Topiramate may not increase risk of urolithiasis: A nationwide population-based cohort study.
Topiramate is an effective anti-epileptic drug and can be associated with increased risk for urolithiasis because of its effects on acid-base profile. Evidences that supported an association of topiramate and urolithiasis were limited to case reports or series. We investigated the association of topiramate and urolithiasis in a nationwide population-based cohort study. We analyzed 1377 patients receiving topiramate and 1377 age- and gender-matched control patients (not receiving topiramate) between 1997 and 2008. The risk of urolithiasis was analyzed using Kaplan-Meier analysis, followed by Cox proportional hazard regression. Of the 2754 patients, 79 (2.9%) patients developed urolithiasis in two (interquartile range: 1.2-4.2) years. The proportion of patients who developed urolithiasis in the patients receiving topiramate was not different from that of the control patients (p=0.138, χ(2) test). The urolithiasis free survival was not different between the patients receiving topiramate and the control patients (p=0.168) in Cox proportional hazard regression. The duration and total dosage of topiramate were not associated with risk of urolithiasis in patients receiving topiramate (p=0.482 and p=0.751). Topiramate may not increase the risk of urolithiasis. The duration and the total dosage of topiramate were not associated with urolithiasis risks.


Isolation, detection of virulence genes, antibiotic resistance genes, plasmid profile, and molecular typing among Vibrio parahaemolyticus isolated in Malaysian seawater from recreational beaches and fish.
Despite the importance of the global emergence of Vibrio parahaemolyticus infections worldwide, there has been scanty information on its occurrence in Malaysian seawaters and fish. This study aimed to determine the occurrence of V. parahaemolyticus isolates using polymerase chain reaction targeted at toxin operon gene, thermostable direct hemolysin (tdh), and tdh-related hemolysin genes and to determine antibiotic resistance pattern, genes, and plasmid profile of V. parahaemolyticus from Malaysian seawaters and fish. Samples were collected from four recreational beaches in Malaysia (Port Klang; Bachok; Port Dickson; and Mersing). Thiosulfate-citrate-bile salts-sucrose (TCBS) agar and chromogenic Vibrio agar were used for isolation and identification. Colonies with yellow color on TCBS and green color on chromogenic vibrio (CV) agar were considered to be V. parahaemolyticus and they were subjected to biochemical tests. All V. parahaemolyticus isolates were further subjected to identification using seven specific gene markers. Seventy-three Vibrio isolates were recovered. Only one gene thermostable direct hemolysin (tdh) from seawater isolates of Vibrio has high virulence gene percentage (95.23%). Two genes alkaline serine protease (asp) and (tdh) had high percentage of virulence (83.87% and 80.64%, respectively) from fish. Comparatively, fish isolates have a higher virulence percentage compared to seawater isolates. Only gene streptomycin resistance B (strB) from seawater had 100% of the resistance genes. All isolates were multi-antibiotic resistant. Seventeen antibiotic resistance patterns were observed. The isolates had plasmids of varying sizes ranging from 2.7 kb to 42.4 kb. Dendrogram based on antibiotic resistance patterns of V. parahaemolyticus isolates discriminated the isolates into three clusters. This study demonstrated the occurrence of pathogenic, multi-antibiotic-resistant V. parahaemolyticus strains in Malaysian coastal waters and fish, and this could constitute potential public health risks.


Inhibition of ciramadol glucuronidation by benzodiazepines.
Studies on the inhibition of ciramadol glucuronidation by benzodiazepines were performed in vitro and in vivo. Ciramadol glucuronidation was slower (Vmax, 1.56 vs. 5.40 nmol/min/mg of microsomal protein) in human than in dog liver microsomes. Inhibition constants (Ki) for lorazepam and oxazepam were 3 to 4 times higher than that calculated for diazepam. Rates of morphine glucuronidation in human liver microsomes were assessed for comparative purposes and agreed with literature values. Each benzodiazepine appeared to be a competitive inhibitor of ciramadol and morphine UDP-glucuronyltransferase activity. The in vivo disposition of ciramadol was unchanged in dogs pretreated with lorazepam. After diazepam treatment no change in the Vdss of ciramadol occurred, but plasma clearance was significantly reduced, resulting in a prolongation of t1/2. Diazepam caused a significant reduction in the oral clearance of ciramadol, whereas no change occurred in systemic availability. Thus, diazepam may have had a secondary effect on hepatic blood flow (QH) and produced offsetting alterations in both intrinsic clearance (Cl int) and QH. A decrease in the area under the plasma concentration time curves of ciramadol aryl O-glucuronide following iv treatment with diazepam coupled with the in vitro data indicate that the mechanism for the decrease in the clearance of ciramadol is inhibition of its glucuronidation by diazepam. Since glucuronidation plays a major role in the elimination of ciramadol in man and dog, these experiments suggest that the disposition of ciramadol in man would not be affected by coadministration of lorazepam, whereas the potential for a diazepam/ciramadol drug interaction in humans exists.


Obstetric risk factors associated with placenta previa development: case-control study.
To evaluate potential risk factors and perinatal outcome of pregnancies complicated with placenta previa in Croatian population of pregnant women recruited from the largest tertiary care perinatal center in Croatia. This retrospective case-control study included a total of 202 singleton pregnancies with placenta previa during a 10-year study period and 1,004 randomly selected simple singleton controls. Data on potential risk factors for placenta previa development were carefully extracted from medical records, reviewed, and compared with a control group of women. Data were statistically analyzed with chi-square test and Mann-Whitney U test, and crude odds ratio (OR) with 95% confidence interval (95% CI) were provided. The incidence of placenta previa was 0.4%. Factors significantly associated with a placenta previa development were advanced maternal age (especially >34 years, even after adjustment for high parity), gravidity of 3 and more (OR, 4; 95% CI, 2.5-6.6), more than one previous delivery (OR, 2.76; 95% CI, 1.7-4.3), history of previous cesarean sections (OR, 2.0; 95% CI, 1.17-3.44), abortions (OR, 2.8; 95% CI, 2.04-3.83), and presence of various uterine abnormalities (OR, 8.5; 95% CI, 1.75-44.5). The risk was significantly increased after two previous cesarean sections (OR, 7.32; 95% CI, 2.1-25) and after one previous abortion (OR, 4.8; 95% CI, 2.7-8.3). No difference between the groups was found regarding the history of previous placenta previa, drug abuse, and male sex at birth. Smoking history was significantly less frequent in women with placenta previa than controls (16.3% vs 25.6%, chi-square=7.9, p=0.007). The main perinatal complication was preterm birth, with 14-fold higher risk in women with placenta previa. Preterm infants of mothers with placenta previa were more likely to have lower first- (6 vs 10, p<0.001) and fifth-minute median Apgar scores (8 vs 10, p<0.045). Term infants of mothers with placenta previa had significantly lower birth weight then their controls (3,300 vs 3,500 g, p<0.001). The most important obstetric factors for placenta previa development were advanced maternal age especially >34 years, 3 or more previous pregnancies, parity of 2 and more, rising number of previous abortions, and history of previous cesarean section, but not child sex at birth, history of drug abuse and previous placenta previa. Smoking cigarettes was significantly less frequent in women with placenta previa. Preterm delivery still remains the greatest problem in pregnancies complicated with placenta previa.


The importance of the microbiome of the plant holobiont.
Plants can no longer be considered as standalone entities and a more holistic perception is needed. Indeed, plants harbor a wide diversity of microorganisms both inside and outside their tissues, in the endosphere and ectosphere, respectively. These microorganisms, which mostly belong to Bacteria and Fungi, are involved in major functions such as plant nutrition and plant resistance to biotic and abiotic stresses. Hence, the microbiota impact plant growth and survival, two key components of fitness. Plant fitness is therefore a consequence of the plant per se and its microbiota, which collectively form a holobiont. Complementary to the reductionist perception of evolutionary pressures acting on plant or symbiotic compartments, the plant holobiont concept requires a novel perception of evolution. The interlinkages between the plant holobiont components are explored here in the light of current ecological and evolutionary theories. Microbiome complexity and the rules of microbiotic community assemblage are not yet fully understood. It is suggested that the plant can modulate its microbiota to dynamically adjust to its environment. To better understand the level of plant dependence on the microbiotic components, the core microbiota need to be determined at different hierarchical scales of ecology while pan-microbiome analyses would improve characterization of the functions displayed.


Patient education and access of ESRD patients to renal replacement therapies beyond in-center hemodialysis.
Nephrologists report that patients' choice should play an important role in the selection of renal replacement therapy (RRT) for end-stage renal disease (ESRD). In the United States, kidney transplant rates remain low and <10% of patients utilize home dialysis therapies. This study examined the effect of pre-ESRD processes on the selection of RRT among incident ESRD patients. Using surveys, data were collected for all patients admitted to 229 dialysis units in ESRD Network 18 between April 1, 2002 and May 31, 2002. A total of 1365 patients began chronic dialysis and 1193 facility (87%) and 428 patient (31%) surveys were returned. Substantial proportions of patients were unaware of their kidney disease (36%) or were not seeing a nephrologist (36%) until <4 months before first dialysis. The presentation of treatment options was delayed (48% either after or < 1 month before the first dialysis). The majority of ESRD patients were not presented with chronic peritoneal dialysis, home hemodialysis, or renal transplantation as options (66%, 88%, and 74%, respectively). Using multivariate analyses, variables significantly associated with selection of chronic peritoneal dialysis as dialysis modality were the probability of chronic peritoneal dialysis being presented as a treatment option and the time spent on patient education. An incomplete presentation of treatment options is an important reason for under-utilization of home dialysis therapies and probably delays access to transplantation. Improvements in and reimbursement for pre-ESRD education could provide an equal and timely access for all medically suitable patients to various RRTs.


Pharmaceutical approaches of binge drinking.
Binge Drinking (BD) is often considered to be recurrent alcohol abuse amongst adolescents and young adults. However, the close link between adolescence and impulsivity has led many authors to define BD as intoxication-seeking behaviour. Medications may sometimes be justified because of the major short-term and long-term risks that underlie the most severe BD-related behaviours. The most common consequences in the long run are the occurrence of alcohol dependence, psycho- and neurodevelopmental disruptions and alcohol liver disease. To understand the specificities of BD among other forms of alcohol addiction, this article is based on a two-headed conception of alcohol dependence: on one hand, psychological dependence, which refers to the behavioural habituation of alcohol intake, clinically results in craving and is neurobiologically supported by the reward system, particularly the dopaminergic mesolimbic pathway (MLP); on the other hand, physical dependence, which refers to the pharmacological tolerance induced by chronic alcohol intake, results in Alcohol Withdrawal Syndrome (AWS) and is neurobiologically supported by the imbalance between GABA and Glutamate-NMDA neurotransmission. Medications for psychological dependence include anticraving drugs, which all act by regulating MLP. Medications for physical dependence on alcohol include GABA-A and perhaps GABA-B agonists and some NMDA antagonists. In practice, many alcohol-dependence treatments seem to have a dual action. This article proposes an attempt to classify current and forthcoming medications for alcohol addiction based on this two-headed approach to treating alcohol dependence. Drawing from this classification, specific therapeutic schemes for treating BD are proposed, with currently approved alcohol medications and possible future treatments. These schemes are justified by recent literature on the subject and propose to prioritize pure anticraving medications, taking into account the clinical specificities of BD. Furthermore, these schemes also mention harm-reductive neuroprotective and hepatoprotective strategies, which could be included in the arsenal of possible medications for BD in the near future.


Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation.
Recently adopted regulatory standards on infant and follow-on formula for the European Union stipulate that from February 2020 onwards, all such products marketed in the European Union must contain 20-50 mg omega-3 DHA (22:6n-3) per 100 kcal, which is equivalent to about 0.5-1% of fatty acids (FAs) and thus higher than typically found in human milk and current infant formula products, without the need to also include ω-6 arachidonic acid (AA; 20:4n-6). This novel concept of infant formula composition has given rise to concern and controversy because there is no accountable evidence on its suitability and safety in healthy infants. Therefore, international experts in the field of infant nutrition were invited to review the state of scientific research on DHA and AA, and to discuss the questions arising from the new European regulatory standards. Based on the available information, we recommend that infant and follow-on formula should provide both DHA and AA. The DHA should equal at least the mean content in human milk globally (0.3% of FAs) but preferably reach 0.5% of FAs. Although optimal AA intake amounts remain to be defined, we strongly recommend that AA should be provided along with DHA. At amounts of DHA in infant formula up to ∼0.64%, AA contents should at least equal the DHA contents. Further well-designed clinical studies should evaluate the optimal intakes of DHA and AA in infants at different ages based on relevant outcomes.


Pro-angiogenic gene expression is associated with better outcome on sunitinib in metastatic clear-cell renal cell carcinoma.
Clear-cell renal cell carcinomas (ccRCC) are characterized by hyper-vascularization and can respond to vascular endothelial growth factor receptor (VEGFR) inhibitors such as sunitinib. We aimed to study the predictive value of the expression of genes in the hypoxia induced factor (HIF) - vascular endothelial growth factor (VEGF) - VEGFR-pro-angiogenic pathway in metastatic ccRCC (m-ccRCC) patients treated with sunitinib and the correlation between the expression of these genes and the molecular ccrcc-classification, the expression of genes involved in the immune-suppressive microenvironment and Von Hippel-Lindau (VHL) - and Polybromo-1 (PBRM1) - mutational status. m-ccRCC patients treated with sunitinib as first-line targeted therapy were included. Gene expression was studied in the primary nephrectomy sample by qRT-PCR, VHL- and PBRM1-mutational status by sequencing. Response rate by RECIST, progression-free survival (PFS) and overall survival (OS) were study endpoints. One hundred and four patients were included. On multivariate-analysis, HIF2A-, platelet derived growth factor receptor beta (PDGFRB)-, VEGFC-, VEGFR1- and VEGFR2-expression were correlated with PFS and HIF1A-, HIF2A-, VEGFR1- and VEGFR2-expression with OS. VEGFR2-expression showed the strongest association with outcome, being significantly correlated with all outcome parameters. HIF2A, VEGFA, VEGFR1, VEGFR2 and VEGFR3 were highly expressed in the transcriptomic ccrcc2-subtype of tumors, known to be highly sensitive to sunitinib. In the total tumor series, there was no correlation nor inverse correlation between the expression of genes involved in angiogenesis and in the immune-suppressive microenvironment. In tumors with a bi-allelic PBRM1-inactivation, HIF2A-, VEGFA-, VEGFR1- and VEGFR2-expression were higher, compared to tumors with one or two functional PBRM1-alleles. Intratumoral expression of genes involved in the HIF-VEGF-VEGFR-pro-angiogenic pathway, especially VEGFR2, is associated with favorable outcome on sunitinib in m-ccRCCs. Several genes involved in this pathway are upregulated in the molecular ccrcc2-subgroup, which usually responds well to sunitinib.


A simple and rapid identification method for newly emerged porcine Deltacoronavirus with loop-mediated isothermal amplification.
Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 101 copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1-2 log more sensitive than conventional RT-PCR in detection of PDCoV. The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology.


Management of common bile duct stone late after laparoscopic Roux-en-Y gastric bypass for obesity.
Rapid weight loss following Roux-en-Y gastric bypass (RYGBP) for the treatment of obesity can increase the incidence of cholelithiasis formation. Nevertheless, routine simultaneous cholecystectomy at the time of bariatric surgery remains controversial. However, in case of delayed occurrence of common bile duct (CBD) stones, the difficulty to reach endoscopically the biliary tract after RYGBP should be kept in mind. We here report the case of a patient who presented with CBD stones seven years after gastric banding followed five years later by RYGBP without associated cholecystectomy. Our approach of transgastric laparoscopic assisted endoscopic retrograde cholangiopancreaticography followed by sphincterotomy and balloon stones extraction is illustrated.


miR-29c-3p represses the angiogenesis of esophageal squamous cell carcinoma by targeting SERPINH1 to regulate the Wnt signaling pathway.
Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future.


The visible problems of an "invisible" profession: the crisis and challenge for nursing.
Although I found the special fall 1986 issue of Inquiry, on social responsibility in health care, thought provoking, the nursing profession was conspicuous by its absence. This evoked a letter to the editor, which resulted in an invitation to write this paper, dealing with the challenges and issues facing nursing in the years to come. Among the matters I discuss are the looming shortage of skilled registered nurses, the expanding roles of and opportunities for nurses, the alarming drop in the numbers of highly qualified young people interested in nursing careers, and the necessity of educating nurses in mainstream university baccalaureate programs.


Synthesis and biological evaluation of truncated α-tubulin-binding pironetin analogues lacking alkyl pendants in the side chain or the dihydropyrone ring.
The preparation of several new truncated analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the suppression of some of the alkyl pendants in either the side chain or the dihydropyrone ring. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all analogues are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus strongly suggesting that, like natural pironetin, they also display a covalent mechanism of action. Their cytotoxicity is, however, lower than that of the parent compound. This indicates that all alkyl pendants are necessary for the full biological activity, with the ethyl group at C-4 seemingly being particularly relevant. Most likely, the alkyl groups cause a restriction in the conformational mobility of the molecule and reduce the number of available conformations. This makes it more probable that the molecule preferentially adopts a shape which fits better into the binding point in α-tubulin.


Visual memory errors in Parkinson's disease patient with visual hallucinations.
The occurrences of visual hallucinations seem to be more prevalent in low light and hallucinators tend to be more prone to false positive type errors in memory tasks. Here we investigated whether the richness of stimuli does indeed affect recognition differently in hallucinating and nonhallucinating participants, and if so whether this difference extends to identifying spatial context. We compared 36 Parkinson's disease (PD) patients with visual hallucinations, 32 Parkinson's patients without hallucinations, and 36 age-matched controls, on a visual memory task where color and black and white pictures were presented at different locations. Participants had to recognize the pictures among distracters along with the location of the stimulus. Findings revealed clear differences in performance between the groups. Both PD groups had impaired recognition compared to the controls, but those with hallucinations were significantly more impaired on black and white than on color stimuli. In addition, the group with hallucinations was significantly impaired compared to the other two groups on spatial memory. We suggest that not only do PD patients have poorer recognition of pictorial stimuli than controls, those who present with visual hallucinations appear to be more heavily reliant on bottom up sensory input and impaired on spatial ability.


Collagen cross-links. A mass-spectrometric and 1H- and 13C-nuclear-magnetic-resonance study.
1. The structure of a tetrafunctional cross-link (compound C) isolated from borohydride-reduced cow skin collagen has been determined by the combined use of mass spectrometry and (1)H and (13)C n.m.r. spectroscopy. 2. A new technique, of potentially wide applicability, is described for the mass-spectrometric determination of functional groups. 3. Detailed study of protonation shifts in the (13)C spectrum has allowed an unambiguous assignment of the exact structural relationship of the component parts of the molecule. 4. New interpretations of existing data on this molecule are given.


Refinement of Animal Experiments: Replacing Traumatic Methods of Laboratory Animal Marking with Non-Invasive Alternatives.
Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than 6 million rodents are used in animal studies each year. Currently, there are extensive regulations in place to ensure adequate anesthesia and to reduce animal suffering during experiments. At the same time, not enough attention is paid to the comfort of rodents during routine identification procedures, which can be painful and cause some complications. In order to achieve the highest ethical standards in laboratory research, we must minimize animal discomfort during the identification phase. In this article, we discuss traumatic methods of identification and describe several painless methods for marking in long-term experimental studies. The use of non-traumatic and non-invasive methods requires the renewal of marks as they fade and additional handling of the rodents. Laboratory personnel must be trained in stress-minimizing handling techniques to make mark renewal less stressful.


[Joint recomendations for clinical priority in arterial surgery from Portuguese Society of Cardiothoracic and Vascular Surgery and Portuguese Society of Cardiology].
There is a gap in international guidelines for acceptable wait times for cardiovascular surgery. Most patients benefit from surgery as fast as possible after the establishment of an indication. However due to extrinsic factors a continuous and cost-effective response is not feasible to all of them. Priority criteria for surgery after the indication is heterogeneous. The physician/surgeon is responsible for the surgical prioritization upon experience-based criteria. The prioritization is accepted by the hospitals most of the times, but incorrections are verified in excess and defect. There is a press in need for evidence-based prioritization criteria in cardiac and vascular surgery that maintains an adequate waiting time with maximum benefit. Surgical waiting times superior to what is clinically reasonable affects not only the patient but also the health system by indirect costs (morbidity, absence from work). The objective is to establish recommendations in extra-carotid disease, abdominal aortic disease, peripheral artery disease and vascular access construction. A review from the data is made to define an appropriate balance between the surgical scheduling and the prevention of pre an perioperatory adverse events.


Ground-state structures of superparamagnetic two-dimensional dusty plasma crystals.
Ground-state structures of finite, cylindrically confined two-dimensional Yukawa systems composed of charged superparamagnetic dust grains in an external magnetic field are investigated numerically, using molecular dynamic simulations and lattice summation methods. The ground-state configuration of the system is identified using, as an approximation, the experimentally obtained shape of the horizontal confinement potential in a classical single-layer dusty plasma experiment with nonmagnetic grains. Results are presented for the dependence of the number density and lattice parameters of the dust layer on (1) the ratio of the magnetic dipole-dipole force to electrostatic force between the grains and (2) the orientation of the grain magnetic moment with respect to the layer.


Immediate, but not delayed, microsurgical skull reconstruction exacerbates brain damage in experimental traumatic brain injury model.
Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI.


Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability.
Matrix metalloproteinase-1 (MMP-1) is one of three collagenases that can degrade the interstitial collagens, types I, II, and III at neutral pH. As these collagens are the most abundant proteins in the body, collagenase plays a critical role in modeling and remodeling the extracellular matrix. Therefore, it is not surprising that MMP-1 gene expression can be regulated at multiple points. Procollagenase can be activated by mechanisms that generate an active enzyme with differing specific activities, and the active enzyme can be inhibited by complexing with either the tissue inhibitor of metalloproteinases (TIMPs) or alpha 2 macroglobulin. The activator protein-1 (AP-1) site in the collagenase promoter plays a prominent role in the transcriptional control of the collagenase gene. It is essential for basal transcription, and contributes to induction by phorbol esters, although other sites in the proximal promoter are essential. In contrast, transactivation by cytokines such as Interleukin-1 depends on sequences in more distal regions of the promoter. Posttranscriptional mechanisms also regulate gene expression, and several cytokines and growth factors increase the stability of the collagenase transcript. Finally, glucocorticoid hormones repress transcription of the collagenase gene by the interaction of glucocorticoid receptors with the AP-1 proteins, Fos and Jun. Retinoids also suppress transcription by mechanisms that involve down-regulation of fos and jun mRNA, sequestration of Fos and Jun proteins, and the formation of complexes of retinoic acid receptors (RAR/RXR heterodimers) and AP-1 proteins on the DNA. These multiple points of regulation assure precise control of collagenolytic activity in a variety of physiologic and pathologic conditions.


Conventional Sampling Plan for Scouting Neoleucinodes elegantalis (Lepidoptera: Crambidae) Eggs on Tomato Fruits.
The small tomato borer, Neoleucinodes elegantalis (Guenée), is an important pest of tomato (Solanum lycopersicum L.) in South and Central America. This pest is a potential threat for many tomato-producing areas and was listed in 2014 as an A1 quarantine pest by the European and Mediterranean Plant Protection Organization. Soon after hatching, the neonate N. elegantalis larvae penetrate the fruits where they feed until pupation. Therefore, effective N. elegantalis management relies on the timely scouting of egg densities to allow decision-making prior to penetration of neonates into fruits. This study aimed to develop a conventional sampling plan for scouting N. elegantalis eggs on tomato plants. The most representative and precise sampling unit was the most basal fruit cluster for plants bearing up to three clusters (S1 plants). For plants with more than three fruit clusters (S2 plants), the most representative and precise sampling unit was the combination of the second and third fruit clusters. Among the four variables evaluated (eggs/fruit, egg masses/fruit, percentage fruit with eggs, and percentage clusters with eggs), the percentage of clusters with eggs was the most economical for N. elegantalis sampling based on the number of samples and cost required. For this variable, the number of samples determined at the 25% error level was 42 and 36 samples for S1 and S2 plants, respectively. The sampling plan developed for scouting N. elegantalis is fast, reflects pest infestation in tomato fields, and costs less than US$1.50 per field scouted.


[Nerve gas--guidelines for care of victims of terrorism].
The threat from chemical warfare agents such as nerve agents against civilians has traditionally been considered irrelevant. Following the recent terrorist attacks in the US on 11 September 2001 and in Madrid, Spain on 11 March 2004, the threat from such weapons is taken seriously. Hospitals must therefore be prepared to take care of civilian victims. Emergency preparedness implies education and training of healthcare professionals, stocking of antidotes, and training of personnel. This involves decontamination of patients, establishment of routines to avoid contamination of hospitals, and the ability to determine if patients and first responders are contaminated with chemicals and to avoid such contamination. Treatment against nerve agents includes atropine, acetylcholinesterase reactivators (obidoxime or pralidoxime) and benzodiazepines (diazepam). Because these drugs are not sufficiently effective in protecting the brain, new and more effective countermeasures must be developed.


Development of a level I fieldwork evaluation.
The Wisconsin Council on Education (Wiscouncil) developed and pilot tested an evaluation of student performance for Level I fieldwork to be use for both occupational therapy and occupational therapy assistant students. Data were gathered from 259 students, fieldwork supervisors, and faculty who rated the form on a number of variables. The majority of students and clinical faculty believed the form was good to excellent in meeting their needs, in being useful in a variety of settings, in being applicable for both occupational therapy and occupational therapy assistant students, and in overall efficiency. On the basis of the results of the 1-year pilot study, short (23-item) and long (38-item) versions of the form were developed. Implications for use and the importance of future research to determine reliability and validity are discussed.


[Preoperative chemotherapy of esophageal cancer].
A series of 25 patients with advanced esophageal cancer treated from Mar. 1981 to Sep. 1982 by preoperative chemotherapy plus surgery is reported. All the patients came from the hospitals of the cooperative research group and were randomized into chemotherapy and control groups. They were proved by X-ray, cytology and histopathology prior to treatment. By histology, 22 cases were squamous cell carcinoma, 1 adenocarcinoma and 2 squamous adenocarcinoma. The COF chemotherapy consisted of Vincristine 1 mg, cyclophosphamide 600 mg and 5-fluorouracil 500 mg IV on days 1 and 8 with or without the addition of Pingyangmycin, a drug equivalent to Bleomycin A5, at the dose of 10 mg IM on days 1, 3, 6 and 8. The interval between the ending of chemotherapy and the surgical resection was 5-6 days. The results showed that preoperative chemotherapy caused no myelosuppression, but merely mild gastrointestinal symptoms. All patients were operated and resected without difficulty. The subjective improvement in various degrees and the shrinkage of tumor in the X-ray films were present in 5/25 cases who received preoperative chemotherapy. The histopathological changes in the chemotherapy and control groups (16 specimens) were different. In the chemotherapy group, excessive keratinization in the squamous component of the esophageal cancerous tissue appeared in the resected specimens. The incidence of degeneration and necrosis in the squamous epithelium adjacent to carcinoma was higher in the chemotherapy group (P less than 0.01). The results suggested that such combined modality is worth further study.


Sorption of 75 per cent DDT water-dispersible powder on different mud surfaces.
The loss of residual insecticide particles on absorbent mud surfaces due to the phenomenon of sorption has been well investigated from various physical, chemical and biological aspects. The present report describes an attempt to correlate the relative sorption capacities of representative Indian and African soils and a synthetic soil with the physicochemical characteristics of these soils and their surfaces. The investigation has further elucidated the mode of sorption of non-volatile residual insecticides on mud surfaces and the role of certain physicochemical factors.


Treatment of Navicular Stress Fractures With an Algorithmic Approach.
Navicular stress fractures are becoming increasingly more common. There is no universal consensus on treatment. We provide an algorithm that we feel will be useful in determining treatment. A retrospective study was performed on all patients having operative treatment of navicular stress fractures during a 10-year period. Acute fractures were treated with open reduction internal fixation. Chronic fractures greater than 3 months were treated with open reduction and internal fixation (ORIF) and iliac crest bone grafting. Chronic fractures with evidence of sclerosis, avascular changes, or those who failed previous surgery were treated with ORIF, iliac crest bone grafting, as well as vascular bone grafting. Patients' pain scores were recorded and a return-to-sports scale was used. Radiographic union was compared among the 3 groups using computed tomographic (CT) scans or radiographs. Forty-three patients were identified. Fifteen received ORIF alone, 12 were treated with ORIF and bone graft, and 16 had ORIF with vascularized bone grafting. No difference was found among the median age of the 3 groups. In terms of radiographic healing, 3 patients in the ORIF group received radiographs alone. All other patients had follow-up CT scans. ORIF alone group had 80% union, ORIF with bone graft had 75% union, and ORIF with vascularized bone grafting had 100% union. Return to sports did not show any difference among the 3 groups. The algorithm dividing navicular stress fractures into 3 distinct groups with different operative techniques helped us address these difficult cases. Vascularized bone grafting certainly appeared to be beneficial for the more difficult cases. Level IV, case series.


FLT3 ligand promotes engraftment of allogeneic hematopoietic stem cells without significant graft-versus-host disease.
Graft-versus-host (GVH) reactions contribute to stable engraftment of allogeneic hematopoietic stem cell transplants. It was hypothesized that the in vivo expansion of recipient dendritic cells (DC) with the administration of ligand for Flt3 (FL) could promote allogeneic engraftment after reduced-intensity conditioning by enhancing the GVH effect. FL was first administered to three nonirradiated healthy dogs for 13 days at a dosage of 100 microg/kg/day. Next, nine dogs received 4.5 Gy total-body irradiation (TBI) and unmodified marrow grafts from dog leukocyte antigen (DLA)-identical littermates without posttransplant immunosuppression. FL was administered to the recipients at a dosage of 100 microg/kg/day from day -7 until day +5. In normal dogs, FL produced significant increases in monocytes (CD14+) and neutrophils in the peripheral blood, a marked increase in CD1c+ cells with DC-type morphology in lymph nodes, and increased alloreactivity of third-party responders to peripheral blood mononuclear cells in mixed lymphocyte reactions (P<0.001). Sustained engraftment was observed in eight of nine (89%) FL-treated dogs compared with 14 of 37 (38%) controls (P=0.02, logistic regression). All engrafted FL-treated dogs became stable complete (n=2) or mixed (n=6) hematopoietic chimeras without significant graft-versus-host disease (GVHD). Recipient chimeric dogs (n=4) were tolerant to skin transplants from their marrow donors but rejected skin grafts from unrelated dogs within 7 to 9 days (median, 8 days). In this study, the authors showed that FL administered to recipients promotes stable engraftment of allogeneic marrow from DLA-identical littermates after 4.5 Gy TBI without significant GVHD.


Preoperative evaluation of pancreaticobiliary tumor using MR multi-imaging techniques.
To evaluate the clinical value of MR multi-imaging techniques in diagnosing and preoperative assessment of pancreaticobiliary tumor. MR multi-imaging techniques, including MR cross-sectional imaging, MR cholangiopancreatography (MRCP) and 3D dynamic contrast-enhanced MR angiography (3D DCE MRA), were performed to make prospective diagnosis and preoperative evaluation in 28 patients with suspected pancreaticobiliary tumors. There were 17 cases of pancreatic adenocarcinoma, 8 cases of biliary system carcinoma and 3 cases of non-neoplastic lesions. Using MR multi-imaging techniques, the accuracy in diagnosing the patients with pancreaticobiliary tumors was 89.3% (25/28). The accuracy in detecting the range of tumor invasion was 80.3% (57/71). The sensitivity, specificity, accuracy, positive and negative predictive value of MR multi-imaging techniques in preoperative assessment of the resectability of pancreaticobiliary tumor were 83.3%, 89.5%, 88.0%, 71.4%, and 94.4%, respectively. There was well diagnostic consistency between MR multi-imaging techniques and CT (kappa = 0.64, P<0.01). The fusion image could be made from MRCP and 3D DCE MRA images. MR multi-imaging techniques can integrate the advantages of various MR images. The non-invasive "all-in-one" MR imaging protocol is the efficient method in diagnosing, staging and preoperative assessment of pancreaticobiliary tumor.


The Emotion Process: Event Appraisal and Component Differentiation.
Much emotion research has focused on the end result of the emotion process, categorical emotions, as reported by the protagonist or diagnosed by the researcher, with the aim of differentiating these discrete states. In contrast, this review concentrates on the emotion process itself by examining how ( a) elicitation, or the appraisal of events, leads to ( b) differentiation, in particular, action tendencies accompanied by physiological responses and manifested in facial, vocal, and gestural expressions, before ( c) conscious representation or experience of these changes (feeling) and ( d) categorizing and labeling these changes according to the semantic profiles of emotion words. The review focuses on empirical, particularly experimental, studies from emotion research and neighboring domains that contribute to a better understanding of the unfolding emotion process and the underlying mechanisms, including the interactions among emotion components.


Dynamic joint loading following hamstring and patellar tendon anterior cruciate ligament reconstruction.
This study compared lower limb dynamic joint loading after hamstring (HS) and patellar tendon (PT) anterior cruciate ligament (ACL) reconstruction. A three-dimensional motion analysis and force plate system were used to determine sagittal plane kinematics and kinetics in 20 subjects who had undergone ACL reconstruction (10 HS, 10 PT) whilst they performed both horizontal and vertical hopping tasks. Results for both activities showed significantly smaller knee flexion angles and external flexion moments in the operated than the non-operated limbs in PT subjects but no difference between limbs in HS subjects. There was no difference in the summated moment (hip plus knee plus ankle) between limbs for either graft type. The peak vertical ground reaction force was greater in the operated than the non-operated limb in PT subjects during the horizontal hop. These data show functional knee kinematic and kinetic differences between the two graft types that point to an earlier or better functional recovery in patients undergoing ACL reconstruction with HS graft than PT graft.


Mycobacterium tuberculosis induces connective tissue growth factor expression through the TLR2-JNK-AP-1 pathway in human lung fibroblasts.
Mycobacterium tuberculosis (M.tb) infection in lung causes pulmonary fibrosis, which leads to the irreversible reduction of pulmonary function. Fibrotic protein connective tissue growth factor (CTGF) expression has been confirmed to play a crucial role in lung fibrosis. However, the underlying signal pathway and effect of M.tb on CTGF expression in human lung fibroblasts are unclear. Our results revaled that M.tb caused time- and concentration-dependent increases in CTGF expression in human lung fibroblasts. A mechanistic investigation revealed that M.tb induced CTGF expression through TLR2 but not TLR4. The promoter activity assay indicated that M.tb-induced CTGF activity was mainly controlled by the promoter region at -747 to -184 bp, which contained signal transducer and activator of transcription 3 and activator protein 1 (AP-1) binding sites. Moreover, curcumin (AP-1 inhibitor) restrained M.tb-induced CTGF expression. M.tb also induced increases in AP-1 luciferase activity and DNA binding activity of c-Jun and c-Fos on the CTGF promoter. Furthermore, the knockdown of c-Jun by small interfering RNA attenuated M.tb-induced CTGF expression and AP-1 luciferase activity. A JNK inhibitor (SP600125) and a JNK dominant-negative mutant suppressed M.tb-induced CTGF expression. We also discovered that M.tb could induce the phosphorylation of JNK and c-Jun. Furthermore, SP600125 inhibited M.tb-induced c-Jun phosphorylation and AP-1- luciferase activity. M.tb-induced fibronectin expression was inhibited by anti-CTGF antibody. These results demonstrate that M.tb is activated through TLR2 to induce JNK activation, further increasing the DNA binding activity of c-Jun and c-Fos and finally inducing CTGF expression and extracellular matrix production.-Lee, H.-S., Hua, H.-S., Wang, C.-H., Yu, M.-C., Chen, B.-C., Lin, C.-H. Mycobacterium tuberculosis induces connective tissue growth factor expression through the TLR2-JNK-AP-1 pathway in human lung fibroblasts.


[Pneumonia in an internal medicine service].
A retrospective study was performed in 107 patients with pneumonia in a total of 2231 who were admitted in a Medicine ward, of an University Hospital in Lisbon during 1990. From the studied patients, 50 (46,7%) were females and 57 (53,3%) males. The mean age was 70,7 +/- 15,3 years, with a mean of 12.8 admission days. In the past history it was identified 43 (40%) patients with respiratory illness. In this, the chronic obstructive airways disease were the more prevalent disease in 22 (20.5%) patients. In the other chronic debilitating diseases, registered in 90 (84.1%), we reported in 58 (54.2%) patients among cardiovascular illness, hypertension (H) in 17 (15.8%) cases and H with diabetes mellitus II (DMII) in 14 (13.1%). The most common radiographic pattern was bronchopneumonia in 56 (52.3%) cases and in the respiratory functional study, the partial respiratory insufficiency occurred in 25 (23.4%) cases. In blood test at admission, it was found anaemia in 35 (32.7%) patients, leukocytosis in 72 (67.3%), elevated sedimentation rate in 70 (65.4%), renal dysfunction in 12 (11.2%) and hyperglycemia in 67 (62.6%). Concerning therapeutics, the ampicillin was the most used antimicrobial therapy in 50 (46.7%) cases and the oxygenotherapy was necessary in 45 (42%). Only 29 (27.1%) needed bronchodilators and 3 (2.8%) required mechanical ventilatory support. The evolution was good in 76 (71%) cases and 31 (29%) patients died. The authors conclude that the pneumonia is a frequent disease in the Internal Medicine Clinics, either as admission cause either as complication of other comorbid medical condition and has a high mortality rate. The most important factors for the prognosis were the age of patients and previous diseases. The aim of the authors is to enhance prevention infection in lower respiratory tract, principally in the weak constitutions patients and the prescription of the appropriate therapy according with the judgment presumption and if possible with the isolated microorganism. Identify with the retrospective study, important elements in the clinical process for interpretation of diagnosis and therapeutic attitude and to learn with the preceding experience for future orientation.


Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity.
Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at room temperature and upon cholesterol depletion, indicating a complex dependence on membrane fluidity and microdomain organisation. Lipidomic analyses show that in comparison to HeLa cells HEK cells have an endogenously low sphingomyelin content. Interestingly, direct permeation in HEK cells and also in HeLa cells treated with exogenous sphingomyelinase is independent of membrane potential. Membrane potential is only required for induction of sphingomyelinase-dependent uptake which is then associated with a strong hyperpolarization of membrane potential as shown by whole-cell patch clamp recordings. Next to providing new insights into the interplay of membrane composition and direct permeation, these results also refute the long-standing paradigm that transmembrane potential is a driving force for CPP uptake.


Parasite reproductive strategy and evolution of castration of hosts by parasites.
A modification of the Euler equation is used to describe a simple parasite life history in which survival decreases with age at a rate determined by mortality of the parasitized host. The advantages of castration of hosts by parasites are discussed using the modified equation in which castration is equivalent to reducing parasite virulence in the host to near zero or zero. It is suggested that castrating parasites can infest a wider range of hosts with higher mortality rates and that within parasite groups having castrating and noncastrating species, the former should infest hosts with higher mortality rates and relatively larger gonads.


Theoretical and experimental study of optothermal expansion and optothermal microactuator.
A new type of microactuators based on optothermal (OT) expansion is introduced. The mechanism of the OT expansion is theoretically analyzed, and comprehensive models for OT expansion and bi-direction microactuator are presented in this paper. An expansion arm and a microswitch-like OT microactuator with 1200microm-length are fabricated by an excimer laser micromachining system using single layer material. A laser diode (650nm) is employed as the external power source to activate the arm and the microactuator. Experimental results indicate that the OT expansion increment is approximately linear with the laser power irradiating the expansion arm, coinciding with theoretical predictions quite well. As to the switch-like microactuator, an enlarged bi-direction deflection has been obviously observed. The OT expansion and deflection amplitude that can reach micron scale is generally large enough for most microsystems. The new technique of OT microactuators can be widely applied in those fields where simple structure, easy fabrication, large displacement, wireless and remote controlling are required.


Solar radiation-induced mortality of marine pico-phytoplankton in the oligotrophic ocean.
We examined the response of pico-phytoplankton communities sampled at the equatorial, tropical and temperate Central Atlantic Ocean to subsurface underwater solar radiation in order to test the generality of the reported cell mortality for these populations when exposed to high ultra violet radiation (UVR) and photosynthetically active radiation. The natural communities of pico-phytoplankton populations tested experienced high cell mortality when exposed to high solar radiation, despite inhabiting tropical waters. Synechococcus and eukaryotes were more resistant to solar radiation than Prochlorococcus. The decay rates of all pico-phytoplankton groups examined tended to be much higher when exposed to total solar radiation than when UVB-R was filtered out. We also show that even short exposures of 30 min to high solar radiation were able to induce cell mortality in Prochlorococcus. The variability in the decay rates of living Prochlorococcus cells were strongly related to the condition of the original population. However, Synechococcus decay rates were higher in populations from the tropical area, with eukaryotes sensitivity increasing with increasing the trophic degree. The data reported in this study and in the literature revealed contrasting capacities of Prochlorococcus, Synechococcus and eukaryotes to survive under high solar radiation. Although the mechanisms involved are as yet unclear, their elucidation may help explain niche partitioning among these organisms in the ocean.


[Homeostasis preserving therapy in reconstructive surgery].
The main provisions gomeostasis preserving intensive care patients, operated on the delayed effects of traumatic tissue injuries in conditions of regional anesthesia are presented. There are key indicators that characterize the stability of the homeostasis system during the intensive care unit.


Physiological Support of Goal-Directed Activity in Human.
The effectiveness of goal-directed human behavior and the processes underlying organization of such activity are the subjects of various biomedical studies. Here we review both classical and modern evidence on the fundamental principles of goal-directed human activity. Facts are presented about the basic mechanisms that ensure the effectiveness of goal-directed behavior and determine its physiological cost.


Evaluation of in vivo and in vitro quality of apheresis-collected RBC stored for 42 days.
New technological developments make it possible to collect red blood cells (RBCs) by apheresis, which allows for better product consistency and has the potential for improved RBC quality. The purpose of these studies was to evaluate the quality and consistency of units of RBCs collected by apheresis using the MCS+(R) machine (Haemonetics Corp., Braintree, Mass., USA). Two studies were performed. In study 1 (n = 10), using containers and CP2D/AS-3 solutions from Medsep Corp. (Covina, Calif. USA), one-unit apheresis RBCs were compared to manually collected RBCs in a random crossover design. In study 2 (n = 12), 6 subjects had one unit collected, while the remaining 6 subjects had two units of RBCs collected with comparison to previously manually collected RBCs from the same donors. Haemonetics containers and solutions were used in study 2. Low RBC volume variability was found for the apheresis collections with a standard deviation of only 6 ml difference between actual and target volumes. Combining the data from the two studies (n = 21 pairs), at 42 days of storage, the apheresis units showed slightly lower hemolysis (0.44+/-0.26 vs. 0.61+/-0.50%), lower supernatant potassium levels (50+/-3 vs. 53+/-3 mEq/l), and improved tolerance to osmotic shock (47+/-3 vs. 49+/-3%) as compared to manual units (p < 0.05). There was no statistically significant difference in RBC ATP (3.0+/-0.6 vs. 2.9+/-0.5 micromol/g Hb) or in 24-hour percent recoveries (81+/-6 for apheresis vs. 81+/-4% for apheresis red cells). Apheresis RBC quality was not affected by the manufacturer (Haemonetics vs. Medsep) of solutions and containers. RBC units collected by apheresis demonstrated low variability in volume of RBC mass collected, and showed similar RBC properties as compared to manually collected RBCs after processing and after 42 days of storage.


A Non-Invasive Method for Detection of Antihypertensive Drugs in Biological Fluids: The Salivary Therapeutic Drug Monitoring.
Objectives: Arterial hypertension is still the most frequent cause of cardiovascular and cerebrovascular morbidity and mortality. Antihypertensive treatment has proved effective in reduction of cardiovascular risk. Nevertheless, lifestyle interventions and pharmacological therapy in some cases are ineffective in reaching blood pressure target values, despite full dose and poly-pharmacological treatment. Poor adherence to medications is an important cause of treatment failure. Different methods to assess therapeutic adherence are currently available: Therapeutic drug monitoring in biological fluids has previously demonstrated its efficacy and reliability. Plasma and urine have been already used for this purpose, but they may be affected by some practical limitations. Saliva may represent a feasible alternative. Methods: Fourteen antihypertensive drugs and two metabolites were simultaneously tested in plasma, urine, and saliva. Tested molecules included: atenolol, nebivolol, clonidine, ramipril, olmesartan, telmisartan, valsartan, amlodipine, nifedipine, doxazosin, chlorthalidone, hydrochlorothiazide, indapamide, sacubitril, ramiprilat, and sacubitrilat. Therapeutic drug monitoring was performed using ultra-high performance liquid chromatography, coupled to tandem mass spectrometry (UHPLC-MS/MS). The method has been preliminarily evaluated in a cohort of hypertensive patients. Results: The method has been validated according to US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The application on a cohort of 32 hypertensive patients has demonstrated sensibility and specificity of 98% and 98.1%, respectively, with a good feasibility in real-life clinical practice. Conclusion: Saliva may represent a feasible biological sample for therapeutic drug monitoring by non-invasive collection, prompt availability, and potential accessibility also in out-of-clinic settings.


No significant impact of prior treatment profile with docetaxel on the efficacy of cabazitaxel in Japanese patients with metastatic castration-resistant prostate cancer.
The objective of this study was to retrospectively analyze the oncological outcomes of Japanese patients with metastatic castration-resistant prostate cancer (mCRPC) who received cabazitaxel. This study included a total of 63 consecutive Japanese mCRPC patients treated with cabazitaxel following the failure of docetaxel, and assessed the prognostic significance of cabazitaxel therapy in these patients focusing on the association of efficacies between two taxane agents. After treatment with cabazitaxel (median 5 cycles), prostate-specific antigen (PSA) decline was observed in 39 patients (61.9%), including 13 (27.0%) achieving the response defined by PSA decline ≥50%. The median progression-free survival (PFS) and overall survival (OS) periods after the introduction of cabazitaxel were 4.1 and 14.8 months, respectively. The response rate to cabazitaxel was not significantly different between responders and non-responders to prior docetaxel, and there was no significant correlation between the PFSs with docetaxel and cabazitaxel. Furthermore, univariate analyses of several parameters identified the performance status (PS) and clinical symptoms, but not the cycles of docetaxel therapy, total amount of administered docetaxel or objective response to docetaxel therapy, as significant predictors of OS on cabazitaxel therapy, of which only PS was independently associated with OS on multivariate analysis. These findings suggest that oncological outcomes in Japanese mCRPC patients receiving cabazitaxel are generally satisfactory, irrespective of the profiles related to prior treatment with docetaxel, and that it might be preferable to introduce cabazitaxel to mCRPC patients with a good PS to maximize the prognostic benefit of this agent.


Source attributions for detected new items: Persistent evidence for schematic guessing.
Performance in source-monitoring tests is not only determined by source memory but also by source guessing. Source guessing is not random as it is informed by two distinct mechanisms. (1) People may show a schema-based guessing bias and rely on cross-situationally stable world knowledge. (2) They may apply probability matching and rely on the specific item-source contingency experienced at encoding. According to probability matching theory, source guessing is based on probability matching when a specific contingency representation is available. This conclusion is derived from a source-monitoring paradigm in which no source judgements for detected new items are required. Here, we extend this paradigm to examine source guessing not only for detected old items but also for detected new items. The results suggest that participants take the old-new recognition status of the items into account when making source attributions. Probability matching is used only for detected old items: Source guessing sensitively reflects the item-source contingency for these items. For detected new items, participants resort to schema-based guessing. Using schema-based guessing rather than probability matching when judging detected new items may have the advantage that a newly acquired contingency representation that may only be locally valid is not generalised too readily at the expense of a schematic expectation that reflects a larger and more comprehensive learning history.


18F-FDG PET/CT in the Evaluation of Solitary Extramedullary Plasmacytoma: A Case Series.
The role of fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) in patients with multiple myeloma (MM) and other plasma cell disorders is well-known. Solitary plasmacytoma (SP), an extremely rare form within this entity accounting for approximately 4% of plasma cell malignancies, can be classified as solitary bone plasmacytoma (SBP) or solitary extramedullary plasmacytoma (SEMP). Extramedullary plasmacytoma (EMP) is a rare neoplasm characterized by the monoclonal proliferation of plasma cells outside the bone marrow. Breast and craniocerebral regions are the uncommon sites of the presentations of EMP, rarely reported in the literature. The most frequent site of presentation is the upper airways. The EMPs have similar pathogenesis as MM; however, they differ in management as they are radiosensitive in nature, and radiotherapy is the preferred treatment modality. As SEMP has a better prognosis than SPB with a lower conversion rate to MM, accurate staging is essential to plan for the treatment. The 18F-FDG PET/CT has higher sensitivity for the evaluation of treatment response. In the present case series, it was aimed to depict the role of 18F-FDG PET/CT in newly diagnosed SEMP with different sites of origin to exclude further lesions leading to changes in the treatment plan and treatment response assessment.


Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).
Despite major advances in the management of trauma victims, the incidence of sepsis has increased significantly over the past two decades. The increasingly high morbidity and mortality associated with sepsis could be attributed to the fact that early alterations of cellular functions are not recognized, thereby leading to delayed or inadequate treatment of the septic patient. In this regard, studies have demonstrated that hepatocellular function is depressed early after the onset of sepsis. Due to its major role in metabolism and host defense mechanisms, it is becoming increasingly evident that the liver is an important organ in the development of multiple organ dysfunction during sepsis. Mediators which are released from the gut have been implicated in initiating hepatocellular dysfunction via the release of inflammatory cytokines such as TNF-alpha by Kupffer cells, the resident macrophages present in the hepatic sinusoids. Kupffer cells, by virtue of their location in the mainstream of splanchnic blood flow, are positioned to receive a constant exposure to gut-derived mediators known to activate macrophages. In this review article, we will first describe the animal model of cecal ligation and puncture which has led to our understanding of the consequences of sepsis. We will then discuss the occurrence of hepatocellular dysfunction during early sepsis. The mechanism responsible for such a deleterious alteration in organ function, focusing especially on the role of gut-derived norepinephrine and its effect on TNF-alpha release by Kupffer cells, will be specifically discussed. Moreover, we will discuss potential approaches for modulating Kupffer cell inflammatory cytokine release and improving hepatocellular function during sepsis.


High prevalence of infection with Entamoeba dispar, but not E. histolytica, in captive macaques.
A total of 268 nonhuman primates (20 species) kept in the Primate Research Institute, Kyoto University, Japan, were surveyed for intestinal amebas. Total positive rates as based on the presence of cysts in the stool following formalin-ether sedimentation were as follows: Entamoeba histolytica/E. dispar, 53%; E. coli, 34%; E. hartmanni, 34%; Iodamoeba buetschlii, 25%; Endolimax nana, 8%; and E. chattoni, 3%. Positive rates were higher in Old World monkeys and lower in New World monkeys. All the 141 E. histolytica/E. dispar-positive animals were Macaca monkeys. The E. histolytica/E. dispar-positive samples were analyzed by polymerase chain reaction (PCR) for identification of E. histolytica and E. dispar. E. dispar DNA was detected in 137 samples, whereas no E. histolytica DNA was seen. Zymodeme analysis and reactivity to monoclonal antibodies of cultured trophozoites also supported the presence of E. dispar and the absence of E. histolytica. When the sera of 93 macaques were examined by an indirect fluorescent antibody test, only 3 animals proved to be positive for E. histolytica, showing the lowest titer. These results demonstrate that infection with E. dispar, but not E. histolytica, is predominant in macaques.


A brief historical overview of the past two decades of soy and isoflavone research.
During the past 20 years, a remarkable amount of research into the health effects of soy consumption has been conducted, which in large part can be attributed to the presence of isoflavones in the soybean. Isoflavones first came to the attention of the scientific community in the 1940s because of fertility problems observed in sheep grazing on a type of isoflavone-rich clover. In the 1950s, as a result of their estrogenic effects in rodents, isoflavones were studied as possible growth promoters for use by the animal feed industry, although shortly thereafter, it was shown that isoflavones could also function as antiestrogens. Despite this early work, it was not until the 1990s, largely because of research sponsored by the U.S. National Cancer Institute, that the role of soyfoods in disease prevention began to receive widespread attention. Subsequently, isoflavones and soyfoods were being studied for their ability to alleviate hot flashes and inhibit bone loss in postmenopausal women. In 1995, soy protein attracted worldwide attention for its ability to lower cholesterol. At this same time, isoflavones began to be widely discussed as potential alternatives to conventional hormone therapy. In 2002, it was hypothesized that individuals possessing the intestinal bacteria capable of converting the soybean isoflavone daidzein into the isoflavan equol were more likely to benefit from soy intake. More recently, in vitro and animal research has raised questions about the safety of isoflavone exposure for certain subsets of the population, although the human data are largely inconsistent with these concerns.


45(th) Annual Scientific Meeting of the American Headache Society June 19 -22, 2003, Chicago, IL, USA.
The 45(th) Annual Scientific Meeting of the American Headache Society focused on new areas of headache research: revised diagnostic criteria, increased the understanding of the pathogenesis of migraine and expansion of identified physiological changes in migraine beyond head pain to include cognitive, sleep and vestibular disturbances. A preview of the new International Headache Society criteria described changes in diagnostic categories, including special criteria for research. New definitions to categorise chronic daily headache, menstrual migraine and secondary headaches were the main highlights of the modified criteria. In addition, novel data on activation within trigeminovascular pathways expand the understanding of the pathogenesis of migraine. Identification of the ability of treatment to impact activation and sensitisation of peripheral and central neurons results in: an explanation for initial headache worsening and neck/chest tightness that commonly occur with triptans, a better understanding of the mechanisms of triptans, and a strong recommendation for early triptan intervention (within 20 min of headache onset). Application of matrix metalloproteinase models to migraine helps explain the ability of medications to cross the blood-brain barrier during a migraine episode, as well as describe possible ischaemia with repeated migraine (e.g., white matter abnormalities seen on magnetic resonance scanning). Improved classification of headache disorders, along with increased understanding of the physiology of migraine and mechanism of action of common treatments, should enhance future development and evaluation of effective headache therapy.


Immunodepression secondary to malnutrition: assay by lymphocyte subset analysis using monoclonal antibodies and the cell sorter.
It has been well documented that the hospitalized child frequently is malnourished, and the considerably greater morbidity and mortality of such children, in large part, is due to the associated secondary immunodepression. To assess the mechanism of such immunodepression in acute and chronically malnourished subjects, we chose an experimental murine model of malnutrition. Immune function was assayed by lymphocyte subset population and mixed lymphocyte culture (MLC) assessment, determining whether an alteration of the T helper (TH) to T suppressor-cytotoxic (TS-C) lymphocyte ratio is the mechanism that produces immunoincompetence in malnutrition. Ten-week-old A/J mice were rendered acutely or chronically malnourished by graded protein restriction using a 2.5% protein diet. These animals were studied before and after protein depletion with the fluorescent activated cell sorter (FACS) and the MLC. FACS cell populations were defined by the monoclonal antibodies to THY 1.2, LYT 1 (TH), and LYT 2 (TS-C) antigens. MLC reactivity was assessed with A/J v C 57 BL/6 mouse lymphocytes and expressed as a stimulation index (S.I.). Results are expressed in Table 1, and suggest that these malnourished animals were significantly immunodepressed as measured in the MLC reaction. However, the mechanism of this depression is not mediated by an inversion of the TH/TS-C ratio. These data contrast with those previously reported for the immunodepression of the burned or traumatized patient in which the TH/TS-C ratios are reversed; these data suggest that a different, as yet to be elucidated, mechanism exists for the immunodepression of malnutrition.


Impacts of the combined exposure to seawater acidification and arsenic on the proteome of Crassostrea angulata and Crassostrea gigas.
Proteomic analysis was performed to compare the effects of Arsenic (As), seawater acidification (Low pH) and the combination of both stressors (Low pH + As) on Crassostrea angulata and Crassostrea gigas juveniles in the context of global environmental change. This study aimed to elucidate if two closely related Crassostrea species respond similarly to these environmental stressors, considering both single and combined exposures, to infer if the simultaneous exposure to both stressors induced a differentiated response. Identification of the most important differentially expressed proteins between conditions revealed marked differences in the response of each species towards single and combined exposures, evidencing species-related differences towards each experimental condition. Moreover, protein alterations observed in the combined exposure (Low pH + As) were substantially different from those observed in single exposures. Identified proteins and their putative biological functions revealed an array of modes of action in each condition. Among the most important, those involved in cellular structure (Actin, Atlastin, Severin, Gelsolin, Coronin) and extracellular matrix modulation (Ependymin, Tight junction ZO-1, Neprilysin) were strongly regulated, although in different exposure conditions and species. Data also revealed differences regarding metabolic modulation capacity (ATP β, Enolase, Aconitate hydratase) and oxidative stress response (Aldehyde dehydrogenase, Lactoylglutathione, Retinal dehydrogenase) of each species, which also depended on single or combined exposures, illustrating a different response capacity of both oyster species to the presence of multiple stressors. Interestingly, alterations of piRNA abundance in C. angulata suggested genome reconfiguration in response to multiple stressors, likely an important mode of action related to adaptive evolution mechanisms previously unknown to oyster species, which requires further investigation. The present findings provide a deeper insight into the complexity of C. angulata and C. gigas responses to environmental stress at the proteome level, evidencing different capacities to endure abiotic changes, with relevance regarding the ecophysiological fitness of each species and competitive advantages in a changing environment.


Safety and efficacy of perforator flap breast reconstruction with combined intraabdominal procedures.
Genetic testing for BRCA mutations has led to greater needs for breast reconstruction and prophylactic gynecologic procedures. A retrospective review of all perforator flap breast reconstructions was performed over 5 years. A total of 316 flaps were performed on 232 patients. Nineteen patients had an intraabdominal procedure at the time of their breast reconstruction, including 8 unilateral and 11 bilateral reconstructions (22 flaps). The concomitant procedures incurred an additional mean operative time of 61 minutes. One arterial thrombosis occurred leading to a single flap failure (1/30, 3.3%). No significant differences were noted in complication rates between the combined group and those who did not have a simultaneous procedure (anastomotic complications 3.3% vs. 7.7%; failure rate 3.3% vs. 3.1%; abdominal wound 10.5% vs. 15%; fat necrosis 10% vs. 12.2%). The coordinated effort allowing simultaneous intraabdominal procedures and perforator flap breast reconstruction affords effective reconstruction for those requiring additional procedures without an increase in postoperative complication rates.


[Encephalitis lethargica. The epidemic at the dawn of neurology].
Lethargic encephalitis is a neurological illness that shows a wide range of symptoms and signs, including neurological and psychiatric spectrum. It presented in an epidemic way, following influaenza relapses. The last relapse started at the beginning of 20th century and it was deeply described by Constantin von Economo. The illness described first in Europe and North America, was described in many others countries including Chile. There were beautiful descriptions by Chilean physicians like Lea-Plaza, Tello, Iturra and Cienfuegos. Their works showed the complexity of the illness like European physicians did too. The etiology is still unknown; however growing evidence about autoinmune aetiology is gaining force with the use of actual medical technology. In this work, we show encephalitis lethargica, focusing in clinical picture, the beauty of medical descriptions that physicians did at this date.


The scholarly work of Janice Morse: synthesis and reflection.
The author was afforded opportunity during her doctoral studies to compile and reflect upon the scholarly work of nurse researcher, Dr Janice Morse. Morse's refinement and development of patient-centred, empirically based concepts and theories, and her mastery of a diverse research repertoire, are an indisputable contribution to nursing knowledge. The author delineates four ways by which Morse's work contributes to nursing's disciplinary body of knowledge: (i) the consistent focus on the nurse-patient domain; (ii) the multiplicity of knowledge forms; (iii) the promotion of paradigm integration and methodological pluralism; and (iv) the predominance of prescriptive theories. Additionally, conjecture is put forth regarding the philosophical assumptions underpinning Morse's work. Morse serves as an excellent role model for nurse researchers who strive to ensure that nursing theories are amenable to clinical application, to research investigation and to utilization as a pedagogical tool.


Psychrosphaera aquimarina sp. nov., a marine bacterium isolated from seawater collected from Asan Bay, Republic of Korea.
Cells of strain SW33T, isolated from the seawater of Asan Bay, Republic of Korea, were characterized as Gram-stain-negative, aerobic, rod-shaped, motile and non-spore-forming. Phylogenetic analysis revealed that strain SW33T belonged to the genus Psychrosphaera and clustered distantly with the other genera in the family Pseudoalteromonadaceae in the phylogenetic tree. The 16S rRNA sequences of strain SW33T revealed high similarities to Psychrosphaera saromensis SA4-48T (98.7 %), Psychrosphaera haliotis KDW4T (97.4 %) and Psychrosphaera aestuarii PSC101T (97.3 %). The major fatty acids were C16 : 0 (27.9 %), summed feature 3 (32.2 %) and summed feature 8 (17.2 %). The predominant quinone was Q-8, and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified amino lipid. The DNA G+C content was 38.3 mol%. The DNA-DNA relatedness values with the three species of Psychrosphaera saromensis KCTC 23240T, Psychrosphaera haliotis KCTC 22500T and Psychrosphaera aestuarii KCTC 32274T were 22, 23 and 18 %, respectively. Based on the phenotypic characteristics and taxonomic analyses, we propose that strain SW33T represents a novel species within the genus Psychrosphaera, for which the name Psychrosphaera aquimarina sp. nov. with the type strain SW33T (=KCTC 52743T=CICC 24249T) is proposed.


New immunolatex spheres: visual markers of antigens on lymphocytes for scanning electron microscopy.
New immunochemical reagents consisting of antibodies bound to small latex spheres were used as visual markers for the detection and localization of cell surface antigens by scanning electron microscopy. Cross-linked latex spheres of various sizes from 300 to 3,4000 A in diameter were synthesized by aqueous emulsion copolymerization of methacrylate derivatives containing hydroxyl and carboxyl functional groups. Proteins and other molecules containing primary amino groups were covalently bonded to the acrylic spheres under a variety of mild conditions by the aqueous carbodiimide, cyanogen bromide, and glutaraldehyde methods. For use in the indirect immunochemical-labeling technique, goat antibodies directed against rabbit immunoglobulins were bonded to the spheres. These immunolatex reagents were shown to bind only to cells (red blood and lymphocytes) which had previously been sensitized with rabbit antibodies against cell surface antigens. Mouse spleen lymphocytes with exposed immunoglobulins on their surface (B cells) were labeled with these spheres and distinguished from unlabeled or T lymphocytes by scanning electron microscopy. The distribution of Ig receptors on lymphocytes was also studied using the spheres as visual markers. When lymphocytes were fixed with glutaraldehyde and subsequently labeled with the immunolatex reagents, a random distribution was observed by scanning electron microscopy; a patchy distribution was observed when unfixed lymphocytes were used. These results are consistent with studies using ferritin-labeled antibodies (S. De Petris and M. Raff. 1973. Nature [Lond.]. 241:257.) and support the view that Ig receptors on lymphocytes undergo translational diffusion. In addition to serving as visual markers for scanning electron microscopy, these latex spheres tagged with fluorescent or radioactive molecules have applications as highly sensitive markers for fluorescent microscopy and as reagents for quantitative studies of cell surface antigens and other receptors.


The association of sexual trauma with persistent pain in a sample of women veterans receiving primary care.
Women veterans report high rates of persistent pain and high rates of sexual trauma. We sought to determine whether the presence and intensity of persistent pain, as well as level of pain-related interference, in the VA Connecticut Women's Clinic population was positively associated with reports of sexual trauma. Women presenting for routine appointments at the VA Connecticut Women's Health Center were recruited for study. Participants (N = 213) provided detailed information about their demographic, psychosocial, clinical, pain, and sexual trauma status. Bivariate and multivariate analyses were conducted to determine whether a report of sexual trauma was independently associated with the presence of pain, and levels of pain intensity and pain-related interference. A substantial majority (78%) reported an ongoing pain problem, whereas the prevalence of any reported sexual trauma was 36%. In bivariate analysis, persistent pain was associated with a greater number of chronic conditions (P < 0.01), depression symptom severity (P < 0.05), a history of military sexual harassment (P < 0.05), and military forced sex (P < 0.05). In a multivariate logistic regression analysis, persistent pain was independently associated with having at least two (OR 3.32, 95% CI 1.11, 9.90), or three or more chronic conditions (OR 7.56, 95% CI 2.34, 24.4) and depressive symptom severity score (OR 1.10, 95% CI 1.02, 1.19), but was not associated with sexual trauma (OR 1.70, 95% CI 0.66, 4.42). In multivariate linear regression analyses that included only those who reported pain at the time of the assessment, white race (P < 0.05) and sexual trauma histories (P < 0.05) were significantly associated with level of pain intensity, whereas being married (P < 0.01) was negatively associated with pain intensity. Depressive symptom score (P < 0.001) and sexual trauma (P < 0.05) were also significantly associated with level of pain interference. Reported sexual trauma is prevalent and while not independently associated with the presence of pain among women veterans in our study, for those who have pain, it is associated with greater pain intensity and pain-related interference.


Planning health care for patients with Graves' orbitopathy.
To describe disease parameters of patients with Graves' orbitopathy in a tertiary referral center in order to plan health care resource allocations. To investigate whether the clinical activity and/or the severity of the disease can be used as a predictor of the duration of treatment. Retrospective, observational, non-comparative case series. One hundred and seventeen charts of GO-patients, randomly chosen out of a pool of 1600, referred to the Orbital Unit of the University Medical Centre Utrecht between 1 January 1992 and 1 January 2002, were analysed. Relevant parameters, such as age, gender, race, disease duration, smoking habits, concomitant diseases, previous treatment, symptoms and signs, number and sort of investigations, severity and activity scores, number and sort of treatments, treatment duration and outcome of treatment were retrieved and analysed. Disease activity and severity at entry were tested as possible predictors of disease duration and extent of treatment. Clinical profile at presentation; duration of the disease; extent of treatment; predictors of disease duration and of number of treatment interventions were the main outcome measures. Three percent of patients had Only Signs, but No Symptoms (OSNS), 61% had mild, 27% had moderately severe and 9% had severe GO. Fifteen percent had inactive disease at presentation, 65% had borderline activity and only 20% had active orbitopathy. Sixty percent complained about eyelid swelling and/or proptosis. The average period of eye treatment was 2.5 years (range: 0-110 months), during which patients were seen at an average of 8 times. Twenty percent needed no treatment at all. Fifteen percent were treated with nothing but lubricants and/or prisms. Twenty-five percent were treated with immunosuppressive modalities. Fifty-six percent underwent one or more surgical corrections. The Clinical Activity Score (CAS) was found to be significantly related to the duration of the treatment (p < 0.001), to the number of visits (p < 0.001), and to the number of surgical interventions (p < 0.001). The majority of GO patients referred to a tertiary referral centre has no or borderline disease activity and 'mild' orbitopathy, disfiguring eyelids and proptosis being the most frequent complaints. The disease activity as assessed with the CAS can be used to predict the duration and extent of the treatment.


An interaction between host and microbe genotypes determines colonization success of a key bumble bee gut microbiota member.
There has been a proliferation of studies demonstrating an organism's health is influenced by its microbiota. However, factors influencing beneficial microbe colonization and the evolution of these relationships remain understudied relative to host-pathogen interactions. Vertically transmitted beneficial microbes are predicted to show high levels of specificity in colonization, including genotype matching, which may transpire through coevolution. We investigate how host and bacterial genotypes influence colonization of a core coevolved microbiota member in bumble bees. The hindgut colonizing Snodgrassella alvi confers direct benefits, but, as an early colonizer, also facilitates the further development of a healthy microbiota. Due to predominantly vertical transmission promoting tight evolution between colonization factors of bacteria and host lineages, we predict that genotype-by-genotype interactions will determine successful colonization. Germ-free adult bees from seven bumble bee colonies (host genotypic units) were inoculated with one of six genetically distinct strains of S. alvi. Subsequent colonization within host and microbe genotypes combinations ranged from 0 to 100%, and an interaction between host and microbe genotypes determined colonization success. This novel finding of a genotype-by-genotype interaction determining colonization in an animal host-beneficial microbe system has implications for the ecological and evolutionary dynamics of host and microbe, including associated host-fitness benefits.


Similarities and differences in adolescent siblings' alcohol-related attitudes, use, and delinquency: evidence for convergent and divergent influence processes.
A growing body of research indicates that siblings influence each other's risky and deviant behaviors during adolescence. Guided by research and theory on sibling similarities and differences, this study examined the operation and implications of three different influence processes--social learning, shared friends, and sibling differentiation--during adolescence. Participants included one parent and two adolescent siblings (earlier born age: M = 17.17 years, SD = 0.94; later born age: M = 14.52 years, SD = 1.27) from 326 families. Data were collected via telephone interviews. Using reports from both older and younger siblings, two-stage cluster analyses revealed three influence profiles: mutual modeling and shared friends, younger sibling admiration, and differentiation. Additional analyses revealed that mutual modeling and shared friends as well as younger sibling admiration were linked to similarities in brothers' and sisters' health-risk behaviors and attitudes, whereas differentiation processes were associated with divergence in siblings' characteristics. The discussion focuses on refining the study of sibling influence, with particular attention paid to the operation and implications of both convergent and divergent influence processes.


Protective effects of nanostructures of hydrated C(60) fullerene on reproductive function in streptozotocin-diabetic male rats.
Diabetes mellitus is a well-recognized cause of male sexual dysfunction and impairments of male fertility. Streptozotocin (STZ) is used for medical treatment of neoplastic islet β-cells of pancreas and producing of animal model of diabetes mellitus type 1 that is characterized by suppression of reproductive activity due to the hyperglycaemia-induced oxidative stress and histopathological alterations in testes. Seeking for the agents that could alleviate diabetes-induced damage to reproductive system is yet the important area of inquiry. The present study was designed to evaluate whether hydrated C(60) fullerene (C(60)HyFn), which is known to be powerful bioantioxidant, eliminate testicular dysfunction induced by STZ-diabetes in rats. Wistar strain male albino rats were divided into four groups of six animals each: (1) control group, (2) C(60)HyFn-treated nondiabetic group, (3) STZ-diabetic group and (4) C(60)HyFn-treated diabetic group. Once hyperglycaemia was induced by STZ, rats in the second and fourth groups were treated with C(60)HyFn (in the form of drinking water) at the dose of 4μg/kg daily for 5 weeks. In diabetic rats, relative weights of right cauda epididymis, seminal vesicles, prostate, sperm motility and epididymal sperm concentration were significantly less than those of control group, but which were restored in the fourth group treated with C(60)HyFn (p<0.001). In hematoxylin and eosin staining, marked histopathological changes including degeneration, desquamation, disorganisation and reduction in germinal cells, interstitial oedema and congestion were evident in the testis of diabetic rats, but C(60)HyFn treatment resulted in recovery of histopathological changes and an increase in Johnsen's testicular score significantly (p<0.001). C(60)HyFn treatment restores the increased apoptosis induced by STZ-diabetes. In diabetic rats, levels of serum testosterone, testicular reduced glutathione (GSH) and alpha-tocopherol were significantly reduced and testicular lipid peroxidation level was increased (p<0.001). Nevertheless, treatment of diabetic rats with C(60)HyFn resulted in significant corrective effects on these parameters towards the control levels. C(60)HyFn, applied alone, did not exert any toxic effects in testicular tissues. Furthermore, C(60)HyFn treatment in diabetic and nondiabetic rats resulted in considerable elevations of some important polyunsaturated fatty acids. In conclusion, we have presented for the first time substantial evidence that administration of C(60)HyFn significantly reduces diabetes-induced oxidative stress and associated complications such as testicular dysfunction and spermatogenic disruption.


[A missed unstable cervical vertebra fracture in a patient with ankylosing spondylitis].
A 53-year-old man with a 13-year history ofankylosing spondylitis presented to the emergency clinic of another hospital because of neck pain after a fall from a low stepladder. The patient was put at ease and discharged after physical examination and X-ray of the cervical spine revealed nothing out of the ordinary. Because his neck pain persisted, the patient contacted his rheumatologist. New cervical X-rays revealed fractures of the body and articular process of CVI and CVII. The patient was referred to our hospital for orthopaedic treatment. The fractures healed during 2.5 months' treatment with halotraction and a halovest. All patients with ankylosing spondylitis with neck pain after trauma have an unstable cervical fracture until proven otherwise. Cervical fractures should be excluded in all cases and other diagnostic tools (CT-scan or MRI) must be used whenever necessary.