[Computerized tomography guided biopsy in the diagnosis of neoplastic and inflammatory lesions of the pelvis].
To assess the efficacy of percutaneous CT-guided biopsy in the diagnosis and therapeutic planning of neoplastic and flogistic diseases of the pelvis. From July 1990 to December 1999 193 patients (113 males, 80 females: mean age 49, standard deviation 16) were submitted to CT-guided percutaneous biopsy of the pelvic region; 117 biopsies (61%) were performed at iliac, pubic and ischial segments and 76 (39%) at sacral region; 107 patients were admitted to the hospital and 86 were in clinic. Needles were 8 G (4 mm), 10 to 15 cm long. Approach to pelvic lesions was performed according to the specific site. Lesions of the lateral pelvic region have always been approached through the lateral surgical incision according to Enneking. Lesions of the posterior pelvic region have always been approached by the introduction of the needle along the posterior surgical incision according to Enneking. Lesions of the anterior region have always been approached through the anterior surgical incision according to Enneking. From July 1990 to May 1997 pelvic percutaneous biopsies have been carried out with a CT Sytec 3000. From May 1997 to December 1999 the device was replaced by a High Speed CTi. The introduction of spiral CT allowed reduction of performance mean time from 45 minutes (standard deviation 15) to 30 minutes (standard deviation 10). In 154 patients (80%) we observed a neoplastic, inflammatory or not classified degeneration. In 8 patients (4%) the retrieved material ended to be inadequate for a diagnosis. In 31 patients (16%) no disease was revealed at the histological examination. Such patients with negative histological examination have been kept under clinical and radiological control in the following period in order to verify the manifestation or the presence of an alteration previously not observed. On 31-3-2000 none of them had been submitted to a new percutaneous biopsy of the pelvic region. The overall mean accuracy has been 96% considering the negative patients as really negative. In 5 cases (2.6%) we have had complications represented by pain at the introduction and penetration site of the needle. The choice of the needle, the approach to the lesion and the position of the patient are conditioned by the site of the tumor, its extension, the distance skin-neoplastic disease and by the respect of the incision lines of Enneking, in order not to complicate the job of the orthopaedic surgeon spreading tumoral cells outside the chosen surgical approach. The mean time of the procedure is 30 minutes (standard deviation 10). There are no absolute contraindications to percutaneous biopsy except the suspect or the presence of an hydatideal cyst. The risks have to be compared with those correlated with alternative methods or with the more concerning risk of a missed diagnosis. Complications in the literature range from 0% to 10%, the incidence varying according to the location; pain is the most frequent complication. Altogether the most negative event, although not a true complication, is the retrieval of an inadequate sample: the only drawback of percutaneous biopsy in comparison with incisional biopsy. The accuracy rate of percutaneous biopsy varies in relation to the involved anatomical region, to the pathological process, to the experience of the user, to the amount of the retrieved tissue and to the cooperation of the patient. Our experience shows that, in selected patients, percutaneous biopsy is a virtually safe and almost painless procedure which saves the patient from a surgical procedure in regional or general anestesia as for an incisional biopsy, and allows immediate planning and scheduling of a correct therapy for primitive or secondary neoplastic lesions.


Autonomic responsiveness in obesity with and without hypertension.
Evidence from animals models of obesity, eg the ob/ob mouse, and from studies in man are consistent with the autonomic regulation of brown tissue being one of the principal pathways involved in the normal thermogenic regulation of energy balance. Studies in man on other components of the sympathetic nervous system do not suggest generalized autonomic abnormalities in obese patients. Patients placed on a reduced carbohydrate intake show a fall in metabolic rate, a reduction in cardiovascular indices of sympathetic activity and a fall in venous noradrenaline concentrations. The hypotensive effect is accompanied by a precipitous fall in hydroxy-methoxymandelic acid excretion. These changes are not nearly so evident in those obese patients who are also hypertensive so there may be altered control of catecholamine metabolism in obese hypertensive patients.


Time course of verapamil interaction with morphine effects on physiological parameters in rats.
The effects of subcutaneous doses of morphine and verapamil on respiratory and cardiovascular parameters have been assessed in conscious rats. Verapamil (10 mg kg-1) was injected simultaneously with morphine (16 mg kg-1) or at 10, 30, or 60 min before morphine administration. Morphine induced respiratory depression, as indicated by marked hypercapnia, hypoxia and acidosis, and caused marked tachycardia. Although morphine produced only a minor and inconsistent (but statistically significant, P less than 0.01) reduction of mean arterial blood pressure, morphine potentiated verapamil-induced hypotension. Verapamil suppressed morphine-induced hypercapnia only when injected simultaneously with morphine. Verapamil alone did not affect arterial blood gases or pH, but decreased heart rate and mean arterial blood pressure. Verapamil attenuated and delayed the maximum positive chronotropic effects of morphine at all times tested. Antagonism by verapamil of respiratory depression and tachycardia produced by morphine was unrelated to morphine levels in plasma. Thus, the explanation of verapamil-morphine interactions on respiration and cardiovascular function is not pharmacokinetic.


Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease.
Manzamine A and related derivatives isolated from a common Indonesian sponge, Acanthostrongylophora, have been identified as a new class of GSK-3beta inhibitors. The semisynthesis of new analogues and the first structure-activity relationship studies with GSK-3beta are also reported. Moreover, manzamine A proved to be effective in decreasing tau hyperphosphorylation in human neuroblastoma cell lines, a demonstration of its ability to enter cells and interfere with tau pathology. Inhibition studies of manzamine A against a selected panel of five different kinases related to GSK-3beta, specifically CDK-1, PKA, CDK-5, MAPK, and GSK-3alpha, show the specific inhibition of manzamine A on GSK-3beta and CDK-5, the two kinases involved in tau pathological hyperphosphorylation. These results suggest that manzamine A constitutes a promising scaffold from which more potent and selective GSK-3 inhibitors could be designed as potential therapeutic agents for Alzheimer's disease.


Decrease in ATP biosynthesis and dysfunction of biological membranes. Two possible key mechanisms of phenoptosis.
Metabolic syndrome is extremely prevalent in the world and can be considered as one of main factors leading to accelerated aging and premature death. This syndrome may be closely linked with age-related disruptions in hypothalamic-pituitary system function, which perhaps represent a trigger mechanism of development of endocrine and cardiovascular pathologies. Age-related elevation of the sensitivity threshold of the hypothalamus to regulatory signals in association with low mobility and excessive diet trigger a cascade of biochemical reactions that might be used for activation of programmed death of the organism - phenoptosis. Accumulation of fatty acids in a cell and resulting lipotoxicity include resistance to insulin and leptin, endoplasmic reticulum stress, uncoupling of oxidation and phosphorylation, and dysfunction of biological membranes. Decrease in ATP synthesis is correlated with accumulation of calcium ions in cells, dysfunction of mitochondria, and increasing apoptotic activity. Age-related activation of mTOR (which is greatly influenced by excess energy substrates) has deleterious impact on one of the main mechanisms of cell defense by which defective mitochondria are replaced: mitophagy and biogenesis of mitochondria will be suppressed, and this will increase in greater degree mitochondrial dysfunction and oxidative stress. Fatty acid-induced inflammation will increase activity of nuclear factor NF-κB, the well-known stimulator of age-related pathologies. The final stage of phenoptosis can be represented by endothelium dysfunction related with oxidative stress, insulin resistance, and the most prevalent cardiovascular pathologies.


Bring the magic back to the bullets.
Governments must act swiftly and decisively to incentivize antibiotic R&D and clarify regulations.


Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress.
Mitochondrial biogenesis and mitochondrial DNA (mtDNA) maintenance depend on coordinated expression of genes in the nucleus and mitochondria. A variety of intracellular and extracellular signals transmitted by hormones and second messengers have to be integrated to provide mammalian cells with a suitable abundance of mitochondria and mtDNA to meet their energy demand. It has been proposed that reactive oxygen species (ROS) and free radicals generated from respiratory chain are involved in the signaling from mitochondria to the nucleus. Increased oxidative stress may contribute to alterations in the abundance of mitochondria as well as the copy number and integrity of mtDNA in human cells in pathological conditions and in aging process. Within a certain level, ROS may induce stress responses by altering expression of specific nuclear genes to uphold the energy metabolism to rescue the cell. Once beyond the threshold, ROS may cause oxidative damage to mtDNA and other components of the affected cells and to elicit apoptosis by induction of mitochondrial membrane permeability transition and release of pro-apoptotic proteins such as cytochrome c. On the basis of recent findings gathered from this and other laboratories, we review the alterations in the abundance of mitochondria and mtDNA copy number of mammalian cells in response to oxidative stress and the signaling pathways that are involved.


The von Hippel-Lindau tumor suppressor gene protects cells from UV-mediated apoptosis.
The familial cancer syndrome, von Hippel-Lindau (VHL) disease, characterized by a predisposition to renal cell carcinoma and certain other tumor types, is caused by mutational inactivation of the VHL tumor suppressor gene. Loss of VHL gene function is detected also in the vast majority of sporadic renal cell carcinomas. Previous reports have determined a protective role for VHL in response to serum withdrawal and glucose deprivation. In this study, the effect of UV irradiation on VHL-negative and VHL-positive renal carcinoma cells was examined. VHL-negative 786-O renal carcinoma cells underwent apoptosis following UV irradiation. In contrast, reintroduction of wild-type VHL expression protected 786-O cells from UV-mediated cell death. p53 and Bax levels were equivalent in VHL-negative and VHL-positive 786-O cells. Strikingly, cyclin-dependent kinase inhibitors p21 and p27 underwent proteasome-dependent degradation in VHL-negative 786-O cells following UV treatment. However, p21 and p27 protein levels were stable in VHL-positive cells. Also, levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xL were elevated in VHL-positive cells, consistent with the protection from apoptotic stimuli. UV treatment led to increased S phase in VHL-negative, but not VHL-positive cells. Thus, following UV irradiation, diminution of p21 and p27 levels resulted in a hyperproliferative state in VHL-negative cells, leading to apoptosis. These results suggest that loss of VHL function promotes apoptosis and may provide selective pressure toward cells that are able to escape apoptosis, leading to tumorigenesis.


[Hygienic and economic significance of sewer drainage in hospitals. Architectural changes in the guidelines of the Federal Health Office].
The hygienic importance of barrier zoning in hospitals has been evaluated on the basis of the relevant international literature between 1970 and 1989. There have been only a very few pertinent publications and in none has there been any pointer which would support the hypothesis of barriers having an infection-preventing effect. Using four University Hospitals in Baden-Würtemberg as paradigms, a model was prepared for calculating what space and cost savings were possible, if a simpler system could be installed, instead of the one demanded under federal regulations and already planned for the four hospitals. It was found that it would save a realizable area of 319,5 m2 at a potential cost saving of DM 1,138,335. By dispensing with hygienically not justifiable building work at the planning stage of new hospitals considerable greater costs could be avoided.


Mice lacking cyclin-dependent kinase inhibitor p19Ink4d show strain-specific effects on male reproduction.
p19(Ink4d) is a member of the INK4 family of cyclin-dependent kinase inhibitors, which are important negative regulators of the G1-phase cyclin-dependent kinases CDK4 and CDK6. On a mixed C57BL/6 x 129P2/OlaHsd background, mice deficient for p19(Ink4d) exhibited defects in male reproductive function including testicular atrophy, alteration in serum follicle stimulating hormone, qualitative increase in germ cell apoptosis, and delayed kinetics of meiotic prophase markers (Zindy et al., 2001. Mol Cell Biol 21:3244-3255; Zindy et al., 2000. Mol Cell Biol 20:372-378). In this study, a quantitative assessment of these aspects of reproductive capacity demonstrated relatively mild deficits in p19(Ink4d-/-) males compared to controls. These effects did not dramatically worsen in older males although some seminiferous tubule defects were observed. Following marker-assisted backcrossing into the C57BL/6 background, p19(Ink4d-/-) males did not display defects in testis weights, sperm numbers, serum FSH, germ cell apoptosis, or kinetics of selected meiotic prophase markers. These studies indicate that a reduction in Ink4 family function by the loss of p19(Ink4d) is sufficient to induce mild reproductive defects in male mice with a mixed genetic background, but not in the C57BL/6 genetic background.


Lycopene I--effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in rat bone marrow cultures.
Osteoclasts have been shown to produce reactive oxygen species (ROS) that can stimulate bone resorption. We explored the hypothesis that lycopene, the antioxidant carotenoid from tomatoes, can inhibit mineral resorption by inhibiting osteoclast formation and the production of ROS. Cells from bone marrow prepared from rat femur were plated into 16-well calcium phosphate-coated Osteologic Multi-test Slides and cultured in alpha-minimal essential medium supplemented with dexamethasone, beta-glycerophosphate, and ascorbic acid. The cells were treated with varying doses of lycopene in the absence or presence of parathyroid hormone (PTH) at the start of culture and at each medium change (i.e., every 48 hours). On day 8, mineral resorption pits were quantitated. Similar, parallel experiments were carried out in 12-well plastic dishes to assess tartrate-resistant acid phosphatase (TRAP) activity. Results showed that lycopene inhibited TRAP + formation of multinucleated cells in both vehicle- and PTH-treated cultures. Osteoclasts reduced nitroblue tetrazolium (NBT) to purple-colored formazan, indicating the presence of ROS in these cells. The formazan-staining cells were decreased by treatment with 10(-5) M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. In conclusion, we have shown that lycopene inhibits basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP + multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are novel and may be important in the pathogenesis, treatment, and prevention of osteoporosis.


Middle school special education teachers' perceptions and use of assistive technology in literacy instruction.
In this research the authors examined middle school special education teachers' perceptions of assistive technology during literacy instruction with students with high incidence disabilities. A survey explored the use, effectiveness, and factors impacting use or effectiveness of assistive technology for literacy teaching and learning. Results suggested teachers' perceived assistive technology to be an effective tool for literacy, but use it minimally. When assistive technology was used, teachers indicated it was an effective literacy support. Teachers also reported barriers to using assistive technology in literacy including cost, usability, and lack of training/experience. However, factors such as previous successful experiences with assistive technology and assistive technology supporting students' learning encouraged assistive technology use. The consistency of teachers' reports of needing more experience and knowledge in assistive technology to fully use it suggests implications for preservice preparation such as providing additional experiences and information on assistive technology.


Simultaneous assay of corticosterone and cortisol in plasma by reversed-phase liquid chromatography.
We have developed a simple, specific, and sensitive reversed-phase liquid-chromatographic method for accurate and simultaneous analysis of corticosterone and cortisol in human plasma. We achieved a detection limit of 300 ng/L for both steroids by modifying the old solid-phase extraction method to make use of "Tef Elutor" C18 columns, using a minibore (100 x 2 mm) analytical column, and using an ultraviolet detector with a 10-mm-pathlength flow cell. With the new extraction method absolute extraction efficiencies were greater than 90% for all the analytes, including the internal standard, flumethasone. The mobile phase was water (containing 5 mL of triethylamine per liter and citric acid to adjust the pH to 6.5), tetrahydrofuran, and acetonitrile (82/10/8 by vol). The average interassay CV for corticosterone at 0-25 micrograms/L was 6.5%; that for cortisol at 0-300 micrograms/L was 3.8%. The analytical recovery relative to the internal standard was 100.2% for cortisol and 102.6% for corticosterone. Possible interferences from drugs and other steroids were studied.


Analysis of different medulloblastoma histotypes by two-dimensional gel and MALDI-TOF.
The purpose of this study is to detect different protein profiles in medulloblastoma (MDB) that may be clinically relevant and to check the correspondence of histological classification of MDB with proteomic profiles. Surgical specimens, snap frozen at the time of neurosurgery, entered the proteomic study. Eight samples from patients (age range, 4 months-26 years) with different MDB histotypes (five classic, one desmoplastic/nodular, one with extensive nodularity, and one anaplastic) were analyzed by two-dimensional gel electrophoresis. One sample for each histotype was further characterized by matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis. Eighty-six unique proteins were identified and compared to histology, with the determination of proteins expressed by single histotypes and of a smaller number of proteins shared by two or three histotypes. The sharp difference of protein expression was found to be in agreement with WHO histological classification, with the identification of type-specific proteins with limited overlapping between histotypes. Proteomic analysis confirmed and strengthened the difference between histotypes as biologically relevant. Cluster analysis enhanced the distance of extensive nodularity MDB from other histotypes. Possible innovative approaches to therapy may rely upon a proteomic-based classification of MDB tightly correlated to histology. The utility of snap freezing tumoral samples must be stressed and should become a mandatory task for pathologists.


Shunt nephritis associated with Moraxella bovis.
Moraxella bovis was repeatedly isolated from cerebrospinal fluid in a girl with two episodes of shunt nephritis. Clinical remission of nephritis was achieved only after shunt replacement. A list of about 20 infectious agents reported to date in patients with shunt nephritis is given. M. bovis is yet another agent previously not reported in patients with shunt nephritis.


[Hormonal component of the gastrointestinal diseases pathogenesis].
This article summarizes results of numerous experimental and clinical studies conducted in the laboratory of gastrointestinal hormones CSRIG that was made to examine the endocrine status and metabolic changes in the digestive system with its physiological and pathological conditions.


Intracranial pressure variation associated with changes in end-tidal CO2.
Maintaining intracranial pressure (ICP) below 20-25 mmHg is an important clinical goal in the treatment of patients with traumatic brain injury (TBI). It is well known that the partial pressure of arterial CO2 (PaCO2) can affect cerebral blood flow, cerebral blood volume, and therefore ICP. The end-tidal CO2 (ETCO2) is usually monitored by clinicians as a proxy for PaCO2. We show examples where subclinical fluctuations in ETCO2 are associated with clinically significant fluctuations in ICR. We estimated ICP from past and present values of ETCO2 with a linear estimator. The variance of the ICP residuals was 37 percent of the variance of the ICP signal at frequencies above 0.33 mHz. We suggest that a large proportion of clinically significant ICP fluctuations could be eliminated or reduced if the patients ventilation and CO2 levels were more tightly regulated.


Creating healthier workplaces: The American Psychological Association/National Institute of Occupational Safety and Health cooperative agreement. Introduction and historical overview.
This article introduces the special section on the American Psychological Association/National Institute for Occupational Safety and Health (APA/NIOSH) collaboration. The section includes an overview statement of National Institute for Occupational Safety and Health research by Linda Rosenstock and 5 competitively peer-reviewed articles submitted to the Journal of Occupational Health Psychology following their presentation in an earlier form at the 3rd APA/NIOSH conference in September 1995. This article provides a brief history of the APA/NIOSH collaboration forged at the turn of this decade.


PepNovo: de novo peptide sequencing via probabilistic network modeling.
We present a novel scoring method for de novo interpretation of peptides from tandem mass spectrometry data. Our scoring method uses a probabilistic network whose structure reflects the chemical and physical rules that govern the peptide fragmentation. We use a likelihood ratio hypothesis test to determine whether the peaks observed in the mass spectrum are more likely to have been produced under our fragmentation model than under a model that treats peaks as random events. We tested our de novo algorithm PepNovo on ion trap data and achieved results that are superior to popular de novo peptide sequencing algorithms. PepNovo can be accessed via the URL http://www-cse.ucsd.edu/groups/bioinformatics/software.html.


Mapping the binding domains involved in the interaction between the Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) and the cytoadherence ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1).
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) clusters at electron-dense knob-like structures on the surface of malaria-infected red blood cells and mediates their adhesion to the vascular endothelium. In parasites lacking knobs, vascular adhesion is less efficient, and infected red cells are not able to immobilize successfully under hemodynamic flow conditions even though PfEMP1 is still present on the exterior of the infected red cell. We examined the interaction between the knob-associated histidine-rich protein (KAHRP), the parasite protein upon which knob formation is dependent, and PfEMP1, and we show evidence of a direct interaction between KAHRP and the cytoplasmic region of PfEMP1 (VARC). We have identified three fragments of KAHRP which bind VARC. Two of these KAHRP fragments (K1A and K2A) interact with VARC with binding affinities (K(D(kin))) of 1 x 10(-7) M and 3.3 x 10(-6) M respectively, values comparable to those reported previously for protein-protein interactions in normal and infected red cells. Further experiments localized the high affinity binding regions of KAHRP to the 63-residue histidine-rich and 70-residue 5' repeats. Deletion of these two regions from the KAHRP fragments abolished their ability to bind to VARC. Identification of the critical domains involved in interaction between KAHRP and PfEMP1 may aid development of new therapies to prevent serious complications of P. falciparum malaria.


Effects of cadmium and verapamil on ketamine-induced anesthesia in mice.
Previous studies have shown that pretreatment with cadmium and verapamil potentiated the effects of some CNS active drugs. The objective of this study was to determine the influence of these agents on ketamine anesthesia in adult male mice. Intraperitoneal administration of 300 mg ketamine/kg produced sleeping time of 40.88 +/- 2.98 min. Pretreatment with a single dose of either 3 mg cadmium/kg sc or 5 mg verapamil/kg ip alone significantly increased the duration of sleeping time (40.88 +/- 2.98 vs 55.09 +/- 4.20 and 49.01 +/- 3.09 min). Pretreatment with cadmium plus verapamil produced significant additive effects on ketamine-induced anesthesia (40.88 +/- 2.98 vs 70.32 +/- 4.64 min). Pretreatment with 3 mg cadmium/kg sc before 1 w caused a reduction in the potentiating effects of a 2nd dose of cadmium in ketamine-induced anesthesia in mice. These results indicate that prolongation of ketamine-induced anesthesia by cadmium and verapamil could be mediated either by inhibition of hepatic P450 metabolizing enzymes or neuronal calcium channels blockade. The tolerance to the potentiating effects of cadmium could be mediated by hepatic metallothionein induction and a reduction in total body cadmium burden.


Meta-analysis of the relationship between homocysteine, vitamin B₁₂, folate, and multiple sclerosis.
A meta-analysis was conducted to assess the relationship between serum homocysteine, vitamin B(12), and folate levels in patients with multiple sclerosis (MS). The DerSimonian and Laird Q test was used to evaluate the degree of heterogeneity between studies and a funnel plot was used to assess publication bias. The pooled effect size (standardized mean difference [SMD]) between patients with MS and control patients) from a random effects model was 0.84 (95% confidence interval: 0.18, 1.49) for homocysteine and -0.25 (-0.45, -0.04) for vitamin B(12), and from a fixed effects model was 0.98 (0.80, 1.16) for homocysteine and -0.25 (-0.41, -0.09) for vitamin B(12). Both nutrients were statistically significant, but the SMD for folate was not. Patients with MS were found to have raised homocysteine levels but low B(12) levels, which might contribute to the pathogenesis of MS.


Volunteerism, health, and civic engagement among older adults.
In North America, 40-50 per cent of older adults are actively involved as formal volunteers in providing diverse health and human services. We review empirical studies concerning older adults' motivations for volunteering, as well as the health and morale benefits they derive from this expression of altruism. Knowledge of the exact nature and amount of volunteer activity necessary to produce these effects is limited, and studies have yet to identify the behavioural and psychological mechanisms that are implicated. We propose that older adult volunteers may enjoy good health and longevity because being useful to others instills a sense of being needed and valued. We present several theoretical perspectives on the developmental significance of volunteering, discuss the challenges to volunteerism imposed by the baby boom cohort, and identify future research priorities.


Interleukin-1 and interleukin-1 antagonism in sepsis, systemic inflammatory response syndrome, and septic shock.
Interleukin-1 (IL-1) is one of several proinflammatory cytokines produced during infection, sepsis, and the systemic inflammatory response syndrome (SIRS) that serves to initiate the host inflammatory response and to integrate nonspecific immunity. Many of IL-1's biologic effects are beneficial to the host in times of stress, but when produced for extended periods of time or in excessive quantities, IL-1 contributes to morbidity and mortality. In fact, excessive IL-1 production has been directly linked to the development of hypotension, shock, multi-organ system failure, hematologic dyscrasia, and death in patients and animals with sepsis, SIRS, and septic shock. Recent research interest has focused on IL-1 inhibition to improve outcome in sepsis and septic shock. This article will review the role for IL-1 in sepsis and septic shock, and the function and status of the IL-1 receptors and IL-1 receptor antagonist in modulating IL-1 actions. The results of investigations of IL-1 inhibition in animal models and in human subjects with sepsis and septic shock will also be reviewed.


Esophageal tamponade in the treatment of bleeding varices. A decadel progress report.
Previous reports from this hospital in 1958 and 1967 have revealed that esophageal tamponade is a relatively dangerous type of treatment. Other investigators have been able to avoid many of the hazards of this technique. We have again assessed our results in 50 episodes of esophageal tamponade in bleeding esophageal varices in 39 patinets. Thirty-seven had alcoholic cirrhosis, one Wilson's disease, and one portal vein thrombosis. The diagnosis of variceal hemorrhage was established by endoscopy or angiography in virtually all. The great majority (86%) had had unsuccessful infusions of vasopressin previously. The Sengstaken-Blakemore tube (SBT) was used in 41 and the Linton tube (LT) in nine. Hemorrhage was controlled for at least 24 consecutive hours in 20 episodes (40%). Ninety percent of the patients died. Rupture of the esophagus following inflation of the gastric balloon in the esophagus caused three deaths (8%). Major nonfatal complications such as aspiration pneumonia occurred on five other occasions. Although the complications of esophageal tamponade were greatly reduced from our previous series, the efficacy of esophageal tamponade also decreased. There were no significant differences in the efficacy or complications of the SBT and LT. The high mortality and complication rates are still discouraging. We believe that the role of esophageal tamponade in the treatment of hemorrhage from varices is a secondary one.


Modifying illness beliefs in recent onset psychosis carers: Evaluating the impact of a cognitively focused brief group intervention in a routine service.
At first-episode psychosis (FEP), many patients will be routed within familial networks and supported by informal carers who are predominately close family members such as parents. Carer burden, distress and poorer coping styles are associated with different illness beliefs. The current study sought to examine the impact and acceptability of a 3 session, cognitively informed, group intervention targeting illness beliefs previously linked to distress and poorer caregiving experiences in FEP carers. Carers attending a routine FEP service were invited to attend the group intervention and completed a measure of illness beliefs at baseline and post intervention. Data on 68 carers with complete datasets are presented. Carers were predominately females (64.2%). Group attendance was linked to positive improvements in carer baseline beliefs about the negative consequences of the illness for the patient and themselves, attributions of blame about the illness to the patient and themselves and their overall understanding about the illness. Significant improvements in their understanding of the illness timeline and course, and confidence in dealing with difficulties were also identified. A cognitively informed group approach to targeting the less adaptive illness beliefs reported by FEP carers may offer an effective and acceptable pathway to facilitate their understanding of the illness and adjustment. Further studies using controlled designs are required.


Short communication: rearrangement of rumenic Acid in ruminant fats: a marker of thermal treatment.
Rumenic (cis-9,trans-11 18:2) acid is the main conjugated linoleic acid (CLA) isomer in milk and other ruminant fats. Anhydrous regular and high-CLA butterfats were heated at 200 degrees C for 2, 4, and 6 h under atmospheric conditions. [1,5] Sigmatropic isomerization of rumenic acid occurred, resulting in the formation of trans-8,cis-10 18:2 acid, as determined by mass spectrometry of its 4,4-dimethyloxazoline derivative. Rate of isomerization was monitored by gas-liquid chromatography, using a 120-m capillary column coated with 70% equivalent cyanoalkylpolysiloxane polymer, and reaction was of first order. Furthermore, [1,5] sigmatropic rearrangement product analysis can be used as an indicator of heat treatment of natural fats and oils containing CLA.


Management of Breast Deformity After Removal of Injectable Polyacrylamide Hydrogel: Retrospective Study of 200 Cases for 7 Years.
Polyacrylamide hydrogel (PAAG), once used as an injection for breast augmentation, has been banned in the medical field for cosmetic purposes for more than 10 years in China. But a large number of breasts have characteristic deformities due to the gel's feature of erosion. Our aim is to explore a retrospective study on PAAG's long-term effects on women, ensuing breast deformity and the strategy for breast plasticity after removing the gel in our center from 2007 to 2014. From 2007 to 2014, 200 patients, whose breasts were injected with PAAG, underwent the operation to remove the injectable material. Complications were summarized. Ultrasound or MRI was performed before the operation to disclose the general distribution of the gel and the muscle and gland infiltration. According to the gel distribution, muscle and gland infiltration, infection, gel residue, and other factors, the patients were treated, respectively, with or without prosthesis implantation surgery after the removal of the gel. According to the decision about whether or when to undergo prosthesis implantation, the patients were classified into three types: group I-prosthesis implantation at the first stage, group II-prosthesis implantation at the second stage, and group III-only removing the material without prosthesis implantation. The scores of the BREAST-Q program were used to evaluate the preoperative and postoperative differences. Seventy-seven patients underwent prosthesis implantation at the first stage and 61 patients were operated on by placing the prosthesis at the second stage. A total of 62 patients only underwent the PAAG removal operation. By BREAST-Q evaluation, changes are summarized in Tables 1, 2, and 3 between mean preoperative scores and mean postoperative scores through categories of satisfaction with appearance of breasts, psychosocial wellbeing, sexual wellbeing, and physical wellbeing, in which all categories were presented with statistical significance (p < 0.001). Table 1 Patient demographics General patient data Number Number of patients 200 Age range 25-48 Follow-up period 6-12 months Injection material Domestic material 84 (42 %) Imported material 93 (46.5 %) Domestic + imported 23 (11.5 %) Injection site Regular hospital 47 (23.5 %) Clinics 153 (76.5 %) Complication Inflammation 10 (2 %) Pain 75 (37.5 %) Induration 155 (77.5 %) Shift 50 (25 %) Deformation 17 (8.5 %) Bilateral asymmetry 48 (24 %) Deposition milk 2 (1 %) Psychological fear 150 (75 %) Systemic symptoms 34 (17 %) Single complication 25 (16.97 %) Two or more complications 160 (80 %) Preoperative aspiration 48 (24 %) Table 2 Group I-changes in mean preoperative scores and mean postoperative scores Category Preoperatively (n = 77) Postoperatively (n = 77) p Satisfaction with appearance of breasts 18.8 ± 16.2 81.6 ± 13.1 <0.001 Psychosocial wellbeing 39.5 ± 20.2 84.5 ± 19.3 <0.001 Sexual wellbeing 38.7 ± 23.1 77.2 ± 20.5 <0.001 Physical wellbeing 42.4 ± 16.3 81.7 ± 10.5 <0.001 Table 3 Group II-changes in mean preoperative scores and mean postoperative scores Category Preoperatively (n = 61) Postoperatively (n = 61) p Satisfaction with appearance of breasts 19.6 ± 15.3 82.5 ± 11.1 <0.001 Psychosocial wellbeing 38.9 ± 19.3 83.6 ± 20.1 <0.001 Sexual wellbeing 37.6 ± 22.4 79.3 ± 20.4 <0.001 Physical wellbeing 41.3 ± 15.1 82.2 ± 9.9 <0.001 CONCLUSIONS: Timely removal is critical for women who have received the PAAG removal operation. However, the surgery may destroy the shape of the breast. It is recommended that preoperative communication and local tissue condition are guidelines for surgeons to choose conservative or aggressive surgery. A balance must be maintained between removing the gel as much as possible and retaining soft tissue to reshape breasts. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Numerical investigation of explosion suppression by inert particles in straight ducts.
This paper is devoted to the mitigation of explosions in long galleries by means of an inert dust cloud. In practice, this technique bases on mounting shelves under the roof, on which the inert dust is distributed. This issue was numerically investigated in this research. The medium was assumed to be a two-phase mixture consisting of a fast flowing gas (representing the explosion) and a cloud of solid particles (representing the dust phase). The model makes use of the Eulerian-Lagrangian approach, where the solid particles are modelled as moving points, interacting with the gas flow. The objective was to analyse the suppression process and compare with experimental findings.


Spin pseudogap in Ni-doped SrCuO2.
The S=1/2 spin chain material SrCuO2 doped with 1% S=1 Ni impurities is studied by inelastic neutron scattering. At low temperatures, the spectrum shows a pseudogap Δ≈8 meV, absent in the parent compound, and not related to any structural phase transition. The pseudogap is shown to be a generic feature of quantum spin chains with dilute defects. A simple model based on this idea quantitatively accounts for the experimental data measured in the temperature range from 2 to 300 K, and allows us to represent the momentum-integrated dynamic structure factor in a universal scaling form.


Phorbol ester-stimulated T lymphocytes show enhanced adhesion to human endothelial cell monolayers.
Phorbol esters have been used to study changes in the adhesiveness of T cells to endothelial cells (EC) after activation. The phorbol esters 12-O-tetra-decanoylphorbol-13-acetate (TPA) and 4-beta-phorbol-12,13-dibutyrate (P(Bu)2), but not the biologically inert 4-alpha-phorbol-12,13-didecanoate, strongly increased the binding of 51Cr-labeled T cells to human umbilical vein EC monolayers in microtiter wells. Binding to fibroblasts and gelatin-coated plastic was also increased, but to a lesser extent. Increased binding was observed at 0.3 ng/ml, with maximal enhancement at 33 to 100 ng/ml. Enhancement occurred within 1 min, with maximal increase after 15 min. Preincubation studies with P(Bu)2 showed that binding enhancement was entirely attributable to an effect on T cells, with no action on EC. Additive binding enhancement was seen when phorbol esters and agents that alter adhesion by acting on EC (LPS, IL 1, or IFN-gamma) were used together. The increase in T cell adhesion to EC after T cell activation may contribute to the selective emigration of activated T cells from the blood into developing inflammatory lesions. The rapid increase in binding suggests that this may be an important mechanism for immediate localization of circulating T cells, particularly sensitized T cells, in the cellular immune response, perhaps involving the activation of these cells at the endothelial blood-tissue interface.


Oncocytic ependymoma: a new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells.
Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as "dot-like" staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of "zipper-like" intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.


Variable length tandem repeat polyglutamine sequences in the flexible tether region of the Tsr chemotaxis receptor of Escherichia coli.
Methyl-accepting chemotaxis proteins (MCPs) are receptors that play an important role in bacterial chemotaxis. Methylation of Tsr, the MCP that mediates chemotaxis towards serine in Escherichia coli, is thought to be facilitated by binding of the methyltransferase to a flexible tether region at the C-terminal end of Tsr. This study analysed natural length variants of the tether that occur in E. coli due to genetic instability in tandem repeat DNA sequences that code for glutaminyl (Q) residues, creating polyQ sequences of variable lengths in the tether region. The tsr gene of E. coli K-12 (strain MG1655) codes for 4Q at the beginning of its 35 aa tether region. The tether varies in length from 35 to 47 residues among pathogenic and non-pathogenic strains of Escherichia, Shigella spp., Salmonella, Yersinia and Photorhabdus. Among previous sequences, Escherichia and Shigella mostly have 4Q and 7Q variants, and one strain (E. coli HS) has 10Q. In E. coli isolated from 50 humans and 75 animals (dogs, cats, horses, birds, etc.), polyQ up to 13Q (44 aa tether) were identified (6 strains); relative frequencies were 7Q ( approximately 77 % of the total) >4Q (14 %) >13Q (5 %) >10Q (4 %). Phylogenetic analysis revealed that E. coli strains with 10Q or 13Q largely fell within two clusters. Serine chemotaxis was not significantly different among 7Q, 10Q and 13Q strains, and was comparable to chemotaxis in the frequently studied K-12 strain. These results are consistent with models indicating that polyQ sequences from 7Q to 13Q are flexible, and that longer tethers, within this range, would not change the precision of adaptation mediated by methylation. Studies of this naturally variable polyQ region in E. coli may also have relevance to mechanisms that mediate polyQ instability in human genetic diseases.


Over-expression of tau results in defective synaptic transmission in Drosophila neuromuscular junctions.
We have shown that over-expression of human tau (0N3R) in Drosophila larval motor neurons causes significant morphological and functional disruption to the neuromuscular junctions (NMJs). Tau-expressing NMJs are reduced in size with irregular and abnormal bouton structure. Immunocytochemical analysis shows that the abnormal NMJs still retain synaptotagmin expression and form active zones. Functionally, the NMJs exhibit abnormal endo/exocytosis as revealed by incorporation of the styryl dye FM1-43. Electrophysiological studies showed that with low frequency stimulation (1 Hz), evoked synaptic potentials produced from tau over-expressing motor neurons were indistinguishable from wild type, however, following high frequency stimulation (50 Hz), evoked synaptic potentials were significantly decreased. Analysis of the number and distribution of mitochondria showed that motor neurons over-expressing tau had a significant reduction in functional mitochondria in the presynaptic terminal. Collapsing the mitochondrial membrane potential in wild type larvae phenocopied the effects of tau over-expression on synaptic transmission. Our results demonstrate that tau over-expression in vivo cause a synaptic dysfunction, which may be caused by a reduced complement of functional mitochondria.


Fecal incontinence, sexual complaints, and anorectal function after third-degree obstetric anal sphincter injury (OASI): 5-year follow-up.
Our aim was to evaluate alterations in anorectal function after anal sphincteroplasty for third-degree obstetric anal sphincter injury (OASI) in relation to clinical outcome. In this retrospective, descriptive, cross-sectional study conducted between 1998 and 2008, women with persisting fecal incontinence (FI) after 3a OASI and all women with grade 3b or 3c OASI were sent for anorectal function evaluation (AFE) consisting of anal manometry and endosonography 3 months after sphincteroplasty. In 2011, questionnaires regarding FI (Vaizey/Wexner), urinary incontinence (UI) [International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)], sexual function [Female Sexual Function Index (FSFI)], and quality of life (QOL) (Rand-36) were sent and women were asked to undergo additional AFE. Sixty-six women underwent AFE. Mean follow-up was 5.0 years. Forty (61%) patients returned questionnaires regarding FI and UI. Prevalence of FI was 63% flatus, 50% liquid stool, and 20% solid stool. Thirty-two of 40 also reported on QOL and SF. Sexual dysfunction was present in the majority of women (cutoff value 26.55) and more pronounced in larger OASI. Sixteen of 40 women underwent additional AFE. Women with combined internal (IAS) and external (EAS) anal sphincter injury (n = 6) had worse FI (P < 0.050) and lower anal pressures (P = 0.040) than women with isolated EAS injury (n = 10). Follow-up after third-degree OASI suggests poor anorectal and sexual function. Women with combined external and internal OASI show more deterioration in anorectal function and experience worse FI. Therefore, special attention should be paid to these women in order to mitigate these symptoms later in life.


Effects of unilateral flocculus lesions on vestibulo-ocular responses in the cat.
Unilateral lesions of the cerebellar flocculus were performed in three chronically-implanted adult cats. Following the lesion a spontaneous nystagmus was observed in the dark, with the fast phase directed to the lesioned side. Vestibulo-ocular responses in the dark became asymmetrical. Responses to velocity steps exciting the labyrinth ipsilateral to the lesion were strongly increased. A decrease, although less marked, was observed in the opposite direction. Responses to sinusoidal oscillations in the dark were also asymmetric with respect to both the cumulative eye displacement during rotation in the two directions and the interval between two consecutive reversals of eye movement. These differences were greater at the lower tested frequencies (0.01 HZ) than at the higher (0.1 HZ). Spontaneous nystagmus disappeared in about 10 days and a complete symmetry of the vestibulo-ocular responses was restored in about 3 weeks. It is concluded that a unilateral lesion of the flocculus leads to two separate, but interacting, effects upon vestibulo-ocular responses.


Detection of delayed cerebral ischemia using objective pupillometry in patients with aneurysmal subarachnoid hemorrhage.
OBJECTIVECerebral vasospasm causing delayed cerebral ischemia (DCI) is a source of significant morbidity after subarachnoid hemorrhage (SAH). Transcranial Doppler is used at most institutions to detect sonographic vasospasm but has poor positive predictive value for DCI. Automated assessment of the pupillary light reflex has been increasingly used as a reliable way of assessing pupillary reactivity, and the Neurological Pupil Index (NPi) has been shown to decrease hours prior to the clinical manifestation of ischemic injury or herniation syndromes. The aim of this study was to investigate the role of automated pupillometry in the setting of SAH, as a potential adjunct to TCD.METHODSOur analysis included patients that had been diagnosed with aneurysmal SAH and admitted to the neuro-intensive care unit of the University of Texas Southwestern Medical Center between November 2015 and June 2017. A dynamic infrared pupillometer was used for all pupillary measurements. An NPi value ranging from 3 to 5 was considered normal, and from 0 to 2.9 abnormal. Sonographic vasospasm was defined as middle cerebral artery velocities greater than 100 cm/sec with a Lindegaard ratio greater than 3 on either side on transcranial Doppler. Most patients had multiple NPi readings daily and we retained the lowest value for our analysis. We aimed to study the association between DCI and sonographic vasospasm, and DCI and NPi readings.RESULTSA total of 56 patients were included in the final analysis with 635 paired observations of daily TCD and NPi data. There was no statistically significant association between the NPi value and the presence of sonographic vasospasm. There was a significant association between DCI and sonographic vasospasm, χ2(1) = 6.4112, p = 0.0113, OR 1.6419 (95% CI 1.1163-2.4150), and between DCI and an abnormal decrease in NPi, χ2(1) = 38.4456, p < 0.001, OR 3.3930 (95% CI 2.2789-5.0517). Twelve patients experienced DCI, with 7 showing a decrease of their NPi to an abnormal range. This change occurred > 8 hours prior to the clinical decline 71.4% of the time. The NPi normalized in all patients after treatment of their vasospasm.CONCLUSIONSIsolated sonographic vasospasm does not seem to correlate with NPi changes, as the latter likely reflects an ischemic neurological injury. NPi changes are strongly associated with the advent of DCI and could be an early herald of clinical deterioration.


Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens.
Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.


Assessing the corneal power change after refractive surgery using Scheimpflug imaging.
To investigate whether the Pentacam HR could accurately predict the surgically induced refractive change in patients operated with small-incision lenticule extraction (SMILE) for myopia or femto-second laser in situ keratomileusis (FS-LASIK) for myopia or hyperopic astigmatism. Data from three groups consisting of (1) 410 myopic eyes of 410 patients operated with SMILE, (2) 111 myopic eyes of 111 patients operated with FS-LASIK, and (3) 40 eyes of 40 patients with hyperopic astigmatism operated with FS-LASIK were retrospectively analysed. The change in manifest refraction due to surgery was compared with the objectively measured change in corneal power by the Pentacam HR in three different ways: Sagittal Power (calculated as for placido topographers), True Net Power (calculated by a Gaussian optics formula), and Total Corneal Refractive Power (calculated by ray tracing). Multiple linear regression analysis was performed to investigate which parameters influenced the Pentacam HR's prediction of the change in subjective refraction due to surgery. The Total Corneal Refractive Power Apex, Zone calculation in a diameter of 4.0 mm effectively predicted the surgically induced refractive change for all three patient groups. The spherical equivalent was predicted with an error of 0.08 ± 0.41 D for the SMILE eyes, 0.05 ± 0.61 D for the myopic eyes operated with FS-LASIK, and -0.15 ± 0.49 D for the hyperopic astigmatic eyes treated with FS-LASIK. Regression showed that preoperative refractive error had a significant impact on the prediction error of the Pentacam HR. Ray tracing calculations based on Scheimpflug imaging accurately assessed the change in manifest refraction due to corneal laser surgery.


Substrate and product trafficking through the active center gorge of acetylcholinesterase analyzed by crystallography and equilibrium binding.
Hydrolysis of acetylcholine catalyzed by acetylcholinesterase (AChE), one of the most efficient enzymes in nature, occurs at the base of a deep and narrow active center gorge. At the entrance of the gorge, the peripheral anionic site provides a binding locus for allosteric ligands, including substrates. To date, no structural information on substrate entry to the active center from the peripheral site of AChE or its subsequent egress has been reported. Complementary crystal structures of mouse AChE and an inactive mouse AChE mutant with a substituted catalytic serine (S203A), in various complexes with four substrates (acetylcholine, acetylthiocholine, succinyldicholine, and butyrylthiocholine), two non-hydrolyzable substrate analogues (m-(N,N,N-trimethylammonio)-trifluoroacetophenone and 4-ketoamyltrimethylammonium), and one reaction product (choline) were solved in the 2.05-2.65-A resolution range. These structures, supported by binding and inhibition data obtained on the same complexes, reveal the successive positions and orientations of the substrates bound to the peripheral site and proceeding within the gorge toward the active site, the conformations of the presumed transition state for acylation and the acyl-enzyme intermediate, and the positions and orientations of the dissociating and egressing products. Moreover, the structures of the AChE mutant in complexes with acetylthiocholine and succinyldicholine reveal additional substrate binding sites on the enzyme surface, distal to the gorge entry. Hence, we provide a comprehensive set of structural snapshots of the steps leading to the intermediates of catalysis and the potential regulation by substrate binding to various allosteric sites at the enzyme surface.


Effects of hibernation on mitochondrial regulation and metabolic capacities in myocardium of painted turtle (Chrysemys picta).
Painted turtles hibernating during winter may endure long-term exposure to low temperature and anoxia. These two conditions may affect the aerobic capacity of a tissue and might be of particular importance to the cardiac muscle normally highly reliant on aerobic energy production. The present study addressed how hibernation affects respiratory characteristics of mitochondria in situ and the metabolic pattern of turtle myocardium. Painted turtles were acclimated to control (25 degrees C), cold (5 degrees C) normoxic and cold anoxic conditions. In saponin-skinned myocardial fibres, cold acclimation increased mitochondrial respiratory capacity and decreased apparent ADP-affinity. Concomitant anoxia did not affect this. Creatine increased the apparent ADP-affinity to similar values in the three acclimation groups, suggesting a functional coupling of creatine kinase to mitochondrial respiration. As to the metabolic pattern, cold acclimation decreased glycolytic capacity in terms of pyruvate kinase activity and increased lactate dehydrogenase (LHD) activity. Concomitant anoxia counteracted the cold-induced decrease in pyruvate kinase activity and increased creatine kinase activity. In conclusion, cold acclimation seems to increase aerobic and decrease anaerobic energy production capacity in painted turtle myocardium. Importantly, anoxia does not affect the mitochondrial functional integrity but seems to increase the capacity for anaerobic energy production and energy buffering.


A first survey of organized cervical cancer screening programs in Italy. GISCi working group on organization and evaluation. Gruppo Italiano Screening Citologico.
In Italy, where no national screening program for cervical cancer exists, organized programs have developed on a local basis. We performed the first survey of existing organized programs by mailing a standard questionnaire to a large network of possibly involved services. For the present survey, a program was defined as organized if personal invitations were sent. We identified 29 already active organized programs and 4 others in a starting phase. The target population of active programs included 2,074,820 women in the age range 25-64 years, corresponding to 13.5% of the Italian female population of the same age. The situation is rapidly evolving since many regional programs are being implemented. Most programs followed Italian and European recommendations as regards the age limits, interval between screening rounds, presence of a fail-safe system for women referred for colposcopy, presence of protocols for diagnostic workup and treatment, and presence of referral centers for such phases. However, many programs did not meet national guidelines as regards the size of laboratories interpreting smears, which were frequently small. Second-level referral centers also frequently had a very small activity. The average (weighted for size of the invited population) compliance to invitation and coverage (proportion of women with at least one test in the last 3 years) was 32.6% and 66.0%, respectively, therefore needing to be improved. Compliance to colposcopy (weighted for number of referred women) was 81.4%. We found a very high variability in the proportion of women referred for colposcopy that could only be partly explained by different referral protocols and could depend on different criteria of smear interpretation: the average (weighted for number of tested women) was 2.01%. A need for improvement in the process of evaluation and for homogenization of criteria of cytology interpretation was identified: work in this regard is on-going.


Half-metallicity in zigzag phosphorene nanoribbons with magnetic edges.
Phosphorene nanoribbons with magnetic edges are potentially attractive for nanoelectronic and spintronic applications. Here, the attention is focused on electronic and magnetic properties of these materials. Using a self-consistent computational method it is shown that, in general, two types of configuration with spontaneous edge magnetization can be responsible for lifting the spin degeneracy, and consequently for the appearance of the half-metallic behavior. Namely, in addition to the well-known configuration with edge states ferromagnetically coupled along each edge and aligned in parallel between the two edges, there is another one (much less explored) with edge states ferromagnetically aligned on only one edge. The ground state magnetic configurations strongly depend on the chemical potential position (electron filling factor), and can be controlled by means of the external perpendicular gate voltage, and by changing the nanoribbon width. It is also shown that the magnetic edge configurations responsible for the half-metallicity can be stabilized with ferromagnetic substrates, due to the proximity effect.


Darwinian aesthetics: sexual selection and the biology of beauty.
Current theoretical and empirical findings suggest that mate preferences are mainly cued on visual, vocal and chemical cues that reveal health including developmental health. Beautiful and irresistible features have evolved numerous times in plants and animals due to sexual selection, and such preferences and beauty standards provide evidence for the claim that human beauty and obsession with bodily beauty are mirrored in analogous traits and tendencies throughout the plant and animal kingdoms. Human beauty standards reflect our evolutionary distant and recent past and emphasize the role of health assessment in mate choice as reflected by analyses of the attractiveness of visual characters of the face and the body, but also of vocal and olfactory signals. Although beauty standards may vary between cultures and between times, we show in this review that the underlying selection pressures, which shaped the standards, are the same. Moreover we show that it is not the content of the standards that show evidence of convergence--it is the rules or how we construct beauty ideals that have universalities across cultures. These findings have implications for medical, social and biological sciences.


Determination of lead, cadmium and copper in roadside soil and plants in Elazig, Turkey.
The concentrations of lead, cadmium and copper in roadside soil and plants in Elazig, Turkey were investigated. Soil samples were collected at distances of 0, 25 and 50 m from the roadside. The concentrations of lead, cadmium and copper were measured by Flame Atomic Absorption Spectrophotometry (FAAS). A slotted tube atom trap (STAT) was used to increase the sensitivity of lead and cadmium in FAAS. Lead concentrations in soil samples varied from 1.3 to 45 mg kg(-1) while mean lead levels in plants ranged from120 ng g(-1) for grape in point-4 to 866 ng g(-1) for apple leaves in point-2. Lead analyses showed that there was a considerable contamination in both soil and plants affected from traffic intensity. Overall level of Cd in soil samples lies between 78 and 527 ng/g while cadmium concentration in different vegetations varied in the range of 0.8-98.0 ng g(-1). Concentrations of copper in soil and plant samples were found in the range of 11.1-27.9 mg kg(-1) for soil and 0.8-5.6 mg kg(-1) for plants. Standard reference material (SRM) was used to find the accuracy of the results of soil analyses.


Negative priming: a meta-analysis of fMRI studies.
A phenomenon termed negative priming is defined as an increase in reaction time and/or decrease in performance during instances in which current target stimuli are employed as distractor stimuli in the previous trial. A recent qualitative review on negative priming reported neural regions of interest underlined by activity within the right middle frontal gyrus and left middle temporal gyrus; however, these areas of interest have not been tested and supported by using coordinate-based, quantitative meta-analysis. We compiled functional magnetic resonance imaging studies that examined neural correlates of priming tasks using perceptual, conceptual and lexical primes. Effect-size signed differential mapping was used to perform a neuroimaging meta-analysis on the negative priming effect. Results from fourteen studies (245 participants; 85 foci) show concordance across studies in the right middle frontal gyrus and the left superior temporal gyrus, as suggested by the previous review; however, results also yielded concordance within the anterior cingulate cortex. Our data support the extant hypothesis and offer new insights into the neural mechanisms of the negative priming effect.


Renal protective effect and action mechanism of Huangkui capsule and its main five flavonoids.
The flower of Abelmoschus manihot (Linn.) Medicus (A. manihot), as a traditional Chinese Herbal medicine, was used widely in China with efficacy of inducing diuresis for treating strangurtia, and subdhing swelling and detoxicating. It has been reported that Huangkui capsule, prepared by the extract of the flower of A. manihot, can reduce the content of urinary protein, serum creatinine and serum urea nitrogen in nephropathy rats and processes renoprotective activity, while the action mechanism need to illuminate deeply. In this study, we investigated the protection effect of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF) rats and its mechanism against high glucose-induced epithelial to mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive components. The animals were divided into normal group, CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue of different groups. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. HK-2 cell damaged model was established to access the protection effect and action mechanism of five main flavonoids from Huangkui capsule. The experimental cells were divided into eight groups: control group, model group, positive drug group and five main flavonoids treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) in different groups. Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups. The results stated that Huangkui capsule significantly inhibited the elevation of Scr, BUN, UP, the expression of α-smooth muscle actin (α-SMA), phosphorylation-extracellular signal-regulated kinase (p-ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY), isoquercitrin (IQT), gossypetin-8-O-β-D-glucuronide (GG) and quercetin-3'-O-glucoside (QG) at the dosage of 100µM, like NADPH oxidase inhibitor diphenyleneiodonium, exhibited a significant effect on inhibiting the expression of α-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in high glucose-induced HK-2 cells, especially GG. These results demonstrated that Huangkui capsule and the flavonoids components prevent tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of inhibiting NADPH oxidase/ROS/ERK pathway.


Human rights and health disparities for migrant workers in the UAE.
Systematic violations of migrant workers' human rights and striking health disparities among these populations in the United Arab Emirates (UAE) are the norm in member countries of the Gulf Cooperation Council (GCC). Migrant laborers comprise about 90 percent of the UAE workforce and include approximately 500,000 construction workers and 450,000 domestic workers. Like many other GCC members countries, the UAE witnessed an unprecedented construction boom during the early 2000s, attracting large numbers of Western expatriates and increasing demand for cheap migrant labor. Elite Emiratis' and Western expatriates' dependence on household staff further promoted labor migration. This paper offers a summary of existing literature on migrant workers and human rights in the UAE, focusing on their impact on related health ramifications and disparities, with specific attention to construction workers, domestic workers, and trafficked women and children. Construction workers and domestic laborers are victims of debt bondage and face severe wage exploitation, and experience serious health and safety problems resulting from inhumane work and living conditions. High rates of physical, sexual, and psychological abuse impact the health of domestic workers. Through a review of available literature, including official reports, scientific papers, and media reports, the paper discusses the responsibility of employers, governments, and the global community in mitigating these problems and reveals the paucity of systematic data on the health of migrant workers in the Gulf.


Irrelevant peripheral visual stimuli impair manual reaction times in Parkinson's disease.
In three experiments, the effects of irrelevant visual information on the time to initiate and to complete a simple movement of the hand in response to a visual signal were studied in patients with a diagnosis of Parkinson's disease, and in age-matched normal controls. Subjects gazed at the centre of a TV monitor and were instructed to move their preferred hand from one metal plate to another as soon as a blue disc appeared in the centre of the screen. This control condition was compared with other conditions in which the surrounding area of the screen was simultaneously filled with fields of irrelevant discs, which in Experiment 1 were either stationary, or streamed out from or in towards the centre of the screen. Reaction times, but not movement times, were significantly slowed in the patients (but not the controls) by the irrelevant disc fields. When the irrelevant dots were continuously present (between as well as within trials--Experiment 2), they had no effect on RT. When they were present between trials, but turned off as the movement signal was turned on, RT was again slowed in patients. The results are discussed in relation to the akinesia ("freezing") experienced by some patients in confined spaces (such as doorways), and to possible abnormalities of visual cortical and striato-nigro-collicular activity.


What has become of the psychotherapy of schizophrenia?
The psychotherapy of schizophrenia has undergone major changes in the past two generations and mirrors larger paradigmatic shifts in thinking about severe mental illness and its treatment. Despite being endangered acutely by fiscal crises in our current health care systems, the psychotherapy of schizophrenia continues to evolve in a healthy manner as advances are made in our understanding of schizophrenia.


Cognitive function--victim of disease or hostage to treatment?
In persons suffering from epilepsy, cognitive functioning may be compromised for various reasons, including--first and foremost--the learning and behavioral effects of the conditions causing the epilepsy. In addition, the epilepsy itself may cause changes in the nervous system through the metabolic and excitotoxic effects of the seizures and the neurotransmitter elements involved at the membrane level. The effect of the treatment modality, be it pharmacologic or surgical, may also play havoc with cognitive function. The neurobehavioral effects of antiepileptic drugs, although probably less important with the newer agents than in the past, must be considered, especially in polypharmacy, as recent reports have indicated. With increasing data, the effects of various surgical procedures on the cognitive elements of human behavior are becoming better recognized.


Peer-led, school-based nutrition education for young adolescents: feasibility and process evaluation of the TEENS study.
Peer education has become a popular strategy for health promotion interventions with adolescents, but it has not been used widely in school-based nutrition education. This paper describes and reports on the feasibility of the peer leader component of a school-based nutrition intervention for young adolescents designed to increase fruit and vegetable intakes and lower fat foods. About 1,000 seventh-grade students in eight schools received the nutrition intervention. Of these, 272 were trained as peer leaders to assist the teacher in implementing the activities. Results from a multicomponent process evaluation based on peer leader and classroom student feedback, direct classroom observation, and teacher ratings and interviews are presented. Results show that peer-led nutrition education approaches in schools are feasible and have high acceptability among peer leaders, classroom students, and teachers.


["Protect the next generation": promote the end of female genital mutilation in the Kayes health district in Mali].
Female genital mutilation (FGM) comprises all procedures that involve partial or total removal of the external female genitalia, or other injury to the female genital organs for non-medical reasons. FGM is not just a public health problem, but a violation of the human rights of girls and women. Equilibres & Populations and AMSOPT are developing a pilot project designed to promote abandonment of FGM in the Kayes health district by demonstrating that social change is possible and reproducible. The strategy is based on the organized diffusion of change among communities linked by marital ties. The communication process is based on promotion of health and human rights. The project collaborates with political and social actors so that they can take charge of the ongoing changes. The project also works in France with migrants from villages involved in these interventions because they also have an important role to play. Evaluation of the results showed that 80 of the 250 villages of the district declared abandonment of FGM. A positive debate is emerging in the communities, but messages must be repeated. The response of the health system has been reinforced, as 1328 women received medical care for complications of excision. The project now needs to be further developed in order to achieve its goals. Although the search for funding has been an obstacle, the acquisition of pluriannual funds will provide greater flexibility in management of the project. Beyond abandonment of FSM, the project also wants to reinforce the status and health of women and give them the possibilities to defend their rights.


Assessment of the anticholinergic effects of antidepressants in a single-dose cross-over study of salivation and plasma levels.
In order to evaluate the anticholinergic effect of antidepressant drugs, 11 healthy volunteers were given single oral doses of reference drug, test drugs or placebo on a double-blind basis at weekly intervals. The doses corresponded to average daily patient medications. Spontaneous whole mouth and parotid salivation, and plasma levels of drug and possible metabolites were measured 2, 6 and 10 h after drug administration. Moderate, statistically significant inhibition of salivation was found when nortriptyline, imipramine-N-oxide and mianserin were given. Less pronounced, but still statistically significant inhibition occurred after ingestion of nomifensine and zimelidine. The zimelidine effect was exclusively due to the metabolite norzimelidine, and the inhibition after imipramine-N-oxide was mainly due to the metabolite imipramine, but imipramine-N-oxide itself also had slight activity. Isocarboxazide and lithium had no effect on salivation. From these results and reported values of pharmacokinetic variables, the average level of anticholinergic activity during long-term treatment may be predicted: for mianserin and (nor-)zimelidine moderate inhibition of salivation, although less pronounced than with nortriptyline; for nomifensine no clinically significant effect; and for imipramine-N-oxide a negligible contribution from the unmetabolized drug.


Subarachnoid hemorrhage as the initial presentation of cerebral venous thrombosis.
Cerebral venous thrombosis presenting as subarachnoid hemorrhage (SAH) is very rare. We present a woman with thrombosis of the superior sagittal, straight, transverse and sigmoid sinuses who presented with SAH in the right temporal sulcus and bilateral cerebellar sulci. Brain perfusion CT demonstrated a delay of the mean transit time and high cerebral blood volume around the right posterior temporal lobe and cerebellum. These findings were compatible with venous congestion and they suggest the possibility that extension of the dural sinus thrombosis into the superficial veins caused localized venous hypertension with dilatation of the thin, fragile-walled cortical veins which eventually ruptured into the subarachnoid space.


The IWGT in vitro Mammalian Cell Gene Mutation (MCGM) assays working group-Introductory remarks & consensus statements.
Assays for gene mutations in cultured mammalian cells, i.e., Mammalian Cell Gene Mutation (MCGM) assays, are widely used in genetic toxicology laboratories worldwide; over the past four decades they have been commonly employed in safety assessment studies, and studies designed to address hypothesis-driven research questions. Despite many advances in the fields of cellular and molecular biology over the past four decades, the MCGM assays commonly used for regulatory evaluations continue to be those developed in the 1970s, including assays that enumerate induced mutations at the hprt or tk loci of several commonly used cell lines. Consequently, the Steering Committee of the 7th International Workshops on Genotoxicity Testing (IWGT) convened a working group (WG) to critically assess the state-of-the-science in regards to the current and emerging tools for the detection of mutagens using cultured mammalian cells. The WG was divided into four sub-groups that evaluated the state-of- the-science with respect to the: (1) in vitro Pig-a gene mutation assay, (2) in vitro assays based on cells from transgenic rodents, (3) technologies and innovations to improve MCGM assays using TK6 cells, and (4) novel and emerging technologies and approaches for detection and enumeration of gene mutations in mammalian cells. Each of these sub-groups critically reviewed the scientific literature, along with other unpublished data, to develop consensus statements on the status of the test systems in their respective focus areas. These reviews, with their associated consensus statements, are presented in the accompanying works by Bemis and Heflich., White et al., Honma et al., and Evans et al. The MCGM assay WG, in consultation with the entire IWGT, formulated consensus statements regarding the overall utility of MCGM assays for identification and assessment of mutagenic hazard.


Optically switchable transistor via energy-level phototuning in a bicomponent organic semiconductor.
Organic semiconductors are suitable candidates for printable, flexible and large-area electronics. Alongside attaining an improved device performance, to confer a multifunctional nature to the employed materials is key for organic-based logic applications. Here we report on the engineering of an electronic structure in a semiconducting film by blending two molecular components, a photochromic diarylethene derivative and a poly(3-hexylthiophene) (P3HT) matrix, to attain phototunable and bistable energy levels for the P3HT's hole transport. As a proof-of-concept we exploited this blend as a semiconducting material in organic thin-film transistors. The device illumination at defined wavelengths enabled reversible tuning of the diarylethene's electronic states in the blend, which resulted in modulation of the output current. The device photoresponse was found to be in the microsecond range, and thus on a technologically relevant timescale. This modular blending approach allows for the convenient incorporation of various molecular components, which opens up perspectives on multifunctional devices and logic circuits.


Multiple dose vaccination with heterologous H5N2 vaccine: immune response and protection against variant clade 2.2.1 highly pathogenic avian influenza H5N1 in broiler breeder chickens.
Circulation of an antigenically variant lineage of highly pathogenic avian influenza (HPAI) H5N1 virus in chicken breeder flocks in Egypt is a continuing problem. The protective efficacy of multiple repeated vaccinations using the currently available H5N2 vaccines is unclear. Here, broiler breeder chickens were vaccinated at weeks 6, 12 and 18 with an inactivated H5N2 commercial vaccine. HI-titer against an Egyptian H5N1 field isolate of classic clade 2.2.1 (EGYcls/H5N1) were significantly lower after the first immunization but increased after booster vaccinations. In contrast, no HI titers were induced against an antigenically distinct field virus of the variant lineage of clade 2.2.1 (EGYvar/H5N1). Upon challenge at week 50 mild, if any, clinical signs were observed in the group infected with EGYcls/H5N1 although one of eight (12.5%) birds died. Mortality reached 6/8 (75%) in the EGYvar/H5N1 challenge group. Virus excretion in all vaccinated groups was reduced in amplitude, but in vaccinated surviving birds, time of virus excretion was extended to up to ten days. Strikingly, challenged vaccinated birds kept laying eggs almost throughout the observation period. Virus was detected on the outer egg-shell of 17 of 40 eggs. The majority of the infected eggs were derived from the EGYcls/H5N1 challenged animals; here the virus was detected also in the yolk and albumin. Repeated vaccination using a commercial H5N2-based vaccine broadened the antigen profile of induced antibodies but did not provide adequate protection against heterologous virus variant. In addition, the observation of AIV contaminated eggs from infected flocks highlights the risk of silent virus spread by vaccinated animals and point to eggs as a possible vector.


A problem with refusing certain forms of psychiatric treatment.
Certain affective disorders are associated with compromised cognitive and emotional capacities and thus, with one's ability to act as a fully autonomous individual. Some of these personality problems have been treated very successfully with specified drug regimes. Continued treatment with lithium has rendered previously incompetent manic patients fully capable of competent self-governance. If the competent have the right to refuse medical attention (even when the refusal is not in the patient's best interest) does the drug-induced competent psychiatric patient have the right to refuse that medical treatment necessary for his continued competency? This paper investigates this issue.


Partogram use in the Dar es Salaam perinatal care study.
To assess the quality of partograms used to monitor labor in Dar es Salaam hospitals, Tanzania. The study team reviewed the records of the parameters of labor, and maternal and fetal conditions in 367 partograms, and interviewed 20 midwives. All midwives interviewed had been previously trained to use the partogram. Of all partograms reviewed, 50% had no records of duration of labor. Although cervical dilation and fetal heart rates were recorded in 97% and 94% of the partograms respectively, 63% and 91% of these were judged to be substandard. Substandard monitoring of fetal heart rates was strongly associated with poor fetal outcome (P<0.001). Blood pressure, temperature, and pulse rates were not recorded in 47%-76% of partograms. These findings reflect poor management of labor and indicate urgent in-service training to address the importance of documentation and regular partogram audit in order to reduce maternal and perinatal deaths.


Histochemical detection of carbohydrates of Blastocystis hominis.
The carbohydrates of Blastocystis hominis were detected by histochemical techniques using light and electron microscopy. B. hominis, fixed with various fixatives, followed by treatment with detergents, were stained with periodic acid-Schiff (PAS) or alcian blue (AB). Intense PAS reactions were observed in cells fixed with glutaraldehyde or 1/2 Karnovsky fixative. The cells fixed with other fixatives showed weak or no reactions with PAS staining. Similar results were seen in the case of AB stain. These results indicated that, depending on the fixative used, B. hominis contained PAS- or AB-reactive carbohydrates. At the electron microscopic level, ultrathin sections of B. hominis were stained with periodic acid methenamine silver (PA-MS) or periodic acid thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining techniques. Intense, positive reactions with PA-MS or PA-TCH-SP were observed on the central vacuole, Golgi apparatus, and cytoplasmic vesicles. The filamentous layer showed moderate reactions with PA-MS, whereas in PA-TCH-SP stain, it was stained more densely. The staining intensity of the central vacuole varied from cell to cell. The presence of membrane fusions of the cytoplasmic vesicles with the central vacuole indicated the accumulation of carbohydrates in the central vacuole.


Direct protein sequencing of wheat mitochondrial ATP synthase subunit 9 confirms RNA editing in plants.
RNA editing, a process that results in the production of RNA molecules having a nucleotide sequence different from that of the initial DNA template, has been demonstrated in several organisms using different biochemical pathways. Very recently RNA editing was described in plant mitochondria following the discovery that the sequence of certain wheat and Oenothera cDNAs is different from the nucleotide sequence of the corresponding genes. The main conversion observed was C to U, leading to amino acid changes in the deduced protein sequence when these modifications occurred in an open reading frame. In this communication we show the first attempt to isolate and sequence a protein encoded by a plant mitochondrial gene. Subunit 9 of the wheat mitochondrial ATP synthase complex was purified to apparent homogeneity and the sequence of the first 32 amino acid residues was determined. We have observed that at position 7 leucine was obtained by protein sequencing, instead of the serine predicted from the previously determined genomic sequence. Also we found phenylalanine at position 28 instead of a leucine residue. Both amino acid conversions, UCA (serine) to UUA (leucine) and CUC (leucine) to UUC (phenylalanine), imply a C to U change. Thus our results seem to confirm, at the protein level, the RNA editing process in plant mitochondria.


The effect of motilin agonist ABT-229 on gastro-oesophageal reflux, oesophageal motility and lower oesophageal sphincter characteristics in GERD patients.
ABT-229, a motilin agonist without antibacterial activity, has been shown to enhance both lower oesophageal sphincter pressure in cats and gastric emptying in humans. To investigate the effect of oral treatment with ABT-229 10 mg b.d., ABT-229 5 mg b. d. and cisapride 10 mg q.d.s. on gastro-oesophageal reflux, lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations and symptoms in GERD patients. Twenty-four GERD patients completed the study. A randomized, double-blind, placebo-controlled, three-period incomplete crossover design was used with three dosing periods of 7 days. All patients received ABT-229 10 mg b.d. and placebo during two of the three periods. In the remaining period 12 patients were given ABT-229 5 mg b.d. and 12 received cisapride 10 mg q.d.s. Ambulatory 24 h recordings of oesophageal pH and pharyngeal, oesophageal, lower oesophageal sphincter and gastric pressures were performed on day 7 using an assembly incorporating a Dent sleeve connected to a portable water-perfused manometric system. Oesophageal acid exposure was not affected by ABT-229 or cisapride, but the incidence of reflux episodes was reduced by cisapride. None of the drugs affected oesophageal motility, lower oesophageal sphincter pressure or the incidence of transient lower oesophageal sphincter relaxations. Both ABT-229 10 mg b.d. and cisapride reduced the severity of daytime heartburn. The value of ABT-229 in the treatment of GERD appears to be limited.


Retinopathy of prematurity occurrence and evaluation of screening policy in a large tertiary Greek cohort.
To assess the frequency of retinopathy of prematurity (ROP) and evaluate the appropriateness of screening guidelines in a tertiary hospital in Thessaloniki, Greece. Retrospective review of consecutive infants admitted to the IInd Department of the Neonatal Care Unit of Aristotle University in the period April 2004-2015. ROP screening took place according to the Royal College of Paediatrics and Child Health and Royal College of Ophthalmologists (UK) guidelines [i.e. gestational age < 32 weeks and/or birth weight < 1501 g)], plus a few additional cases due to comorbidity. 1178 out of the 8782 admitted infants underwent ROP screening. ROP was detected in 232 (19.7%) infants of whom 87 developed severe form of the disease (i.e. ≥ stage 3). Treatment was required in 30 (2.5%) infants, all of whom fulfilled the screening criteria. Two of the 206 infants who were additionally screened due to comorbidity developed severe ROP which regressed spontaneously. Disease regression was achieved in 27/29 (93%) treated infants who survived. The frequency of ROP observed in this cohort was as low as that reported in other developed countries. The currently used screening criteria permitted identification of all infants who were at risk and, therefore, need not be changed.


The assessment of diffuse pollution from acid-mine drainage using an updated and revised diatom assessment procedure as an added-value bio-monitoring tool.
Three data sources (physico-chemistry, bio-monitoring and eco-toxicology) are currently used in South Africa to establish environmental water quality conditions. Environmental water quality in turn is key information required for the "ecological reserve determination" of river reaches. Bio-monitoring in South Africa has been limited in recent times mostly to the use of the SASS procedure which relies on invertebrates only. This paper describes the re-introduction of a diatom-based water quality assessment as an added-value bio-monitoring tool. A specific example is discussed citing the response of diatom assemblages to diffuse pollution from acid mine drainage and how effective diatoms are as indicators of ecological integrity and river recovery measured downstream of the area of impact. The advantages of applying this bio-monitoring technique over other biological measures are presented in the context of technological advances in rapid image processing, species identification and software applications of diatom-based water quality indices. The valuable records of the diatom assemblages of the past, held in the South African Diatom Collection at the CSIR (KwaZulu-Natal), can now be accessed and interpreted as historical environmental water quality reference points for several rivers in South Africa.


A randomized clinical trial to compare two different approaches in women with chronic pelvic pain.
One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach.


Novel Salmonella Variant Associated with Mortality in Two Great Spotted Woodpeckers (Dendrocopos major).
Two adult Great Spotted Woodpeckers (Dendrocopos major) from separate sites in Great Britain were examined postmortem in 2013 and 2016. A Salmonella sp. was isolated from multiple tissues in both birds. Histopathology and immunohistochemistry confirmed disseminated salmonellosis. Whole-genome sequencing and biochemical analyses putatively identified both isolates as a novel variant of Salmonella enterica subsp. enterica serovar Hessarek (S. Hessarek). Salmonellosis has seldom been reported in Piciformes, and never before in association with S. Hessarek infection. These findings, therefore, add to current knowledge regarding the range of wild bird species susceptible to this Salmonella serovar, and our understanding of the pathogens affecting Great Spotted Woodpeckers, in particular.


Effects of premedication with oral hydroxyzine on patient motion during inhalation of 32% xenon for regional cerebral blood flow mapping.
Because of its anesthetic properties, inhalation of 30-35% Xenon is associated with uncontrolled patient motion in 3-15% of the cases. This constitutes a major setback to regional cerebral blood flow studies with Xenon-enhanced computed tomography (Xe-CT CBF). The present study attempted to determine the effects of oral premedication with hydroxyzine (H) in the control of motion. Patients scheduled for Xe-CT CBF, aged 20-55 years, were randomly allocated to 3 groups: H 50 mg (n = 41), H 100 mg (n = 36) or Placebo (n = 43). The drugs were administered orally 90 minutes before Xenon inhalation. This consisted a gas mixture of 32% Xe and 25% oxygen. Motion was classified as controlled or uncontrolled depending on whether CBF data acquisition was possible or not. Anxiolysis and sedation were evaluated by a visual analogue scale. Motion was significantly reduced in the H 50 mg (0.8% vs 2.5% in the H 100 mg and 6.7% in the Placebo group). An anxiolytic effect of hydroxyzine was suggested.


[Antitumoral immunity induced by the administration of homologous and isologous tumoral cells treated by moderate heating].
Treatment of tumour cells with heat ranging between 46 and 52 degrees C attenuates strongly their virulence and renders the tumour cells immunogenic to the host. By repeated administration of heat treated tumour cells suspended in Freund's complete adjuvant, the animals acquire a state of immunity which makes them tolerant to tumour inocula 100% lethal in the controls. The immunity so conferred is cell-mediated and can be adoptively transferred to isogenic recipients with donor peritoneal exudate and, to a lesser degree, splenic cells.


Visual information for prospective control of tracking irregular target paths with isometric force production.
The prospective control of isometric force tracking was investigated as a function of the duration of visual information about past and future properties of target paths that varied in regularity. Longer duration of information specifying future behavior significantly enhanced performance when past information was not available. Furthermore, target path regularity differentially influenced local and global performance properties as the duration of prospective information increased. For more regular target paths, longer duration of prospective visual information improved local properties (e.g., decreased error), whereas, for less regular target paths, longer duration of prospective visual information enhanced global properties of force production (e.g., spectral slope). The strategies of prospective control depend on the interaction of the regularity of motor output and the available informational support.


[Continuous arteriovenous hemofiltration and hemodiafiltration in a newborn infant with acute kidney insufficiency].
A boy of 10 days old with acute renal failure was treated with continuous arterio-venous hemofiltration and continuous arterio-venous hemodiafiltration over a period of 14 days. Hemodynamically both technics were well tolerated. Fluid overload was treated effectively by continuous fluid withdrawal and during continuous arterio-venous hemodiafiltration there was an adequate solute removal. One bleeding episode was observed during controlled general heparinization and was probably related to thrombopenia. In conclusion, continuous arterio-venous hemofiltration and hemodiafiltration are efficient modes of treatment in hemodynamically unstable infants in whom other forms of conventional dialytic therapy are contraindicated. Only continuous arterio-venous hemodiafiltration offers both fluid withdrawal and adequate solute removal and consequently may be preferred to continuous arterio-venous hemofiltration.


An automated method for micro-state segmentation of evoked potentials.
We present a method for segmenting evoked potentials into functional micro-states. The method is based on measuring the similarity between all the topographic maps in the evoked potential and grouping them into functional micro-states based on minimizing an error function. The similarity is measured as the normalized cross-correlation coefficient. The method was validated on simulated data and tested on its ability to segment a visual evoked potential. On simulated data the method missed from 1% to 8.5% of the micro-state boundaries for evoked potentials with a signal-to-noise ratio of 20-1dB, respectively. The proposed segmentation method was compared with segmentation based on K-mean clustering. It was found that the proposed method was better at detecting the correct number of micro-states and was computationally more efficient. The automatic segmentation of the visual evoked potential was compared to the manual segmentation performed by eleven EEG specialists. No significant difference in the deviation of micro-state boundaries was observed between two random EEG specialists and between a random EEG specialist and the automatic method. Thus it was found that the method could reliably segment evoked potentials into their functional micro-states.