Completeness of reporting of diagnosed HIV-infected hospital inpatients.
To assess the completeness of human immunodeficiency virus (HIV) reporting among hospital inpatients whose records listed diagnostic codes for HIV infection but who did not meet the 1987 AIDS case definition, we conducted a statewide hospital study of admissions between January 1, 1986 and December 31, 1990. Of the 396 HIV-infected hospital inpatients identified, 313 (79%) had been reported to the State HIV Registry. HIV reporting was less complete for patients who were older and/or were blood product recipients. Of the 313 reported patients, 189 (60%) had been reported prior to their first hospital admission. Temporal improvements were noted in the completeness of HIV reporting among the hospital patients (1986: 65%; 1987: 81%; 1988: 64%; 1989: 82%; 1990: 86%; Chi square for linear trend 9.6, p < 0.01) and prior to their first hospital admission (1986: 31%; 1987: 34%; 1988: 49%; 1989: 64%; 1990: 72%; Chi square for linear trend 26.6; p < 0.01). Women were more likely than men to be reported prior rather than during or after their first hospital admission (71% vs. 55%; p < 0.01). Of the 155 patients with CD4+ T-lymphocyte test results, 41 had CD4+ counts < 200 mm3 and met the 1993 but not the 1987 AIDS case definition. In South Carolina most (79%) diagnosed, hospitalized, HIV-infected patients had been reported to the State HIV REgistry, with improvements in reporting occurring over time. Findings suggest that the 1993 AIDS case definition will improve our ability to monitor severe morbidity related to HIV.


Cardiac resynchronization therapy for the causal treatment of heart failure with preserved ejection fraction: insight from a pressure-volume loop analysis.
This case describes a middle-aged patient with normal ejection fraction (64%) and significant dyspnoea which could not be explained by results from routine examinations. A pressure-volume loop analysis revealed severe left ventricular (LV) dyssynchrony to be the underlying mechanism of heart failure. The patient underwent implantation of a biventricular pacemaker. Cardiac resynchronization therapy (CRT) was associated with an immediate reduction in LV dyssynchrony from 32 to 13%, decrease in LV end-diastolic pressure from 19 to 8 mmHg, and increased exercise tolerance during follow-up. Thus, CRT may be considered a causal therapy in selected patients with heart failure and preserved ejection fraction.


The protein C pathway and sepsis.
After the discovery of the key components of the protein C (PC) pathway a beneficial effect on survival of the infusion of activated protein C (APC) in animal models of sepsis was demonstrated, leading to the development of recombinant human activated protein C (rh-APC) as a therapeutic agent. It soon became clear that rather than the anticoagulant and profibrinolytic activities of APC, its anti-inflammatory and cytoprotective properties played a major role in the treatment of patients with severe sepsis. Such properties affect the response to inflammation of endothelial cells and leukocytes and are exerted through binding of APC to at least five receptors with intracellular signaling. The main APC protective mechanism involves binding of the Gla-domain to the endothelial protein C receptor (EPCR) and cleavage of protease activated receptor 1 (PAR-1), eliciting suppression of proinflammatory cytokines synthesis and of intracellular proapoptotic pathways and activation of endothelial barrier properties. However, thrombin cleaves PAR-1 with much higher catalytic efficiency, followed by pro-inflammatory, pro-apoptotic and barrier disruptive intracellular signaling, and it is unclear how APC can exert a protective activity through the cleavage of PAR-1 when thrombin is also present in the same environment. Interestingly, in endothelial cell cultures, PAR-1 cleavage by thrombin results in anti-inflammatory and barrier protective signaling provided occupation of EPCR by the PC gla-domain, raising the possibility that the beneficial effects of rh-APC might be recapitulated in vivo by administration of h-PC zymogen to patients with severe sepsis. Recent reports of h-PC infusion in animal models of sepsis support this hypothesis.


Facial nerve function in 100 consecutive parotidectomies.
The risk of facial nerve paresis after parotidectomy is thought to be within acceptable limits, although it is difficult to find published data regarding the specific magnitude of this risk. This study reviews the subject and reports postoperative facial function in 100 consecutive patients who had parotidectomies at the Henry Ford Hospital during a 9-year period. Permanent weakness of a major branch was identified in 2 of 77 patients having lateral lobectomy for parotid disease. Both patients demonstrated marginal mandibular paresis after surgery for adenolymphoma. No weakness was noted in 16 patients undergoing total parotidectomy. No unanticipated nerve disability was noted in 4 patients having partial nerve sacrifice in extended procedures; 3 patients had complete sacrifice of the nerve.


Overview of risk prediction models in cardiovascular disease research.
Many risk prediction models have been developed for cardiovascular diseases in different countries during the past three decades. However, there has not been consistent agreement regarding how to appropriately assess a risk prediction model, especially when new markers are added to an established risk prediction model. Researchers often use the area under the receiver operating characteristic curve (ROC) to assess the discriminatory ability of a risk prediction model. However, recent studies suggest that this method has serious limitations and cannot be the sole approach to evaluate the usefulness of a new marker in clinical and epidemiological studies. To overcome the shortcomings of this traditional method, new assessment methods have been proposed. The aim of this article is to overview various risk prediction models for cardiovascular diseases, to describe the receiver operating characteristic curve method and discuss some new assessment methods proposed recently. Some of the methods were illustrated with figures from a cardiovascular disease study in Australia.


Mononuclear cell infiltration of the aortic intima in domestic swine.
The preparation of thick endothelial "häutchen" from microscopically lipid-free areas of the thoracic and abdominal aorta of 22 domestic pigs proved that there is a surprisingly frequent penetration of mononuclear blood cells into the subendothelial space. They are deposited on the intima in a diffuse or focal distribution as dense epi-, inter- and subendothelial cell infiltrates.


Incidence and Population Density of Plant-Parasitic Nematodes Associated with Olive Planting Stocks at Nurseries in Southern Spain.
Nematode population densities were determined in 259 soil and root samples collected from 18 olive nurseries in Córdoba, Jaén, and Sevilla provinces (southern Spain), between October 1997 and May 1998. The most important plant-parasitic nematodes detected, in order of decreasing frequency of infestation (percentage of samples), were Mesocriconema xenoplax (39.0%), Pratylenchus penetrans (32.1%), P. vulnus (25.9%), Meloidogyne incognita (14.7%), M. javanica (11.2%), and M. arenaria (2.7%). No disease symptoms were noted on aboveground organs of infected plants. However, population densities of Pratylenchus and Meloidogyne spp. were at potentially damaging levels in most of the olive nurseries surveyed. Histopathological studies of galled roots from the naturally infected olive planting stocks showed a susceptible response to root-knot nematode infection. Large numbers of egg masses were present within the galled root tissues that might contribute to secondary infections. Feeding by root-knot nematodes induced the expected cellular alterations in the cortex, endodermis, pericycle, and vascular system, including giant-cell formation and the alteration of vascular tissues.


Sonication technique to produce emulsions: The impact of ultrasonic power and gelatin concentration.
The production of food emulsions has increased the demand for processes, natural emulsifiers and stabilizers that provide reasonable stability. This study approaches the influence of parameters that affect the stability of emulsions produced by sonication, such as ultrasonic power (150, 225 and 375 W) and gelatin concentration, when producing alginate, potato starch and gelatin stabilized emulsions. The results showed that sonication reduced viscosity, surface charge and improved the interfacial properties of biopolymeric solutions. Emulsions presented visual kinetic stabilization after 7 days of storage. The increase of sonication power reduced particle size but increased flocculation. The use of ultrasonic power at 225 and 375 W and gelatin in a concentration above 0.5% resulted in stable emulsions with smaller particle size, which is desirable for its application in food systems.


Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry.
Vortioxetine is a multimodal antidepressant that has been recently utilized globally. Vortioxetine hemi-hydrochloride is a novel salt that was previously reported in our research. However, the pharmacokinetics of this salt and the metabolites of Vortioxetine in vivo remain unknown. In this study, the pharmacokinetics of the Vortioxetine hemi-hydrochloride salt is explored in rats through a newly developed ultra-performance liquid chromatography with tandem mass spectrometry method. In addition, ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was used to identify the metabolites of Vortioxetine in vivo. The results demonstrate that after a single, 3 mg/kg oral dose, the maximum concentration for the Vortioxetine hemi-hydrochloride salt is 14.63 ± 4.00 ng/mL, and is attained in 1.00∼4.00 h. The area under the plasma concentration-time curve from time 0 to 24 h is 67.30 ± 23.78 ng·h·mL-1 . Additionally, 29 metabolites were identified after the oral administration of 10 mg/kg, including 17 metabolites in the plasma, nine in the urine, and 12 in the feces. Eleven metabolites were novel. The major metabolic pathways include methylation, hydroxylation, oxidation, and glucuronidation. In conclusion, this study provides insight for further development of the Vortioxetine hemi-hydrochloride salt.


Detection of hypervascular hepatocellular carcinoma by dynamic MRI and dynamic spiral CT.
Our goal was to evaluate the detectability of hypervascular hepatocellular carcinomas (HCCs) by multislice dynamic MRI and dynamic spiral CT. Prior to transcatheter arterial chemoembolization (TACE) with iodized oil, the liver was subjected to T1- and T2-weighted SE-MRI, multislice dynamic MRI after intravenous bolus injection of Gd-DTPA, early phase imaging with spiral CT (dynamic spiral CT) after intravenous bolus injection of contrast medium (at a rate of 2 or 3 ml/s), and delayed phase CT in 64 patients with 208 HCC nodules. The detectability of HCCs by MRI and CT was evaluated retrospectively compared with CT after TACE as a gold standard. The detectability of nodules < 1 cm in diameter was superior with dynamic MRI (67%) and dynamic spiral CT (50%) in comparison with SE-MRI (26%) and delayed phase CT (11%) (p < 0.01). The detectability of these tumors with dynamic MRI was significantly superior to that with dynamic spiral CT using an injection rate of 2 ml/s (p < 0.01), but not significantly different from that of dynamic spiral CT using a rate of 3 ml/s. Dynamic MRI and dynamic spiral CT are comparable for detecting hypervascular intrahepatic metastases of HCC.


[Sludge Conditioning Performance of Polyaluminum, Polyferric, and Titanium Xerogel Coagulants].
The sludge conditioning performance of inorganic Al, Fe, and Ti coagulants were systematically compared in terms of specific resistance to filtration (SRF), the content of protein and polysaccharide in extracellular polymeric substances (EPS), the change in three-dimensional excitation emission matrix fluorescence (3D-EEM), the molecular weight of organic matter in EPS, and the floc size and surface morphology. The sludge conditioning ability and the mechanism were systematically analyzed. The results showed that the sludge conditioning ability of the three inorganic coagulants was in the order of polyaluminum chloride (PAC) > titanium xerogel coagulant (TXC) > polymeric ferric sulfate (PFS). After conditioning, the contents of protein and polysaccharide in the EPS were greatly reduced, especially in the loosely bound EPS (LB-EPS). The combined capacity for coagulation between TXC/PFS and organic matter was stronger than that of PAC. The content of polysaccharide in LB-EPS was the key factor affecting the sludge dewatering performance but not the coagulated floc size. The surface charge and the chelating ability with organic matter co-determined the sludge dewatering ability. The organic cationic polymer, polyacrylamide (PAM), made the sludge aggregate via charge neutralization. However, the use of PAM alone was not a good choice owing to the low dewatering ability and the loose sludge structure. The results here are helpful for the selection of suitable coagulants for sludge conditioning.


The changing survival profile of people with Down's syndrome: implications for genetic counselling.
Cohort studies have indicated that the survival of individuals with Down's syndrome has dramatically increased over the past 50 years. Early childhood survival in particular has shown major improvement, due largely to advances in cardiac surgery and in general health management. The present study was based on a continuous cohort of 1332 people with Down's syndrome in Western Australia, registered for intellectual disability services between 1953 and 2000. Their life expectancy was 58.6 years, 25% lived to 62.9 years, and the oldest living person is 73 years of age. Life expectancy for males was greater than females by 3.3 years. The substantial increase in survival across the study period means that the life expectancy of people with Down's syndrome is approaching that of the general population, but accompanied by a range of significant mid-life health problems. The findings are of relevance to all developed countries and have considerable implications in terms of the counselling information provided to families at risk of having a child with Down's syndrome.


Effects of epithelial growth factor receptor (EGFR) kinase inhibitors on genetically reconstituted mouse mammary glands.
The aim of the study was to determine the effects of a specific epithelial growth factor Receptor kinase inhibitor (EGFR-KI) and Taxol on tumor growth in a novel tumor model. A genetically engineered tumor model which uses "transgenic" organs in immune competent mice was used. NeuT-transfected immortalized HC11 epithelial cells and primary mouse mammary epithelial cells have been transplanted into the gland-free mammary fat pad of female BALB/c mice. Mammary tumors developed after a latency period of three to four weeks. The mice were thereafter daily orally treated over a 19 or 22-day period with 0, 38, 75, 2 x 75 mg/kg body weight (b.w.) EGFR-KI (n: 7-9 per group) or intravenously with 10 mg/kg b.w. Taxol. After necropsy the histopathological evaluation of the tumors was performed in a coded manner. The proliferation activity of tumor cells was analyzed by laser scanning cytometry (LSC) using anti-Ki67-antibodies. Oral Treatment with EGFR-KI in this transgenic organ model showed clear antitumor efficacy in a dose-dependent manner in the range between 38 and 75 mg/kg b.w. This antiproliferative effect appears to be minimally increased at 75 mg/kg/day twice per day. For all treatments a strong correlation between the biological behavior of the tumor, histopathology and cell proliferation could be established. In contrast, treatment with Taxol showed no significant reduction of tumor growth or cell proliferation in this model. This new transgenic organ model comprising histopathological evaluation and cell proliferation analysis appears to be a suitable test system for drug candidates that affect specific biochemical pathways. It may have greater predictive nature for clinical effects in humans as compared to conventional tumor models because of its c-erb B2 gene overexpression.


Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis.
Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection. A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant. Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study. Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease.


[Expression and clinical significance of Nrf2 in esophageal squamous cell carcinoma].
To study the expression and clinical significance of Nrf2 (Nuclear factor E2 p45-related factor 2) in esophageal squamous cell carcinoma (ESCC). The expression of Nrf2 in 32 cases of EC tissues, 30 cases of adjacent tissues, 21 positive Lymph node tissues and 24 negative Lymph node tissues was assessed by SP immunohistochemical method. The main location of Nrf2 was nuclear, and the positive rates of Nrf2 in the cancer tissues was 78.13%, while that in the adjacent tissues group was 13.33%, and showed 66.67% and 20.83% in the positive Lymph node tissues and negative Lymph node tissues respectively, there was a significant difference between the two groups (P<0.05). The Nrf2 positive rate was closely correlated with the lymph node metastasis (P<0.05), but showed no statistical associated with age, sex, TNM stage, degree of tumor differentiation and the location of tumor. The Nrf2 has high expression in ESCC tissues, and the positive rate is closely correlated with the lymph node metastasis, The Nrf2 may play an important role in ESCC oncogenesis and drug resistence.


Muscle weakness and neuromuscular junctions in aging and disease.
A critical issue in today's super-aging society is the need to reduce the burden of family care while continuing to make our medical institutions supportive. A rapidly emerging, major health concern is the debilitating effect of muscle weakness and atrophy from aging, termed sarcopenia; however, the molecular basis of this condition is not well understood. Our research aim is to elucidate the molecular mechanisms of age-related muscle atrophy and to devise new measures for preventing and treating this disability. A promising treatment for muscle atrophy is the promotion of muscle regeneration by recruiting stem cells into the targeted region. The first requirement is to understand how the motor system, which consists of muscles and motoneurons, is maintained to accomplish that goal. Recent studies in the field of neuroscience have focused on neuromuscular junctions (NMJ), which play important roles in the maintenance of both motor nerves and muscle fibers. Signaling between muscles and motoneurons at NMJ supports interactions within the motor system. To understand the mechanisms involved, we focus our research on the pathogenic processes underlying neuromuscular diseases. The well-known autoimmune disease, myasthenia gravis (MG), serves as a model not only for tracking the pathogenesis and treatment outcomes of all autoimmune diseases, but also for understanding synaptic functions in maintaining the motor system. Here, we describe recent insights into the molecular mechanisms required for the maintenance of NMJ and the related causes of muscle atrophy.


Human biological adaptability. The ecological approach in physical anthropology.
Adaptation is an aspect of virtually all questions of human biology. Besides their interest in evolution through adaptive selection of the primates, including man, physical anthropologists are concerned with biological adaptability as a human attribute. In this sense adaptation has been examined at three overlapping levels: (i) those represented by differences in the extent of inherent capacities in subpopulations long exposed to different conditions, such as differences in the inherited determinants of body form and skin pigment in peoples in different climatic zones; (ii) adaptations acquired during the growth period of the individual such as residual stunting and reduced caloric needs in individuals receiving low caloric diets throughout childhood; and (iii) reversible acclimatization to the immediate conditions such as the changes which make it easier to work at high altitudes after the first few days there. Greater resilience to change is achieved if adaptations are reversible in each generation or within a lifetime. This implies an evolutionary tendency to shift human adaptability from genetic selection to ontogenetic plasticity to reversible adaptability.


Manufacture and sensory analysis of reduced- and low-sodium Cheddar and Mozzarella cheeses.
High sodium intake negatively affects consumer health, thus there is active interest in lowering sodium levels in dairy foods. Cheddar and low-moisture, part-skim Mozzarella cheeses were made with total salt levels of 0.7, 1.0, 1.25, 1.35, and 1.8% (wt/wt) in triplicate, thus reducing sodium by 25 to 60%. Multiple manufacturing protocols for salt reduction were used to produce cheeses with similar postpress moisture and pH, independent of the final salt levels in cheese, in order to study the role of salt in cheese acceptability. Cheese flavor was evaluated by a descriptive taste panel on a 15-point intensity scale. Consumer acceptance was evaluated by a consumer panel on a 9-point hedonic scale. Taste panels conducted with cubed Cheddar cheese (at 3 and 6mo) and cold shredded Mozzarella cheese (at 3wk) showed that consumer liking for cheese was low at 0.7 and 0.9% salt, but all cheeses containing higher salt levels (1.25, 1.35, and 1.8% salt) were comparably preferred. The cheeses had acceptable liking scores (≥6) when served as quesadilla or pizza toppings, and consumers were able to differentiate cheeses at alternate salt levels; for example, 1.8 and 1.5% salt cheeses scored similarly, as did cheeses with 1.5% and 1.35% salt, but 1.35% salt cheese scored lower than and was discernible from 1.8% salt cheese. Descriptive panelists perceived salty, sour, umami, bitter, brothy, lactone/fatty acid, and sulfur attributes as different across Mozzarella cheeses, with the perception of each significantly increasing along with salt level. Salty and buttery attributes were perceived more with increasing salt levels of Cheddar cheese by the descriptive panel at 3mo, whereas bitter, brothy, and umami attributes were perceived less at the higher salt levels. However, this trend reversed at 6mo, when perception of salty, sour, bitter, buttery, lactone/fatty acid, and umami attributes increased with salt level. We conclude that consumers can distinguish even a 30% salt reduction and a gradually phased sodium reduction is needed to improve acceptability of lower sodium cheeses.


In vivo evidence for short- and long-range cell communication in cranial neural crest cells.
The proper assembly of craniofacial structures and the peripheral nervous system requires neural crest cells to emerge from the neural tube and navigate over long distances to the branchial arches. Cell and molecular studies have shed light on potential intrinsic and extrinsic cues, which, in combination, are thought to ensure the induction and specification of cranial neural crest cells. However, much less is known about how migrating neural crest cells interpret and integrate signals from the microenvironment and other neural crest cells to sort into and maintain the stereotypical pattern of three spatially segregated streams. Here, we explore the extent to which cranial neural crest cells use cell-to-cell and cell-environment interactions to pathfind. The cell membrane and cytoskeletal elements in chick premigratory neural crest cells were labeled in vivo. Three-dimensional reconstructions of migrating neural crest cells were then obtained using confocal static and time-lapse imaging. It was found that neural crest cells maintained nearly constant contact with other migrating neural crest cells, in addition to the microenvironment. Cells used lamellipodia or short, thin filopodia (1-2 microm wide) for local contacts (<20 microm). Non-local, long distance contact (up to 100 microm) was initiated by filopodia that extended and retracted, extended and tracked, or tethered two non-neighboring cells. Intriguingly, the cell-to-cell contacts often stimulated a cell to change direction in favor of a neighboring cell's trajectory. In summary, our results present in vivo evidence for local and long-range neural crest cell interactions, suggesting a possible role for these contacts in directional guidance.


The management of unacceptable bleeding patterns in etonogestrel-releasing contraceptive implant users.
The aim of this guidance is to review the management of unacceptable vaginal bleeding patterns in etonogestrel (ENG)-releasing contraceptive implant users concentrating, where possible, on the evidence for pharmacological treatments and identifying a pragmatic approach where this is not possible. This article was developed in accordance with methodology used for producing Royal College of Obstetricians and Gynaecologists' Green Top Guidelines. The Cochrane Library (including the Cochrane Database of Systematic Reviews, DARE and EMBASE) and Medline (1966-2010) were searched using the relevant MeSH terms, including all subheadings, and this was combined with a keyword search. Search words included "progestogen only contraceptives," "contraceptive implants," "progestogen implants," "etonogestrel implants," "irregular bleeding," "unpredictable bleeding," "bleeding irregularity" and "bleeding pattern," and the search was limited to humans and English language. Enquiries for relevant information were also made to the pharmaceutical industry and researchers for missing studies. Although this is not a systematic review, two of the authors (D.M., I.S.F.), qualitatively assessed those papers reporting quantitative results involving treatments given either to stop or prevent bleeding in ENG or levonorgestrel contraceptive implants users.


Involvement of root ABA and hydraulic conductivity in the control of water relations in wheat plants exposed to increased evaporative demand.
We studied the possible involvement of ABA in the control of water relations under conditions of increased evaporative demand. Warming the air by 3°C increased stomatal conductance and raised transpiration rates of hydroponically grown Triticum durum plants while bringing about a temporary loss of relative water content (RWC) and immediate cessation of leaf extension. However, both RWC and extension growth recovered within 30 min although transpiration remained high. The restoration of leaf hydration and growth were enabled by increased root hydraulic conductivity after increasing the air temperature. The use of mercuric chloride (an inhibitor of water channels) to interfere with the rise on root hydraulic conductivity hindered the restoration of extension growth. Air warming increased ABA content in roots and decreased it in shoots. We propose this redistribution of ABA in favour of the roots which increased the root hydraulic conductivity sufficiently to permit rapid recovery of shoot hydration and leaf elongation rates without the involvement of stomatal closure. This proposal is based on known ability of ABA to increase hydraulic conductivity confirmed in these experiments by measuring the effect of exogenous ABA on osmotically driven flow of xylem sap from the roots. Accumulation of root ABA was mainly the outcome of increased export from the shoots. When phloem transport in air-warmed plants was inhibited by cooling the shoot base this prevented ABA enrichment of the roots and favoured an accumulation of ABA in the shoot. As a consequence, stomata closed.


Azidophosphenium cations: versatile reagents in inorganic synthesis.
This work describes the synthesis and characterization of a series of iminophosphorane-substituted phosphenium cations of the type [R2NPNP(Cl)2NPNR'2][GaCl4] [R = iPr; R' = iPr (7[GaCl4]), SiMe3 (8)], which are directly derived from azidophosphenium salt [iPrNPN3][GaCl4] (2iPr[GaCl4]) and the corresponding chlorophosphane R2NPCl2. The reactivity of 7[GaCl4] toward 2,3-dimethylbutadiene (dmb) and 2,2'-bipyridine (bipy) was investigated, resulting in the formation of 7-dmb[GaCl4] and 7-Cl. In addition, self-condensation of [(Me3Si)2NPN3][GaCl4] (2SiMe3[GaCl4]) was studied in detail, and [(Me3Si)2NPNP(XY)N(SiMe3)2][GaCl4] [X = Cl; Y = Cl (13), N3 (14)] were determined as products on the basis of (31)P NMR spectroscopy. The reaction of 2SiMe3[GaCl4] with [(Me3Si)2NPCl][GaCl4] (1SiMe3[GaCl4]) yielded an unprecedented bicyclic 1,3,2λ(3),4λ(5)-diazadiphosphetidine (15), which was formed via a GaCl3-assisted Me3SiCl elimination starting from 13. Furthermore, cations of the type [R2NPNPR'3][GaCl4] [R = iPr; R' = cHex (19)] were obtained by the effective combination of 2R[GaCl4] (R = iPr, SiMe3) with PR'3 (R' = Ph, cHex). Azidochlorophosphanes R2NP(N3)Cl [R = iPr, SiMe3 (20R)] are shown to be accessible when 2R[GaCl4] was combined with bipy. All new compounds were fully characterized by means of X-ray, vibrational spectroscopy, CHN analysis, and NMR experiments. All compounds were further investigated by means of density functional theory, and the bonding situation was accessed by natural bond orbital analysis.


Organochlorine levels in subcutaneous blubber biopsies of fin whales (Balaenoptera physalus) and striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea.
Polychlorinated biphenyls (PCBs) and DDT compounds were determined in subcutaneous blubber of fin whales (Balaenoptera physalus) and striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea. From 1990 to 1993, 68 fin whale and 89 dolphin blubber biopsies were analysed. The whales were sampled while passing through the Ligurian Sea, whereas the dolphins were collected in different areas of the Mediterranean: the Ligurian, Tyrrhenian and Ionian Seas. Total PCBs and DDTs were 5.5-7.1 ppm and 4.2-9.5 ppm, respectively, in the whales and 15.5-86.0 ppm and 15.6-63.5 ppm, respectively, in the dolphins. Thirty PCB congeners were identified for each sample, IUPAC numbers 153, 138, 187, 180 and 170 being the most abundant, totalling an average of 55% of total PCBs in the whale and 60% in the dolphin. The large differences in accumulation are related to position in the food chain. In striped dolphins significant differences were found in relation to sampling site, and in fin whales in relation to sex.


Quantitative changes in reference segments during IVUS-guided stent implantation: impact on the criteria for optimal stent expansion.
Intravascular ultrasound is an established method to optimize stent implantation. Stent expansion is estimated from the relation between minimal in-stent cross-sectional area and reference lumen area. We analyzed the periprocedural lumen increment in the reference segments and its impact on intravascular ultrasound (IVUS) criteria for optimized stenting. Seventy-five consecutive patients were studied with a 2.9 Fr, 30-MHz system and motorized pullback (0.5 mm/sec). Lumen area was measured by planimetry; absolute and relative differences in area (delta area) were calculated. Lumen area increment for reference segments proximal and distal to the stent was 6.4% +/- 10.3% and 6.1% +/- 10.8%; 49/75 patients fulfilled all IVUS criteria for optimal stent expansion at the final IVUS assessment, and 10/75 patients met all the IVUS criteria in relation to the first measurement of reference lumen area, but not in relation to the final measurement of reference lumen area. During high-pressure dilatation within the stent, reference lumen increment is visible. If reference lumen planimetry is not repeated after additional high-pressure balloon inflation, the final relative stent expansion may be overestimated.


[Activity of lipoprotein lipase in different adipose deposits and its relation to adipocyte size in the cow during fattening or early lactation].
Twelve dry and eight lactating cows were slaughtered and the whole body was chemically analysed. Adipose tissue lipid and adipose cell size varied greatly with body condition and also with anatomical site (perirenal, omental, intermuscular, rump subcutaneous, leg subcutaneous). Lipoprotein lipase activity per adipose cell was very low in lactating cows, but very high in dry cows during fattening. Activity tended to be higher in omental adipose tissue and lower in subcutaneous adipose tissue. Total adipose lipoprotein lipase activity per cow was positively related with energy balance and negatively related with plasma non-esterified fatty acids. There was no correlation with body fatness or adipose cellularity.


[The hepatic porphyrias].
Among the different types of hepatic porphyrias, acute intermittent porphyria (AIP) and the group of chronic hepatic porphyrias (CHP) are most frequently seen in Europe. Both diseases are supposed to be inherited, but clinical manifestation mostly occurs following endogenous and especially exogenous stimulation. While recurrent attacks of abdominal and neuropsychiatric symptoms in AIP are frequently precipitated by therapeutic doses of commonly used drugs, the gradual development of porphyria cutanea tarda (PCT) from a clinically non-apparent type of CHP seems to be most commonly due to excessive and prolonged intake of alcohol. The characteristic and with regard to the laboratory findings important pathobiochemical features, the clinical symptoms, and the present therapeutic concepts of both disorders of hepatic porphyrin metabolism are discussed. The prognosis of hepatic porphyrias will be determined above all by early diagnosis of the metabolic disorder as well as by a profound medical information of the patient to avoid strictly all well-known exogenous factors which may initiate or exacerbate the disease.


Condyle-disk-fossa position and relationship to clinical signs and symptoms of temporomandibular disorders in women.
The aim of the present study was to assess the disk-condyle-fossa relationship through magnetic resonance imaging and determine its association with clinical signs and symptoms of temporomandibular disorder in patients with myofascial pain and disk displacement (with and without reduction). Sixty-two female patients with complaints of pain were clinically examined using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and divided into the following groups: Group I, myofascial pain (n = 19); Group IIa, disk displacement with reduction (n = 32); and Groups IIb and IIc, disk displacement without reduction (n = 11). Classification of disk position was based on the positioning on a clock face (> or < than 11 o'clock) and condylar excursion was determined as (1) the proximal side of the apex of the articular eminence; (2) at the level of the articular eminence; and (3) beyond the apex of the articular eminence. Condylar position was determined in the sagittal images based on Gelb's template (normal, posteriorly displaced). Pain was assessed using a visual analogue scale (VAS). The univariate logistic regression, Mann-Whitney, Kruskall-Wallis and Pearson's correlation tests were used in the statistical analysis (P < or = .05). No significant association was found between the independent variables (condylar position, disk position, and condylar excursion) and the dependent variables (pain, maximal opening of the mouth, maximal lateral movement). However, there was a significant association between increased condyle excursion and pain (P = .035) and also maximum mouth opening movement was associated with lateral movement (P = .01; r = 0.31). Increase in condyle excursion may significantly influence pain perception in TMD patients. The type of dysfunction and severity of alterations on the imaging exams were not related to the severity of pain or range of motion of the mandible.


Emergency medicine in the general practice internship in Finnmark county.
It is preferred that duty doctors in municipal health services participate in call-outs in emergency situations. The frequency of participation has previously been shown to vary. We wanted to examine the newly qualified doctors’ expectations and experiences – both before and after the general practice internship – of emergency medicine and ambulance call-outs. All 23 of the interns who were to undertake their general practice internship in Finnmark county in the period 2015–16 answered a questionnaire and participated in a focus group interview before the start of the internship. Twenty-one of the interns participated in the focus group interview after completing the internship. Each doctor took part in two interviews. We analysed the transcripts from the focus group interviews using the grounded theory method. The responses from the questionnaire before the general practice internship showed that the interns felt they needed more training in intravenous cannulation and in teamwork. Their expectations in connection with the challenges of call-outs are best characterised by the core category ‘Can I do anything useful?’ from the focus groups before the internship. After the internship, however, the core category ‘It all went well in the end’, was the best fit. Due to short transport times and their knowledge of certain patients, some of the doctors chose not to take part in call-outs. During the general practice internship, the interns were initially anxious about whether they might be superfluous in call-outs, but eventually found their footing in the call-out role. The study shows that there is a need for more practice in certain practical procedures, and that doctors’ non-technical skills need to be improved. This can be done through training in team leader roles before the general practice internship.


Scribes in an ambulatory urology practice: patient and physician satisfaction.
The increasing use of electronic medical records during the clinical encounter brings not only benefits but also barriers that may affect the doctor-patient relationship and increase the work burden of the physician. We evaluated whether the use of an electronic medical record scribe in an academic urology program would ameliorate these problems. We randomly assigned electronic medical record scribes to the office hours of 5 academic urologists, and using surveys we evaluated patient and physician acceptance and satisfaction. Patients were accepting of an electronic medical record scribe and satisfaction rates were high (93% vs 87% in the absence of a scribe, p = 0.36). Patients were comfortable disclosing urological information in the presence of the scribe. Physicians were dramatically more satisfied with office hours when a scribe was present (69% vs 19%, p <0.001). We were unable to determine whether the presence of a scribe improves productivity. Electronic medical record scribes in a urology practice may be a practical solution to provide documentation while maintaining or improving the doctor-patient relationship because they increase physician satisfaction and do not detract from patient satisfaction.


Establishing and maintaining good referral relationships.
Establishing and maintaining a good referral network is important to the success of both the specialist and the medical center where he or she practices. Consequently, as this article will discuss, specialists should be alert to the many factors that can affect their relationships with referring physicians and should be careful to avoid any actions that might threaten those relationships.


Collision of basic and applied approaches to risk assessment of thyroid toxicants.
Thyroid hormone (TH) is essential for normal brain development; therefore, any environmental chemical that interferes sufficiently with thyroid function, TH metabolism, or TH action may exert adverse effects on brain development. Important known differences in aspects of thyroid endocrinology between the fetus, infant, and adult allow us to identify age-dependent vulnerabilities to thyroid toxicants with some confidence. These differences include the size of the hormone pool stored in the thyroid gland at different ages as well as the age-dependent sensitivity to mild TH insufficiency. Several recent studies that describe risk assessments of the environmental contaminant, ammonium perchlorate, provide good examples of conclusions based on the selective consideration of these known aspects of the thyroid system. Specifically, authors who consider age-dependent differences in thyroid endocrinology suggest that safe levels of perchlorate should be set at relatively low levels (low parts per billion). In contrast, authors who do not consider these known age-dependent differences in thyroid endocrinology recommend safe levels of perchlorate at high (hundreds) parts per billion to parts per million. Emerging evidence indicates that a variety of high production volume chemicals can directly interact with the TH receptor. As testing paradigms are designed by regulatory agencies, these age-dependent differences in thyroid endocrinology must be considered.


Atmospheric oxidation of peroxyacetic acid.
The full reactive atmospheric oxidation profile of peroxyacetic acid under high NO conditions was examined using electronic structure calculations at various levels of theory. The three pathways resulting from the reaction of peroxyacetic acid with the hydroxyl radical were (1) addition of OH to the central carbon, (2) abstraction of the acidic hydrogen, and (3) abstraction of the methyl hydrogen. These pathways were followed to terminal product steps, the major products being acetic acid for pathway 1 and formaldehyde for pathways 2 and 3.


Pseudothrombocytopenia associated with vasculitis.
A patient with pseudothrombocytopenia due to the anticoagulant EDTA is described. The thrombocytopenia was secondary to platelet agglutination and required the presence of EDTA in a critical concentration and the patient's plasma. Both homologous and autologous platelets were affected by this plasma factor in the presence of EDTA. The platelet agglutination was temperature independent and could be prevented by divalent cations. The agglutination phenomenon was irreversible. The platelet count in oxalate, not heparin, and citrate anticoagulated blood was normal. The patient's clinical course was benign and no hemorrhagic complications occurred. We believe this is the first reported case of pseudothrombocytopenia associated with a vasculitis. The diagnosis of this disorder, its implications and the pertinent literature is discussed.


PedVizApi: a Java API for the interactive, visual analysis of extended pedigrees.
PedVizApi is a Java API (application program interface) for the visual analysis of large and complex pedigrees. It provides all the necessary functionality for the interactive exploration of extended genealogies. While available packages are mostly focused on a static representation or cannot be added to an existing application, PedVizApi is a highly flexible open source library for the efficient construction of visual-based applications for the analysis of family data. An extensive demo application and a R interface is provided. http://www.pedvizapi.org


RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations.
The RET finger protein (RFP) is a transcription factor belonging to the TRIM (tripartite motif) superfamily of proteins. RFP is expressed in a variety of human and rodent tumor cell lines and in several kinds of human cancer. Expression of RFP is associated with prognosis of colon and endometrial cancers. In the present study, we evaluated the expression of RFP in lung cancer and assessed its clinical significance. Tissue microarrays were constructed from 108 cases of lung cancer, and the sections were analyzed for RFP expression by immunohistochemistry. RFP expression was detected in the nucleus in 66.7% of lung cancer tissues examined. RFP expression was statistically significantly associated with thyroid transcription factor 1 (TTF-1) expression (P= 0.028). However, no significant association was observed between RFP expression and other clinicopathological or genetic factors, including epidermal growth factor receptor (EGFR) mutations. Interestingly, we found that RFP expression correlated with poor prognosis in patients with EGFR mutations (P= 0.032). Our results suggest that RFP has a role in mutated EGFR signaling and that RFP status may be a prognostic factor for lung cancer with EGFR mutations.


Growth hormone-releasing factor (GRF) regulates expression of its own receptor.
Recent studies have demonstrated that passive immunization of neonatal rats to GRF inhibited their somatic growth through the suppression of GH secretion. In this study, we investigated the changes in pituitary GRF receptor (GRFR) expression in GRF antibody (GRF-ab) treated rats. Neonatal rats were treated from day 1 to day 10 after birth with every other day sc injection of 50 microliters of normal rabbit serum (groups I: control & III) or rabbit serum containing GRF-ab (groups II & IV). In addition, groups III & IV received twice daily injection of recombinant human GH (0.4 microgram/kg, sc). The rats were sacrificed on day 11 and pituitaries were removed. The pituitary weights in all treatment groups were decreased compared to the control group (I). Total pituitary RNA was extracted and GRFR mRNA levels were determined by RNase protection assay. Receptor RNA levels were quantitated and normalized to an internal standard, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The ratios of GRFR mRNA to GAPDH mRNA were significantly decreased to 49.6 +/- 4.9 (mean +/- SD), 73.0 +/- 8.7, 43.6 +/- 9.5% of control group I in the experimental groups II, III, and IV, respectively (P < 0.01). These data suggest that (1) suppression of GH secretion in GRF-ab treated animals was due, at least in part, to a decrease in GRFR expression, (2) GRF may be necessary for its own receptor expression, (3) exogenous administration of GH suppresses pituitary GRFR mRNA.


[Ischemic postconditioning and its application in organ transplantation].
The concept of "ischemic postconditioning" was first raised in 2002, and the following 5 year research shows that it can protect organs from reperfusion injury. Although the mechanism of ischemic postconditioning is similar to ischemic preconditioning in many ways, it still has its own characteristics. Reperfusion injury is an inevitable problem in organ transplantation. It may accelerate the function recovery of the transplants to lessen the reperfusion injury. So ischemic postconditioning may have a fine prospect in organ transplantation for its good controllability during reperfusion. This article is going to briefly introduce the distinct mechanisms of ischemic postconditioning to protect organs from reperfusion injury and approach the possibilities of its application in organ transplantation.


Surface roughness of three types of modern plastic bracket slot floors and frictional resistance.
To quantitatively analyze the surface roughness of the slot floors of three types of modern plastic brackets and to measure static frictional force during sliding mechanics in vitro. Control groups comprised stainless steel brackets and monocrystalline ceramic brackets. Test groups comprised three types of 0.022-in slot, Roth prescription, plastic, maxillary right central incisor brackets. Test groups included glass fiber-reinforced polycarbonate, filler-reinforced polycarbonate, and hybrid polymer with inserted metal slot brackets. The static frictional resistance caused by sliding movements with an archwire (stainless steel) in vitro was quantitatively analyzed. Both scanning electron microscope and three-dimensional optical surface profiling were used. Scanning electron microscope and three-dimensional optical surface profiler revealed that all as-received brackets had irregular slot floor surfaces, and both irregularity and roughness increased after the archwire sliding test. The ceramic brackets in the control group showed significantly lower surface roughness values and higher frictional values during the archwire sliding test compared with the other brackets. The glass or filler-reinforced plastic brackets exhibited significantly higher static frictional values than the metallic slot type brackets (P < .001). The hybrid polymer with inserted metal slot brackets showed relatively lower surface roughness and frictional values compared with the stainless steel control bracket. Glass or filler-reinforced plastic brackets showed higher frictional resistance than metallic slot-type brackets. A plastic bracket with inserted metal slot may be the best choice among plastic brackets for low frictional resistance and to avoid damage from sliding movements of the archwire.


The use of Flivasorb in highly exuding wounds.
Exudate can be an excellent indicator of what is happening within a wound and, therefore, provides valuable information during patient assessment. The volume, consistency, and particularly odour and colour, of any exudate will inform the practitioner about bacterial contamination, infection and stage of healing (Hampton and Collins, 2003). However, in the chronic wound, exudate must be effectively managed if the optimal moist environment necessary for wound healing is to be created, the negative effects of chronic exudate on fibroblasts are to be avoided (Phillips et al, 1998), and the surrounding skin protected from the risks of maceration (White, 2006). It is, therefore, important to understand chronic exudate and its effects so that appropriate treatment for the wound and peri-wound area is provided. Flivasorb (Activa Healthcare) dressings, which include superabsorber particles, can absorb the exudate and retain it firmly within the dressing, ensuring that the potentially damaging chronic wound exudate does not reflect back onto the wound, causing maceration. This article will describe the role of exudates in wound healing, the problems associated with chronic wound exudates and how Flivasorb dressings with superabsorbent particles can provide an optimum healing environment in highly exuding wounds.


Over-the-counter medicines: professional expertise and consumer discourses.
Ideas of participation and partnership in health care consultations have attracted increasing attention in recent years; however the consequences in terms of the necessary shifts in existing relationships are often overlooked. We examine how pharmacists work to maintain their professional expertise against the rise of health-care consumerism. We draw on the following data from a UK study of consultations for over-the-counter (OTC) medicines in two pharmacies: (i) an outline of the pharmacy owners' views of their practice model, (ii) data from observations and tape recorded consultations (iii) interviews with customers and pharmacists and (iv) views expressed in two feedback sessions discussing vignettes developed from observational and interview-based fieldwork. There was no suggestion that attempts to engage customers in discussions about their treatment necessitated a diminution of the importance of pharmaceutical expertise. Indeed, both pharmacists and customers acknowledged the importance of the asymmetry of knowledge between pharmacists and customers. Pharmaceutical expertise was however not always perceived to be necessary and transactions in pharmacies may be treated like those in any other retail environment. Further research using a larger dataset to investigate problems in interactions resulting from tensions between pharmaceutical expertise and consumerism is indicated.


[The concept of health in Italian occupational health legislation].
This study describes the evolution of the concept of health in Italian occupational health legislation (1900-2001). Mental health dimensions at work (such as reduction in monotony and repetitiveness, mental risks in pregnancy and so on) were introduced only recently. This can be explained with: 1) poor working conditions; 2) the delay of the occupational health community in including mental health in the concept of health; 3) the gap between scientific knowledge of risk factors for mental health and legislation aimed at prevention.


Practical considerations in the evaluation and management of adrenocortical cancer.
Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and management of ACC. We conclude that the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) remains unclear and that it should be employed sparingly. Biopsies should be performed only when metastatic disease is present and a primary tumor has not been clearly established. Care should be taken in using the Weiss criteria to make decisions regarding prognosis. Surgery is the preferred intervention initially and at the time of recurrence, and every effort should be made to attempt a surgical resection. The latter should be an open resection; laparoscopic resection should not be performed if there is a high suspicion of ACC. The use of mitotane in patients without evidence of disease remains controversial. Systemic chemotherapy is effective in patients with widely metastatic disease or as an adjunct to a surgical intervention and should focus on regimens that have been shown to effect responses; "novel targeted therapies" should not be employed as first-line treatment. Radiofrequency ablation (RFA) and cryoablation can be very helpful but are still under evaluation; embolization with or without chemotherapy may be used as a surgical adjunct. The role of radiation remains to be defined. Finally, physicians caring for these patients need to recognize that Cushing's disease is a debilitating problem that should be managed aggressively; expecting chemotherapy to solve this complication is not appropriate.


Evidence for the light hole in GaAs/AlGaAs quantum wells from optically-pumped NMR and Hanle curve measurements.
Optically-pumped (69)Ga NMR (OPNMR) and optically-detected measurements of polarized photoluminescence (Hanle curves) show a characteristic feature at the light hole-to-conduction band transition in a GaAs/AlxGa1-xAs multiple quantum well sample. OPNMR data are often depicted as a "profile" of the OPNMR integrated signal intensity plotted versus optical pumping photon energy. What is notable is the inversion of the sign of the measured (69)Ga OPNMR signals when optically pumping this light hole-to-conduction band energy in OPNMR profiles at multiple external magnetic fields (B0=4.7T and 3T) for both σ(+) and σ(-) irradiation. Measurements of Hanle curves at B0=0.5T of the same sample exhibit similar phase inversion behavior of the Hanle curves at the photon energy for light hole excitation. The zero-field value of the light-hole state in the quantum well can be predicted for the quantum well structure using the positions of each of these signal-inversion features, and the spin splitting term in the equation for the transition energy yields consistent values at 3 magnetic fields for the excitonic g-factor (g(ex)). This study demonstrates the application of OPNMR and optical measurements of the photoluminescence to detect the light hole transition in semiconductors.


Comparison of electrochemical detection of acetylcholine-induced nitric oxide release (NO) and contractile force measurement of rabbit isolated carotid artery endothelium.
Since the identification of nitric oxide (NO) as an endothelial-derived relaxing factor, it became very important to quantify NO in biological models eventhough it is present in very low concentrations with a very short half-life. The use of electrochemistry as an alternative detection method is quite promising and electrochemical probes are now being developed to detect NO. This paper consists of an amperometric, bi-polymer modified, platinum-iridium microelectrode (Pt 90%-Ir 10% alloy, multistranded, total diameter 130 microm) design and its application for NO detection in acetylcholine (Ach) introduced, rabbit isolated carotid artery endothelium model. In a pH range of 3.0-10.0. pH 3.0 was found to be the optimum pH. As the pH values increased up to 10.0, the response current decreased as the oxidation of NO is catalyzed by H(+) in the acidic media. Temperature effect was checked at 25 degrees C (room temperature), 30 and 40 degrees C. An increasing trend was observed in sensor response with the increasing temperature. Most common biological interferences as ascorbic acid, uric acid and glucose were eliminated via bi-polymer coatings of four layers of Nafion and a layer of 50 mM o-phenylenediamine (OPD). When S/N ratio was accepted as 3, limit of detection was calculated as 15 nM. NO release from carotid artery endothelium was also determined by measuring response force in thermostatic isolated organel baths. Obtained force responses (mg) were compared with the electrochemical (nA) sensor responses.


Insomnia and Impaired Quality of Life in the United States.
This analysis characterizes the individual-level and population-level burden of insomnia in relation to other medical conditions and describes the comorbidity of insomnia with other medical conditions, including the dependence of these comorbidities on pain, life events, and mental disorders. Information from 34,712 adults in the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012-2013) was analyzed. Quality-adjusted life-years (QALYs) were measured with the SF-6D, a 6-dimensional health state classification derived from the Short-Form-12, version 2. In the last 12 months, 27.3% of adults reported insomnia. The US annual loss of QALYs associated with insomnia (5.6 million; 95% CI, 5.33-5.86 million) was significantly larger than that associated with any of the other 18 medical conditions assessed, including arthritis (4.94 million; 95% CI, 4.62-5.26 million), depression (4.02 million; 95% CI, 3.87-4.17 million), and hypertension (3.63 million; 95% CI, 3.32-3.93 million). After control for demographic factors, all conditions examined from obesity (adjusted odds ratio [aOR] = 1.25) to mania (aOR = 5.04) were associated with an increased risk of insomnia. Further controlling for pain, stressful life events, and mental disorders decreased the odds of the co-occurrence of insomnia with these conditions. The decrease in insomnia comorbidity associated with pain was greatest for fibromyalgia (31.8%) and arthritis (20.1%); the decrease in insomnia comorbidity associated with life events was greatest for mania (13.4%) and drug use disorders (11.2%); and the decrease in insomnia comorbidity associated with mental disorders was greatest for peptic ulcer disease (11.2%) and liver diseases (11.1%). Insomnia is prevalent and associated with substantial population-level burden in self-assessed health. The co-occurrence of insomnia with common medical conditions is differentially related to pain and to a lesser extent to stressful life events and mental disorders.


Targeting BRG1 chromatin remodeler via its bromodomain for enhanced tumor cell radiosensitivity in vitro and in vivo.
Radiotherapy treats cancer by inducing DNA double-strand breaks (DSB) in tumor cells using ionizing radiation. However, DNA repair in tumor cells often leads to radioresistance and unsuccessful outcome. Inhibition of DNA repair by targeting repair proteins can increase radiosensitivity of tumor cells. The BRG1 chromatin remodeling enzyme assists DSB repair by stimulating γ-H2AX formation and BRG1 binding to acetylated histones at DSBs via bromodomain (BRD) is critical for this activity. Here, we show that ectopic expression of BRG1-BRD inhibited γ-H2AX and DSB repair after irradiation and increased the radiosensitivity in various human cancer cells, including HT29 colon cancer. Dimerization of BRG1-BRD, increasing its chromatin binding affinity, aggravated the defects in γ-H2AX and DSB repair and further enhanced the radiosensitivity. While little affecting the upstream ATM activation, BRG1-BRD in irradiated HT29 cells inhibited the recruitment of 53BP1 to damaged chromatin, the downstream event of γ-H2AX, and compromised the G2-M checkpoint and increased apoptosis. Importantly, in a xenograft mouse model, BRG1-BRD increased the radiosensitivity of HT29 tumors, which was further enhanced by dimerization. These data suggest that BRG1-BRD radiosensitizes tumor cells by a dominant negative activity against BRG1, which disrupts γ-H2AX and its downstream 53BP1 pathways, leading to inefficient DNA repair, G2-M checkpoint defect, and increased apoptosis. This work therefore identifies BRG1-BRD as a novel tumor radiosensitizer and its action mechanism, providing the first example of chromatin remodeler as a target for improving cancer radiotherapy.


Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter.
The role of nitric oxide in relaxation of the internal anal sphincter (IAS) in response to the rectoanal reflex was studied in the opossum. Resting pressures in the IAS (IASP) were monitored using low-compliance continuously perfused catheters. The NO-synthase inhibitor L-NG-nitro-arginine (L-NNA) caused significant and dose-dependent suppression of the decrease in IASP in response to the reflex mimicked by the rectal balloon distention. NO-synthase inhibitor blocked IAS relaxation in response not only to rectoanal reflex but also to other neural stimuli such as sacral nerve stimulation, local intramural stimulation, and the nicotinic ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium. Suppression of the neurally mediated IAS relaxation by L-NNA was stereoselective; D-NNA had no effect on the relaxation. The suppression of the rectoanal reflex-induced IAS relaxation by L-NNA was completely reversed by NO precursor L-arginine stereoselectively as D-arginine failed to reverse the suppressed IAS relaxation. Sodium nitroprusside caused a decrease in IASP that was modified neither by the neurotoxin tetrodotoxin nor by L-NNA. Furthermore, the decrease in IASP by the direct-acting beta-adrenoceptor agonist isoproterenol was also not modified by the inhibitor of NO synthase. It is concluded that NO or an NO-like substance is an important mediator of IAS relaxation in response to noradrenergic, noncholinergic nerve stimulation.


Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2.
This paper aimed to elucidate the traditional use of Rosmarinus officinalis through the investigation of cholinergic activities and neuronal differentiation in rat pheochromocytoma PC12 cells. These effects were examined in relation to the plant's habitat, the extraction procedure, and the major active compounds of R. officinalis. Cell viability, cell differentiation, acetylcholinesterase (AChE) activity, total choline, acetylcholine (ACh) and extracellular signal-regulated kinases (ERK1/2) were determined in PC12 cells treated with extracts and HPLC-identified polyphenols of R. officinalis originated from Tunisian semi-arid and subhumid area in comparison with nerve growth factor (NGF). R. officinalis extracts potentiated cell differentiation and significantly enhanced AChE activity in PC12 cells. The highest AChE activity was induced by semi-arid hydro-ethanolic extract (137% of control). Among HPLC-identified and screened polyphenols, carnosic acid (CA) and rosmarinic acid (RA) significantly induced cell differentiation, increased ACh level, and enhanced AChE activity in PC12 cells. U0126, inhibitor of ERK1/2, significantly reduced CA and RA effects on cell differentiation and AChE activity. R. officinalis' CA and RA exhibited neurotrophic effects in PC12 cells through cell differentiation induction and cholinergic activities enhancement. These effects could be regulated by mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway.


[Pyoderma gangrenosum in Crohn's diseases of the colon].
A case of much less frequent association of the pyoderma gangrenosum and granulomatous disease of the colon (Crohn's disease of the colon) is presented. A literature review is made about the association of the same with other gastrointestinal affections. It is brought up to date the possible atiopathogenical mechanisms and therapeutical effects.


Vestigial respiratory burst activity in wound macrophages.
Macrophages from experimental wounds in rats were tested for their capacity to generate reactive oxygen intermediates. Measurements of superoxide and H2O2 release, O-2-dependent lucigenin chemiluminescence, oxygen consumption, hexose monophosphate shunt flux, and NADPH oxidase activity in cell lysates indicated, at best, the presence of a vestigial respiratory burst response in these cells. The inability of wound cells to release O-2 was not rekindled by priming with endotoxin or interferon-gamma in vivo or in vitro. NADPH oxidase activity in a cell-free system demonstrated that wound macrophage membranes, but not their cytosols, were capable of sustaining maximal rates of O-2 production when mixed with their corresponding counterparts from human neutrophils. Immune detection experiments showed wound macrophages to be particularly deficient in the cytosolic component of the NADPH oxidase p47-phox. Addition of recombinant p47-phox to the human neutrophil-cell membrane/wound macrophage cytosol cell-free oxidase assay, however, failed to support O-2 production. Present findings indicate an unexpected deficit of wound macrophages in their capacity to generate reactive oxygen intermediates.


A method for reconstruction of large full-thickness defects of the bony thorax.
Wide resection in 12 cases of malignant or potentially malignant lesions of the chest wall resulted in full-thickness loss of skeleton and frequently of overlying soft tissues (defect greater than or equal to 15 cm in its smallest diameter or at least 90% of the sternum resected). In reconstruction of the defect, steel bars were used to replace lost ribs and a double layer of Marlex mesh for intercostal spaces. Soft-tissue coverage and primary closure were accomplished with current plastic surgical procedures and good stability of the chest wall was achieved. Protracted respiratory support was required in only one case. Postoperative pain was managed with epidural anesthesia and routine analgesics. Functionally and cosmetically satisfactory long-term results were obtained, with no infection and no need for removal of prosthetic material. The overall 5-year and 10-year actuarial survival rates were 60% and 37.5%. If lesions are radically resectable, the extent of thoracic wall resection need not be restricted because of inability to close the defects.


The phylogenetic analysis of hepatitis C virus isolates obtained from two Iranian carriers revealed evidence for a new subtype of HCV genotype 3.
Classification of hepatitis C virus is based on phylogenetic analysis of the strains reported world wide. Different strains are classified within 6 major genotypes and several minor groups (subtypes). In addition to epidemiologic value of determining genotype/subtype of this virus, the result may change the therapeutic strategy used for a patient. During a survey on hepatitis C in Iran, we found two cases assigned as 1b genotype by PCR-RFLP on 5' UTR, but three based on core region sequencing. Fragments from 5' UTR, Core and NS5b regions were PCR-amplified and sequenced followed by phylogenetic analysis. Although the 5' UTR of this new strain is very similar to genotypes 1 and 6, analysis of core region classifies it in a separate branch of genotype 3, close to subtypes h and k. Further analysis of NS5b region put this new strain in a separate branch near other subtypes of genotype 3 and 4. These data are suggestive of a new subtype within genotype 3.


Cerebral salt wasting: pathophysiology, diagnosis, and treatment.
Cerebral salt wasting (CSW) is a syndrome of hypovolemic hyponatremia caused by natriuresis and diuresis. The mechanisms underlying CSW have not been precisely delineated, although existing evidence strongly implicates abnormal elevations in circulating natriuretic peptides. The key in diagnosis of CSW lies in distinguishing it from the more common syndrome of inappropriate secretion of antidiuretic hormone. Volume status, but not serum and urine electrolytes and osmolality, is crucial for making this distinction. Volume and sodium repletion are the goals of treatment of patients with CSW, and this can be performed using some combination of isotonic saline, hypertonic saline, and mineralocorticoids.


Stability of soybean recombinant plastome over six generations.
The stability of a plastid transgene has been evaluated in soybean transformants over six generations. These transformants had integrated the aadA selection cassette in the intergenic region between the rps12/7 and trnV genes. Three independent homoplasmic T0 transformation events were selected and ten plants from each event propagated to generation T5 in the absence of selection pressure. No transgene rearrangement nor wild-type plastome were detected in generation T5 by Southern blot analysis. All tested progenies were uniformly resistant to spectinomycin. Therefore, soybean transformants of generations T0 and T5 appear to be genetically and phenotypically identical.


Possible Influences on the Interpretation of Functional Domain (FD) Near-Infrared Spectroscopy (NIRS): An Explorative Study.
The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb + Mb] and deoxy[Hb + Mb]) values (in %). A regression analysis was carried out for ATT and maximal-minimum oxy[Hb + Mb], deoxy[Hb + Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb + Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb + Mb] (r = 0.53; P < 0.001), oxy[Hb + Mb] (r = 0.57; P < 0.001), and SmO2 amplitudes (r = 0.57; P < 0.001). No significant relations were found between ATT and relative oxy[Hb + Mb] (r = 0.37; P = 0.07) and deoxy[Hb + Mb] (r = 0.09; P = 0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r = 0.66; P < 0.001), maximal differences in deoxy[Hb + Mb] (r = 0.353; P = 0.032) and totHb (r = 0.512; P = 0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb + Mb] (r = -0.267; P = 0.111) and SmO2 (r = -0.267; P = 0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb + Mb] (r = 0.51; P = 0.001), oxy[Hb + Mb] (r = -0.50; P = 0.001), SmO2 (r = -0.54; P = 0.001), and totHb amplitude (r = 0.61; P < 0.001). No significant correlations were found when using relative oxy[Hb + Mb] (r = -0.01; P = 0.957) and deoxy[Hb + Mb] (r = -0.02; P = 0.895). Based on these findings, caution is advised when using NIRS values, as subcutaneous ATT and O2 delivery significantly influence NIRS measurements. To eliminate these influences, use of relative deoxy[Hb + Mb] is advised, especially in clinical settings or in people with a higher subcutaneous ATT layer.


Reproductive factors, subfertility, and risk of neural tube defects: a case-control study based on the Oxford Record Linkage Study Register.
Periconceptual exposure to subfertility treatments is increasingly common, raising concerns about the possibility of malformations in the offspring. The authors conducted a case-control study to determine whether subfertility or its treatment was associated with increased risk of neural tube defects (NTDs). Cases were 694 women diagnosed with an NTD-affected pregnancy in Oxfordshire or West Berkshire, England, between 1970 and 1987. Cases were individually matched on maternal year of birth and year of index pregnancy to controls randomly selected from a computerized database. Data on demographic, reproductive, and obstetric factors were abstracted from patient hospital records. Overall, the period prevalences of subfertility and of subfertility treatment were 7% and 3%, respectively, No evidence was found that the risk of NTD-affected pregnancies was increased by either subfertility (odds ratio (OR) = 1.2, 95% confidence interval (CI): 0.7, 2.1) or its treatment (OR = 0.9, 95% CI: 0.4, 2.0). After adjustment, NTD-affected pregnancies were associated with female offspring (OR = 2.3, 95% CI: 1.8, 3.1), multiple birth (OR = 4.8, 95% CI: 1.2, 18.8), and higher numbers of pregnancies (p for trend = 0.005). The findings from this large, population-based study were wholly consistent with those from smaller studies that found no increased risk of NTD associated with exposure to fertility treatments but reported associations with various pregnancy outcomes.


F2 screen for resistance to Bacillus thuringiensis Cry2Ab2-maize in field populations of Spodoptera frugiperda (Lepidoptera: Noctuidae) from the southern United States.
The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a target pest of transgenic maize and cotton expressing Bacillus thuringiensis (Bt) proteins in both North and South America. In 2013 and 2014, a total of 215 F2 two-parent families of S. frugiperda were established using single-pair mating of field individuals collected from seven locations in four states of the southern U.S.: Texas, Louisiana, Georgia, and Florida. The objective of the investigation was to detect resistance alleles in field populations to Cry2Ab2, a common Bt protein produced in transgenic maize and cotton. For each F2 family, 128 F2 neonates were screened on leaf tissue of Cry2Ab2 maize plants in the laboratory. A conservative estimate of the frequency of major Cry2Ab2 resistance alleles in S. frugiperda from the four states was 0.0023 with a 95% credibility interval of 0.0003-0.0064. In addition, six families were considered to likely possess minor resistance alleles at a frequency of 0.0082 with a 95% credibility interval of 0.0033-0.0152. One F2 family from Georgia (GA-15) was confirmed to possess a major resistance allele to the Cry2Ab2 protein. Larvae from this family survived well on whole maize plants expressing Cry2Ab2 protein and demonstrated a significant level (>15-fold) of resistance when fed with the same protein incorporated in a meridic diet. The detection of the major resistance allele along with the relatively abundant minor resistance alleles revealed in this study may have important implications for resistance management.


Brain functional imaging in obese and diabetic patients.
Obesity and type 2 diabetes are associated with greater risk of brain damage. Over the last decade, functional imaging techniques (functional magnetic resonance imaging, fMRI, positron emission tomography, PET, electroencephalography, magnetoencephalography, near infrared spectroscopy) have been exploited to better characterize behavioral and cognitive processes, by addressing cerebral reactions to a variety of stimuli or tasks, including hormones and substrates (e.g., glucose, insulin, gut peptides), environmental cues (e.g., presentation of sensory stimuli), and cognitive tasks. Among these techniques, fMRI and PET are most commonly used, and this review focuses on results obtained with these techniques in relation to brain substrate metabolism, appetite control and food intake, and cognitive decline in obesity and type 2 diabetes. The available knowledge indicates that there are a series of cerebral abnormalities associating with, or preceding obesity and type 2 diabetes, including impaired substrate handling, insulin resistance, disruption of inter-organ cross-talk and of resting state networking. Some of these abnormalities are reversed by metabolic interventions, suggesting that they are partly a consequence rather than cause of disease. Therefore, causal implications and mechanisms remain to be determined.


An inductive assessment of radiation risks in space.
Procedures for the assessment of risks or vulnerabilities from radiation in space are evaluated in terms of model-independent inductive approaches. The reliability of risks calculated for space applications on the basis of accelerator-based physical and biological data is examined from a microdosimetric perspective. Probability distributions for energy deposition in biologically significant sites extend over several decades in lineal energy even for monoenergetic high-energy particles of relatively high atomic number. Because the response depends on a large number of variables and because of the difficulty of incorporating all such factors into calculations, a precise correlation between a physical descriptor of the field and observed effects in space is not feasible. For the same reasons, it is equally difficult to estimate the accuracies of such risk assessments. We use recently published microdosimetric spectra for HZE particles and biological weighting functions, including those derived from biological measurements with maximum entropy techniques, to illustrate some problems associated with the evaluations of risks from radiation fields in space.


Phencyclidine disposition after intravenous and oral doses.
[3H]-Phencyclidine (PCP) hydrochloride was given in intravenous (0.1 or 1 mg) or oral (1 mg) doses to male subjects. After 1 mg IV, drug and metabolites were recovered in urine (72.8 +/- 4.0% of dose), feces (4.7 +/- 0.9%), and perspiration. Fecal excretion was low (3.4 +/- 0.4%) after oral dosing and oral bioavailability was estimated at 72%. PCP comprised 16% of urinary radioactivity with 31% consisting of enzymatically hydrolyzable conjugates of hydroxylated metabolites. Both cis and trans isomers of 4-phenyl-4-(1-piperidinyl)cyclohexanol were found. Maximum average plasma PCP concentrations of 2.7 to 2.9 ng/ml were observed after oral and intravenous 1-mg doses. Blood/plasma ratios were approximately 1.0 and plasma binding was about 65%. Parent drug was found in saliva. Apparent terminal phase half-lifes averaged 21 +/- 3 hr (harmonic mean 17 hr, range 7 to 46 hr). The volume of distribution averaged 6.2 +/- 0.3 l/kg. Renal clearances were variable, but the average was 9% of the total clearance. Thus, PCP is cleared principally by metabolism.


Synthesis, intramolecular hydrogen bonding, and biochemical studies of clitocine, a naturally occurring exocyclic amino nucleoside.
The total synthesis of clitocine [6-amino-5-nitro-4-(beta-D-ribofuranosylamino)pyrimidine] (1), a nucleoside recently isolated from the mushroom Clitocybe inversa, has been accomplished. Glycosylation of 4,6-diamino-5-nitropyrimidine (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose afforded the protected nucleoside 6-amino-5-nitro-4-[(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl) amino]pyrimidine (5) in good yield exclusively as the beta-anomer. Deprotection of 5 with NaOMe/MeOH gave 1 as an 11.5:1 mixture of the beta- and alpha-anomers, respectively. Recrystallization from MeOH, followed by chromatography, afforded 1 containing less than 1% of its alpha-anomer. X-ray crystal data revealed a planar aglycon moiety in clitocine with each oxygen atom of the nitro group intramolecularly hydrogen bonded to the hydrogen atoms of the two adjacent amino functions. Clitocine inhibited L1210 cells in vitro with an ID50 of 3 X 10(-8) M. Clitocine was also found to be a substrate and inhibitor of adenosine kinase with a Ki value of 3 X 10(-6) M.


Effect of indomethacin on atropine-resistant transmission in rabbit and monkey urinary bladder: evidence for involvement of prostaglandins in transmission.
The effects of 2.9 x 10(-5)M atropine and 2.8 x 10(-6)M indomethacin on responses of rabbit and monkey detrusor muscle to transmural stimulation were investigated. Response to transmural stimulation were partially inhibited by atropine. Indomethacin caused further inhibition in the presence of atropine, but did not alter responses to acetylcholine. Prostaglandins E2 and F2alpha contracted rabbit and monkey detrusor. It is suggested that prostaglandins are liberated during stimulation of excitatory nerves to the rabbit and monkey detrusor, and contribute to the resultant contractile response.


Preoperative location of the pituitary bright spot in patients with pituitary macroadenomas.
The purpose of this study was to determine the location of the pituitary bright spot in patients with pituitary macroadenomas before surgery. A total of 54 patients with pituitary macroadenomas were retrospectively included in this study. Nonenhanced spin-echo T1-weighted MR images were reviewed to identify the location of the high-intensity-signal posterior pituitary lobe that indicates antidiuretic hormone (ADH) storage. Images were acquired with a 1.5-T machine by using 3-mm-thick contiguous sections in two or three orthogonal planes and a 300 x 512 matrix. The bright spot corresponding to ADH storage was identified in 44 (81%) patients. Two groups of patients were defined by the height of the macroadenoma: Group A patients (n = 27) had pituitary macroadenomas less than 20 mm in height, and group B (n = 27) had macroadenomas 20 mm or larger. In group A, the bright spot was identified in 25 patients (93%); it was located in the sella in 24 of these cases (96%). In group B, the bright spot was identified in 19 patients (70%); it was in an ectopic location in 14 of these cases (74%). MR imaging can be used to depict the pituitary bright spot in most patients with pituitary macroadenomas before surgery. The bright spot is usually identified at its expected location within the sella in patients with pituitary macroadenomas less than 20 mm in height, whereas an ectopic location is common when pituitary macroadenomas are larger more than 20 mm.


Circulatory adaptation to the increased metabolism in the skin at the site of the tuberculin reaction.
The sequence of changes at the site of a positive tuberculin test response were studied in 19 healthy young adults who had been immunised with BCG in childhood. The development of erythema preceded that of induration and both were most intense at 48-72 h. The strongest reactions showed higher laser Doppler (LD) flux at the periphery than at the center (central relative slowing). All showed a substantial reduction in steady-state (ss) tcpO2 from 24 h onwards and the oxygen consumption rate (mlO2.kg-1.min-1), calculated from the rate of fall in tcpO2 during temporary cuff occlusion of arterial input, was raised (greater than two-fold) throughout the period of study (to 96 h). The density of lymphocytes and macrophages in the inflammatory infiltrate in the dermis was related to the fall in tcpO2.ss and to the extent of thickening of the dermis. These experiments showed that the previously healthy dermal microcirculation can adapt to temporary increase in metabolic demands of leucocytes emigrated from the circulation into the tissue: in intense delayed hypersensitivity (DHS) reactions there is considerable hypoxia and respiratory debt, but maintenance of viability in the short-term. It is likely that similar adaptations occur in the period of establishment of microbial infection.


Experimental models of inflammatory bowel disease.
Etiology of inflammatory bowel disease (IBD) is still unknown. A lot of experimental models of these diseases have been developed during the last years. They can be classified as spontaneous and induced models. Spontaneous models are infectious, genetic or of unknown etiology. Induced models are infectious, immune-mediated, chemical or genetic. All these models share some characteristics with IBD. In general, they are characterized by a chronic inflammation of the gut, and often, this inflammation appears secondary to mucosal abnormalities leading to an abnormal immune and inflammatory response toward luminal material. The most interesting models are thus those that share not only clinical and pathological characteristics with IBD, but also early mucosal abnormalities. From that point of view, the nonsteroidal anti-inflammatory drug (NSAID) enteropathy is probably one of the most interesting model for Crohn's disease (CD). In effect, this model shares an early modification with CD, that is increased intestinal permeability. In animals NSAID enteropathy, the increased intestinal permeability appears early after NSAID administration and is followed by inflammatory lesions. These lesions seem to be secondary to the increased permeability and depend on intraluminal materials, such as alimentary antigens or bacterial fragments. A possible link between the increased permeability and the inflammatory lesions could be an abnormal immune and inflammatory response toward the intraluminal materials. If the increased intestinal permeability in CD was confirmed, the same mechanisms could be implicated in its pathophysiology.


Nutraceuticals and Functional Foods: The Foods for the Future World.
The health and wellness of human beings is largely dictated by the consumption of nutritious foods. Various studies have linked foods as helpful in combating a number of degenerative diseases; as such, a lot of research on functional attributes linked directly to the health benefits of various plant and animal foods have been witnessed in recent years. Although vast number of naturally occurring health-enhancing substances are of plant origin, there are a number of physiologically active components in animal products as well that deserve attention for their potential role in optimal health. Consumption of biologically active ingredients in fruits and vegetables has been linked to help combat diseases such as cancer, cardiovascular diseases, obesity, and gastrointestinal tract disorders. Lot of research is required to substantiate the potential health benefits of those foods for which the diet-health relationships are not sufficiently validated, and create a strong scientific knowledge base for proper application of naturally present foods in combating various diseases and disorders.


Pharmacokinetic drug interactions involving Ginkgo biloba.
Ginkgo biloba leaf extracts (GLEs) are popular herbal remedies for the treatment of Alzheimer's dementia, tinnitus, vertigo and peripheral arterial disease. As GLEs are taken regularly by older people who are likely to also use multiple other drugs for the treatment of, e.g. hypertension, diabetes, rheumatism or heart failure, potential herb-drug interactions are of interest. Preclinical studies of high doses/concentrations of GLEs of varying quality and standardization hinted at both an inhibition and induction of metabolic enzymes and transporters. However, in humans, positive in vitro-findings could not be replicated in vivo. At maximum recommended doses of 240 mg/day, a clinically relevant interaction potential of the standardized GLE EGb 761 could not be shown. GLE doses higher than the recommended ones led to a weak induction of the CYP2C19-mediated omeprazole 5-hydroxylation, and a weak inhibition of the CYP3A4-mediated midazolam 1'-hydroxylation, respectively. Also, the regular intake of a poorly characterized GLE at a dose of 360 mg/day slightly increased the bioavailability of talinolol, a substrate of P-glycoprotein and various organic anion-transporting polypeptides. Thus, regarding pharmacokinetic herb-drug interactions, the intake of the standardized GLE, EGb 761, together with synthetic drugs appears to be safe as long as daily doses up to 240 mg are consumed. If this applies to other extracts prepared according to the European Pharmacopoeia remains uncertain. Also, a relevant potential for drug interactions cannot be excluded for poorly standardized GLEs used in many food supplements.


Multicell spheroid response to drugs predicted with the comet assay.
Multicell spheroids were exposed to DNA-damaging agents with the aim of determining whether prompt DNA damage could be predictive for cell killing and drug resistance. Chinese hamster V79 cells, SiHa human cervical carcinoma cells, and WiDr human colon carcinoma cells were grown as spheroids and exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), doxorubicin, etoposide, actinomycin D, 1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol (RSU 1069), 3-amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine), and nitrogen mustard. Average DNA damage measured using the alkali comet assay generally correlated with cell killing irrespective of exposure times or drug concentration. However, better predictive power was achieved by using DNA damage levels in individual cells to identify the fraction of cells containing sufficient numbers of DNA strand breaks to cause death. Using this concept of a "threshold" for DNA damage, cell survival could be predicted for exposure to 4NQO, tirapazamine, nitrogen mustard, RSU 1069, and actinomycin D and was largely independent of cell type. The threshold value varied for each drug. For 4NQO, tirapazamine, and RSU 1069, DNA damage equivalent to about 10,000 strand breaks/cell was not toxic to cells of any spheroid type. Conversely, for actinomycin D, any DNA damage above background levels (approximately 100 breaks) was toxic for all three cell types. For some DNA-damaging drugs, the lack of correlation between DNA damage and cell killing was also informative. For etoposide and doxorubicin, no common threshold for cell killing could be determined, consistent with the hypothesis that DNA damage is only one of the actions of these drugs leading to cell death. For MNNG, the tail moment threshold varied significantly for the different spheroid types, probably indicating differences in repair. Overall, for five of the eight drugs, DNA damage measured using the comet assay was an effective and quantitative method of predicting drug cytotoxicity in complex multicelled systems.


A clinical comparison of guided bone regeneration with platelet-derived growth factor-enhanced bone ceramic versus autogenous bone block grafting.
The objective of this study was to evaluate the efficacy of guided bone regeneration (GBR) employing recombinant human platelet-derived growth factor-BB (rhPDGF-BB) incorporated into a beta-tricalcium phosphate (β-TCP)/hydroxyapatite (HA) carrier as a graft material and to compare it to autogenous bone block grafting. Adult patients with a site that required bone grafting to increase the thickness of the alveolar bone ridge were treated. After mucoperiosteal flap elevation, experimental bone defects were treated by GBR with rhPDGF incorporated into β-TCP/HA, and control defects were treated with autogenous bone. Primary tension-free wound closure was obtained for all treated sites. Thirty patients were treated. No significant differences were observed between the groups for any of the parameters evaluated, including the amount of bone regeneration and a need for additional grafting. A composite bone ceramic graft that incorporated rhPDGF appears to be a suitable substitute for autogenous bone block grafting when employed in conjunction with GBR in humans.


Probiotic administration and the incidence of nosocomial infection in pediatric intensive care: a randomized placebo-controlled trial.
To evaluate the efficacy of probiotics in reducing the rates of nosocomial infection in pediatric intensive care. Randomized, double-blind, placebo-controlled trial. A 16-bed pediatric intensive care unit in a university-affiliated children's hospital. Sixty-one pediatric patients were enrolled from April 2004 until December 2004. Screening of all patients admitted occurred on a daily basis. Patients were excluded if they had the following: evidence/suspicion of intestinal perforation, evidence/suspicion of mechanical gastrointestinal obstruction, absolute neutrophil count <or =0.5 x 10(9) cells/L, judgment by the attending physician that unable to tolerate the enteral volume necessary for administration, use of a probiotic preparation at any time in the week before study entry, participation in another clinical trial, lack of parental presence, or lack of parental consent. Patients were randomized to receive either one capsule of Lactobacillus rhamnosus strain GG (Culturelle, ConAgra Foods, Omaha, NE) or placebo capsule of insulin once a day until discharge from the hospital. Sixty-one patients were randomized: 31 in the treatment group and 30 on the placebo group. Three patients in the control group developed four infections. Six patients in the treatment group developed 11 infections. The relative risk of developing infection in the treatment group was 1.94 (confidence interval [CI], 0.53 to 7.04; p = .31). The mean number of infections in the treatment and control groups was 1.83 and 1.33, respectively, with a difference of 0.5 (p = .52). No serious adverse effects in the study population were noted. However, due to recent safety concerns regarding the administration of L. rhamnosus strain GG and a lack of benefit in this interim analysis, the study was terminated by the study investigators. The results of this preliminary investigation were unexpected but important in view of the increased use of probiotic preparations in medically fragile pediatric patients. In this randomized, placebo-controlled trial, L. rhamnosus strain GG was not shown to be effective in reducing the incidence of nosocomial infections. In fact, a statistically nonsignificant trend toward an increase in infection was seen (four vs. 11). Further studies with a larger patient population are needed to establish both safety and efficacy of probiotics in pediatric critical care.


Persistence of behaviours in the Forced Swim Test in 3xTg-AD mice at advanced stages of disease.
Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study characterizes the behavioural responses of 12-month-old male 3xTg-AD mice in FST as compared to age-matched no-transgenic (NTg) mice. Paradoxical results were consistently found from what would be expected from their BPSD (Behavioural and Psychological Symptoms of Dementia)-like profile. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration, frequency of episodes and mean duration). Both genotypes showed equal number of swimming episodes and climbing attempts during the first interval, that resulted in high swimming times, short climbing and scarce immobility. Thereafter, the NTg mice showed a behavioural shift over time and the immobility response showed up. In contrast, all the measures consistently evidenced that 3xTg-AD persisted with the previous behavioural pattern. Genotype differences consisted in less number of episodes of immobility and swimming, and a low immobility time in favour of swimming. No differences were found in 'climbing' attempts. The behavioural response observed is discussed as a lack of ability of 3xTg-AD mice to shift behaviour over time that may result of poorest cognitive flexibility and copying with stress strategies more than behavioural despair per se.


[Effectiveness of acidified fluoride solutions in prevention of dental caries in school children].
The purpose of the study was assessment of the influence of locally applied acidified fluoride solutions on the condition of teeth of school children living in a town district with fluoridated drinking water and in another district without fluoridation of drinking water. Acidified fluoride solutions were applied locally by brushing--5 procedures at two-week intervals in the first and second year of the experiment. The condition of teeth was assessed calculating the indices CMF and CMFp. In the light of the obtained results it may be said that the externally applied acidified solutions of fluorides had an approximately evident effectiveness in prevention of caries both in children drinking fluoridated or non-fluoridated water.