The Evolution of Post-Traumatic Stress Disorder following Moderate-to-Severe Traumatic Brain Injury.
Increasing evidence indicates that post-traumatic stress disorder (PTSD) may develop following traumatic brain injury (TBI), despite most patients having no conscious memory of their accident. This prospective study examined the frequency, timing of onset, symptom profile, and trajectory of PTSD and its psychiatric comorbidities during the first 4 years following moderate-to-severe TBI. Participants were 85 individuals (78.8% male) with moderate or severe TBI recruited following admission to acute rehabilitation between 2005 and 2010. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders (SCID-I), participants were evaluated for pre- and post-injury PTSD soon after injury and reassessed at 6 months, 12 months, 2 years, 3 years, and 4 years post-injury. Over the first 4 years post-injury, 17.6% developed injury-related PTSD, none of whom had PTSD prior to injury. PTSD onset peaked between 6 and 12 months post-injury. The majority of PTSD cases (66.7%) had a delayed-onset, which for a third was preceded by subsyndromal symptoms in the first 6 months post-injury. PTSD frequency increased over the first year post-injury, remained stable during the second year, and gradually declined thereafter. The majority of subjects with PTSD experienced a chronic symptom course and all developed one or more than one comorbid psychiatric disorder, with mood, other anxiety, and substance-use disorders being the most common. Despite event-related amnesia, post-traumatic stress symptoms, including vivid re-experiencing phenomena, may develop following moderate-to-severe TBI. Onset is typically delayed and symptoms may persist for several years post-injury.


Uses of homograft conduits for right ventricle to pulmonary artery connections in the neonatal period.
A significant number of congenital heart defects share the common characteristic that surgical interventions to either "repair" or palliate these defects generally require the use of nonautologous conduits to substitute for an absent right ventricle to pulmonary artery connection. Tetralogy of Fallot with pulmonary atresia, truncus arteriosus, transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction, and certain forms of double-outlet right ventricle are among the defects in which these conduits are used to create a pathway from the right ventricle to the pulmonary arteries. Such a conduit should ideally have growth potential, be nonthrombogenic, and function indefinitely. No such conduit has yet been devised, although efforts continue to be made with "tissue engineering" techniques to develop a conduit with one or more of these characteristics. In addition, when these conduits are used in the neonate, other characteristics including stiffness, conduit bulk, ease of passing sutures, and porosity are critically important to the success of a neonatal repair. We have found homografts to be the conduits which currently best fulfill the physical and handling requirements for neonatal applications in patients with defects in which autologous vascular tissue cannot easily make up for an absent right ventricle to pulmonary artery connection. The current discussion is therefore focused on the use of homograft conduits interposed between the right ventricle and pulmonary artery as part of neonatal reparative operations.


Activation of periprosthetic connective tissue in aseptic loosening of total hip replacements.
In aseptic loosening of initially well inserted total hip prostheses, implant wear debris and cyclic mechanical loading lead to a foreign body type of chronic inflammatory reaction, then to osteolysis, and finally to loosening of the implant. In the present work the reactive and adaptive changes of the periprosthetic tissues and pseudojoint were characterized by analysis of the local cell proliferation. Immunohistochemical demonstration of proliferating cells was performed by application of affinity purified rabbit antihuman Ki-67 antibodies to periprosthetic tissues obtained from revision operations for loose total hip prostheses. The fibrous areas and, in particular, the cell rich, vascular areas of the interface tissue (between implant and bone) and the pseudocapsule around aseptically loosened implants contained higher numbers of proliferating cells than the tissues around well fixed implants. In addition, the pseudosynovial lining occasionally contained some Ki-67 positive proliferating cells. Somewhat surprisingly, proliferating vascular endothelial cells were relatively rare. These findings suggest that reactive (interface tissues) and adaptive (pseudojoint and capsule formed around the artificial joint) tissue changes in loosening total hip prostheses comprise proliferation of local fibroblastlike cells. It is concluded that periprosthetic tissues of the loosened total hip prosthesis represent activated mesenchymal tissue.


Symmetry of neurological signs in Pakistani patients with probable inherited spastic cerebral palsy.
Seven Pakistani families are described with children manifesting a spastic cerebral palsy-like syndrome. One feature common to all affected patients was symmetry of neurological signs. Only one of these families had been offered genetic counselling and fewer than half had undergone clinical investigations. The importance of symmetry of neurological signs is reaffirmed as an indicator of a probable genetic aetiology in children with spasticity. Many families at risk of recurrence are not offered appropriate genetic advice, and some children with potentially diagnosable conditions are given a label of cerebral palsy without investigation of possible underlying inherited disorders.


Kinetics of 125I-beta 2-microglobulin turnover in dialyzed patients.
The kinetics of beta 2-microglobulin (beta 2m) were studied in 17 anephric or functionally anephric hemodialyzed patients and five healthy subjects as controls. Highly purified beta 2m was radiolabeled with 125I and infused into patients. The radioactivity in plasma and dialysis fluids was measured during a week including two or three dialysis sessions. Patients were classified in four groups according to treatment: hemodialysis on Cuprophan (N = 5) or on AN69 membranes (N = 5), hemofiltration (N = 4) and CAPD (N = 3). Plasma activity was fitted to a three compartment model. In controls almost 100% of the radioactivity was recovered in urine within 96 hours and there was no extrarenal catabolism. In patients the fractional catabolic rate ranged from 0.0008 to 0.0022 min-1 versus 0.026 to 0.047 min-1 in controls. The synthetic rate was within the range of values from controls in 10 patients but higher in the seven others. It was correlated with plasma beta 2m concentration. Kinetic data indicate a retention of intact beta 2m. The original model was therefore modified with an additional compartment representing beta 2m captation. The amount of capted beta 2m was more elevated in hemodialyzed patients than in patients treated by hemofiltration or CAPD, in whom it could reach 5 mg/kg/day. Hemofiltration or CAPD may eliminate about 30 to 100% of beta 2m produced and therefore contribute to the low captation amount of these patients, as compared with that of patients treated by hemodialysis.


The impact of genetic variation on sensitivity to opioid analgesics in patients with postoperative pain: a systematic review and meta-analysis.
Individual response to opioid analgesics varies among patients. This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain. A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain. This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain. A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases. Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms. Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information. The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.


Disinhibition and spontaneous recovery of response decrements produced by free reinforcement in rats.
Spontaneous recovery and disinhibition were studied in 3 experiments in which, after rats had been trained to bar press on a variable interval schedule of reinforcement, response rates were reduced by the introduction either of extinction or of a response-independent (free) reinforcement schedule. Spontaneous recovery was consistently obtained in extinction, especially when session durations were long. Under free reinforcement conditions there was little sign of spontaneous recovery, even when with high reinforcement rates response reduction was almost as rapid as in extinction. In disinhibition tests the introduction of noise produced increased responding under free reinforcement conditions, but not in extinction. The results are interpreted as demonstrating a dissociation between spontaneous recovery and disinhibition.


The role of vascular endothelial growth factor in the tissue specific in vivo growth of prostate cancer cells.
Despite the fact that cancer cells can be found in many vascular beds, continued growth of the metastatic tumor focus exhibits a significant degree of 'organ tropism', with only certain organs exhibiting the ravages of metastatic disease. Since a limiting factor to the growth of metastases beyond 2 mm in diameter, may be a lack of angiogenesis, we sought to determine whether tumor overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic factor related to prostate cancer metastasis, is causally related to organ specific tumor growth in a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human prostate cancer cell line LnCaP which unlike its parent, has a predilection for growth in bone, a common site for human prostate cancer metastasis. LnCaP-C4-2, is tumorigenic when injected intrafemorally in mice but requires co-injection of stromal components (Matrigel) to be tumorigenic in the subcutaneous site. Because of this site-specific tumorigenicity profile and relatively low VEGF mRNA and protein expression, this line was transfected with a full length cDNA encoding the 165 isoform of VEGF. Cells either overexpressing or not expressing the transfected gene were selected for study in vivo and in vitro. Overexpression of VEGF did not seem to affect in vitro cell growth. Such overexpression did affect tumorigenicity and in vivo tumor growth rates when cells were inoculated in the subcutaneus site. Interestingly, the dependency of subcutaneous tumorigenicity on Matrigel co-inoculation was still observed in cells overexpressing VEGF. In contrast to the impact that VEGF overexpression has on subcutaneous tumorigenicity, no such effect was observed when cells were inoculated in orthotopic/prostate (primary) or intrafemoral (metastatic) sites. In view of the importance of tumor-stromal interactions in growth of xenografts, we sought to determine if the host strain is important to the observed tumorigenicity effects of VEGF overexpression. No differences in subcutaneous tumorigenicity as a function of either Matrigel use or VEGF expression levels were observed when SCID/bg and RAG/pfp mouse strains were compared. In conclusion, our data indicate that the biological impact of prostate tumor VEGF overexpression is organ/site specific, leading to the speculation that it may play a part in the observed organ tropism of metastatic spread. In addition, these results highlight the importance of the tumor microenvironment in determining the biological impact of transfected and overexpressed genes in the study of tumor biology.


Gastric Banding for Morbid Obesity: the St Paul's experience.
A group of 300 consecutive morbidly obese patients who underwent a gastric banding procedure (gastric segmentation) by a single surgeon (F.S.W.) has been analyzed as to their sex, age, hospitalization, complications and sequelae, reversal or reoperation, and weight loss. The time frame was born August 1984 to January 1991. Eighty-eight percent were females and the average age was 37 years. The operative mortality was zero, and the complications were minor (1%). Eight women have had one or more normal pregnancies after the operation. Thirty-eight cases (12.7%) have had a reversal or a reoperation. Thirty-one patients (10.3%) were lost to follow-up. 271 cases have been operated on for more than 1 year and up to 6.5 years. In those patients not lost to follow-up or who have not had a reoperation, 109 or 54% had a weight loss of 30% or more and 140 or 68% had a weight loss of 25% or more. We conclude that in our setting, the gastric banding is successful in promoting weight loss with a minimum risk and an acceptable reoperation or reversal rate.


Laser versus stapler: outcomes in endoscopic repair of Zenker diverticulum.
To analyze a single surgeon's experience with endoscopic CO(2) laser and stapler repair of Zenker diverticulum (ZD) by comparing dysphagia and regurgitation outcomes. Retrospective chart review of 148 patient charts. Medical records of all patients receiving endoscopic repair of ZD with either CO(2) laser (61 patients) or stapler (67 patients) were reviewed. Additional data included demographics (age and sex), size (cm), preoperative and postoperative symptoms, need for revision, and complications. Symptoms of dysphagia were graded based on a modified Functional Oral Intake Scale 1 to 4 scale (1 = normal intake; 4 = severely limited/G-tube dependent). Regurgitation was also graded on a 1 to 4 scale (1 = no regurgitation; 4 = aspiration events). We noted no difference in patient age or defect size (laser, 3.26 cm; stapler, 3.53 cm; P .135). Significant differences were noted in return trips to the operating room for failed procedures (laser, 0; stapler, 7; P = .009), length of stay (laser, 3.19 days; stapler, 1.29 days; P < .001), time to oral intake (laser, 3.01 days; stapler, 1.22 days; P < .001). Significant improvement occurred in laser and staple patient symptom scales following surgery (P < .001). Laser dysphagia and regurgitation scores showed greater improvement when compared to stapler scores (P < .001). Endoscopic CO(2) laser and staple methods are effective in treating ZD. The laser can have greater efficacy and result in lower recurrence rates. Both methods are analyzed and compared.


Characterization of two monoclonal antibodies against the RON tyrosine kinase receptor.
RON is a receptor protein tyrosine kinase belonging to the hepatocyte growth factor (HGF) receptor family. Using Récepteur d'Origine Nantais (RON) transfected cell lines, Macrophage Stimulating Protein (MSP) was identified as the ligand of RON. RON is synthesized as a single chain precursor, which subsequently is cleaved to yield a disulfide-linked heterodimer, with a 40-kDa alpha chain and a 150-kDa beta chain. Activation of RON by MSP results in cell migration, shape change, and proliferation. The present work centers on the production and characterization of two monoclonal antibodies (MAbs) to RON called ID-1 and ID-2. Antibodies were generated by immunization of mice with Madin-Darby Canine Kidney (MDCK) cells expressing human RON (clone RE7). Both antibodies recognized the mature and precursor form of RON. The specificity of the anti-RON antibodies was confirmed using a hepatocarcinoma cell line HepG2 expressing both task MET and RON receptors. Specific immunoprecipitation with ID-1 and ID-2 or anti-MET antibody followed by Western blotting under reducing conditions with rabbit polyclonal antibodies against RON and MET showed that our anti-RON antibodies recognize specifically the RON receptor. Ligand binding experiments showed that both antibodies are able to block the binding of radiolabeled MSP to RON and showed also that the antibodies recognize two different epitopes in the molecule. The blocking of MSP binding to RON by the anti-RON antibodies was confirmed by inhibition of cell migration induced by MSP in HT-29-D4 cells. Significant immunostaining was not observed in any subpopulation of whole blood with either ID-1 or ID-2. We analyzed the expression of RON receptor in a number of human hematopoietic and nonhematopoietic cells lines by flow cytometry. We found a strong mean of fluorescence intensity (MFI) in colon adenocarcinoma cells SW620 and HT-29-D4, low MFI in SVK14 and HepG2 cells, and no immunostaining in melanoma, lymphoma, and leukemia cells. Immunohistochemistry revealed that RON was expressed in germinal centers of tonsil, in skin, small intestine, and colon. These antibodies defined RON as CDw136 during the last leucocyte typing VI.


Estimating the impact of alcohol policies on youth suicides.
Alcohol consumption has been identified as one of the most important risk factors for youth suicide. Previous research has shown a strong, empirical link between alcohol use and suicide. If alcohol use is a contributing factor in determining suicidal behaviors, then policies designed to reduce the alcohol consumption may succeed in reducing youth suicides as well. This paper looks at the role of alcohol-related policies in reducing completed suicides by American youths and young adults. This hypothesis comes from two well established relationships: i) the observed correlation between alcohol consumption and incidents of suicide, and ii) the negative relationship between the full price of alcohol and consumption. The alcohol policies examined are excise taxes on beer, measures of alcohol availability, and drunk driving laws. Data on completed suicides for each state in the United States are analyzed for the period 1976-1999. Negative binomial regressions are used to estimate a reduced form model of youth suicide. Suicides are analyzed by gender and age groups (ages 10-14, 15-19 and 20-24). The results indicate that increases in the excise tax on beer are associated with a reduced number of male suicides. This tax, however, has no impact on female suicides. Suicides by males ages 20-24 are positively related to the availability of alcohol, and negatively related to the presence of a 0.08 BAC (blood alcohol concentration) law and a zero tolerance law for drunk driving. Female suicides are not impacted by the availability of alcohol, although the drunk driving laws may impact suicides by teenage females. Policies designed to reduce alcohol consumption may have the unintended benefit of reducing suicides, particularly among young males. While this research shows that alcohol policies may be successful in reducing male suicides, such policies have little impact on female suicides. Future research should explore other potential types of policies and programs to reduce female suicides. Also, illegal drug use has been linked to suicides in a similar manner as alcohol consumption. Future research should consider the role of illegal drug consumption and related policies in determining youth suicides.


Penetrating neck injuries.
The modern approach to patients presenting with penetrating injuries to the neck requires the cautious integration of clinical findings and appropriate imaging studies for formulation of an effective, safe, and minimally invasive modality of treatment. The optimal management of these injuries has undergone considerable debate regarding surgical versus nonsurgical treatment approaches. More recent advances in imaging technology continue to evolve, providing more accurate and timely information for the management of these patients. In this article the authors review both historic and recent articles that have formulated the current management of penetrating injuries to the neck.


Associative deficit accounts of disrupted latent inhibition and blocking in schizophrenia.
Latent inhibition (attenuated responding to a signal due to signal-alone presentations preceding the signal-outcome pairings) and blocking (attenuated responding to Signal B due to Signal A being paired with the outcome prior to pairings of an AB compound with the outcome) are reportedly absent in acute schizophrenics. The common assumption that these phenomena reflect the normal functioning of attention and the observation that rats administered low doses of amphetamine show a similar disruption has resulted in the development of an animal model of attentional dysfunction in acute schizophrenia. Here, we selectively review the experimental and clinical literature concerning latent inhibition and blocking, their disruption in acute schizophrenia, and the current status of this model. We conclude that the construct validity of the model is compromised if latent inhibition and blocking are viewed in attentional terms because experimental data indicate both phenomena can be better understood in associative terms. We favor a framework in which disruption of latent inhibition and blocking in acute schizophrenics is viewed as an inability to compare and express stored representations (i.e. associative performance deficit). This change of perspective does not undermine the potential value of the model, but rather suggests that the nature of its validity should be reconsidered.


Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro.
Peroxynitrite (ONOO-) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO- on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO-, then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO- could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO- led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO- treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO- can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO--induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.


Phospholipase activation and arachidonic acid release in isolated intestinal epithelial cells.
A novel method for studying the mobilization of free arachidonic acid (AA) in isolated intestinal epithelial cells is described. The method is based on labeling the cellular phospholipids with 14C-AA and studying the release of this 14C-AA on subsequent phospholipase activation. Cells of high viability were isolated from the small intestine of guinea pigs and incubated with 14C-AA for 2 h; most of the incorporated 14C-AA was then esterified into phosphatidylethanolamine and phosphatidylcholine. When the labeled cells were stimulated with the calcium ionophore A23187 in the presence of external calcium, they released significant amounts of AA. In contrast, the cells released no AA when stimulated with A23187 in the absence of external calcium or in the presence of chlorpromazine or 4-bromophenacyl bromide, both of which are known to inhibit phospholipase A2 activity. On the other hand, the cells released significant AA in response to exogenous phospholipase C from Clostridium perfringens. These findings indicate that AA release in intestinal cells may be caused by calcium-mediated phospholipase A2 activation or by products of microbial phospholipase C activity. They also suggest the further use of 14C-AA-labeled cells for studying agents and mechanisms that may influence the release of AA in the gastrointestinal tract.


The two forms of bronchiolitis obliterans in heart-lung transplant recipients.
Bronchiolitis obliterans has emerged as the major long-term complication of heart-lung transplantation. We reviewed the histologic findings in lungs obtained from 11 patients who had received a combined heart-lung transplant at The Johns Hopkins Hospital. Ten lungs were obtained at autopsy, and one was obtained from a patient who was retransplanted because of severe bronchiolitis obliterans. Bronchiolitis obliterans was identified in seven of these 11 lungs. Three of the seven lungs with bronchiolitis obliterans were from patients who had received their transplants more than 6 months previously; the bronchiolitis obliterans in these patients was characterized by a relatively acellular concentric fibrosing process that was limited to the terminal bronchioles. The bronchiolitis obliterans in these three patients was felt to be secondary to chronic lung allograft rejection. Four of the seven patients with bronchiolitis obliterans had received their transplants less than 6 months previously; the bronchiolitis obliterans in these patients was focal and cellular. It extended into the distal alveolar spaces and, in several cases, was associated with aspirated material and foreign body-type giant cells. All four of these patients had concurrent infections, aspiration, or large airway obstruction, which were felt to be responsible for the development of bronchiolitis obliterans. Bronchiolitis obliterans in lung allograft recipients may have a variety of etiologies, and the etiology of this process in a particular case can often be deduced by the morphologic appearance of this lesion.


Determination of organochlorine pesticides in ground water using solid-phase microextraction followed by dual-column gas chromatography with electron-capture detection.
A rapid, sensitive, convenient, and highly quality-assured method is presented for the determination of 19 organochlorine pesticides (OCPs) in small samples (10 ml) of ground water. Samples are initially fortified with 2,4,5,6-tetrachloro-m-xylene (surrogate) and decachlorobiphenyl (retention time marker), then extracted with a 30-micron thickness polydimethylsiloxane solid-phase microextraction fiber. The analytes collected are thermally desorbed in a heated gas chromatographic inlet, separated using independent fused-silica capillary columns ("primary" and "confirmatory"), and detected using electron-capture detection. Two independent statistical procedures were used to evaluate the detection limits, which typically range between 10 and 40 ng l-1, for these analytes. Method performance was also evaluated using two additional protocols employing "performance evaluation" samples, in which authentic ground water samples were fortified to ca. 100 ng l-1 in each of at least six OCPs. The method satisfies additional strict criteria based on uniformity of fiber performance and minimal degradation of the thermally-sensitive analytes endrin and DDT.


On supertaskers and the neural basis of efficient multitasking.
The present study used brain imaging to determine the neural basis of individual differences in multitasking, the ability to successfully perform at least two attention-demanding tasks at once. Multitasking is mentally taxing and, therefore, should recruit the prefrontal cortex to maintain task goals when coordinating attentional control and managing the cognitive load. To investigate this possibility, we used functional neuroimaging to assess neural activity in both extraordinary multitaskers (Supertaskers) and control subjects who were matched on working memory capacity. Participants performed a challenging dual N-back task in which auditory and visual stimuli were presented simultaneously, requiring independent and continuous maintenance, updating, and verification of the contents of verbal and spatial working memory. With the task requirements and considerable cognitive load that accompanied increasing N-back, relative to the controls, the multitasking of Supertaskers was characterized by more efficient recruitment of anterior cingulate and posterior frontopolar prefrontal cortices. Results are interpreted using neuropsychological and evolutionary perspectives on individual differences in multitasking ability and the neural correlates of attentional control.


Human psyche and headache: tension-type headache.
The role of psychological factors related to headache, particularly tension-type headache (TTH), has long been a focus of investigation. The subject at issue is a complex one, with some aspects that are still being debated by experts. In episodic TTH, it is possible to hypothesise that headache is not only a "primary" headache that causes gratuitous pain to sufferers. In fact, it might represent an improper mode of communicating the sufferers' intimate discomfort, caused by an inadequate relationship between their personality profiles and events in their lives. As in migraine, in TTH, too, evidence has been found of comorbidity between headache and psychiatric disorders, including depression and anxiety disorder. Such evidence will have to be confirmed by further studies on the general population. As regards behaviour and personality traits, subjects with TTH had significantly higher scores than healthy controls on measures of automatic thoughts and alexithymia, and lower scores on assertiveness. Patients with chronic TTH had higher automatic thoughts scores than patients with episodic TTH. These findings suggest that people with TTH may have difficulty in expressing their emotions. Finally, psychological factors and emotional disturbances have been indicated as risk factors for TTH. Indeed, stress and mental tension are the most common factors that cause TTH.


Germany between 1780 and 1810.
A study of the relationships between the nobility, townsfolk, artisans and those living in rural areas, as well as the legislation that binds them together, are important for the understanding of dental treatments needed and/or requested by all of these groups. Education, literacy, citizenship, religious tolerance (or the lack of it) are also analysed in this chapter which provides a relevant background to the subsequent studies on German dental practice.


[Initial experiences with a new painless vascular approach in hemodialysis in children].
The necessity of hemodialysis in children is pointed out to be treated at specialized pediatric dialysis centers. In this connection a new vascular access is presented. The device is made from vitreous carbon and is mounted on a PTFE vascular prosthesis. By means of disposable connectors it can be dialysed without puncturing the implant. The device was implanted for the first time in the world in a small boy of 19 kg bodyweight. Our conclusion is that the biocarbon device is a welcome alleviation and an alternative for angio-access in children.


Pleomorphic adenomas of the lacrimal gland: a clinicopathological analysis.
To analyse retrospectively 32 cases of pleomorphic adenoma of the lacrimal gland diagnosed over a 10-year period in a tertiary referral eye centre from North India. The clinical features of 32 cases of pleomorphic adenomas diagnosed between 1991 and 2000 were analysed and the histopathological features reviewed light microscopically. Among the clinical features, a marked male predominance with younger age of presentation and left-sided dominance was noted. The duration of symptoms was less than 10 months in 28% cases. Histopathologically, the features included presence of cystic degeneration (15.6%) and squamous metaplasia (18.7%). Calcification, osteoid formation and malignant transformation (3.1% each) were occasionally observed. Pleomorphic adenomas of the lacrimal gland may present with duration of symptoms of less than 10 months. Cystic degeneration, squamous metaplasia, calcification or ossification may be observed in lacrimal gland pleomorphic adenomas, as has been described in pleomorphic adenomas of salivary glands. However, the presence of calcification and bone erosion radiologically in a lacrimal gland tumour does not necessarily indicate malignancy.


Expression of the apoptosis-related oncogenes bcl-2, bax, and p53 in Merkel cell carcinoma: can they predict treatment response and clinical outcome?
Chemotherapy and radiation therapy act predominantly through the induction of apoptosis in malignancies. Merkel cell carcinoma, an aggressive malignancy with prominent apoptosis, has proved to be sensitive to both modes to a certain degree. We used immunohistochemical methods to examine 25 Merkel cell carcinomas and 8 of their lymph node metastases to assess the status of the antiapoptotic gene bcl-2 and 2 proapoptotic genes, wild-type p53 and bax. All tumors showed prominent bax immunopositivity; 76% were positive for bcl-2, and only 28% were positive for p53, the latter presumably reflecting mutated p53. No statistically significant relationship was found between tumor immunopositivity and therapy response or survival. The widespread bax immunopositivity and the apparently low rate of p53 mutations, as suggested by the low rate of p53 immunopositivity, may be related to the presence of prominent apoptosis in Merkel cell carcinoma. The finding of bcl-2 immunopositivity in 76% of the tumors suggests that some of the tumor cells may be resistant to apoptosis-inducing agents.


Characterization of the AB loop region of TIMP-2. Involvement in pro-MMP-2 activation.
Tissue inhibitor of metalloproteinases-2 (TIMP-2) is unique as it is the only member of the TIMP family that is involved in the cellular activation of promatrix metalloproteinase-2 (pro-MMP-2) by virtue of forming a trimolecular complex with membrane type 1 matrix metalloproteinase (MT1-MMP) on the cell surface. TIMP-4 is similar in structure to TIMP-2 but is unable to support the activation of the proenzyme. Several reports have highlighted the importance of the TIMP-2 C-terminal domain in the pro-MMP-2 activation complex; however, very little is known about the role of the extended AB loop of TIMP-2 in this mechanism even though it has been shown to interact with MT1-MMP. In this study we show by mutagenesis and kinetic analysis that it is possible to transfer the MT1-MMP binding affinity of the TIMP-2 AB loop to TIMP-4 but that its transplantation into TIMP-4 does not endow the inhibitor with pro-MMP-2 activating activity. However, transfer of both the AB loop and C-terminal domain of TIMP-2 to TIMP-4 generates a mutant that can activate pro-MMP-2 and so demonstrates that both these regions of TIMP-2 are important for the activation process.


The psychological factors associated with poor compliance with treatment in asthma.
Poor patient compliance with inhaled medication is known to cause morbidity and mortality in asthma. The reasons for nonadherence are not fully understood. We wondered whether psychological factors, such as patient attitudes to asthma and its treatment, anxiety, depression, and interpersonal problems, may be related to asthma self-care and compliance. In a prospective study, 102 patients with asthma, aged 18-70 yrs, requiring treatment with regular inhaled corticosteroids and beta-agonists were recruited from a hospital out-patient clinic and four general practices in South East London. They underwent psychological assessment using the Hospital Anxiety and Depression Scale (HADS), the Inventory of Interpersonal Problems (IIP), and a semi-structured interview focusing on patient attitudes, self-care, compliance, social support and treatment beliefs. Patients were given terbutaline and budesonide turbohalers to use twice daily over 12 weeks. Turbohaler Inhalation Computers (TICs) recorded each inhalation, providing a measurement of compliance. Seventy two patients completed the study. Thirty seven took less than 70% of the prescribed dose over the study period or omitted doses for 1 week and were defined as noncompliant. The noncompliant group had a higher mean (SD) score for depression (4.7 (3.3)) than the compliant group (3.2 (2.5)). The sample had a high mean (SD) score for anxiety (8.3 (4.4)), but there was no significant difference between the compliant and noncompliant groups. Patients' self-report and clinicians' impressions of compliance were not good predictors of actual compliance. Using discriminant analysis, a model was obtained from the questionnaires and interview items, which correctly classified 74% of the patients as compliant or non-compliant.(ABSTRACT TRUNCATED AT 250 WORDS)


Anti-infectious phytotherapies of the tree-savannah of Senegal (West-Africa) II. Antimicrobial activity of 33 species.
The screening of the antimicrobial activity of 33 medicinal plants from Senegal is reported. None of these plants showed activity against the gram-negative test bacteria and against Candida albicans. Extracts of Cnestis ferruginea and Voacanga africana showed strong activity against Aspergillus niger. The former plant was also active against dermatophytes. Twenty-five of the plants tested showed activity against gram-positive bacteria.


Influence of milk on the antimutagenic potential of green and black teas.
The objective of this study was to evaluate whether addition of milk to green, black and decaffeinated black teas alters their antimutagenic activity. Two model mutagens were used, the direct-acting N'-methyl-N'-nitro-nitrosoguanidine (MNNG) and the indirect-acting 2-amino-3-methylimidazo-[4,5-flquinoline (IQ), and their mutagenic activity was determined in the Ames test, in the presence of tea and milk/tea mixtures. Solids from the milk/tea mixtures were removed by centrifugation and the supernatant analysed by HPLC for individual catechins and gallic acid in green tea, and thearubigins, theaflavins and flavonol glycosides in black teas. Addition of skimmed milk to all the teas failed to influence their antimutagenic activity towards the two mutagens. Addition of milk to green tea resulted primarily in loss of (-)-epigallocatechin gallate whereas in the black teas it primarily reduced theaflavins levels. The antimutagenic activity of green and black teas is not modulated by the presence of skimmed milk, even at high concentrations.


Knowledge and practices regarding tuberculosis: a survey of final-year medical students from Canada, India and Uganda.
Tuberculosis is one of the most common infectious diseases worldwide and is responsible for the largest number of deaths from a single infectious cause. The objective of this study was to compare the knowledge of and practices regarding tuberculosis in final-year medical students at schools from endemic and non-endemic areas. Final-year medical students at McMaster University in Canada, the Christian Medical College in India, and Makerere University in Uganda. A questionnaire consisting of 20 multiple-choice questions assessing knowledge, practices, and exposure. A total knowledge score (maximum=13) and a total practice score (maximum=5) were created for each study site. 160 questionnaires were returned; the response rate was 68.4% (65/95) for McMaster University, 39.7% (23/58) for the Christian Medical College and 78.3% (72/92) for Makerere University. Students from Makerere University had the highest knowledge scores but differences were non-significant after adjustment for patient exposure and curriculum time (F(2,153)= 1.80, P=0.16). Differences in practice scores, however, remained significant after adjusting for curriculum time and patient exposure (F(2,153)=5.14, P=0.006). Knowledge score (F(1,156)=5.05, P=0.02), patient exposure (F(1,153)=9.11, P=0.003), and curriculum time and patient exposure (F(2,153)=5.14, P=0.006) were statistically significant positive predictors of the total practice score. This study demonstrated significant differences in undergraduate exposure to tuberculosis, total knowledge, and practice competency at three medical schools in Canada, India, and Uganda. In general, the knowledge base and practice competency of all three graduating classes was adequate.


Lipoid pneumonia: CT findings.
To assess the CT findings of lipoid pneumonia. Chest radiography and CT performed in six patients with proven lipoid pneumonia were reviewed by two observers. Diagnosis was confirmed by biopsy (five cases) or bronchoalveolar lavage (one case). The clinical history of taking oily substance could be obtained retrospectively in all patients. Chest radiography showed bilateral air space consolidation in three cases, irregular mass-like lesions in two, and a reticulonodular pattern in one case. Computed tomography demonstrated diffuse parenchymal consolidation in three cases, localized areas of consolidation in two, and subpleural pulmonary fibrosis in one case. In two cases, fat with localized areas of consolidation could be seen on CT. In three cases with diffuse consolidation the attenuation was decreased but higher than that of subcutaneous fat. In one case with subpleural fibrosis no areas of low attenuation could be seen on CT. We conclude that in patients with lipoid pneumonia CT may demonstrate areas with low attenuation diagnostic of fat or areas with nonspecific low attenuation or soft tissue density.


Feasibility of structured light plethysmography for the evaluation of lung function in preschool children with asthma.
Structured light plethysmography (SLP) is a new noninvasive technology to capture the movement of the thoracic and abdominal wall, and to assess some parameters indicative for lung function. The purpose of the study was to evaluate the feasibility of SLP in children with asthma. A total of 52 patients were enrolled: 25 with asthma exacerbation (group 1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3). Every patient underwent SLP evaluation and a lung function test. SLP evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt) to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest wall movement, and flow is taken to be the time derivative of the chest wall movement (IE50) value increased in group 1 compared with groups 2 and 3, with statistical significance (p = 0.018); the data were consistent with the spirometry parameter. A correlation between the IE50 and forced expiratory volume in the first second of expiration was highlighted (r = -0.35, p = 0.019). SLP assessed airway obstruction, and its use in clinical practice could be applied in preschool children in future studies.


Cognitive, psychomotor, and physical performance in cold air after cooling by exercise in cold water.
This study evaluated performance after lowering core temperature at different rates while local tissues were either cooled (lower body) or not cooled (upper body). There were 10 men who volunteered to perform up to 8 cold water immersions (CWI) at combinations of 2 water temperatures (10 degrees C and 15 degrees C), 2 depths [waist (W), chest (C)], and 2 walking speeds (0.44 or 0.88 m x s(-1)) until their core temperature fell to 35.5 degrees C, stabilized above that temperature, or they requested to stop. They also completed a control trial (120 min rest in 19 degrees C air). Immediately following each CWI and control, cognitive and physical performance tests were performed in cold air (10 degrees C; CAE). Overall, the CWI protocol lowered rectal temperature by 0.3-1.0 degrees C. Mean skin temperature was approximately 26 degrees C and finger temperature was approximately 15 degrees C during CAE. No statistical differences were observed across trials for any cognitive test. On the physical performance tests, step test performance was degraded approximately 12% on CWI trials compared with control, but there were no differences in manual dexterity, hand grip strength, marksmanship, or pull-ups. These results indicate that cognitive performance can be maintained despite mild hypothermia, and that physical performance is related to local tissue temperature, not a moderately reduced core temperature.


Studies on cystic fibrosis using isoelectric focusing. II. Demonstration of deficient proteolytic cleavage of alpha2-macroglobulin in cystic fibrosis plasma.
A protein with an isoelectric point (pI) of 5.48 was found to be deficient in plasma from most cystic fibrosis (CF) homozygotes and obligate heterozygote carriers of CF as compared with normal control plasma. Purification of the protein with a pI of 5.48 from normal plasma was performed using ammonium sulfate precipitation, DEAE-cellulose and CM-cellulose chromatography, Sephadex G-200- gel filtration, starch block electrophoresis, and Sepharose 4B gel filtration. The purified protein migrated as a single band on polyacrylamide gel electrophoresis, and displayed a single arc on immunoelectrophoresis against polyvalent antiserum to whole human serum. Results from various techniques used in its characterization indicate that this protein is a fragment of alpha2-macroglobulin (alpha2M) which is derived from alpha2M by proteolytic cleavage of intact alpha2M subunits. Quantitation of alpha2M levels in plasma indicated no significant differences between levels of alpha2M in CF homozygote, obligate heterozygote carrier, or normal control plasma samples. Quantitation of arginine esterase activity in plasma treated with cloroform and ellagic acid indicated that both the total arginine esterase activity and that fraction of arginine esterase activity inhibited by soybean trypsin inhibitor (SBTI) were decreased in most CF homozygote and obligate heterozygote plasma samples relative to normal control values. The results of this study indicate that plasma samples from CF homozygotes and obligate heterozygote carriers for CF show deficient proteolytic cleavage of alpha2M as compared with normal control plasma, and suggest that a structural abnormality in alpha2M or a deficiency in plasma proteolytic activity may be responsible for this deficiency in proteolysis.


Fulminant parvovirus infection following erythropoietin treatment in a patient with acquired immunodeficiency syndrome.
We report the case of a 41-year-old black man with acquired immunodeficiency syndrome who developed a severe chronic anemia due to parvovirus infection. Bone marrow biopsy revealed erythroid aplasia. The infectious nature of the anemia was not recognized, and the patient was treated with erythropoietin. The patient's reticulocyte response was inadequate, however, and he remained anemic. A second bone marrow biopsy showed erythroid hyperplasia and prominent intranuclear parvovirus inclusions within erythroid progenitors. Erythropoietin was discontinued and was followed by a course of intravenous immunoglobulin, which resulted in rapid correction of anemia. To our knowledge, this is the first reported case of fulminant human parvovirus infection exacerbated by erythropoietin administration and documented by sequential bone marrow histologic examination. This case illustrates the critical importance of considering parvovirus in the etiology of chronic anemia with erythroid aplasia in immunocompromised patients.


Dynamics of radiationless transitions: effects of displacement-distortion-rotation of potential energy surfaces on internal conversion decay rate constants.
General expressions for calculating the internal conversion decay rate constants between two adiabatic electronic states and between two diabatic electronic states are derived. The expressions include the displacements, distortions, and rotations of potential energy surfaces as well as the temperature. For illustration, internal conversion rate constants between various singlet electronic states of ethylene and between the first excited S1 and the ground S0 singlet electronic states of azulene are calculated.


Comparison of reduced metagenome and 16S rRNA gene sequencing for determination of genetic diversity and mother-child overlap of the gut associated microbiota.
Use of the 16S rRNA gene in microbiota studies is limited by the lack of taxonomic and functional resolution. High resolution analyses are particularly important for understanding transmission and persistence of bacteria. The aim of our work was therefore to compare a novel reduced metagenome sequencing (RMS) approach with 16S rRNA gene sequencing to determine both the metagenome genetic diversity and the mother-to-child sharing of the microbiota in a cohort of 17 mother-child pairs. We found that although both approaches gave comparable results with respect to sample separation and taxonomy, RMS gave higher resolution and the potential for genomic-/functional assignment. Using RMS we estimated that the metagenome size increased from about 60 Mbp for 4-day-old children to about 225 Mbp for mothers. The 4-day-old children shared 7% of the metagenome sequences with the mothers, while the metagenome sequence sharing was >30% among the mothers. We found 15 genomes shared across >50% of the mothers, of which 10 belonged to Clostridia. Only Bacteroides showed a direct mother-child association, with B. vulgatus being abundant in both 4-day-old children and mothers. For the functional assignments, we identified a significant association between antibiotic usage during labor, and quantity of Fosfomycin resistance genes. In conclusion, our results show a higher functional and taxonomic resolution for RMS compared to 16S rRNA gene sequencing, where RMS enabled a detailed description of mother to child gut microbiota transmission - supporting a late recruitment of most gut bacteria and an effect of antibiotic treatment during labor on infant antibiotic resistance gene patterns.


Molecular mechanism of magnet formation in bacteria.
Magnetic bacteria have an ability to synthesize intracellular ferromagnetic crystalline particles consisting of magnetite (Fe3O4) or greigite (Fe3S4) which occur within a specific size range (50-100 nm). Bacterial magnetic particles (BMPs) can be distinguished by the regular morphology and the presence of an thin organic membrane enveloping crystals from abiologically formed magnetite. The particle is the smallest magnetic crystal that has a regular morphology within the single domain size. Therefore, BMPs have an unfathomable amount of potential value for various technological applications not only scientific interests. However, the molecular and genetic mechanism of magnetite biomineralization is hardly understood although iron oxide formation occurs widely in many higher animals as well as microorganisms. In order to elucidate the molecular and genetic mechanisms of magnetite biomineralization, a magnetic bacterium Magnetospirillum sp. AMB-1, for which gene transfer and transposon mutagenesis techniques had been recently developed, has been used as a model organism. Several findings and information on the BMPs formation process have been obtained within this decade by means of studies with this model organism and its related one. Biomineralization mechanism and potential availability in biotechnology of bacterial magnets have been elucidated through molecular and genetic approach.


[New criteria for the classification of the popliteal artery entrapment syndrome. Our experience with 14 extremities].
Authors explain their experiences with eight patients (14 affected limbs) with a popliteal artery entrapment syndrome. Classification, diagnosis and treatment were reviewed. Six limbs, with any malformation and presenting as a unique sign an important hypertrophy of their intern gastrocnemius muscle, couldn't be classified. As a result, a new classification of this pathology is presented being based on the anatomical and arteriographic aspects as well as oh the surgical indication. The important correlation between anomaly, physical complexion typus athletic and sports is noted.


A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).
Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. NCT01830231.


A study of stimulation-evoked activation of alpha 2-adrenoceptors in the rat isolated vas deferens.
Experiments were performed with prostatic and epididymal segments of rat vas deferens to determine whether alpha 2-adrenoceptors in this organ were activated during field stimulation of sympathetic terminals with short trains of pulses applied at low frequencies. In prostatic segments the magnitude of twitches evoked by trains of ten field pulses at 1 or 2 Hz declined after 2-3 s of stimulation. In contrast, facilitation of twitches and fusion of contractions occurred when similar stimulation was applied to epididymal segments. In prostatic segments from rats treated with reserpine (2.5 mg/kg i.p.) 24 h previously, there was no decline in the magnitude of twitches produced by successive impulses in a train of stimulating pulses. In epididymal segments from reserpine-treated rats facilitation of twitches in response to successive impulses in each train still occurred. In prostatic segments cocaine (5 and 10 mumol/l) enhanced twitch fade with stimulation at 1 and 2 Hz without altering the time for onset of this effect. In epididymal segments cocaine led to enhancement and prolongation of contractile responses. In prostatic segments yohimbine (0.01-0.06 mumol/l) reduced or reversed the effect of cocaine in enhancing twitch fade. In preparations where the reversal of the effect of cocaine by yohimbine was incomplete, subsequent addition of phentolamine (1 mumol/l) produced complete reversal. In epididymal segments yohimbine (0.01 mumol/l) produced a further enhancement in the twitch responses to stimulation at 1 and 2 Hz. Subsequent addition of phentolamine (1 mumol/l) reversed the facilitatory effects of cocaine and yohimbine. Propranolol (10 mumol/l) was without effect upon responses to stimulation in either segment of rat vasa deferentia. These experiments indicate that noradrenaline, released by short trains of impulses applied at low frequency to hypogastric nerve terminals activates prejunctional alpha 2-adrenoceptors in the prostatic segment of the vas deferens. In the epididymal portion the effects arising from activation of prejunctional alpha 2-adrenoceptors are outweighed by the consequences of activation of extrajunctional alpha 1-adrenoceptors located on longitudinally arranged muscle.


Distribution of two tumor-associated antigens in gastric lesions as detected by two monoclonal antibodies on tissue sections.
Two monoclonal antibodies antitumor-associated antigens, B1.1 and B72.3, have been used with the immunoperoxidase technique on tissue sections to study gastric carcinomas, dysplasia, intestinal metaplasia, and adenomas. B1.1 reacts with carcinoembryonic antigen (CEA); B72.3 reacts with a 220-400 kd glycoprotein present in colon, breast, and other carcinomas. CEA was found in 89% (34 of 38) and B72.3 antigen in 92% (35 of 38) of carcinomas. In half of these more than 50% of tumor cells were positive. The normal epithelium was usually negative or sporadically positive in a few cells. In dysplastic areas and adenomas the number of cells that were positive for the two antigens was greater than in normal epithelium and smaller than in carcinomas. In intestinal metaplasia B72.3 antigen was almost always present, whereas CEA was sometimes undetectable. Both the antigens proved to be good markers of neoplastic versus normal cells. The presence of B72.3 antigen in addition to CEA in dysplasia, adenomas, and intestinal metaplasia adds further evidence of their close relationship with gastric cancer.


Species-specific TT viruses in humans and nonhuman primates and their phylogenetic relatedness.
By means of polymerase chain reaction with a primer pair (NG133-NG147) deduced from the untranslated region (UTR) of TT virus (TTV), TTVs with markedly distinct genomic lengths were recovered from sera of humans and nonhuman primates, and their entire nucleotide sequences were determined. A human TTV [TGP96 of 2908 nucleotides (nt)] was obtained that was about 900 nt shorter than heretofore reported TTVs (3787-3853 nt). Likewise, TTVs of chimpanzee occurred in two distinct genomic sizes [Pt-TTV6 (3690 nt) and Pt-TTV8-II (2785 nt)]. Two TTVs of Japanese macaque [Mf-TTV3 (3798 nt) and Mf-TTV9 (3763 nt)] were comparable in genomic length, but only 55% similar in sequence. These five human and nonhuman primate TTVs, along with TTVs of tamarin [So-TTV2 (3371 nt)] and douroucouli [At-TTV3 (3718 nt)], were compared over the entire nucleotide sequence. Although the seven TTVs were only < or = 55% similar, they share a common genomic organization with two open reading frames (ORFs), designated ORF1 (654-735 amino acids) and ORF2 (91-152 amino acids). The N-terminal sequences of ORF1 proteins were rich in arginine, and sequence motifs necessary for transcription and replication were conserved among them all. Like the human prototype TTV (TA278), all seven TTVs from various animals possessed in common two 15-nt sequences (CGAATGGCTGAGTTT and AGGGGCAATTCGGGC) in the UTR that were covered by NG133 and NG147, respectively. These primers would be instrumental in research on TTVs in previously unexamined species for defining their virological characteristics and evolutionary relationships.


[Depressive and anxiety symptoms, coping strategies in patients with irritable bowel syndrome and inflammatory bowel disease].
Psychological factors play an important role in the etiopathogenesis of functional gastrointestinal disorders, like irritable bowel syndrome. In our study we compared certain psychological characteristics of patients suffering from functional and organic gastrointestinal disorders and healthy subjects. Age and gender matched irritable bowel syndrome and inflammatory bowel disease patients and healthy subjects were compared on their depressive symptoms (Beck Depression Inventory), anxiety symptoms (Spielberger State-Trait Anxiety Inventory) and coping strategies (Folkman-Lazarus Ways of Coping Questionnaire). GI patients groups were characterized by significantly more severe depressive and anxiety symptoms and by the prevalence of passive coping strategies. On the Beck Depression Inventory "Performance Difficulty" and "Somatic Symptoms" subscales, significant differences were observed between patients and healthy subjects, while on the "Negative affect" subscale, only IBS patients but not IBD patients scored significantly higher compared to healthy subjects. The functional GI group showed significantly more severe depressive and also more severe anxiety symptoms, but this latter did not reach statistical significance. No differences were detected regarding the use of coping strategies. Psychological screening and psychological and/or pharmacological interventions are recommended for GI patients, at least in the most severe and treatment resistant cases. Differences between IBS and IBD groups underline the importance of the increased psychic vulnerability of functional GI patients and emphasize the role of affective components in the etiopathogenesis of the disorder. Future studies should be directed toward the assessment of disease-specific psychic characteristics (e.g. pain-coping strategies, cognitive schemas), subjective symptom experience and illness-behavior.


[Synovial chondromatosis of the hip].
The authors report a case of synovial chondromatosis of the hip in physically active male adult operated on three years ago and apparently cured. Review of the literature shows that the diagnosis, essentially based on X-ray examination, bone-scan and arthrography, needs to be confirmed by histological examination. Treatment must be surgical and must be carried out as soon as possible to prevent arthrosis. Surgery should include thorough excision of the synovial membrane and a curettage of the acetabular fossa to avoid recurrence. Under these conditions, prognosis appears to be excellent.


Protein tyrosine phosphatase 1B (PTP1B) is required for cardiac lineage differentiation of mouse embryonic stem cells.
Protein tyrosine phosphatase 1B (PTP1B) has been shown to regulate multiple cellular events such as differentiation, cell growth, and proliferation; however, the role of PTP1B in differentiation of embryonic stem (ES) cells into cardiomyocytes remains unexplored. In the present study, we investigated the effects of PTP1B inhibition on differentiation of ES cells into cardiomyocytes. PTP1B mRNA and protein levels were increased during the differentiation of ES cells into cardiomyocytes. Accordingly, a stable ES cell line expressing PTP1B shRNA was established. In vitro, the number and size of spontaneously beating embryoid bodies were significantly decreased in PTP1B-knockdown cells, compared with the control cells. Decreased expression of cardiac-specific markers Nkx2-5, MHC-α, cTnT, and CX43, as assessed by real-time PCR analysis, was further confirmed by immunocytochemistry of the markers. The results also showed that PTP1B inhibition induced apoptosis in both differentiated and undifferentiated ES cells, as presented by increasing the level of cleaved caspase-3, cytochrome C, and cleaved PARP. Further analyses revealed that PTP1B inhibition did not change proliferation and pluripotency of undifferentiated ES cells. Taken together, the data presented here suggest that PTP1B is essential for proper differentiation of ES cells into cardiomyocytes.


Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.
The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %).


Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents.
SAR studies on a set of novel hydrophilic C-2 aminopyridinyl riminophenazines bearing variously functionalized basic side chains at C-3 were conducted. The novel compounds were evaluated for in vitro activity against two different species of Leishmania promastigotes, intramacrophage Leishmania amastigotes, chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, and also against mature-stage P. falciparum gametocytes. Their cytotoxicity was evaluated as well on BMDM cell lines. Most of the new compounds potently inhibited the growth of both genera of protozoa with IC50 values in the high nanomolar range and good selectivities versus mammalian cells. Besides their potent activity against asexual intraerythrocytic stages of P. falciparum, three compounds showed potential as transmission-blocking agents. The key role of the hydrophilic C-2 aminopyridinyl substituent to improve the leishmanicidal activity and the influence of the length and the nature of the basic side chain on the antiprotozoal activity and cytotoxicity were underlined.


Mammalian actin binding protein 1 is essential for endocytosis but not lamellipodia formation: functional analysis by RNA interference.
Mammalian actin binding protein 1 (mAbp1, also called SH3P7/Hip55) is structurally and functionally related to yeast Abp1 and to cortactin, both of which have been implicated in endocytotic processes. mAbp1 associates through its SH3 domain with dynamin, a large GTPase essential for vesicle fission. To clarify the function of mAbp1, we specifically knocked down its expression in human embryonic kidney 293T cells, using RNA interference (RNAi). Co-transfection of a short interfering RNA (siRNA) together with a plasmid coding for a surface marker, followed by purification of transfected cells, enabled us to obtain a cell population having up to 90% inhibition of mAbp1 expression. In mAbp1-knocked down cells, transferrin (Tf) receptor endocytosis was significantly inhibited and intracellular distribution of the early endosomal compartment was modified. In contrast, in these cells actin and microtubule filaments appeared normal, and formation of lamellipodia induced by active Rac was not inhibited. This study provides definitive evidence that mAbp1 is indispensable for receptor-mediated endocytosis.


Vulvar malignant melanoma: Pathogenesis, clinical behaviour and management: Review of the literature.
Vulvar malignant melanoma (VMM) is a rare disease, accounting for 5% of all vulvar malignancies and is characterized by low survival and high recurrence rates. It is considered as a distinct entity of mucosal melanoma. Prognostic factors are higher age, advanced Breslow thickness, and lymph node involvement whilst central localization and ulceration status are still under debate. Surgery is the cornerstone for the treatment of primary VMM, however, it can be mutilating due to the anatomical location of the disease. Elective lymph node dissection is not part of standard care. The value of sentinel lymph node biopsy in VMM is still being studied. Radiation therapy and chemotherapy as adjuvant treatment do not benefit survival. Immunotherapy in cutaneous melanoma has shown promising results but clinical studies in VMM are scarce. In metastatic VMM, checkpoint inhibitors and in case of BRAF or KIT mutated metastatic VMM targeted therapy have shown clinical efficacy. In this review, we present an overview of clinical aspects, clinicopathological characteristics and its prognostic value and the latest view on (adjuvant) therapy and follow-up.


Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit.
Placebo-controlled trials have shown that vitamin C supplementation decreases the duration and severity of common cold infections. However, the magnitude of the benefit has substantially varied, hampering conclusions about the clinical significance of the vitamin. In this paper, 23 studies with regular vitamin C supplementation (> or = 1 g/day) were analyzed to find out factors that may explain some part of the variation in the results. It was found that on average, vitamin C produces greater benefit for children than for adults. The dose may also affect the magnitude of the benefit, there being on average greater benefit from > or = 2 g/day compared to 1 g/day of the vitamin. In five studies with adults administered 1 g/day of vitamin C, the median decrease in cold duration was only 6%, whereas in two studies with children administered 2 g/day the median decrease was four times higher, 26%. The trials analyzed in this work used regular vitamin C supplementation, but it is conceivable that therapeutic supplementation starting early at the onset of the cold episode could produce comparable benefits. Since few trials have examined the effects of therapeutic supplementation and their results have been variable, further therapeutic trials are required to examine the role of vitamin C in the treatment of colds.


Microanalysis in biology and medicine. A review of results obtained with three microanalytical methods.
Three microanalytical methods have been used : X-ray emission, secondary ion emission and electron energy loss analysis. Althouth X-ray microanalysis is the most used method, many biological problems cannot be solved because of its relatively low sensitivity and inability to analyze light elements. New possibilities are offered by Secondary Ion Mass Analysis and Electron Energy Loss Analysis. Analysis by secondary ion emission permits the study of elements at low and even trace element concentration, and even the lightest elements such as hydrogen and beryllium are detected. Electron Energy Loss Analysis makes possible the study of very small volumes, less than 500 A in diameter. These methods have been applied to the study of a variety of biological tissues (mostly lungs, kidneys and biomineralized tissues) and typical applications to pathology and cell biology will be presented.


Accelerated autoimmune disease and lymphoreticular neoplasms in F1 hybrid PN/NZB and NZB/PN mice.
This report describes the first studies of inheritance of autoimmunity in inbred Palmerston North (PN) mice, a model of systemic lupus erythematosus (SLE). Mating of PN mice with the nonautoimmune DBA/2 strain produced evidence that PN disease had a recessive mode of inheritance. When PN mice were crossed with autoimmune NZB mice, female offspring from both crosses developed anti-DNA antibodies and died prematurely with vasculitis, renal disease, and lymphomas. In contrast, reciprocal hybrid males had different patterns of mortality; PN/NZB males from the PN female X NZB male mating had moderately prolonged life spans, whereas NZB/PN males from the opposite cross (NZB female X PN male) had prolonged survival to the mean age of 104 weeks. To determine if testicular hormones were solely responsible for increased longevity in hybrid males, PN/NZB and NZB/PN mice were castrated at 2 weeks of age and compared to sham-operated littermate controls. Prepubertal castration did not influence longevity in PN/NZB males, but loss of gonadal hormones significantly reduced life spans in reciprocal NZB/PN males. Female hybrids were not affected by oophorectomy. Because castration changed disease expression only in male hybrids from the NZB female X PN male cross, it was concluded that parentage influenced sensitivity to the protective effects of male hormones. Although surgical sterilization had disparate effects on males, castrated PN/NZB and NZB/PN males consistently outlived oophorectomized females. The lack of clear-cut reversal of disease in males subjected to early castration suggested that nonhormonal, possibly genetic, factors contributed to longevity in both groups of male hybrids.


Phase II study of oral tegafur-uracil and folinic acid as first-line therapy for metastatic colorectal cancer: Taiwan experience.
Tegafur-uracil has become an important regimen in the treatment of metastatic colorectal cancer. Tegafur is a prodrug that is converted to 5-fluorouracil (5-FU) and has been reported to be less toxic and to have a higher therapeutic index. The additional advantage of tegafur is oral administration, an important consideration to improve the quality of life in these patients. Tegafur in combination with uracil is thought to have greater anti-tumor activity due to the inhibitory effect of uracil on the degradation of 5-FU by hepatic dihydropyrimidine dehydrogenase. Tegafur with folinic acid has been reported with modest efficacy and acceptable toxicity. The purpose of this study was to evaluate the effectiveness and toxicity profile of oral tegafur-uracil plus folinic acid in Chinese patients with metastatic colorectal cancer. Between May 1998 and August 1999, 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. The initial dose of tegafur-uracil was 300 mg/m2/day for 28 days, followed by a 7-day rest period. Folinic acid was administered orally at a dose of 60 mg/day concurrently with tegafur-uracil. For patients with neutrophil count <1500/microl or a platelet count <100,000/microl after treatment, the treatment was postponed for a maximum of 2 weeks. After that time, if the neutrophil count was 1000-1500/microl and the platelet count was 70,000-100,000 microl, the dose of tegafur-uracil was reduced by 50%, and if lower values resulted, the treatment was discontinued. Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% CI, 18-47%), including five complete remissions and eight partial remissions, was achieved. Toxicity was mild and generally tolerable. Gastrointestinal toxicities, including diarrhea, nausea and vomiting, were the major side effects. Seven incidences (17.5%) of grade 3-4 gastrointestinal toxicity were observed. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. No episode of hepatic, renal, cardiac or neurological toxicity occurred. Two patients (5%) developed transient painful fissuring erythroderma over their palms and soles (the hand-foot syndrome). The data from our study indicate that oral tegafur-uracil plus folinic acid is an active and tolerable first-line treatment for Chinese patients with metastatic colorectal cancer, with the additional advantage of being easily administered at home.


The effects of differing acid concentrations, techniques and etch time on the etch pattern of enamel of erupted and unerupted human teeth examined using the scanning electron microscope.
The effects of varying acid concentration, etch time and agitation, on the etch properties of enamel from unerupted and erupted human teeth, were examined using the scanning electron microscope. Results showed that whilst there are differences in behaviour between erupted and unerupted enamel when conditions are varied, under most circumstances unerupted enamel will behave in a similar manner to erupted enamel. With low acid concentration both the duration of etch and agitation seem to be important factors in producing a roughened surface. It is suggested that the manufacturers' recommendations be more precise for a new low acid concentration orthodontic bonding package.


Preservation of sexual function in men during radical pelvic surgery.
Recent neuroanatomical findings making it possible to intraoperatively identify the branches of the pelvic plexus that innervate the corpora cavernosa have been used to modify standard radical prostatectomy and cystoprostatectomy to prevent postoperative sexual dysfunction.


Why Are Childhood Family Factors Associated With Timing of Maturation? A Role for Internal Prediction.
Children, particularly girls, who experience early familial adversity tend to go on to reach sexual maturity relatively early. This feature of adolescent development is believed to be an evolved strategy that arose because individuals with genes that caused them to mature relatively early under certain conditions left behind more descendants than those who did not. However, although much has been done to uncover the psychological and physiological mechanisms underlying this process, less attention has been paid to the evolutionary reasons behind why it might be advantageous. It has previously been suggested that this strategy evolved because early familial adversity accurately indicated later environmental adversity, under which conditions early reproduction would likely maximize evolutionary fitness. In this article, we contrast this "external prediction" model with an alternative explanation, which builds on the existing explanation and is mutually compatible with it but also distinct from it. We argue that accelerated development is advantageous because early adversity detrimentally affects the individual's body, increasing later morbidity and mortality; individuals may adapt to this internal setback by accelerating their development. Unlike the external prediction model, this "internal prediction" relies not on temporal environmental continuity but on long-term effects of early circumstances on the body.


The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia-reperfusion injury in rabbits: experimental study.
Experimental study. To determine the neuroprotective effects of zinc and melatonin on spinal cord ischemia-reperfusion (I/R) injuries of rabbits. The Experimental Research Centre of Selçuk University, Konya, Turkey. Twenty-four male rabbits underwent spinal cord ischemia by clamping the thoraco-abdominal aorta for 20 min. Twenty minutes before the aortic clamping, animals received zinc, melatonin or a combination of both. Neurological examination of the animals was performed three times during reperfusion period. The animals were killed 24 h after reperfusion. Spinal cord samples were taken for biochemical and histopathological evaluation. Pre-treated animals with zinc, melatonin or combination displayed better neurological outcomes than the I/R group (P<0.05). Zinc, melatonin and combined treatment prevented spinal cord injury by reducing apoptosis rate (P<0.05) and preserving intact ganglion cell numbers (P<0.05). Zinc pre-treatment protected spinal cord by preventing malondialdehyde (MDA) formation (P=0.002), increasing glutathione peroxidase (GPx) activity (P=0.002) and decreasing xanthine oxidase enzyme activity (P=0.026) at molecular level. Melatonin treatment also resulted with MDA formation (P=0.002), increased GPx activity (P=0.002) and decreased xanthine oxidase activity (P=0.026). The results of the study showed that prophylactic zinc and melatonin use in spinal cord I/R not only suppressed lipid peroxidation by activating antioxidant systems but also had significant neuroprotective effects by specifically improving the neurological and histopathological situation.


Anaerobic seminal fluid micro-flora in chronic prostatitis/chronic pelvic pain syndrome patients.
We investigated the seminal micro-flora of 116 men. Eighty-four men had chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and 34 of them were also leukocytospermic. Thirty-two asymptomatic men formed the control group. Micro-organisms were found in all of the 116 seminal fluid specimens. More than 20 different micro-organisms were found in both groups. Neisseria gonorrhoeae and Chlamydia trachomatis were not found. A high frequency of anaerobic bacteria was found in all groups (68-79%), and in most of the specimens, anaerobic micro-organisms were equal to or outnumbered the aerobic strains. We found 1-8 different micro-organisms in each semen sample, the total count of micro-organisms ranged from 10(2) to 10(7)/mL of semen. Both parameters were significantly higher in leukocytospermic CP/CPPS (NIH IIIA category) patients (median=5 different micro-organisms; total median count 5 x 10(4)) than in the control group (median=3 different micro-organisms; total median count 10(3)). In the CP/CPPS patients, the prevalence and/or count of some opportunistic bacteria was higher than in the control group. To show that the micro-organisms do not originate from the urethra, first voided urine was also investigated in 17 prostatitis patients and 15 controls. One patient had significantly fewer micro-organisms (median 1 vs. 4) and a lower total count of micro-organisms (median 10(2) vs. 10(4)/mL) in the first-catch urine than in the seminal fluid. We found only one third of the micro-organisms to be similar in urine and semen while anaerobic bacteria and some aerobic opportunists were infrequent in urine. Semen is a suitable specimen for the diagnosis of prostatitis.


Spatial memory deficits in aged rats: contributions of the cholinergic system assessed by ChAT.
Activity of choline acetylase (ChAT) was measured in basal forebrain cholinergic nuclei and in projection sites of these cells in the hippocampus and cortex of young rats and of aged rats who showed impaired performance on the radial arm maze. Decreased ChAT activity was found in the vertical diagonal band nucleus, the dentate gyrus and striatum of aged rats.


The cost of disability.
Approximately 16.5% of the adult population in the United States is disabled. About half of the disabled are severely limited and unable to work regularly. Musculoskeletal disorders are the most frequent type of disability. In the United States, there are three major types of disability insurance: Social Security Disability Insurance (a federal program), Workers' Compensation Insurance (usually a state-regulated program), and private health insurance. Recent years have seen a greater demand for private long-term disability insurance, as the trend increases toward less than total reliance on public programs to support disabled workers. The most recent statistics available indicate that Social Security Disability Insurance benefits are currently about $16.8 billion per year; workers' compensation benefits, $16.1 billion; and private disability income protection benefits, $5.2 billion. These figures add up to almost $40 billion in insurance costs. However, insurance costs are only part of the total cost because not everyone is covered by insurance, and insurance does not cover all disabilities. Disability can never be totally prevented or eliminated, but disability and its costs can be substantially reduced through more effective treatment and rehabilitation, including patient education and vocational rehabilitation.


Synthesis of a simplified analogue of eleutherobin via a Claisen rearrangement and ring closing metathesis strategy.
The enantioselective synthesis of a simplified eleutherobin analogue by ring closing metathesis (RCM) of the 2,9-divinyl-substituted tetrahydro-oxonin is described; the analogue and an advanced intermediate revealed microtubule stabilising properties in the micromolar range.


Chitosan supports the initial attachment and spreading of osteoblasts preferentially over fibroblasts.
The aim of this study was to determine chitosan's effect on osteoblast and fibroblast cell attachment. Mouse MC3T3-E1 osteoblasts and 3T3 fibroblasts were grown in the presence of serum on two commercially available chitosans, Chitosan-H (CH) and Protasan CL212 (PR). Cell attachment and immunofluorescent analysis at various time points were done to analyze initial phenotypic profiles. At 1h, significantly (P<0.05) fewer fibroblasts attached to CH or PR than serum-coated substrates. Osteoblast attachment to the same biopolymers at 1h was significantly greater than those seen with fibroblasts. At 24 h, levels of cell attachment for fibroblasts to both CH and PR significantly increased and were similar to levels seen in osteoblast cultures at both 1 and 24 h. Morphologically, immunofluorescent analysis showed that osteoblasts plated on the biopolymers were attached and beginning to spread at 1h, whereas fibroblasts appeared more rounded. At 24 h, fibroblasts plated on CH or PR revealed a heterogeneous population of round and semi-spread cells. In comparison, osteoblasts displayed phenotypes that were well spread with a developed cytoskeleton. These results suggest that CH and PR support the initial attachment and spreading of osteoblasts preferentially over fibroblasts, and that manipulation of the biopolymer can alter the level of attachment and spreading.


Barriers to prenatal detection of congenital heart disease: a population-based study.
To evaluate the extent and determinants of missed prenatal detection of congenital heart disease (CHD) in a population-based setting. This was a retrospective cohort study of cases with CHD, excluding minor defects, identified between 1997 and 2007 by a statewide surveillance program. We examined a comprehensive list of potential risk factors for which data were available in the surveillance database from abstracted medical charts. We analyzed the association of fetal, maternal and encounter factors with 1) whether a prenatal ultrasound was performed and 2) prenatal detection of CHD. CHD was detected prenatally in only 39% of 1474 cases, with no improvement in detection rate over the 10-year period. Among the 97% (n = 1431) of mothers who underwent one or more ultrasound examinations, 35% were interpreted as abnormal; fetal echocardiography was performed in 27% of the entire cohort. Maternal and encounter factors increasing the adjusted odds of prenatal detection included: family history of CHD (OR, 4.3 (95% CI, 1.9-9.9)), presence of extracardiac defects (OR, 2.7 (95% CI, 1.9-3.9)) and ultrasound location i.e. high risk clinic vs clinic (OR, 2.1 (95% CI, 1.3-3.1)). Defects that would be expected to have an abnormal outflow-tract view were missed more often (64%) than were those that would be expected to have an abnormal four-chamber view (42%). The majority of CHD cases over the 10-year study period were missed prenatally and detection rates did not increase materially during that time. The failure to detect CHD prenatally was related to encounter characteristics, specifically involving screening ultrasound examinations, which may be targeted for improvement.


Traumatic hip dislocation: early MRI findings.
Objective of this study was to present the spectrum of early magnetic resonance imaging (MRI) findings following traumatic dislocation of the femoral head, and to identify any associated injuries that may have therapeutic or prognostic significance and be better delineated by MRI than by conventional radiography. Prospective MRI of both hips was formed on 18 patients (14 male, 4 female; age range 14-54 years; average age 30.5 years) within 5 weeks of a traumatic femoral head dislocation. The interval between the time of injury and the time of injury and the imaging studies ranged from 2 to 35 days (average 13.2 days). Posterior dislocation was present in 14 patients and anterior dislocation in 4 patients. In the majority of cases, we performed axial T1, coronal T1, and coronal T2* (MPGR) sequences. Images were retrospectively evaluated by consensus of three radiologists for possible abnormalities of the bone and cartilage, joint space, and soft tissues. Because all patients were treated with closed reduction, surgical correlation was not obtained. All patients had a joint effusion or hemarthrosis. Of the 14 patients with posterior dislocation, isolated femoral head contusions (trabecular microfractures) were identified in 6 patients. Four patients had small femoral head fractures, and one had an osteochondral defect. Acetabular lip fractures were seen in six patients, and one patient had a labral tear. Four patients had intra-articular loose bodies and one had ligamentum teres entrapment. Twelve patients had iliofemoral ligament injury. All patients had muscle injury involving the gluteal region and medical fascial compartment, and 13 patients had anterior fascial compartment muscle injury. Seven patients with posterior dislocation had posterior fascial compartment injury. Of the four patients with anterior dislocation, two had bony contusion, two had cortical infraction, one had a labral tear, and all four had an iliofemoral ligament injury. All four patients in this group had muscle injury of the gluteal region and of the anterior and medial fascial compartments. MRI can effectively identify and quantify the muscle injury and joint effusion that invariably accompany traumatic hip dislocations. It is also useful for demonstrating trabecular bone contusion (trabecular injury) and iliofemoral ligament injury, which occur commonly with acute hip dislocation.


Concomitant measurements of serum annexin A5 levels and hematological indices as markers in recent and old myocardial infarction with low ejection fraction: A preliminary study.
Serum annexin A5 (anxA5) level is significantly increased in patients with acute coronary syndrome. Hematological indices are significantly increased in patients with ischemic heart disease. This study aimed to demonstrate the changes in the distribution of blood cells and the levels of anxA5 in patients presented with significant low ejection fraction ST-elevation acute myocardial infarction (STEMI) in comparison with corresponding patients with ischemic heart disease. Patients with low ejection fraction presenting at Hospital of Diyala University of Iraq were enrolled. Electrocardiograph (ECG), echocardiograph, hematological indices, serum annexin V (anxV) levels and the determinants of the cardio-metabolic risk factors were performed. Based on clinical examination, ECG findings and laboratory tests, patients were divided into healthy subjects (n=20); patients with acute MI (n=40) and with chronic MI (n=12). Acute MI has significant high levels of serum triglyceride, uric acid and high mean value of red cell distribution width (RDW) compared with healthy subjects and chronic MI. Platelet distribution width (PDW) is significantly reduced in patients of acute MI and chronic MI compared with healthy subjects, whereas the plateletcrit (PCT) is significantly higher in acute MI compared with healthy subjects. There is an insignificant difference between the means of serum anxA5 levels of acute MI (35.6±7.2ng/ml) and chronic MI (32.4±8.9ng/ml), but significantly higher than the cutoff level of the healthy subjects (5ng/ml). Measurement of serum annexin level is a useful diagnostic marker of acute or chronic MI with low ejection fraction.


[Preparation and in vitro evaluation of tetrandrine-loaded composite microspheres embedded with PLGA nanoparticles].
In this paper, we prepared a type of composite microspheres embedded with poly (lactic-co-glycolic acid) (PLGA) nanoparticles for efficient inhalation delivery of tetrandrine (Tet), which is a traditional Chinese medicine for anticancer, and studied its morphology, drug release profile, cytotoxicity and cellular uptake behavior. PLGA nanoparticles loading tetrandrine were prepared by emulsion solvent diffusion method, and composite microspheres were prepared by spray drying method with mannitol as matrix due to its osmotic effect. Scanning electronic microscopy, dynamic light scattering laser particle analyzer and confocal microscopy were applied to characterize the morphology and size of the microspheres. The drug loading rate, drug encapsulation efficiency and drug release properties were explored by RP-HPLC. The cytotoxicity in A549 cells between crude drug of Tet and Tet-loaded microspheres were compared by MTT assay. The cellular uptake behavior of microspheres in A549 cells was investigated using confocal laser scanning microscopy. The resultant microspheres were composed of 189 nm PLGA nanoparticles exhibited sizes ranging from 1 to 3 μm, with the highest deposition efficiency. The microspheres can easily be dissolved in a mimic lung environment and release redispersible PLGA nanoparticles. Compared with crude drug of Tet, Tet-loaded microspheres showed a certain sustained release property and higher cytotoxicity effect to A549 cells. The cellular uptake experiment demonstrated a higher excellent penetration ability of cells to nanoparticles and time-dependent uptake process. This study provides a basis for developing new inhalation therapies for lung cancer.


Within-subject variation of the salivary 3HC/COT ratio in regular daily smokers: prospects for estimating CYP2A6 enzyme activity in large-scale surveys of nicotine metabolic rate.
Nicotine is the major addictive compound in tobacco and is responsible for tobacco dependence. It is primarily metabolized to cotinine (COT) and trans-3'-hydroxycotinine (3HC) by the liver enzyme cytochrome P-450 2A6 (CYP2A6). The 3HC/COT ratio measured in the saliva of smokers is highly correlated with the intrinsic hepatic clearance of nicotine and, therefore, may be a useful non-invasive marker of CYP2A6 activity and metabolic rate of nicotine. This study assessed within-subject variation in salivary 3HC/COT ratios in six regular daily smokers. Our data provide evidence that 1. variation in the 3HC/COT ratio is not dependent on the time of sampling during the day (i.e., morning vs. night ) (P > 0.1) and 2. the average within-subject biological variation in the 3HC/COT ratio is approximately 26%. These findings should be useful for designing large-scale population surveys to assess the variation in the metabolic rate of nicotine (via CYP2A6) in smokers.


Rapid degradation of an unassembled immunoglobulin light chain is mediated by a serine protease and occurs in a pre-Golgi compartment.
The immunoglobulin kappa light chain produced by the CH12 lymphoma is unusual because it is not secreted when expressed in the absence of a heavy chain. Instead, it undergoes rapid intracellular degradation. This degradation is selective, as another light chain expressed in the same cell is not degraded. It is also a property of the CH12 kappa chain itself, since it is degraded rapidly when expressed either in another myeloma cell or in COS-1 fibroblasts. When provided a heavy chain, this kappa chain assembles into IgM and is then protected from proteolysis. The degradation of kappa requires ATP, is sensitive to reduced temperature and to the thiol reagent diamide. Of all the proteolytic inhibitors tested, 3,4-dichloroisocoumarin, L-1-tosylamido-2-phenylethyl chloromethyl ketone, and to a lesser extent 1-chloro-3-tosylamido-7-amino-2-heptanone, inhibit kappa degradation, suggesting the involvement of a serine protease. The degradation of kappa does not require transport to the Golgi complex, nor is it sensitive to a variety of lysosomotropic agents. Both immunofluorescence and the observed association with the endoplasmic reticulum (ER) stress proteins GRP78/BiP and GRP94 indicate that the kappa chain is localized mostly in the ER. When a point mutation which blocks transport to the Golgi complex is introduced into this kappa chain, the association with the stress proteins is enhanced but the rate of degradation is not significantly decreased. We conclude that the CH12 kappa chain is a particularly good substrate for an ER degradation machinery, and that its sensitivity to the protease(s) is governed by its state of assembly. This ER degradation provides a possible quality control mechanism during the differentiation of B lymphocytes.