the Ru-N bond of 3a-3d gives N(1)-alkylated-5-ethoxycarbonyl triazoles N3(CH2R)C2HCO2Et (4a-4d) and [Ru]-Br, which, on reacting with sodium azide, would afford [Ru]-N3 (1) thus forming a reaction cycle. The treatment of {[Ru]N3(CH2C6F5)C2HCO2Et}[Br] (3e) with sodium azide in refluxing ethanol gives the free triazole N3(CH2C6F5)C2HCO2Et (4e) and 1. The treatment of 2 with an equivalent of 3a affords a dinuclear bis(triazolato) complex {α,α'-bis([Ru]N3C2HCO2Et)-p-xylene}[Br]2 (5) and an organic bis(triazole) complex α,α'-bis(N3C2HCO2Et)-p-xylene (6). The treatment of 2 with CF3COOH in CHCl3 at room temperature affords a mixture of N(2)-bound 1H- and 3H-4-ethoxycarbonyl triazolato complexes {[Ru]N3HC2HCO2Et}[CF3COO] (1H-7) and (3H-7) in a ratio of 5 : 2. The structures of 4e, 5 and 1H-7 were confirmed by single-crystal X-ray diffraction analysis.


Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells.
All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human beta-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the beta-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced beta-defensin expression in airway mucosa, which includes the middle ear. Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods - dominant negative (DN) plasmid and small interfering RNA (siRNA) - were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated beta-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's t-test was used for the statistical analysis of the data. The experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of beta-defensin 2. This study found that the induction of beta-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1alpha-induced beta-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate beta-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.


Selective detection of singlet gerade metastable states of N2.
Metastable N2 molecules produced by electron impact on N2 are detected using a unique solid nitrogen matrix detector. The time-of-flight system is shown to be selectively sensitive to a(1)Πg and (1)Σg (+) or (1)Γg metastable species. The latter species had been identified theoretically previously but was detected experimentally for the first time in the present investigation. Their identification and excitation as a function of electron energy from threshold to 300 eV are presented. Comparison is made with the data obtained by other techniques.


Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability.
Creutzfeldt-Jackob disease (CJD), the most common human prion disorder, is frequently accompanied by ageing-associated neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease. Although cross-seeding of amyloidogenic proteins (APs), including amyloid β and α-synuclein, may be critical in the co-morbidity of neurodegenerative disorders, the direct interaction of APs with prion protein (PrP), the central molecule involved in the pathogenesis of CJD, is unlikely. Currently, the nature of this biological interaction and its significance remain obscure. In this context, the objective of the present study is to discuss such interactions from the perspective of amyloidogenic evolvability, a putative function of APs. Hypothetically, both hereditary- and sporadic CJD might be attributed to the role of PrP in evolvability against multiple stressors, such as physical stresses relevant to concussions, which might be manifest through the antagonistic pleiotropy mechanism in ageing. Furthermore, accumulating evidence suggests that PrP- and other APs evolvability may negatively regulate each other. Provided that increased APs evolvability might be beneficial for acquired CJD in young adults, a dose-reduction of α-synuclein, a natural inhibitor of αS aggregation, might be therapeutically effective in upregulating APs evolvability. Collectively, a better understanding of amyloidogenic evolvability may lead to the development of novel therapies for CJD.


Hedgehog Cholesterolysis: Specialized Gatekeeper to Oncogenic Signaling.
Discussions of therapeutic suppression of hedgehog (Hh) signaling almost exclusively focus on receptor antagonism; however, hedgehog's biosynthesis represents a unique and potentially targetable aspect of this oncogenic signaling pathway. Here, we review a key biosynthetic step called cholesterolysis from the perspectives of structure/function and small molecule inhibition. Cholesterolysis, also called cholesteroylation, generates cholesterol-modified Hh ligand via autoprocessing of a hedgehog precursor protein. Post-translational modification by cholesterol appears to be restricted to proteins in the hedgehog family. The transformation is essential for Hh biological activity and upstream of signaling events. Despite its decisive role in generating ligand, cholesterolysis remains conspicuously unexplored as a therapeutic target.


YouTube as a learning source for contact lens insertion and removal.
Contact lens neophytes often learn about contact lens insertion and removal through YouTube videos of unknown quality. This study evaluates the quality of soft contact lens insertion and removal videos on YouTube. A search for the keywords 'Contact lens insertion', 'Contact lens removal', 'Put in contact lens', and 'Take off contact lens' was performed on YouTube. The first 50 videos for each keyword were evaluated. The number of views, source of the publisher, days since upload, and video quality were scored based on the content in the videos. The maximum score of insertion and removal videos were 7 and 5 respectively. The videos were classified into three groups by publisher category: videos published by eye care professionals, companies and YouTubers. Only 45 contact lens insertion and 44 removal videos met the inclusion criteria and were analysed. Insertion and removal videos published by YouTubers had the highest view and view rate. However, their quality scores were significantly lower than videos published by eye care professionals and companies. Videos uploaded by companies had the highest scores (insertion: 5.00 ± 1.10; removal: 3.25 ± 0.75). The mean scores of insertion and removal videos published by YouTubers were 1.65 ± 0.93 and 1.00 ± 0.89, respectively, while the insertion and removal videos uploaded by eye care professionals scored 3.58 ± 2.07 and 2.75 ± 1.53, respectively. There was also a negative correlation between the quality scores and view rate (p = 0.008, r = -0.41). Contact lens insertion and removal videos uploaded by YouTubers had the highest view rate but the lowest quality. Videos made by companies included most essential elements.


[Cloning and analysis of a novel gene encoding N-terminal acetyltransferase subunit].
N-terminal acetylation is the most common modification in eukaryotic proteins, affecting stability and activity of proteins. NatA is one of the N-terminal acetytransferases in yeast. It is composed of two subunits, NAT1 and ARD1. Defect in one of them leads to loss of activity of NatA. Null mutant of NAT1 in yeast exhibits a variety of phenotypes, including depression of a silent mating type locus (HML), failing to enter G(0) in poor nutrient situations and chromosomes instability. Based on homology of NAT1 between yeast and other organisms, the full-length CDS (coding sequence) of HNAT1 was cloned and sequenced. Result of in situ hybridization in testis of rat showed that expression of NAT1 was high and its expression was different in different phases of spermatogenesis. The gene may play an important role in spermatogenesis.


In situ ATR-FTIR investigation on the preparation and enantiospecificity of chiral polyelectrolyte multilayers.
Chiral polyelectrolyte multilayers (PEMs) consisting of poly(l-lysine) (PLL), poly(N-(S)alkylated 4-vinylpyridinium iodide), or poly(ethyleneimine maltose) (PEI-m) as polycations and poly(styrenesulfonic acid) sodium salt (PSS) or poly(vinyl sulfate) as polyanions, as well as a nonchiral PEM composed of poly(ethyleneimine) (PEI) and PSS were deposited on silicon substrates and poly(tetrafluoroethylene) membranes using the layer-by-layer method. For these PEMs, enantiospecific interaction toward one enantiomer of either l/d-glutamic acid (l/d-GLU), l/d-tryptophan, or l/d-ascorbic acid (l/d-ASC), respectively, was studied under variation of the concentration, pH, and ionic strength. Both deposition and enantiospecific interaction were analyzed by attenuated total reflection Fourier transform infrared spectroscopy. Our results show a significant enantiospecific preference of d-GLU over l-GLU at PEMs containing PLL and of d-ASC over l-ASC at PEMs containing PEI-m. No such enantiospecific preference was found for nonchiral PEMs containing PEI. The enantiospecificity of PEMs of PLL/PSS toward l/d-GLU could be significantly influenced by the ionic strength and pH values, so that increasing attractive electrostatic interactions resulted in higher enantiospecificity.


Overcoming Barriers to Palliative Care Consultation.
Palliative care consultations for patients with life-threatening illnesses provide benefits for the patients and their families as well as for the health care team. Patients have better quality of life and live longer but cost the health care system less. Still, many patients are not offered the opportunity to receive a palliative care consultation. Barriers to palliative care consultation for patients in critical care units include misunderstandings about palliative care and not having agreed upon criteria for referral. Critical care nurses can assist in overcoming these barriers.


Adenosine receptors on rabbit alveolar macrophages: binding characteristics and effects on cellular function.
Adenosine and its synthetic analogues are known to affect many leukocyte functions, in some cases by binding to specific cell surface receptors coupled to adenylate cyclase. In this study, adenosine receptors were demonstrated on normal rabbit alveolar macrophages by examining specific binding of tritiated 5-N-ethylcarboxamide adenosine (NECA) to intact cells. Scatchard analysis suggested a single class of approximately 33,000 binding sites per cell and an estimated Kd of 0.46 mumol/L. Competitive inhibition of tritiated NECA binding was demonstrated for 2-chloroadenosine (2-CA; Ki = 3.68 mumol/L) and L-phenylisopropyl adenosine (L-PIA; Ki greater than 100 mumol/L), a rank order of binding affinities indicative of an A2 receptor. Theophylline and isobutyl methylxanthine had Kis of 368 and 27.6 mumol/L, respectively. For functional correlation, NECA was found to be 10-fold more potent than L-PIA in stimulating an increase in intracellular cyclic adenosine monophosphate. In addition, macrophages were cultured for 24 hours with NECA, 2-CA, or L-PIA to determine whether these analogues modulated expression of either cell-associated procoagulant activity or elaboration of plasminogen activator. Procoagulant activity was suppressed by as much as 62% (P less than 0.05); the rank order of potency and blockade of the effect with theophylline suggest that suppression of procoagulant activity occurred primarily by stimulation of A2 receptors. By contrast, these analogues stimulated production and release of plasminogen activator by 30% (P less than 0.05), but this effect had none of the features of an A2-mediated mechanism. Macrophages were cotreated with nitrobenzylthioinosine (10 mumol/L) and adenosine deaminase (2 U/ml) to allow adenosine accumulation exclusively within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)


[Venous ulcer--present view on aetiology, diagnostics and therapy].
The common aetiology of chronic wounds is chronic venous insufficiency. The prevalence of chronic venous insufficiency ranges from 5 to 8% and the prevalence of venous ulcers is about 1%. Venous ulcer is caused by induction of chronic inflammation. Chronic inflammation leads to deregulations of wound healing mechanisms. Senescent phenotype of wound healing cells is recorded as outcome of chronic inflammation. Diagnosis is based on classical clinical presentation of venous ulcer and on supporting examinations. Supporting examinations include duplex ultrasound, photoplethysmography, ankle brachial index investigation and examination of hemocoagulation status. Malignant transformation is a possible complication of venous ulcers. The relative risk of malignancy in chronic venous ulcers is 5.8%. The first step in venous ulcer treatment is debridement. There is no consensus in speculations about wound colonization treatment. However the signs of infection are indication for general antibiotics treatment. Local antiseptic therapy is increasingly used. On the other side local antibiotics therapy is not recommended. Compression is used as the mainstay of therapy. It is important to rule out arterial disease before initiating compression therapy. Dressings are used as an adjuvant therapy to compression. Venous ulcers treatment is an interdisciplinary problem. Large diagnostic and therapeutic methods are needed for its management.


Investigations on Leydig cell function and regulation after renal transplantation.
The hypothalamic-hypophyseal-Leydig cell axis was investigated in 17 male patients following renal transplantation. Plasma levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were determined by radioimmunoassay under basal conditions and after stimulation with chorionic gonadotrophin (HCG) and hypothalamic releasing hormone (LH/FSH-RH) respectively. The investigations were carried out one to five years after renal transplantation. It was demonstrated, that primary dysfunction of Leydig cells may occur after renal transplantation. In some cases however normal Leydig cell function with adequate testosterone secretion may return. It remains uncertain, whether the Leydig cell dysfunction is a result of preexisting toxic uremic damage or whether it is due to immunosuppressive therapy with prednisone and azathioprine.


Radical perineal prostatectomy: a more optimal treatment approach than laparoscopic radical prostatectomy in obese patients?
In comparison with laparoscopic radical prostatectomy (LRP), the perineal approach to radical prostatectomy offers specific technical advantages related to obesity and its unique surgical challenges. Radical perineal prostatectomy (RPP) reduces operative time and its associated risk of complication, which may be more pronounced in obese men. It allows for low blood loss, low postoperative use of narcotics for pain, short hospital stays, and requires only 1 small perineal incision. With a proven history of success, RPP presents obese men with an advantageous surgical option.


Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma.
The clinical deployment of immune checkpoint inhibitors (ICIs) has created a tandem drive for the identification of biomarkers linked to benefit. Comprehensive genomic profiling was performed to evaluate the frequency of genomic biomarkers of ICI response in 755 patients with advanced hepatocellular carcinoma (HCC). Median age was 62 years' old, 73% were male, 46% had extrahepatic disease, 107 had documented hepatitis C, 96 had hepatitis B and 4 patients were coinfected. Median tumor mutation burden (TMB) was 4 mutations/Mb and only 6 tumors (0.8%) were TMB-high. Out of 542 cases assessed for microsatellite instability (MSI), one (0.2%) was MSI-high and TMB-high. Twenty-seven (4%) patients had POLE/D alterations. One patient had a pathogenic POLE R762W mutation but TMB was 4 mutations/Mb. Forty percent had DNA damage response gene alterations. In a small case series (N=17) exploring the relationship between biomarkers and ICI response, one patient (TMB 15 mutations/Mb, MSI-low) had a sustained complete response to nivolumab lasting > 2 years. Otherwise there were no significant genomic or TMB differences between responders, progressors, and those with stable disease. Overall, markers of genomic instability were infrequent in this cohort. Larger clinically annotated datasets are needed to explore genomic and non-genomic determinants of ICI response in HCC.


[Animal experimental studies on the increase in the humoral immune response caused by whole body irradiation].
The production of antibodies against heterologous erythrocytes (sheep erythrocytes) can be significantly increased in mice and rats by total body irradiation. This effect depends upon the radiation dose applied and can be demonstrated only in animals immunized first and then irradiated at intervals of six hours. In vitro assays show indirectly that the radiogenic immune stimulation is caused by the varying radiosensitivity of the individual cell populations involved in the humoral immune reaction, leading to a relatively selective inactivation of T-suppressor cells.


Effects of stimulus intensity and duration on posterior tibial nerve somatosensory-evoked potential patterns obtained under anesthesia.
This study analyzed systematic changes in stimulus intensity and duration on the latencies and amplitudes of somatosensory-evoked potential peaks obtained upon posterior tibial nerve stimulation of orthopedic patients under anesthesia. To examine the effects of systematic stimulus changes on somatosensory-evoked potential patterns and to compare the sensitivity of different peaks. Previous studies primarily examined the effects of either stimulus intensity or stimulus duration but not their interactions. Nine orthopedic patients were tested using three stimulus intensities and three stimulus durations. Five peak latencies and four amplitudes were measured. Data consisted of frequency of peak occurrences under each condition and analyses of variances of peak latencies and amplitudes. Three latencies yielded stable findings (P40, N50, P60). Peak latencies under anesthesia were not affected by stimulus intensity or duration. Amplitudes, however, were affected differentially. P40-N50 increased with increases in stimulus intensity or stimulus duration, but no significant interaction effects were found. N50-P60 showed no significant changes associated with stimulus intensity or duration. Under combined isoflurane/nitrous oxide anesthesia, somatosensory-evoked potential patterns obtained upon stimulation of the posterior tibial nerves showed no significant changes in major peak latencies with changes in stimulus intensity or duration. However, changes in amplitude were found. Stimulus intensity-duration interaction effects were observed, described, and interpreted.


Adjuvant efficacy of G2 (buffalo spleen extraction) against Yersinia septicemia in rainbow trout (Onchorhynchus mykiss).
Adjuvant effect of G2 (extraction of buffalo spleen) was assessed in intraperitoneally immunized rainbow trout (100-150 g) with killed- Y. ruckeri bacterin biotype I [0.1 mL (1 × 107 cells/fish) of vaccine diluted with the adjuvant in a ratio of 1:1 (V/V)] at 12.4 ± 1.3 °C for 10 weeks. Leukocyte and lymphocyte counts, anti-Y. ruckeri antibody titer and relative percent survival (RPS) in fish vaccinated with vaccine containing the adjuvant were significantly higher than the immunized fish with Y. ruckeri antigen alone throughout the experiment (P < 0.05), but neutrophils count and lysozyme activity were mostly significantly higher in the latter group (P < 0.05). No difference was seen in the complement activity between vaccinated fish containing the adjuvant and vaccine alone (P > 0.05). The results of this work for the first time demonstrated that inclusion of G2 as an adjuvant in Y. urckeri vaccine can improve the efficacy of the vaccine against Yersinia septicemia in rainbow trout.


Spectrum of the hangman's fracture.
The authors review their experience in managing 26 cases of "hangman's fracture." The basic mechanism of injury was hyperextension of the upper cervical spine. Radiographic studies revealed a spectrum of injury beginning with the classical hangman's fracture and progressing to the simple C-2 laminar-pedicle fracture. Appreciation of the fracture instability will dictate the method and duration of fracture treatment. Management by a closed, nonoperative means resulted in solid union of the bone in all fully treated cases, with a minimum of morbidity.


Efficacy and safety of transdermal fentanyl for treatment of oral mucositis pain caused by chemotherapy.
We investigated the efficacy and safety of transdermal fentanyl for severe mucositis pain caused by chemotherapy. Thirty-two patients who had moderate to severe pain using the Numeric Rating Scale (NRS) were enrolled in this study. The analgesic effect, quality of life and side effects were evaluated after the administration of transdermal fentanyl. The median NRS score was reduced from 6 (range 4 - 9) before treatment to 4 (range 0 - 9), 2.5 (range 0 - 8), 2 (range 0 - 8), 2 (range 0 - 6) and 0 (range 0 - 5) on days 3, 5, 7, 10 and 15, respectively, after treatment (p < 0.001). The patients' quality of life also improved significantly (p < 0.01). The side effects of treatment were mild, and disappeared within several days. Transdermal fentanyl is an effective, convenient and well-tolerated treatment for severe mucositis pain caused by chemotherapy that can improve patients' quality of life.


Analysis of CL-20 in environmental matrices: water and soil.
Analytical techniques for the detection of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazatetracyclo(5.5.0.05,9.03,11)dodecane (CL-20) in water and soil are developed by adapting methods traditionally used for the analysis of nitroaromatics. CL-20 (a new explosives compound) is thermally labile, exhibits high polarity, and has low solubility in water. These constraints make the use of specialized sample handling, preparation, extraction, and analysis necessary. The ability to determine the concentrations of this new explosive compound in environmental matrices is helpful in understanding the environmental fate and effects of CL-20; understanding the physical, chemical, and biological fate of CL-20; and can be used in developing remediation technologies and determining their efficiency. The toxicity and mobility of new explosives in soil and groundwater are also of interest, and analytical techniques for quantitating CL-20 and its degradation products in soil and natural waters make these investigations possible.


Fate of MS2 proteins synthesized in Escherichia coli exposed to amino acid analogues.
Incorporation of an analoque into MS2 coded proteins prevents the maturation of phages. In addition, there is an alteration in the relative amount of coat protein to replicase protein synthesized, which supports the hypothesis that normal coat protein serves a physiological role as a translation repressor. Further, abnormal proteins, synthesized from the phage genome, are degraded, presumably by a host catabolic system, more rapidly than the normal gene products.


Apocrine metaplasia in cystic hyperplastic mastopathy. Histochemical and ultrastructural observations.
A histochemical and ultrastructural investigation of apocrine cells in the human breast has been carried out. These cells showed strong oxidative enzymatic activity, large numbers of mitochondria and numerous infoldings of the basal plasma membrane. In these features, such cells resemble the normal apocrine gland cells. These observations support the view that this lesion is a metaplastic change in normal breast epithelium.


Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry of friction modifier additives analyzed directly from base oil solutions.
To develop new products and to apply measures of quality control quick and simple accessibility of additive composition in automo- tive lubrication is important. The aim of this study was to investigate the possibility of analyzing organic friction modifier additives by means of atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry [AP-MALDI-MS] from lubricant solu- tions without the use of additional separation techniques. Analyses of selected friction modifier ethoxylated tallow amines and oleic acid amide were compared using two ionization methods, positive-ion electrospray ionization (ESI) and AP-MALDI, using a LTQ Orbitrap mass spectrometer. Pure additives were characterized from solvent solutions, as well as from synthetic and mineral base oil mixtures. Detected ions of pure additive samples consisted mainly of [M + H]+, but also alkaLi metal adducts [M + Na]+ and [M + K]+ could be seen. Characterizations of blends of both friction modifiers from the base oil mixtures were carried out as well and showed significant inten- sities for several additive peaks. Thus, this work shows a method to directly analyze friction modifier additives used in the automotive industry from an oil blend via the use of AP-MALDI without any further separation steps. The method presented will further simplify the acquisition of data on lubricant composition and additives. Furthermore, it allows the perspective of analyzing additive reaction products directly from formulated oil blends.


Hypokalemic paralysis due to Gitelman syndrome: a family study.
Hypokalemic paralysis is rarely seen as the presenting feature in patients with Gitelman syndrome. We report a Chinese man who presented with periodic paralysis, in whom molecular analysis revealed compound heterozygous inheritance of three mutations of the thiazide-sensitive sodium chloride cotransporter. Family history revealed intrafamilial variation in phenotypes. Gitelman syndrome should be considered as a cause of hypokalemic paralysis, and molecular analysis may help establish the diagnosis.


Visual search for rare targets: distracter tuning as a mechanism for learning from repeated target-absent searches.
In the typical visual search experiment, participants search for targets that are present on half of the trials and absent on the other half. However, many real-world tasks involve targets that are present only occasionally. Given this, it is important to know how people deal with the problem of finding targets they have little experience with. One possibility is that they develop an awareness of the degree to which they have effectively completed a search through complex target-absent scenes. To test this hypothesis, we had participants complete two relatively long search tasks in which only a minority of trials included targets. Stimuli were cluttered real-world scenes, and targets were defined by category. We examined participants' ability to terminate search on the target-absent scenes based on an accurate assessment of scene difficulty. Scene difficulty was estimated by computing the mean correct-trial response time (RT) for each of the target-absent scenes across all participants. These group RTs were then correlated with each participants' individual correct-trial RTs for the same stimuli to assess the degree to which a given participant's search-termination times were correlated with those of the group. These correlations successfully predicted participants' target-detection success in both experiments. These experiments suggest that an integral part of visual search is the need to calibrate search behaviour to scenes of varying levels of complexity even when no targets are present.


Use of Clinical UV Chamber to Disinfect Dental Impressions: A Comparative Study.
Dental impressions are potential source of infection in a prosthodontic practice. Risk of transmission of infection through saliva, blood etc is considered as hazard for both dentist as well as dental auxiliary staff. A number of methods are currently employed for disinfecting the impressions which are technique sensitive and time consuming. This study focuses on disinfecting impression using dental UV chamber which is commonly employed for storing sterilized instruments. The aim of this invitro study was to evaluate the use of clinical UV chamber to disinfect various impression materials at different time intervals and its comparison with 2% glutaraldehyde using standard immersion technique. Total sample size of 180 specimens was taken from three different impression materials. The impressions were made from 30 dentulous subjects. A total of ten impressions were made for each impression material i.e. alginate, addition silicone and polyether impression material. Six punch samples were taken from each impression. Out of 6 punch sample, one was kept as control, second was disinfected by immersing in freshly prepared 2% glutaraldehyde solution for 10 minutes and remaining four were exposed to UV rays for 3 minutes, 6 minutes, 10 minutes and 15 minutes using dental UV chamber. Amount of disinfection achieved was evaluated by counting the colonies over the culture plates with the help of digital colony. The results showed that the mean CFUs for alginate were found to be i.e. 11797.40 ± 5989.73 (mean ± SD). The mean CFUs for addition silicone impression material was found 7095.40 with a standard deviation of 4268.83 and the mean CFUs for polyether impression material was found to be 2168.92 ± 1676 (mean ± SD). For alginate and addition silicone impression material, disinfection was achieved on exposure to UV rays for a period of 10 minutes. However, for polyether impression material 3 minutes of exposure to UV rays was sufficient to cause complete disinfection.


A vision profile of American Indian children.
In an unselected study, Modified Clinical Technique screening plus keratometry was done on 398 American Indian grade school children. The results are compared to screening results for Caucasin grade school children.


Overproduction and purification of the colicin E1 immunity protein.
Colicin E1 immunity protein encoded by the plasmid colicin E1 was overproduced in Escherichia coli from an expression plasmid which was constructed by placing the immunity protein-encoding sequence downstream of the tac promoter and by properly positioning the ribosome binding site on a run-away replication vector. The immunity protein was solubilized with 0.5% Brij 58 from the membrane fraction and purified to homogeneity by a simple batch procedure with hydroxyapatite gel and reverse-phase chromatography. A 15-residue NH2-terminal amino acid sequence was determined to be the same as that deduced from the DNA sequence. The effect of the purified immunity protein on membranes was tested in vitro using solute-loaded liposomes. The immunity protein added to the liposomes showed a small but significant channel or lytic activity that is an indicator of its hydrophobic nature.


Proteostasis, an emerging therapeutic paradigm for managing inflammatory airway stress disease.
Airways stress diseases (ASDs), including chronic obstructive pulmonary disease (COPD), emphysema and asthma, are predicted to become the third leading cause of morbidity and mortality by 2020. An understanding and the treatment of these diseases will have a high impact on human health and the health system. An emerging area of heathspan impact is the link between ASDs and proteome homeostasis or 'proteostasis', a biological system comprised of > 2000 components that direct the generation, maintenance and removal of proteins to achieve normal function. Alpha-1 antitrypsin deficiency (αA1TD) aggregates activating extracellular folding stress pathways, dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and misprocessing by histone acetyltransferase (HAT)/histone deacetylase (HDAC) pathways represent key examples of proteostasis imbalance involved in ASDs. Common to these events in the lung is a chronic inflammatory response in response to nuclear factor-κB (NF-κB) signaling and protein folding stress associated with an excess of mucus secretion, tissue remodeling, peribronchiolar fibrosis, bronchoconstriction and aveolar destruction. All of these emergent properties of disease are a consequence of imbalance in the proteostasis system. Herein, we discuss the role of proteostasis and its consequences on lung pathophysiology in inflammatory ASDs, and suggest how manipulating the proteostasis network through pharmacological intervention of proteostasis pathways could provide multiple routes for the restoration of lung physiology.


Classification in anatomic pathology.
Classification is the activity that allows pathologists to arrange the bewildering morphologic manifestations of disease into comprehensible order Ideally, our precise diagnoses would each be based on some timeless biological law of nature, and these diagnoses would group together patients with identical clinical manifestations and responses to therapy. However, in spite of the amazing success of pathology classification, it is apparent to everyone that diagnostic disagreements are common, and that patients who exactly fit into a diagnostic category often have markedly different disease courses and responses to therapy. At this time, it is unclear how quickly the potential of genomic medicine will be translated into revolutionary changes in pathology classification. However, it is clear that the rules of classification are part of the foundation of diagnostic pathology and that there is a high likelihood that pathology classification will undergo substantial changes in the next few years. This article reviews the topic of classification for pathologists who will practice during these interesting times.


Genetic determinants of childhood and adult height associated with osteosarcoma risk.
Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, to the authors' knowledge the relative contribution of stature during different developmental timepoints remains unclear. Furthermore, the question of how genetic determinants of height impact osteosarcoma etiology remains unexplored. Genetic variants associated with stature in previous genome-wide association studies may be biomarkers of osteosarcoma risk. The authors tested the associations between osteosarcoma risk and polygenic scores for adult height (416 variants), childhood height (6 variants), and birth length (5 variants) in 864 osteosarcoma cases and 1879 controls of European ancestry. Each standard deviation increase in the polygenic score for adult height, corresponding to a 1.7-cm increase in stature, was found to be associated with a 1.10-fold increase in the risk of osteosarcoma (95% confidence interval [95% CI], 1.01-1.19; P =.027). Each standard deviation increase in the polygenic score for childhood height, corresponding to a 0.5-cm increase in stature, was associated with a 1.10-fold increase in the risk of osteosarcoma (95% CI, 1.01-1.20; P =.023). The polygenic score for birth length was not found to be associated with osteosarcoma risk (P =.11). When adult and childhood height scores were modeled together, they were found to be independently associated with osteosarcoma risk (P =.037 and P = .043, respectively). An expression quantitative trait locus for cartilage intermediate layer protein 2 (CILP2), rs8103992, was significantly associated with osteosarcoma risk after adjustment for multiple comparisons (odds ratio, 1.35; 95% CI, 1.16-1.56 [P = 7.93×10-5 and Padjusted =.034]). A genetic propensity for taller adult and childhood height attainments contributed independently to osteosarcoma risk in the current study data. These results suggest that the biological pathways affecting normal bone growth may be involved in osteosarcoma etiology.


Enhanced Ca2+-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation.
Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel antiarrhythmic option. However, the regulation of SK-channels in human atrial cardiomyocytes and its modification in patients with AF are poorly understood and were the object of this study. Apamin-sensitive SK-channel current (ISK) and action potentials were recorded in human right-atrial cardiomyocytes from sinus rhythm control (Ctl) patients or patients with (long-standing persistent) chronic AF (cAF). ISK was significantly higher, and apamin caused larger action potential prolongation in cAF- versus Ctl-cardiomyocytes. Sensitivity analyses in an in silico human atrial cardiomyocyte model identified IK1 and ISK as major regulators of repolarization. Increased ISK in cAF was not associated with increases in mRNA/protein levels of SK-channel subunits in either right- or left-atrial tissue homogenates or right-atrial cardiomyocytes, but the abundance of SK2 at the sarcolemma was larger in cAF versus Ctl in both tissue-slices and cardiomyocytes. Latrunculin-A and primaquine (anterograde and retrograde protein-trafficking inhibitors) eliminated the differences in SK2 membrane levels and ISK between Ctl- and cAF-cardiomyocytes. In addition, the phosphatase-inhibitor okadaic acid reduced ISK amplitude and abolished the difference between Ctl- and cAF-cardiomyocytes, indicating that reduced calmodulin-Thr80 phosphorylation due to increased protein phosphatase-2A levels in the SK-channel complex likely contribute to the greater ISK in cAF-cardiomyocytes. Finally, rapid electrical activation (5 Hz, 10 minutes) of Ctl-cardiomyocytes promoted SK2 membrane-localization, increased ISK and reduced action potential duration, effects greatly attenuated by apamin. Latrunculin-A or primaquine prevented the 5-Hz-induced ISK-upregulation. ISK is upregulated in patients with cAF due to enhanced channel function, mediated by phosphatase-2A-dependent calmodulin-Thr80 dephosphorylation and tachycardia-dependent enhanced trafficking and targeting of SK-channel subunits to the sarcolemma. The observed AF-associated increases in ISK, which promote reentry-stabilizing action potential duration shortening, suggest an important role for SK-channels in AF auto-promotion and provide a rationale for pursuing the antiarrhythmic effects of SK-channel inhibition in humans.


Technology policy and planning in the Third World pharmaceutical sector: the Cuban and Caribbean community approaches.
There has been growing international concern over many aspects of the use and flow of medicines in developing countries. This article briefly reviews factors which have contributed to problems in this area including marketing and promotional practices of the pharmaceutical companies, rising drug import costs, and the unsuitability or poor quality of available drugs. This analysis is primarily concerned with policies that have emerged from efforts to alleviate such problems, to increase control over multinational drug companies, and to bring about changes in the technology transaction processes and in the pharmaceutical sector. It focuses on two cases: the regional cooperation scheme of the Caribbean countries (CARICOM) and the national-level policy of Cuba. It is shown that the CARICOM strategy has significant limitations, primarily due to its voluntary nature and lack of enforcement mechanisms for member countries. On the other hand, the Cuban approach has brought about positive effects and progressive changes, made through political commitment to achieve social benefits, and in conjunction with integrated broad reforms of the entire health system within a socialist framework. Thus, the problems and promises of such strategies are viewed in a context which emphasizes the prevailing forces of the global political economy. The lessons from this study, applicable to other developing countries, not only reveal important measures for the pharmaceutical sector, but also stress the ultimate need for strong commitment to enforce policies at the national level and for major structural changes, in order to adequately meet the health and medical needs of the people.


Selection criteria for probiotic microorganisms.
Probiotics are preparations of live microorganisms which beneficially affect the host by improving the properties of the indigenous microbes. Since the human intestinal flora plays an important role in health and disease of man, probiotics are used to improve intestinal health and to stimulate the immune system. The microbes commonly used as probiotics for humans are the lactic acid bacteria (LAB). In early studies the strains used for fermenting milk products for human consumption were frequently used as probiotics. Subsequently, it was realised that it would be more appropriate if the strains originated from the human intestinal tract and that in addition to LABs, other microorganisms could be used either singly or in combination. Today, strict selection criteria are employed to obtain functional probiotic strains. It is generally agreed that the strain should be of host origin, well characterised, able to survive the rigours of the digestive tract and possibly colonise, biologically active against the target as well as to be stable and amenable to commercial production and distribution. In addition, information on dosages and evidence of efficacy needs to be obtained. In vitro and in vivo studies are frequently combined to allow investigation of the various parameters, and ultimately clinical trials are required. Although lactic acid bacteria have been generally recognised as safe, the question of safety is discussed for LAB and non-LAB probiotic strains in terms of potential pathogenicity of the strains and risk to the individual and the community. Finally, even though the techniques for genetic manipulation of many probiotic strains are available, it is not envisaged that this issue will be addressed in the near future because of regulatory implications. It is proposed that when this type of selection criteria is employed, probiotics strains with demonstrable efficacy can be obtained.


[Genetic aspects of male infertility].
Cytogenetic investigations in sterile males showed that autosomal and sex chromosome anomalies can be responsible of the defect of spermatogenesis. Specific alteration of genes controlling spermatogenesis is excluded because all chromosomes are involved in the anomaly and breakpoints are distributed at random. In the aim to explain the spermatogenic failure, three mechanisms are proposed: X-autosome interaction, asynapsis, somatic lesion of the gonad, each mechanism might act alone or with the other. Beside chromosomal infertility, meiotic or sperm anomalies suggest the presence of gene mutations which interfere with the evolution of spermatogenesis or lead to the formation of abnormal spermatozoa. Insertion of technics of molecular biology in our researches could demonstrate the existence of these mutations; the same technics will allow to resolve the problem of the failure of a germ cell bearing a chromosomal anomaly particularly when this anomaly is balanced and involves the autosomes and not the sex chromosomes.


Acupuncture in the management of anxiety related to dental treatment: a case series.
Anxiety related to dental treatment is a common phenomenon that has a significant impact on the provision of appropriate dental care. The aim of this case series was to examine the effect of acupuncture given prior to dental treatment on the level of anxiety. Eight dentists submitted 21 case reports regarding the treatment of dental anxiety. The level of anxiety was assessed by the Beck Anxiety Inventory (BAI). Only patients with moderate to severe anxiety (BAI score > or =16) were included. The remaining 20 patients, 16 women and 4 men, with a mean age of 40.3 years, had a median BAI score of 26.5 at baseline. The BAI score was assessed before and after the acupuncture treatment. All patients received acupuncture treatment for 5 min prior to the planned dental treatment using the points GV20 and EX6. There was a significant reduction in median value of BAI scores after treatment with acupuncture (26.5 reduced to 11.5; p<0.01), and it was possible to carry out the planned dental treatment in all 20 cases after acupuncture treatment. Previously this had only been possible in six cases. Acupuncture prior to dental treatment has a beneficial effect on the level of anxiety in patients with dental anxiety and may offer a simple and inexpensive method of treatment. However, the present results need to be tested in a larger randomised clinical trial in order to evaluate the effectiveness of the acupuncture treatment in patients with dental anxiety.


Can young adult patients with proteinuric IgA nephropathy perform physical exercise?
It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy. Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age- and sex-matched healthy volunteers. At rest, GFR averaged 141 +/- 23 mL/min; it increased by 16.3% +/- 3.3% (P < 0.005) and 7.1% +/- 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 +/- 0.21 mg/min/100 mL GFR; it increased to 1.55 +/- 0.28 mg/min/100 mL GFR after 60 minutes (P < 0.001) and declined to 0.60 +/- 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria. The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases.


Offering cystic fibrosis carrier screening to an HMO population: factors associated with utilization.
We offered cystic fibrosis (CF) carrier testing to reproductive-age enrollees in an HMO, in order to determine factors associated with test utilization in a primarily nonpregnant population. Male and female enrollees either were mailed an invitation to have the test after attending an educational session (N = 2,713) or were approached in waiting rooms at the HMO sites and given the opportunity to have the test without making an additional visit (N = 608). Uptake was considerably higher when testing could be obtained without making an additional visit (23.5%) than when attendance at an educational session was required as a prerequisite for having the test (3.7%). Utilization was higher among respondents who were planning children. Caucasians, and those with higher educational attainment. Among respondents planning to have children, individuals with higher tolerance for test uncertainty, lower fear of stigma, and higher perceived risk of being a carrier were significantly more likely to have the test. Testing decisions were not associated with the perceived burden of a child with CF or with the likelihood of aborting for CF. Although utilization of CF carrier testing is relatively low among nonpregnant individuals, uptake is significantly higher when testing can be obtained with minimal effort. Factors associated with the decision to be tested had more to do with implications of being a carrier per se than with the concerns of having a child with CF.


Zinc-copper interactions in the pregnant rat: fetal outcome and maternal and fetal zinc, copper and iron.
The interaction between zinc and copper in the pregnant rat was investigated by feeding Sprague-Dawley rats, from mating to term, diets that varied in zinc and copper concentrations. A factorial design was used with diets containing 1, 10, 100 or 1000 micrograms zinc/gram and 0.5, 5, 10 or 100 micrograms copper/gram. Malformations were found only in fetuses from rats fed the zinc-deficient diets (1 microgram/g), and the frequency of malformed fetuses increased as concentration of dietary copper increased. Maternal and fetal tissues of rats fed diets deficient in either zinc or copper were significantly lower in these elements than were those of rats fed a control diet. An antagonistic effect of dietary zinc on maternal and fetal tissue copper concentration was observed. The concentration of fetal liver zinc from rats fed a copper-deficient diet was significantly higher than controls. The concentration of iron in maternal and fetal tissues was significantly affected by the level of dietary zinc, with values highest in the zinc-deficient groups. Maternal plasma cholesterol and triglyceride levels were significantly lower than normal in the zinc-deficient animals. These data show that when the concentration of zinc in the diet is deficient an interaction can occur between dietary zinc and copper such that high levels of copper potentiate the teratogenicity of zinc deficiency.


Nonperfusion of retina and choroid in transgenic mouse models of sickle cell disease.
To determine if vascular occlusion and nonperfusion is associated with the outer retinal atrophy, retinopathy, and choroidopathy (chorioretinopathy) that occurs in the alpha H beta S[beta MDD] and alpha H beta S [alpha MD beta MDD] transgenic mouse models of sickle cell disease. Mice from the alpha H beta S[beta MDD] and alpha H beta S[alpha MD beta MDD] transgenic mouse lines that express high levels of human beta S globin were anesthetized and administered horseradish peroxidase (HRP) intracardially. After 1 min, the animals were sacrificed, and the retina from one eye was excised, fixed, and developed in diaminobenzidine (DAB). The contralateral eye was fixed, embedded whole in glycol methacrylate, and HRP developed in 2.5 microns sections. HRP reaction product (HRP-RP) and stained erythrocytes (RBCs) (due to endogenous peroxidase) were diffusely distributed within all vascular lumens in flatmount retinas from control animals (littermates homozygous for the mouse Beta Major deletion not expressing the beta S transgene). In 42.5% of the transgenic mice expressing beta S without any proliferative retinopathy, many blood vessels contained RBC plugs and lacked lumenal HRP-RP. In addition to packed RBCs, fibrin was sometimes present at sites of occlusion. In sections from whole eyes of the same animals, foci of photoreceptor degeneration were associated with areas of choriocapillaris nonperfusion (lumen that lacked HRP-PR). In areas with normal photoreceptors, the choriocapillaris appeared perfused (HRP-RP was present). In animals with proliferative chorioretinopathy, some neovascular formations lacked luminal HRP-RP, suggesting autoinfarction. Nonperfused retinal and choroidal vessels were observed in mice from the alpha H beta S[beta MDD] and alpha H beta S[alpha MD beta MDD] lines without retinal and choroidal neovascularization, whereas, all mice with neovascularization had nonperfused areas. Furthermore, small foci of PR loss were associated with areas of nonperfused choriocapillaris. These results suggest that sickle cell-mediated vaso-occlusions are an initial event in the chorioretinopathy and outer retinal atrophy that occurs in these models.


Selective fluorescence sensing and quantification of uric acid by naphthyridine-based receptor in biological sample.
Naphthyridine-based fluorescent probe H1 was synthesized and characterized for the quantification and selective detection of Uric Acid (UA) in live cell. In presence of UA, H1 forms the specific host-guest complex mainly through intermolecular hydrogen bonding and aromatic stacking which produces "turn-off" fluorescence. The probe and UA is found to be 1:1 stoichiometry on the basis of absorption and fluorescence titrations. The probe H1 has been shown to detect UA up to 0.6µM at pH 7.4. DFT-TDDFT calculations were performed in order to demonstrate the sensing mechanism and the electronic properties of the receptor-donor complex. The selectivity was evaluated in Vero cells in the presence of UA with other purine derivatives, structurally similar to UA. It was found to exhibit no cytotoxicity effect in tested concentration of H1 and good membrane permeability for the detection of UA in living cell system. The unknown concentration of UA in serum and urine can be measured easily using the fluorescence property of probe H1.


Fansidar prophylaxis, therapy, and immune responses in rodent malaria (Plasmodium berghei).
In order to determine the effect of Fansidar on plasmodial infection in mice, outbred, adult, Swiss-Webster mice were treated with Fansidar (20 mg sulfadoxine and 1 mg pyrimethamine/kg body weight) at various intervals before and/or after inoculation with blood stages of Plasmodium berghei. Drug therapy resulted in cure if it was given before the parasitemia rose to 53%. Oral administration of Fansidar was more effective in reducing or preventing parasitemia than intramuscular injection. Fatal infections were prevented if mice were treated orally with one dose of Fansidar 2 days before inoculation with P. berghei, whereas only partial protection occurred in animals treated 4 or more days before inoculation. Fansidar administered on two consecutive days provided protection if the drug was given at 3 and 2 days before inoculation. Administration of Fansidar for three consecutive days protected all animals if given on days 8 to 6 before inoculation. After oral administration of Fansidar, the parasitemia dropped dramatically and was undetectable at 60 hr. At 12 hr after oral treatment, schizonts and trophozoites were numerous, but there were few merozoites. Schizonts were the predominant stage at 24 hr, whereas merozoites predominated at 36 hr. Swiss-Webster and C57BL/6 mice became immune to a lethal dose of P. berghei after 4 cycles of inoculation and drug cure. Protective immunity was still present at 472 days after the fifth parasite inoculation.


[Establishment of a three-dimensional pancreas model for simulating surgical resection of pancreatic tail carcinoma using virtual-reality technique].
To assess the feasibility of visual-reality technique for simulating surgical resection of pancreatic tail carcinoma using a 3-dimensional pancreas model reconstructed on the basis of the CT data. The original image data of 64-slice spiral CT was obtained from a patient with pancreatic tail carcinoma. Using adaptive region growing algorithm, the serial CT images were segmented and automatically extracted for 3-dimensional reconstruction of the pancreas and the anatomically related structures with a self-designed program. The model was then processed with Freeform Modeling System for image modification and smoothing. With the assistance of GHST SDK and PHANTOM software systems, preoperative simulation of surgical resection of the carcinoma was performed on the basis of the established pancreatic model. The reconstructed 3-dimensional pancreatic model with the related structures clearly visualized the 3-dimensional structures of the pancreas, the pancreatic tail compromised by the carcinoma, and the adjacent organs, displaying also the distribution, courses and the anatomical relations of the ductal systems including the main pancreatic duct, abdominal aorta, portal vein system, and the biliary tract. During simulated surgery for pancreatic tail carcinoma resection, the GHOST SDK system allowed effective application of the virtual surgical instruments, and the use of PHANTOM software produced a surgical experience with high resemblance of that from an actual operation. The serial CT data-based reconstruction of 3-dimensional pancreas model and simulated operation on this model using virtual-reality technique has great potentials for application in individualized surgical planning and surgical risk assessment in cases of pancreatic tail carcinoma, and also facilitates clinical training of the surgeons.