Untangling Cellular Host-Pathogen Encounters at Infection Bottlenecks.
Bacterial pathogens can invade the tissue and establish a protected intracellular niche at the site of invasion that can spread locally (e.g., microcolonies) or to systemic sites (e.g., granulomas). Invasion of the tissue and establishment of intracellular infection are rare events that are difficult to study in the in vivo setting but have critical clinical consequences, such as long-term carriage, reinfections, and emergence of antibiotic resistance. Here, I discuss Salmonella interactions with its host macrophage during early stages of infection and their critical role in determining infection outcome. The dynamics of host-pathogen interactions entail highly heterogenous host immunity, bacterial virulence, and metabolic cross talk, requiring in vivo analysis at single-cell resolution. I discuss models and single-cell approaches that provide a global understanding of the establishment of a protected intracellular niche within the tissue and the host-pathogen landscape at infection bottlenecks during early stages of infection. Studying cellular host-pathogen interactions in vivo can improve our knowledge of the trajectory of infection between the initial inoculation with a dose of pathogens and the appearance of symptoms of disease.


New Formulations of Polysaccharide-Based Hydrogels for Drug Release and Tissue Engineering.
Polysaccharide-based hydrogels are very promising materials for a wide range of medical applications, ranging from tissue engineering to controlled drug delivery for local therapy. The most interesting property of this class of materials is the ability to be injected without any alteration of their chemical, mechanical and biological properties, by taking advantage of their thixotropic behavior. It is possible to modulate the rheological and chemical-physical properties of polysaccharide hydrogels by varying the cross-linking agents and exploiting their thixotropic behavior. We present here an overview of our synthetic strategies and applications of innovative polysaccharide-based hydrogels: hyaluronan-based hydrogel and new derivatives of carboxymethylcellulose have been used as matrices in the field of tissue engineering; while guar gum-based hydrogel and hybrid magnetic hydrogels, have been used as promising systems for targeted controlled drug release. Moreover, a new class of materials, interpenetrating hydrogels (IPH), have been obtained by mixing various native thixotropic hydrogels.


Purification of Escherichia coli 30S ribosomal proteins by high performance liquid chromatography.
High performance liquid chromatography was applied to the separation of proteins derived from the Escherichia coli 30S ribosomal subunit. Several methods of separating this protein mixture has been tested: size-exclusion chromatography on hydrophilic phases; ion exchange and reversed phase chromatography (on C2 to C18 hydrocarbon-bonded supports). Various elution systems were examined in order to obtain pure proteins suitable for micro-sequence analysis. The resolution and yields of the proteins varied considerably, depending on the type of support and gradient system used. The best results were achieved with uniformly globular-shaped supports of large pore size, and by combining high performance size exclusion with rechromatography on reversed phase columns. Purification conditions for the individual proteins are listed. The methods employed avoid any precipitation step and allow easy identification of the proteins by one or two-dimensional gel electrophoresis, amino-acid analysis or direct manual or automatic micro-sequencing. Since the isolation time is much reduced compared with conventional purification procedures, the proteins obtained by the techniques described here are well suited for topographical and immunological studies or reconstitution assays. Ribosomal proteins of other organisms can be separated under similar conditions.


Mechanisms of increased susceptibility of immature and weaned pigs to Escherichia coli heat-stable enterotoxin.
Pigs demonstrate an increased sensitivity and susceptibility to Escherichia coli heat-stable enterotoxin (STa) in the 1st wk of life and immediately after weaning. To determine the possible mechanisms for this increased susceptibility, we compared STa binding, guanylate cyclase activation, and photoaffinity cross-linking to porcine jejunal brush border membranes prepared from immature (less than or equal to 1 wk of age) versus adult pigs as well as 3-wk-old weaned versus unweaned pigs. The STa binding capacity of immature pigs was nearly twice that of adult pigs (11.73 +/- 1.52 versus 6.00 +/- 0.96 x 10(-11) mol/L, p less than 0.001), and the STa binding capacity of weaned pigs was nearly three times greater than that of unweaned pigs (17.48 +/- 2.10 versus 4.86 +/- 1.02 x 10(-11) mol/L, p less than 0.001). Scatchard analysis suggested a single class of STa receptor, with an association of binding constant of approximately 10(9) L/mol at all ages. Maximum guanylate cyclase response (expressed as pmol cyclic GMP generated/mg brush border membrane protein/min) was greater in immature versus adult pigs (1312 +/- 831 versus 320 +/- 92, p less than 0.02). Weaned pigs had a greater maximum guanylate cyclase activation than unweaned pigs (1126 +/- 692 versus 624 +/- 298); however, this difference was not statistically significant. Autoradiograms demonstrated specific cross-linking of 125I-STa to a number of distinct radiolabeled bands (62, 66, 84, 92, 160, and 165 kD). There was a difference in the size and trypsin sensitivity of these radiolabeled bands as a function of age and weaning. Treatment with trypsin decreased the intensity of the 160 to 165-kD bands while increasing the intensity of the 62- to 66- and 84- to 92-kD bands. These differences in STa binding, guanylate cyclase activation, and STa receptor size may increase the susceptibility of pigs during the 1st wk of life and at weaning to STa-mediated diarrheal disease.


Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer.
The objective of this study was to evaluate the efficacy and safety of Endostar combined with concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC). Patients with unresectable stage III NSCLC were treated with Endostar (7.5mg/m(2)/d) for 7days at weeks 1, 3, 5, and 7, while two cycles of docetaxel (65mg/m(2)) and cisplatin (65mg/m(2)) were administered on days 8 and 36, with concurrent thoracic radiation to a dose of 60-66Gy. Primary end points were short-term efficacy and treatment-related toxicity. Fifty patients were enrolled into the study, and 48 were assessable. Of the 48 patients, 83% had stage IIIB and 65% had N3 disease. Median follow-up was 25.0months. Overall response rate was 77%. The estimated median progression-free survival (PFS) was 9.9months, and the estimated median overall survival (OS) was 24.0months. The 1-, 2-, and 3-year local control rates were 75%, 67%, and 51%, PFS rates were 48%, 27%, and 16%, and OS rates were 81%, 50%, and 30%, respectively. All toxicities were tolerable with proper treatment. The combination of Endostar with CCRT for locally advanced NSCLC patients was feasible and showed promising survival and local control rates.


Yoga Pose Estimation and Feedback Generation Using Deep Learning.
Yoga is a 5000-year-old practice developed in ancient India by the Indus-Sarasvati civilization. The word yoga means deep association and union of mind with the body. It is used to keep both mind and body in equilibration in all flip-flops of life by means of asana, meditation, and several other techniques. Nowadays, yoga has gained worldwide attention due to increased stress levels in the modern lifestyle, and there are numerous methods or resources for learning yoga. Yoga can be practiced in yoga centers, through personal tutors, and can also be learned on one's own with the help of the Internet, books, recorded clips, etc. In fast-paced lifestyles, many people prefer self-learning because the abovementioned resources might not be available all the time. But in self-learning, one may not find an incorrect pose. Incorrect posture can be harmful to one's health, resulting in acute pain and long-term chronic concerns. In this paper, deep learning-based techniques are developed to detect incorrect yoga posture. With this method, the users can select the desired pose for practice and can upload recorded videos of their yoga practice pose. The user pose is sent to train models that output the abnormal angles detected between the actual pose and the user pose. With these outputs, the system advises the user to improve the pose by specifying where the yoga pose is going wrong. The proposed method was compared to several state-of-the-art methods, and it achieved outstanding accuracy of 0.9958 while requiring less computational complexity.


Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders.
To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype.


Structural changes in the myosin filament and cross-bridges during active force development in single intact frog muscle fibres: stiffness and X-ray diffraction measurements.
Structural and mechanical changes occurring in the myosin filament and myosin head domains during the development of the isometric tetanus have been investigated in intact frog muscle fibres at 4 degrees C and 2.15 microm sarcomere length, using sarcomere level mechanics and X-ray diffraction at beamline ID2 of the European Synchrotron Radiation Facility (Grenoble, France). The time courses of changes in both the M3 and M6 myosin-based reflections were recorded with 5 ms frames using the gas-filled RAPID detector (MicroGap Technology). Following the end of the latent period (11 ms after the start of stimulation), force increases to the tetanus plateau value (T(0)) with a half-time of 40 ms, and the spacings of the M3 and M6 reflections (S(M3) and S(M6)) increase by 1.5% from their resting values, with time courses that lead that of force by approximately 10 and approximately 20 ms, respectively. These temporal relations are maintained when the increase of force is delayed by approximately 10 ms by imposing, from 5 ms after the first stimulus, 50 nm (half-sarcomere)(-1) shortening at the velocity (V(0)) that maintains zero force. Shortening at V(0) transiently reduces S(M3) following the latent period and delays the subsequent increase in S(M3), but only delays the S(M6) increase without a transient decrease. Shortening at V(0) imposed at the tetanus plateau causes an abrupt reduction of the intensity of the M3 reflection (I(M3)), whereas the intensity of the M6 reflection (I(M6)) is only slightly reduced. The changes in half-sarcomere stiffness indicate that the isometric force at each time point is proportional to the number of myosin heads bound to actin. The different sensitivities of the intensity and spacing of the M3 and M6 reflections to the mechanical responses support the view that the M3 reflection in active muscle originates mainly from the myosin heads attached to the actin filament and the M6 reflection originates mainly from a fixed structure in the myosin filament signalling myosin filament length changes during the tetanus rise.


Ferritin-bearing lymphocytes in patients with cancer.
Ferritins, a group of isomeric proteins that have important functions in iron metabolism and storage, have been demonstrated to be carcinoembryonic antigens. It has been recently shown that a subpopulation of lymphocytes from the peripheral blood of patients with Hodgkin's disease or breast cancer bear ferritin on their surface membranes. In view of the potential diagnostic and prognostic value of ascertaining the number of ferritin-bearing lymphocytes, the authors developed a simple indirect immunofluorescent technique for identifying them and used this technique to examine the peripheral blood lymphocytes of 44 patients with carcinomas of the head and neck (26), colon (14), and lung (4). It was found that patients with cancer had a mean percentage of 10% ferritin-bearing lymphocytes in their peripheral blood as compared with 3.1% in controls. Ferritin binding did not appear to be influenced by a cell's capacity to form sheep erythrocyte (E) rosettes since no correlation could be found between the percentages of lymphocytes bearing ferritin and those forming three different varieties of E-rosettes. There appeared to be no correlation of the percentages of ferritin-bearing lymphocytes with clinical staging except for a small, but significant (P less than 0.05), increase in the number of patients with head and neck cancer and nodal metastases. Although the functional significance of ferritin-bearing lymphocytes is currently unknown, the appearance of this subpopulation of cells in the blood appears to be associated with cancer. This assay may prove to be useful as a diagnostic tool, as a prognostic tool, or as a means of identifying patients at a risk for developing cancer and, therefore, it deserves further exploration.


Psychological distress and mental health service contact of unaccompanied asylum-seeking children.
Evidence is emerging that psychological problems, particularly symptoms of depression and post-traumatic stress disorder, are more prevalent in unaccompanied asylum-seeking children (UASC) than their accompanied peers. However, little is known about help seeking and mental health service (MHS) utilization in this group, and how this relates to their psychological needs. This study aims to describe the level of psychological distress among a group of UASC and the pattern of MHS contact. Socio-demographic data on 71 UASC residing in London was obtained and self-report questionnaires were completed regarding trauma events (Harvard Trauma Questionnaire), general psychological distress [Strengths and Difficulties Questionnaire (SDQ)], post-traumatic stress symptoms (Impact of Event Scale), depressive symptoms (Birleson Depression Self-Rating Scale for Children) and contact with MHS (Attitudes to Health and Services Questionnaire). UASC were mainly male (n = 48, 67.6%), Black African (n = 39, 54.9%) and their median age was 17 years (interquartile range = 15; 17). They had been living in the UK for a median of 18 months. Eight (11.3%) scored on the SDQ borderline/abnormal range for total symptoms, but this was 21 (29.6%) using the SDQ emotional subscale. Forty-seven (66.2%) were at high risk for post-traumatic stress disorder and nine (12.7%) at high risk for depressive disorder. Only 12 (17%) had MHS contact. Predictors of MHS contact were depressive symptoms and duration of time in the UK. UASC had a high level of emotional symptoms, especially post-traumatic stress symptoms. However, only a small proportion of UASC were in contact with MHS. This suggests a high level of MHS under-utilization, and reasons for this are discussed.


Retention of susceptibility to mitogens after direct dansylation of viable human lymphocytes.
The covalently binding fluorescent probe 5-dimethylamino-1-naphthalenesulfonyl (dansyl) chloride was affixed directly to the plasma membrane of viable human peripheral blood lymphocytes via a solid phase transfer method utilizing Sephadex G-10 as the transfer vehicle. After dansylation, lymphocytes retain maximal short-term viability. Dansyl, as the protein conjugate or as the free acid, does not appear to penetrate the cells to any significant extent. Dansylated mixed lymphocyte cultures respond to lectin mitogen stimulation for at least 72 hr. Furthermore, differential response of dansylated lymphocytes in culture to three plant lectin mitogens provides a clue to the binding loci of concanavalin A with respect to phytohemagglutinin and pokeweed mitogen on the lymphocyte surface receptors for these lectins. The ability to sustain functionally responsive dansylated lymphocytes for several days in culture suggest that such probe-tagged cells may be useful in elucidating aspects of the plasma membrane in the regulation of cell behavior.


Pay for performance in behavioral health.
Pay for performance is a rapidly expanding strategy intended to improve the quality and value of health care in the United States. The application of this strategy for behavioral health has not yet been systematically examined. This article presents the results of a targeted national effort to identify pay-for-performance programs in behavioral health and describe their core components. The authors describe pay-for-performance programs currently being implemented in the mental health and substance abuse treatment fields. On the basis of responses from 109 screening informants who were identified as being likely to have knowledge of existing pay-for-performance programs, the authors identified 24 specific pay-for-performance programs and interviewed 28 individuals associated with these programs. The semistructured interview protocol consisted of 36 questions assessing the core program components. Thirteen programs targeted behavioral health specialists or substance abuse treatment providers. Eleven programs targeted primary care providers. Depression was the most common of the behavioral health conditions targeted. Financial incentives offered in behavioral health pay-for-performance programs were often small. Many programs struggled to obtain accurate and valid data on quality and outcomes of care, and the public reporting of results was not widespread. On the basis of this analysis, the authors recommend a number of actions to improve the implementation and impact of behavioral health pay-for-performance programs on quality of care. The authors reaffirm the finding identified by the Leapfrog Group's "Rewarding Results" initiative--that is, pay for performance is not a magic bullet that alone will improve quality and control costs. Although pay-for-performance programs hold promise for advancing the overall performance of the U.S. health care system, more intensive efforts aimed at strengthening the quality infrastructure in behavioral health will be required.


Properties of a novel extracellular cell-free ice nuclei from ice-nucleating Pseudomonas antarctica IN-74.
Some ice-nucleating bacterial strains, including Pantoea ananatis (Erwinia uredovora), Pseudomonas fluorescens, and Pseudomonas syringae isolates, were examined for the ability to shed ice nuclei into the growth medium. A novel ice-nucleating bacterium, Pseudomonas antarctica IN-74, was isolated from Ross Island, Antarctica. Cell-free ice nuclei from P. antarctica IN-74 were different from the conventional cell-free ice nuclei and showed a unique characterization. Cell-free ice nuclei were purified by centrifugation, filtration (0.45 microm), ultrafiltration, and gel filtration. In an ice-nucleating medium in 1 liter of cell culture, maximum growth was obtained with the production of 1.9 mg of cell-free ice nuclei. Ice nucleation activity in these cell-free ice nuclei preparations was extremely sensitive to pH. It was demonstrated that the components of cell-free ice nuclei were protein (33%), saccharide (12%), and lipid (55%), indicating that cell-free ice nuclei were lipoglycoproteins. Also, carbohydrate and lipid stains showed that cell-free ice nuclei contained both carbohydrate and lipid moieties.


Cholesterol-independent effects of statins and new therapeutic targets: ischemic stroke and dementia.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. Statins inhibit cholesterol biosynthesis, leading to enhanced uptake of low-density lipoprotein (LDL) from the circulation via LDL receptors. This strong cholesterol-lowering action contributes to the beneficial effects of statins. For example, large clinical trials have demonstrated that statins significantly reduce cardiovascular risk. Recent research has shown that statins have other multiple actions involved in endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" of statins probably provide a significant contribution to the reduction of cardiovascular events. This review summarizes the pleiotropic actions of statins in both basic and clinical studies. It also considers the potential for statin therapy in the treatment of stroke and dementia.


LPS Pretreatment Attenuates Cerebral Ischaemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis.
Lipopolysaccharide (LPS) pretreatment has a strong neuroprotective effect on cerebral ischaemia/reperfusion injury (IRI), but the mechanism has not been fully elucidated to date. This study investigated the effect of LPS pretreatment on the pathway mediated by endoplasmic reticulum (ER) stress-CCAAT/enhancer-binding protein- homologous protein (CHOP) and the role of this pathway on cerebral ischaemia/reperfusion (I/R)-induced inflammation and apoptosis. Healthy male BALB/c mice were randomised into four groups as follows: sham operation group (sham group, n=30); LPS group (BALB/c mice treated with LPS, n=30); ischaemia/reperfusion group (I/R group, n=30) and I/R+LPS group (BALB/c mice treated with LPS before ischaemia, n=30). The mice were pre-treated with LPS (0.2 mg/kg) intra-peritoneally for three days prior to cerebral ischaemia. After 24 hours, the neurological deficit score, TTC staining and TUNEL assay were used to assess the neuroprotective effect of the LPS pretreatment against cerebral IRI. To assess whether the ER stress-CHOP pathway participated in the LPS-pretreatment neuroprotective mechanism, the expression levels of related proteins (GRP78, CHOP, caspase-12 and caspase-3) from the ischaemic cortical penumbra were detected via a western blot analysis. An immunohistochemical study was used to detect the expression and location of CHOP in the cortical penumbra. To further assess the protective effect of the LPS pretreatment, the concentrations of inflammatory factors (TNF-α, IL-6, IL-1β and IL-10) in the cortical penumbra were measured by ELISA, and ER stress-CHOP pathway inflammation-related caspase-11 was analysed through western blot analysis. As demonstrated by the experiments, the pretreatment with LPS significantly reduced the neurological deficit score and the infarct size of cerebral IRI. The expression levels of ER stress-CHOP pathway related proteins (GRP78, CHOP, caspase-12 and caspase-3) from the cortical penumbra were significantly decreased by LPS, as well as the level of apoptosis in the cells in the brain. Immunohistochemistry showed that the expression of CHOP significantly decreased after the LPS pretreatment. Furthermore, the concentrations of inflammatory factors (TNF-α, IL-1β, IL-6) were reduced after the LPS pretreatment, whereas the anti-inflammatory cytokine IL-10 was upregulated. In addition, ER stress-CHOP pathway inflammation-related caspase-11 expression was significantly suppressed after the pretreatment with LPS. LPS pretreatment significantly ameliorates the effects of cerebral IRI by inhibiting inflammation and apoptosis, and the potential mechanism of the neuroprotective effect may be associated with the ER stress-CHOP mediated signalling pathway.


Causes of Aseptic Persistent Pain after Total Knee Arthroplasty.
Persistent pain after total knee arthroplasty (TKA) is dissatisfying to the patient and frustrating to the surgeon. The purpose of this study is to evaluate the aseptic causes and clinical course of intractable pain following TKA. Of the total 2,534 cases of primary TKA reviewed, 178 cases were classified as having aseptic persistent pain that was not resolved within 1 year after surgery. Except for the cases with periprosthetic fracture (56 knees), 122 cases of aseptic painful TKA were divided into two groups: intra-articular group (83 knees) and extra-articular group (39 knees). In the intra-articular group, the main reasons for pain were aseptic loosening (n = 40), polyethylene wear (n = 16), instability (n = 10), recurrent hemarthrosis (n = 5), patellar maltracking (n = 4), tendon ruptures (n = 4), and stiffness (n = 2). In the extraarticular group, 10 knees (25.6%) were found to have nerve entrapment in the spine, 6 knees (15.4%) were found to have hip osteoarthritis or femoral head avascular necrosis. The reasons for persistent knee pain in the remaining 23 knees (59.0%) still remain elusive. Persistent pain after TKA originated from pathology of extra-articular origin in a considerable number of cases in this study. Therefore, it is important to perform thorough preoperative evaluations to reduce pain resulting from extra-articular causes. Furthermore, meticulous surgical procedures and optimal alignment are required to reduce pain of intra-articular origin related to implant wear, instability, and patellar maltracking.


[Diagnostic concordance between seven definitions of metabolic syndrome in overweight and obese adults].
The aim of this study was to determine the level of diagnostic concordance between seven definitions of metabolic syndrome (MS) in a group of overweight and obese adults. 350 subjects aged from 19 to 70 years were recruited for study from a clinic for overweight and obese subjects. The definitions of MS used were those given by the WHO (World Health Organization), EGIR (European Group for the Study of Insulin Resistance), NCEP- ATPIII (Adult Treatment Panel), AHA/NHLBI (American Heart Association), IDF (International Diabetes Federation), and JIS (Joint Interim Statement) as well as the Szabo criteria. Concordance between the definitions was calculated with the Kappa coefficient. Insulin resistance (IR) was assessed using the HOMA-IR index. According to the Szabo, WHO, EGIR, NCEP-ATPIII, AHA/NHLBI, IDF, and JIS criteria, MS frequency was 74.3%, 42.0%, 46.8%, 56.0%, 52.9%, 58.6%, and 58.6%, respectively. The concordance between the Szabo and AHA/NHLBI criteria was 0.559, while the Kappa coefficient between the Szabo criteria and the rest of the guides (NCEP-ATPIII, IDF, and JIS) was from 0.612 to 0.657, respectively. The concordance of the WHO with the EGIR was 0.602, but it was between 0.358 and 0.422 with the other guidelines. IR was distributed similarly in all guidelines. There is a considerable concordance between the NCEP-ATPIII, IDF, and JIS guidelines and the Szabo criteria. The Szabo criteria could be an option for the active surveillance of MS in populations.


Evaluating the use of anaudit tool to identify health promotion activities in practice.
Lask et al. (1994) noted that Colleges of Nursing, Midwifery and Health were experiencing significant difficulties in obtaining appropriate placements to meet the philosophy ofhealth promotion in the nursing curricula. This paper discusses the experienc es of usingan audit tool to evaluate the extent to which health and health promotion are currently reflected in the nursing curricula and in clinical practice. The tool was commissioned by the South West NHS Executive and developed by South Bank University (Smith et al. 1999). The content of the National Occupational Standardsfor Health Promotion informed the development of the audit tool. The tool was piloted as part of a study investigating the relationship between health promotion/education and the application of theory to practice in clinical areas. The findings suggested that health promotion activity was clearly evident in practice areas, but that it was not always overtly recognized by practitioners. In discussion between the lecturer researchers undertaking the audit, and practitioners, the tool was found to be very useful in identifying valuable health promotion/education experiences in areas not traditionally used for pre-registration student placement. Recommendations included the regular use of the audit tool in all clinical areas, to assist practitioners, teachers and mentors to link theory to practice, and the identification of health promotion in practice.


The Girl Who Wants to Get Rid of Her Left Leg-Body Identity Dysphoria.
One of the strangest kinds of misperceptions of the body is "Body Integrity Dysphoria" (BID), formerly named as "Body Identity Integrity Disorder" (BIID). The affected people have the feeling that a limb is not part of their body. They can feel it, they can use it, they can move it, but they cannot get along with the fact that it is a part of their own body. Most feel the need for an amputation of a leg, others of both legs, some want a palsy and use a wheelchair. Still discussed is whether other disablements such as blindness, dumbness, deafness or a desire to have an incontinency can be included in this diagnosis. This review discusses parallels and differences to transgender/trans identity, body dysmorphic disorder, alien limb syndrome, hemineglect, and self-induced amputations in schizophrenic patients. The cause for the need to be disabled is still unknown; the review gives an overview about psychological and neurological theories of explanation and what kind of therapy may help. This is a narrative review of about 20 years of research about Body Integrity Dysphoria by the author. Overall, no psychopathological deviations were found, none of the affected persons examined by us were actually delusional or schizophrenic, which underlines that there is a neurological malfunction in the brain that has existed since birth. However, psychological mechanisms intensify the symptoms. There are clear parallels to other forms of interference between the external body and mental body representation. Different types of therapies have been able to provide help to better deal with BID, but there has been little to bring about a real cure. In contrast, BID-affected persons who achieved amputation (or other desired forms of disability) were satisfied and able to return to work. BID remains an enigmatic disorder. We have learned a lot over the past 20 years that the mental and physical bodies do not have to match.


Expression of a novel regenerating gene product, Reg IV, by high density fermentation in Pichia pastoris: production, purification, and characterization.
Human regenerating (Reg) gene products are regionally expressed by gut-derived tissues, and are markedly up-regulated in cancer and in diseases characterized by mucosal injury. We recently identified Reg IV, a novel regenerating gene product that is uniquely expressed by the normal distal gastrointestinal mucosa. The function remains poorly understood due to the lack of significant purified Reg IV for biochemical and functional studies. Recombinant human Reg IV was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris using the MutS strain KM71H. We describe the unique conditions that are required for efficient production of Reg IV protein in high density fermentation. Optimal protein expression was obtained by reduction of the fermentation temperature and addition of casamino acids as a supplemental nitrogen source and to minimize the activity of yeast produced proteases. Recombinant Reg IV protein was purified by tangential flow filtration and reverse phase chromatography. The purified protein was characterized by amino terminus sequence analysis and MALDI-TOFMS showing that the engineered protein had the expected sequence and molecular weight without secondary modification. Recombinant Reg IV was further characterized by specific monoclonal and polyclonal reagents that function for Western blot analysis and for immunolocalization studies.


Racial and socioeconomic disparities in oral disadvantage, a measure of oral health-related quality of life: 24-month incidence.
This paper estimates the incidence of oral disadvantage based on the subject's approach to dental care, sex, race, and financial status; identifies demographic and socioeconomic characteristics that were associated with oral disadvantage; and determines if these characteristics were differentially associated with the three domains of oral disadvantage. The Florida Dental Care Study was a longitudinal study of oral health in diverse groups of persons who at baseline had at least one tooth, were 45 years or older, and were either African American or non-Hispanic white. Incidence rates, odds ratios, and 95 percent confidence intervals were used to describe oral disadvantage and its relation to race, income, and other key sociodemographic characteristics. The strongest independent predictors of oral disadvantage were approach to dental care (problem-oriented attenders or regular), and situation if faced with an unexpected $500 dental bill. Demographic and socioeconomic characteristics were differentially associated with each disadvantage domain. African Americans, females, rural residents, individuals who did not graduate from high school, individuals with limited financial resources, and problem-oriented dental attenders had significantly higher occurrences of oral disadvantage. Racial and sex disparities in oral disadvantage were largely explained by differences in approach to dental care and financial resources between these groups.


Detection of fetal auditory evoked responses by means of magnetoencephalography.
MagnetoEncephaloGraphy (MEG) is proposed as a non-invasive technique to detect the physiological activity of fetal brain, due to its ability to record brain activity without direct contact with the head and the transparency of magnetic signals in passing through extracerebral fetal layers and the mother's abdomen. Healthy women with uncomplicated pregnancies and fetuses in breech presentation were examined; gestational ages at time of study ranged between 36 and 40 weeks. In order to evaluate fetal well-being, ultrasound and cardiotocographic data were assessed a few days before and after MEG recording sessions. The participating women were placed in a semi-reclining position in a magnetically shielded room; here the presentation of the fetus and precise region of the mother's abdomen corresponding to the fetal head were determined by ultrasound investigation in order to place the MEG detecting system as near as possible to the fetal brain. MEG recordings were performed by means of a 28-channel neuromagnetic system. Every MEG recording session was performed during the acoustic stimulation of fetuses, in order to detect the cerebral events evoked by peripheral stimuli. The auditory stimuli were delivered from a plastic tube placed on mother's abdomen, near the fetal head, and consisted of a 300 ms 103 dB pure tone at 500 and 1000 Hz, presented at a 0.4 c/s repetition rate. In six cases following accurate digital subtraction of maternal and fetal electrocardiographic (EKG) signals we remained with a stimulus-related response peaking at about 250 ms; this was considered to originate from the fetal brain. In favour of this in three cases a clear dipolar distribution was evident at the peak of brain response centered on the fetal head and consistent with a brain generator. Despite several technical problems requiring solution before a possible routine clinical application, MEG has been found to be suitable for the non-invasive exploration of the fetal brain.


The depressive action of ammonium chloride on the hepatic blood flow in sheep.
Using the 133Xe clearance method it is shown that NH4Cl infusion into the anterior mesenteric vein decreased capillary blood flow in the liver. Phentolamine completely and propranolol partially prevented the depressive action of NH4Cl on hepatic blood flow. NH5Cl infused into the jugular vein provoked a slight increase in the hepatic blood flow. The adrenaline-like action of ammonium ion on the blood circulation in the liver region is discussed.


Fetal alcohol spectrum disorders and assessment of maxillary and mandibular arc measurements.
Fetal alcohol spectrum disorders (FASD) comprise a range of physical differences and neurologic deficits from prenatal alcohol exposure. Previous studies suggest that relative maxillary growth deficiency can accompany FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how maxillary and mandibular arcs and the ratio between them differ between FASD and non-FASD individuals. First, we established normative values for maxillary and mandibular arcs and maxillary-to-mandibular arc ratio. In our control group (545 males, 436 females), mean maxillary and mandibular arcs for males/females were 24.98/24.52 cm and 25.91/25.35 cm, respectively. The ratio was 0.9643 and 0.9676 for males and females, respectively. We then evaluated the effect of microcephaly, short stature, and low weight (<10th centile), individually on arcs in controls. Generally, arcs were reduced significantly but the ratio did not differ. We compared our controls to 138 male and 135 female FASD cases. We noted a significant difference in arcs in male and female groups, but not the ratio. We compared non-FAS controls with reduced growth parameters to similar cases with FASD. We did not find a significant difference in arc or ratio measurements. Therefore, we conclude the effect of prenatal alcohol exposure on maxillary and mandibular arc measurements is primarily on overall facial growth and less on asymmetric growth of the maxilla relative to the mandible, at least using this technique. © 2016 Wiley Periodicals, Inc.


Role for WNT16B in human epidermal keratinocyte proliferation and differentiation.
WNT signalling regulates a variety of cell functions including cell fate, polarity, and differentiation via the canonical or beta-catenin stabilisation pathway and/or the planar cell polarity or non-canonical pathway. We have previously demonstrated that two isoforms (A and B) from the WNT16 locus have differential expression in various adult human tissues. In this study we show that WNT16B but not WNT16A isoform was upregulated in basal cell carcinomas compared with normal skin. We further investigated the cellular and molecular functions of WNT16B in primary human epidermal keratinocytes and a keratinocyte cell line. Cellular expression of WNT16B neither stabilised beta-catenin nor activated the lymphoid enhancer factor or T-cell factor transcriptional reporter in primary keratinocytes. WNT16B activated the Jun-N-terminal kinase cascade suggesting the activation of a non-canonical WNT signalling pathway. Constitutive expression of WNT16B significantly enhanced the rate of cell proliferation and prolonged clonogenicity in primary keratinocytes. Silencing WNT16B by RNA interference reduced keratinocyte proliferation. Furthermore, overexpression of WNT16B induced a hyperproliferation phenotype in an organotypical culture system. This work presents the first evidence that WNT16B activates human keratinocyte proliferation possibly via a beta-catenin-independent non-canonical WNT transduction pathway.


Synthesis of 4-aminotropones from [(sulfinyl or sulfonyl)methyl]-substituted p-quinamines.
An efficient synthesis of 4-aminotropones has been achieved in excellent yields by simple treatment of 4-amino-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienones (p-quinamines) with NaH. The method allowed regiocontrolled access to 3-methyl, 5-methyl- and 3,5-dimethyl-substituted derivatives starting from p-quinamines with adequate substituents at the cyclohexadienone moiety and/or at the carbon linked to the sulfur function. The p-quinamines in turn were easily accessible from N-Boc p-anisidines (Boc=tert-butoxycarbonyl) by electrochemical oxidation in MeOH to quinone imine monoketals, followed by addition of a alpha-lithium sulfinyl carbanion to the imino group, and ketal hydrolysis. Oxidation of the sulfoxide gave the sulfonyl-substituted p-quinamines that, upon basic treatment, behave similarly. The p-quinamine 55 and bis-p-quinamine 56, resulting in the addition of the anion derived from dimethyl sulfone to the p-quinonimine ketal 14, also gave the 4-aminotropone. The mechanism involves the initial formation of a alpha-sulfonyl carbanion, which intramolecularly attacks the cyclohexadienone giving a norcaradiene-like enolate intermediate, the evolution of which through a ring-expansion process, pushes off a methyl sulfinate anion or SO2. This efficient process fulfils the criteria of atom economy. The introduction of a proline substituent in the nitrogen of the starting p-quinamine allowed the synthesis of an enantiopure 4-aminotropone, the asymmetric Diels-Alder reactions of which with maleimide occurred in a highly endo and pi-facial diastereoselective manner.


Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates.
Glucocorticoids have been used in conjunction with zona dissection to improve pregnancy and implantation rates in IVF patients. The aim of this prospective randomized study was to evaluate the effect of low-dose prednisolone in addition to the standard protocol, on pregnancy and implantation rates in routine ICSI patients before and after embryo replacement. A total of 313 patients in 360 consecutive cycles (patients <39 years old and with three or less than three ICSI attempts) performed at our centre were randomly assigned by computer-generated list to receive either prednisolone (10 mg/day in two divided doses), starting on the first day of ovarian stimulation and continuing for 4 weeks (group A), or no treatment (group B). The mean age, number of previously failed IVF attempts, basal FSH levels and the mean rank of trials were comparable between groups A and B. The mean (+/- SD) number of metaphase II oocytes retrieved (11.9 +/- 5.5 versus 12.0 +/- 5.1), 2-pronuclei fertilization rate (67.2 versus 65.8%), the pregnancy and the implantation rates were not different between the study and control groups (49.0 and 23.6% versus 50.0 and 23.3% respectively). Low-dose prednisolone treatment in addition to the standard protocol before and after embryo replacement does not appear to have a significant effect on pregnancy or implantation rates.


Ocular hypotensive effects of medetomidine and its analogs.
The ocular hypotensive effects of medetomidine, a relatively selective alpha 2-agonist, and its analogs were tested in rabbits and cats and their inhibition of adenylate cyclase in the isolated bovine ciliary process was also studied. It was found that topical unilateral administration of medetomidine (0.5-2.0%) to the normotensive rabbits produced a dose-dependent bilateral decrease in IOP with peak reduction in IOP at 2 hr in the treated eye and 1 hr in the untreated eye. A dose-dependent mydriasis was also observed in the treated eye. The dose-response curves of medetomidine and its analogs showed that the ranked order of intrinsic activity at lowering IOP was medetomidine greater than or equal to MPV-1440 greater than detomidine greater than MPV-1441 and MPV-305 BII. At concentrations lower than those used in rabbits, topical application of medetomidine to the normotensive cats lowered IOP in both treated and untreated eyes. Medetomidine and detomidine caused a dose-dependent inhibition of isoproterenol-stimulated adenylate cyclase activity. Detomidine was found to be a partial agonist producing about 43% of maximum inhibition obtained by medetomidine. The IOP efficacy of these alpha 2-agonists paralleled their effects on adenylate cyclase activity. The results demonstrated that these imidazoline derivatives are effective ocular hypotensive agents which may be useful in understanding the contribution of alpha 2-receptors to the regulation of IOP.


An update of immunotherapy for specific allergies.
Allergic diseases are common, disabling and potentially life threatening. The processes that lead to production of excessive allergen-specific IgE production are highly complex and heterogeneous. While current treatment strategies are limited, recent technological advances have provided a better understanding of underlying disease processes and offered new potential therapeutic targets. Optimal treatment strategies permanently modify underlying inflammatory allergic immune responses (immunotherapy) with long term alleviation of symptoms and minimal side-effects. Although these processes are still not completely understood, methods of modifying allergen recognition by the immune system have already been successful. Here, we review recent developments and future directions in allergen immunotherapy and adjunctive therapies. Specifically, we address the molecular mechanisms of allergen immunotherapy and new techniques including allergen modification, allergen gene vaccination, CpG immunostimulation, and peptide immunotherapy. Other non-allergen specific molecular targets (including receptor, cytokine and IgE targets) which may complement specific immunotherapy are also discussed. Ideally these methods will eventually be replaced by strategies targeting the prevention of allergic responses (immunoprophylaxis).


Short-form alternatives to the Judgment of Line Orientation Test.
The Judgment of Line Orientation Test (JLO; Benton, Hamsher, Varney, & Spreen, 1983) is frequently used as a motor-free method of evaluating visuospatial processing but can be time-consuming to administer. We investigated the internal consistency, validity, and utility of two parallel JLO short forms in a mixed clinical sample of 386 patients. Mean scores were equivalent, and correlational analyses supported the internal consistency and validity of both short forms. When compared to the standard JLO, the odd- and even-item short forms demonstrated good sensitivity, specificity, overall hit rate and predicted positive and negative accuracy. We conclude that the JLO short forms possess sufficient internal consistency, validity, and utility for serial assessment in research studies. The JLO short forms may potentially be used in clinical screening situations by applying a single cut-off score to differentiate levels of performance. However, more detailed clinical use of these JLO short forms will necessitate collection of normative data in order to generate accurate percentile rankings.


Identification of activated T cell receptor gamma delta lymphocytes in the liver of tumor-bearing hosts.
T cell receptor (TcR)gamma delta cells are known to be a minor population of T lymphocytes in the blood (less than 10%) and other peripheral lymphoid organs in healthy donors. We demonstrated here that a large proportion of TcR gamma delta cells, i.e., up to 30% of mononuclear cells (MNC) were detectable in the liver, but not other lymphoid organs of cancer patients. More importantly, the majority of such TcR gamma delta cells (greater than 70%) were shown to be lymphoblastic by electron microscopy. An activation marker of T lymphocytes, Leu-19 (CD56) was also highly expressed on the hepatic TcR gamma delta cells. The possibility of hepatic TcR gamma delta cells being activated was further examined in mice. C3H/He mice injected with syngeneic tumor cells were demonstrated to have an increased number of liver MNC; such MNC showed an ability to proliferate in vitro. These mice eventually had a considerable proportion of TcR gamma delta cells in the liver, showing activation markers, the Ia and LFA-1 antigens. These results suggest that the liver may be an important organ for activation and probably expansion of TcR gamma delta cells especially in tumor bearing hosts.


High-fat diet-induced met-hemoglobin formation in rats prone (WOKW) or resistant (DA) to the metabolic syndrome: effect of CoQ10 supplementation.
The aim of this study was to evaluate the effects of a high-fat diet (HFD) on oxidative indexes in WistarOttawaKarlsburg W (WOKW) rats used as a model of metabolic syndrome in comparison with Dark Agouti (DA) rats used as a control strain. This syndrome is defined by the occurrence of two or more risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. Forty rats were used in the study and the effect of HFD was evaluated in terms of body weight and both hemoglobin and CoQ oxidative status. Moreover, 16 rats (8 of each strain) were supplemented with 3 mg/100 g b.w. of CoQ10 for 1 month in view of its beneficial properties in cardiovascular disease due to its antioxidant activity in the lipid environment. HFD promoted an increase in body weight, in particular in WOKW males, and in the methemoglobin (met-Hb) index in both strains. Moreover, HFD promoted endogenous CoQ10 oxidation. CoQ10 supplementation was able to efficiently counteract the HFD pro-oxidant effects, preventing met-Hb formation and CoQ oxidation.


A Leaking-Proof Theranostic Nanoplatform for Tumor-Targeted and Dual-Modality Imaging-Guided Photodynamic Therapy.
Objective: A protein-based leaking-proof theranostic nanoplatform for dual-modality imaging-guided tumor photodynamic therapy (PDT) has been designed. Impact Statement: A site-specific conjugation of chlorin e6 (Ce6) to ferrimagnetic ferritin (MFtn-Ce6) has been constructed to address the challenge of unexpected leakage that often occurs during small-molecule drug delivery. Introduction: PDT is one of the most promising approaches for tumor treatment, while a delivery system is typically required for hydrophobic photosensitizers. However, the nonspecific distribution and leakage of photosensitizers could lead to insufficient drug accumulation in tumor sites. Methods: An engineered ferritin was generated for site-specific conjugation of Ce6 to obtain a leaking-proof delivery system, and a ferrimagnetic core was biomineralized in the cavity of ferritin, resulting in a fluorescent ferrimagnetic ferritin nanoplatform (MFtn-Ce6). The distribution and tumor targeting of MFtn-Ce6 can be detected by magnetic resonance imaging (MRI) and fluorescence imaging (FLI). Results: MFtn-Ce6 showed effective dual-modality MRI and FLI. A prolonged in vivo circulation and increased tumor accumulation and retention of photosensitizer was observed. The time-dependent distribution of MFtn-Ce6 can be precisely tracked in real time to find the optimal time window for PDT treatment. The colocalization of ferritin and the iron oxide core confirms the high stability of the nanoplatform in vivo. The results showed that mice treated with MFtn-Ce6 exhibited marked tumor-suppressive activity after laser irradiation. Conclusion: The ferritin-based leaking-proof nanoplatform can be used for the efficient delivery of the photosensitizer to achieve an enhanced therapeutic effect. This method established a general approach for the dual-modality imaging-guided tumor delivery of PDT agents.


The changing relationship between anatomic and cognitive explanation in the neuropsychology of language.
Changing trends in the approach to neurolinguistics are reviewed. We suggest that these trends are marked by a distinct convergence between linguistic/cognitive and anatomic/physiological approaches to the study of aphasia. With respect to the former, we cite the refinement of analysis of language symptoms and the introduction of experimental methods that reveal real-time aspects of language processing. With respect to the latter, we cite the technical advances in static and dynamic brain imaging that have allowed the in vivo analysis of lesion sites in aphasic patients, and the identification of foci of metabolic activity during linguistic/cognitive tasks in normal brains. We cite recent imaging studies of category-specific lexical dissociations as examples of the productive convergence of anatomic and technological advances to illuminate a particularly challenging problem.


Very early hallucinatory experiences: a school-based study.
The prevalence and clinical significance of hallucinatory experiences among children below 7 years of age remain unknown. We aimed to determine the independent influences of sensory deficits, the presence of an imaginary companion and metacognition on hallucinatory experiences. We assumed that hallucinatory experiences were associated with (a) sensory deficits, (b) the presence of an imaginary companion (IC) and (c) metacognition defaults (i.e. first- and second-order theory of mind default). All children in the third year of preschool from a region of Northern France underwent medical screening. We compared the prevalence rates of visual, auditory and audio-visual hallucinatory experiences based on (a) the presence of visual or auditory deficits, (b) the actual presence of an IC and (c) metacognition. The analyses were adjusted for age. A total of 1,087 children aged between 5 and 7 years were included. The prevalence rates of auditory, visual and audio-visual hallucinatory experiences were 15.8%, 12.5% and 5.8%, respectively. The prevalences of different types of hallucinatory experiences were not significantly different according to sensory deficit. The prevalences of all types of hallucinatory experiences were significantly higher among children with an IC and among children with metacognition defaults. The association between hallucinatory experiences and sensory deficits might concern only long-lasting deficits. The association with the presence of an IC confirms experimental findings of the likelihood of perceiving words among meaningless auditory stimuli. Relations between hallucinatory experiences and theory of mind need to be addressed in longitudinal studies.


Cellular localization of blood group antigens (including HLA markers) in human bladder urothelium.
Expression of A, B, H, Lewis, I, i, HLA class I and class II antigens was studied on 81 urinary bladder samples. Striking variation in the expression of HLA class II and to a lesser extent of HLA class I determinants was observed. Expression of at least five distinct A (or B) determinants, the synthesis of which is controlled by H, A, B, secretor and Lewis genes, was demonstrated by using a panel of reagents directed against different A, B and H epitopes. These results suggest that evaluation of blood group changes during tumoral processes requires the precise determination of the specificity of reagents used and the knowledge of ABO, Lewis and secretor phenotypes for each patient. ABH and related antigens should now be regarded as tissue antigens with a complex genetic regulation and expression.


Analysis of a metallic nano-rod polarizer using finite-difference-time-domain method.
The polarization behavior of metallic nano-rods has been analyzed by means of the finite-difference-time-domain method. When the average spacing between the nano-rods is less than a half wavelength, the layer reflects the light polarized parallel to the nano-rods, as in a nano-slit. However, when the spacing is larger than a half wavelength, the metallic surface absorbs the light, polarized perpendicular to the rods, leading to a polarization switching. Multiple layers of nano-rods can make a polarizer with a high extinction ratio and good transmittance.


Early Postoperative Complications and Associated Variables After Tibial Tubercle Osteotomy: A 15-Year Experience From a Single Academic Institution.
Tibial tubercle osteotomy (TTO) is a well-established surgical treatment option for patients with patellofemoral disorders. To determine the rate of early (≤90 day) postoperative complications after TTO and variables related to postoperative complications. Case series; Level of evidence, 4. Patients who underwent TTO at a single academic institution within a 15-year period (2008-2022) were identified. All patients with a minimum 90-day follow-up were considered for study inclusion. Exclusion criteria were age younger than 14 years and revision surgery. Patient characteristics, surgical history, and concomitant procedures were identified, and risk factor analysis was performed to identify variables associated with early postoperative complications. A total of 344 knees in 313 patients met eligibility criteria and were included in the final analysis. One intraoperative complication (0.3%), a premature closure of the incision before repair of the vastus medialis, was identified. There were 141 postoperative complications (138 surgical, 3 medical) in 118 patients for a complication rate of 34.3%. The most common complications were stiffness requiring a nonstandard-of-care intervention (16.3%), superficial wound infection/wound dehiscence (8.1%), and hemarthrosis/effusion requiring aspiration (5.8%). Patients experiencing postoperative complications were older (mean difference, 3.49 years; 95% CI, 1.26-5.73 years; P = .002), had a higher mean Charlson Comorbidity Index (mean difference, 0.26; 95% CI, 0.08-0.45; P = .006), and were more likely to be current smokers (P = .015) compared with patients with no complications. Inpatient surgery (defined as surgery in a hospital setting with at least 1 overnight stay) was associated with postoperative complications (odds ratio [OR], 2.29; 95% CI, 1.39-3.77; P = .001); this association remained significant generation of a multivariate model (OR, 2.07; 95% CI, 1.19-3.58; P = .010). Previous surgery on the ipsilateral knee (P < .001) and concomitant autologous chondrocyte implantation (P = .046) were also associated with postoperative complications. The study findings indicated a low intraoperative complication rate (0.3%) and a relatively high early postoperative (≤90 day) complication rate (34.3%) after TTO. Variables associated with postoperative complications included greater age, higher Charlson Comorbidity Index, surgery in an inpatient setting, previous surgery on the ipsilateral knee, and concomitant autologous chondrocyte implantation.


Evaluation of complications and short-term outcome after unilateral or single-session bilateral tibial tuberosity advancement for cranial cruciate rupture in dogs.
To compare the resulting complications, short-term results, and client satisfaction for treatment of cranial cruciate ligament rupture using either unilateral or bilateral single-session tibial tuberosity advancement (TTA) in dogs. Medical records of 68 dogs (101 stifles) undergoing unilateral or bilateral single-session TTA were evaluated. Data gathered included signalment, history, physical examination findings, anaesthesia and surgical time, type of cranial cruciate ligament rupture and meniscal injury, implants, and intra-operative and postoperative complications. A mixed effect logistic regression analysis was performed to determine if complications were grouped by surgical procedure. Linear regression was performed to determine the influence of the variables on the occurrence of complications. Values of p <0.05 were considered significant. No major intra-operative complications occurred. Twenty stifles (20%) developed a complication after surgery (11 minor, 9 major). There was no significant difference in occurrence of complications between dogs undergoing unilateral (n = 8) or bilateral single-session (n = 12) TTA (p = 0.69). The only risk factor found to be associated with complication occurrence was age. This is the first report evaluating the use of bilateral simultaneous TTA. There was no significant difference in complication rates between unilateral and bilateral single-session TTA. Additional evaluation is needed to fully determine the extent of complications and long-term outcome of bilateral single-session TTA.


[Mixed gonadal dysgenesis (MGD). Description of a case].
The Authors report a case of mixed gonadal dysgenesis (DGM), with a mosaic karyotype consisting of two cell lines, one with 45 chromosomes and monosomic X (50%), the other with 46 chromosomes and one Y dicentric chromosome (50%). The patient presents a male phenotype, hypospadias (3rd degree), left cryptorchidism, hypotrophic right testis, short stature and a gonadal asymmetry.


Inpatient cardiac rehabilitation programs' exercise therapy for patients undergoing cardiac surgery: National Korean Questionnaire Survey.
Inpatient cardiac rehabilitation (ICR) has been commonly conducted after cardiac surgery in many countries, and has been reported a lots of results. However, until now, there is inadequacy of data on the status of ICR in Korea. This study described the current status of exercise therapy in ICR that is performed after cardiac surgery in Korean hospitals. Questionnaires modified by previous studies were sent to the departments of thoracic surgery of 10 hospitals in Korea. Nine replies (response rate 90%) were received. Eight nurses and one physiotherapist completed the questionnaire. Most of the education on wards after cardiac surgery was conducted by nurses. On postoperative day 1, four sites performed sitting on the edge of bed, sit to stand, up to chair, and walking in the ward. Only one site performed that exercise on postoperative day 2. One activity (stairs up and down) was performed on different days at only two sites. Patients received education preoperatively and predischarge for preventing complications and reducing muscle weakness through physical inactivity. The results of the study demonstrate that there are small variations in the general care provided by nurses after cardiac surgery. Based on the results of this research, we recommended that exercise therapy programs have to conduct by exercise specialists like exercise physiologists or physiotherapists for patients in hospitalization period.


Culturally diverse patient--nurse interactions on acute care wards.
The nurse-patient interaction is central to providing nursing care. This qualitative study explores nurses' and culturally diverse patients' experiences within nurse-patient relationships in acute care wards. Eight nurses and their respective patients volunteered to join the study and were interviewed. The three themes identified in relationships between nurses and culturally diverse patients were shared tension, perceived difference and held awareness. It is concluded from the study that relationships between nurses and culturally diverse patients in acute care wards during short episodes of hospitalization are not easy for nurses and need to receive deeper consideration as to how they can be developed more effectively. It is recommended that educational support be provided to develop more effective interactions between nurses and patients with research being carried out to investigate factors that can strengthen culturally diverse patient-nurse interactions in acute care settings.


Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device.
A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.


Effect on plasma gonadotropins of cyclic steroid replacement in women with premature ovarian failure.
A sequential regimen of steroid replacement of oral estradiol valerate and progesterone (P) by intravaginal suppository was developed for women with premature ovarian failure or ovarian agenesis. The regimen, based on a 28-day cycle, resulted in peripheral plasma concentrations of estradiol and P within the normal range of the menstrual cycle and endometrial differentiation consistent with the normal secretory phase. Pregnancy has now been successfully established in four patients following this regimen of steroid treatment and transfer of donated embryos. Plasma concentrations of LH were within the normal range by the end of the first cycle of treatment with exogenous steroids. However, plasma FSH remained above the normal range, even during the third treatment cycle, consistent with the necessity of a gonadal feedback factor (inhibin?) other than estradiol and P for maintaining FSH in the normal range. Although 7/8 patients had a surge of LH at midcycle, only 3/8 patients had concomitant FSH surges, supporting a role for progesterone in facilitating the midcycle FSH surge.


Disease modeling in multiple sclerosis: assessment and quantification of sources of variability in brain parenchymal fraction measurements.
The measurement of brain atrophy from magnetic resonance imaging (MRI) has become an established method of estimating disease severity and progression in multiple sclerosis (MS). Most commonly reported in the form of brain parenchymal fraction (BPF), it is more sensitive to the degenerative component of the disease and shows progression more reliably than lesion burden. Typically, the reliability of BPF and other morphometric measurements is assessed by evaluating scan-rescan experiments. While these experiments provide good estimates of real-life error related to imperfect patient repositioning in the MRI scanner, measurement variance due to physiological and reversible pathological fluctuations in brain volume are not taken into account. In this work, we propose a new model for estimating variability in serial morphometry, particularly the BPF measurement. Specifically, we attempt to detect and explicitly model the remaining sources of error to more accurately describe the overall variability in BPF measurements. Our results show that sources of variability beyond subject repositioning error are important and cannot be ignored. We demonstrate that scan-rescan experiments only provide a lower bound on the true error in repeated measurements of patients' BPF. We have estimated the variance due to patient repositioning during scan-rescan (sigma(sr)(2) = 3.0e-06), variance assigned to physiological fluctuations (sigma(p)(2) = 5.74e-06) and the variance associated with lesion activity (sigma(les)(2) = 1.09e-05). These variance components can be used to determine the relative impact of their sources on sample size estimates for studies investigating change over time in MS patients. Our results demonstrate that sample size calculations based exclusively on scan-rescan variability (sigma(sr)) are likely to underestimate the number of patients required. If the physiological variability (sigma(p)) is incorporated in sample size calculations, the required sample size would increase by a factor of 5.69 based on standard t-test sample size calculation.


Guided protein/cell patterning on superhydrophilic polymer brushes functionalized with mussel-inspired polydopamine coatings.
A simple approach for preparing bicomponent polymer patterns was developed by coating polydopamine (PDA) on superhydrophilic poly(2-acryl-amido-2-methylpropane sulfonic acid) (PAMPS) brushes. Well-defined and versatile arrays of proteins and cells were achieved without harm to proteins and cells.


Residency program solutions: making a difference in quality residency education.
Residency Program Solutions (RPS) consultants assist family medicine residency programs in solving issues perceived as limiting quality resident education. Residencies ask RPS to assist in preparing for accreditation site visits by the Residency Review Committee-Family Medicine (RC-FM). The RPS Criteria for Excellence in Family Medicine Education (RPS Criteria) may have influenced the accreditation standards of the RC-FM. RPS consultations also may affect accreditation visit cycle length and number of RC-FM citations. The authors reviewed the RC-FM Program Requirements for Family Medicine Residency Education and the RPS Criteria from 1978 to 2007, comparing statements between the two documents for "nearly verbatim" and equivalent "must" or "should" requirements. The average number of citations and cycle length for programs seeking a Comprehensive Accreditation Program (CAP) Consultation from 2004--2010 were compared to cohort programs evaluated at the same RC-FM meeting using an independent samples t test. The strongest relationship between the RC-FM requirements and the RPS criteria occurred in 1983--1984. Nine "nearly verbatim" statements, 15 "must-should" or "must-must" statements, and 11 "should-should" statements existed. Over time, additional concurrences between organizational statements occurred. Residency programs with CAP consultations benefited significantly by both a decrease in number of citations and an increase in the length of accreditation cycle. The RPS Criteria have positively impacted iterations of RC-FM requirements. Family medicine residency programs concerned about successful accreditation by the RC-FM will likely benefit from RPS CAP consultations by increased length of accreditation cycle and/or a decreased number of citations.


Genetic influences on disease course and severity, 30 years after a clinically isolated syndrome.
Multiple sclerosis risk has a well-established polygenic component, yet the genetic contribution to disease course and severity remains unclear and difficult to examine. Accurately measuring disease progression requires long-term study of clinical and radiological outcomes with sufficient follow-up duration to confidently confirm disability accrual and multiple sclerosis phenotypes. In this retrospective study, we explore genetic influences on long-term disease course and severity; in a unique cohort of clinically isolated syndrome patients with homogenous 30-year disease duration, deep clinical phenotyping and advanced MRI metrics. Sixty-one clinically isolated syndrome patients [41 female (67%): 20 male (33%)] underwent clinical and MRI assessment at baseline, 1-, 5-, 10-, 14-, 20- and 30-year follow-up (mean age ± standard deviation: 60.9 ± 6.5 years). After 30 years, 29 patients developed relapsing-remitting multiple sclerosis, 15 developed secondary progressive multiple sclerosis and 17 still had a clinically isolated syndrome. Twenty-seven genes were investigated for associations with clinical outcomes [including disease course and Expanded Disability Status Scale (EDSS)] and brain MRI (including white matter lesions, cortical lesions, and brain tissue volumes) at the 30-year follow-up. Genetic associations with changes in EDSS, relapses, white matter lesions and brain atrophy (third ventricular and medullary measurements) over 30 years were assessed using mixed-effects models. HLA-DRB1*1501-positive (n = 26) patients showed faster white matter lesion accrual [+1.96 lesions/year (0.64-3.29), P = 3.8 × 10-3], greater 30-year white matter lesion volumes [+11.60 ml, (5.49-18.29), P = 1.27 × 10-3] and higher annualized relapse rates [+0.06 relapses/year (0.005-0.11), P = 0.031] compared with HLA-DRB1*1501-negative patients (n = 35). PVRL2-positive patients (n = 41) had more cortical lesions (+0.83 [0.08-1.66], P = 0.042), faster EDSS worsening [+0.06 points/year (0.02-0.11), P = 0.010], greater 30-year EDSS [+1.72 (0.49-2.93), P = 0.013; multiple sclerosis cases: +2.60 (1.30-3.87), P = 2.02 × 10-3], and greater risk of secondary progressive multiple sclerosis [odds ratio (OR) = 12.25 (1.15-23.10), P = 0.031] than PVRL2-negative patients (n = 18). In contrast, IRX1-positive (n = 30) patients had preserved 30-year grey matter fraction [+0.76% (0.28-1.29), P = 8.4 × 10-3], lower risk of cortical lesions [OR = 0.22 (0.05-0.99), P = 0.049] and lower 30-year EDSS [-1.35 (-0.87,-3.44), P = 0.026; multiple sclerosis cases: -2.12 (-0.87, -3.44), P = 5.02 × 10-3] than IRX1-negative patients (n = 30). In multiple sclerosis cases, IRX1-positive patients also had slower EDSS worsening [-0.07 points/year (-0.01,-0.13), P = 0.015] and lower risk of secondary progressive multiple sclerosis [OR = 0.19 (0.04-0.92), P = 0.042]. These exploratory findings support diverse genetic influences on pathological mechanisms associated with multiple sclerosis disease course. HLA-DRB1*1501 influenced white matter inflammation and relapses, while IRX1 (protective) and PVRL2 (adverse) were associated with grey matter pathology (cortical lesions and atrophy), long-term disability worsening and the risk of developing secondary progressive multiple sclerosis.


Hydration makes a difference! How to tune protein complexes between liquid-liquid and liquid-solid phase separation.
Understanding how protein rich condensates formed upon liquid-liquid phase separation (LLPS) evolve into solid aggregates is of fundamental importance for several medical applications, since these are suspected to be hot-spots for many neurotoxic diseases. This requires developing experimental approaches to observe in real-time both LLPS and liquid-solid phase separation (LSPS), and to unravel the delicate balance of protein and water interactions dictating the free energy differences between the two. We present a vibrational THz spectroscopy approach that allows doing so from the point of view of hydration water. We focus on a cellular prion protein of high medical relevance, which we can drive to undergo either LLPS or LSPS with few mutations. We find that it is a subtle balance of hydrophobic and hydrophilic solvation contributions that allows tuning between LLPS and LSPS. Hydrophobic hydration provides an entropic driving force to phase separation, through the release of hydration water into the bulk. Water hydrating hydrophilic groups provides an enthalpic driving force to keep the condensates in a liquid state. As a result, when we modify the protein by a few mutations to be less hydrophilic, we shift from LLPS to LSPS. This molecular understanding paves the way for a rational design of proteins.


[Embolism of the lower limb caused by native aortic valve thrombosis].
Native aortic valve thrombosis is an uncommon event with heart valve disease, during cardiac catheterization, bacterial endocarditis, or a hypercoagulative state as in antiphospholipid antibody syndrome. We report a case of thrombus formation on a native aortic valve, which was found by the transesophageal echocardiography during thrombectomy of the lower limb. We supposed that the atheromatous plaque of aortic valve was related to thrombus formation.


Anatomic study of the morphology of human cervical facet joint.
Geometrical properties of the facet joint including cartilage thickness and gap were obtained using human cadaver cervical spinal columns and cryomicrotomy techniques. To determine the existence of level or gender dependency on facet joint morphology in the human cervical spine. Although measurements of the human cervical spine have been reported in literature, to the best of knowledge of the authors, geometrical data on the facet joint structures such as the cartilage are not available. These data are important to understand the anatomy of the cervical spine and the role of the cartilage in sharing the external load during physiologic and traumatic situations. Furthermore, the data will assist mathematical modelers to accurately simulate this component of the cervical facet joint in finite element analysis of the spine. Six unembalmed human cadaver cervical spinal columns were used. A heavy-duty cryomicrotome was used to obtain the geometrical characteristics. The specimens were sectioned in the sagittal plane at 20- to 40-microm intervals. Geometric properties of the facet joint width, cartilage thickness, and cartilage gap (defined as the distance from the ventral-most or dorsal-most region of the facet joint to the location where the cartilage began to appear) were extracted from the anatomic sections that were midsagittal with respect to the facet joints from occiput to T1 levels. Multiple factorial analysis of variance techniques were used to determine the statistical significance of various geometrical parameters obtained from the anatomic sections. The cartilage gap in the upper cervical spine (UCS) (C1-C2, i.e., UCS, 5.4% +/- 0.8) was lower (P < 0.0001) than the gap in the lower cervical spine (LCS) (C3-C7, i.e., LCS, 16.4% +/- 0.8). The gap at the ventral and dorsal regions was lower in the UCS (ventral 3.8% +/- 0.6, dorsal 7.0% +/- 1.4) than in the LCS (ventral 18.5% +/- 0.9, dorsal 14.2% +/- 1.1) with p values of less than 0.0001 and equal to 0.0004, respectively. Further, the gap in the dorsal region for females (14.7% +/- 1.8) was greater (P = 0.0523) than the gap for males (10.8% +/- 1.1). The overall mean facet cartilage thickness was lower (P = 0.0111) in females (0.6 mm +/- 0.1) than males (0.9 mm +/- 0.2) in the UCS. It was also lower (P = 0.0077) in females (0.4 mm +/- 0.02) than males (0.5 mm +/- 0.03) in the LCS. The facet joint width demonstrated differences only between the UCS and LCS (P < 0.0001), with higher magnitudes in the upper (17.4 mm +/- 0.4) than in the lower (11.3 mm +/- 0.3) region. Facet joint morphology varies with the regions of the cervical spine (upper vs. lower), gender (male vs. female), and location (dorsal vs. ventral). Because of the lack of intervertebral discs in the UCS region, variations in these geometrical characteristics affect the biomechanical behaviors of the human spine secondary to external loads. Furthermore, the lack of adequate cartilage in females may expose the underlying adjacent subchondral bone to direct stresses during normal physiologic and traumatic loads.


Studies of the ocular pulse in primates.
Ocular pulse amplitude (OPA) and intraocular pressure (IOP) were measured in groups of human subjects with primary open-angle glaucoma (POAG), ocular hypertension (OHT), low-tension glaucoma (LTG), retinal degenerations (RD), in OHT volunteers treated with single doses of 2% epinephrine, 4% pilocarpine, 0.5% timolol or 1% p-amino-clonidine, and in normal subjects before and after exercise. Compared to normal controls, OHT subjects showed significantly higher IOP and OPA, while OPA was significantly lower in ocular normotensive LTG and RD subjects groups. All drug treatments lowered IOP in OHT subjects, but did not change OPA significantly. Exercise in normal volunteers increased calculated ocular perfusion pressure by 22.5%, lowered IOP by 32%, but showed no significant change in OPA. When IOP was elevated > or = 5 mmHg in lasered monkey eyes peak pulse volume (PPV) was increased significantly in the unlasered eyes. Epinephrine 2% or 1% p-aminoclonidine lowered IOP moderately with no change in PPV, while treatment with 4% pilocarpine or 0.5% timolol reduced IOP and increased PPV significantly. The findings suggest that LTG may be associated with an ocular vascular abnormality. OPA in OHT or normal human subjects did not change when IOP was decreased by antiglaucoma drug treatments or exercise, respectively. These results indicate that OPA may be physiologically autoregulated in human subjects with IOPs in the 11-21 mmHg range. However, laser-induced glaucomatous monkey eyes with higher IOP (30-35 mmHg) did not autoregulate, but showed a low peak pulse volume, which increased when IOP was reduced 5 mmHg or more by means of antiglaucoma drug treatment.


Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1.
In the acute phase of bacterial infection, a variety of cytokines, including interleukin-1 (IL-1), are elicited by bacterial endotoxin in both the periphery and the central nervous system. Bacterial endotoxin has been previously reported to profoundly activate the hypothalamic-pituitary-adrenal axis, resulting in elevated glucocorticoid secretion that may serve an important role as part of the inhibitory feedback mechanisms on the activated immune system. To determine whether IL-1 acts within the brain to mediate endotoxin-induced CRH gene expression in the hypothalamic paraventricular nucleus (PVN), we studied the effect of administering the human IL-1 receptor antagonist (IL-1ra) into the brain, a competitive inhibitor of IL-1, on CRH gene expression in the PVN after systemic lipopolysaccharide (LPS) treatment. Eight hours after the ip administration of LPS, the paraventricular CRH mRNA content was elevated 3-to 4-fold (P < 0.01) compared to the control value, and this elevation could be completely abolished by central IL-1ra pretreatment (P < 0.05 compared to LPS-treated group; P > 0.05 compared to controls). In contrast, systemic IL-1ra administration did not inhibit endotoxin-induced CRH gene expression in the PVN. These studies demonstrate that LPS stimulates hypothalamic CRH by a mechanism that involves the action of IL-1 within the central nervous system and may proceed independently of peripheral actions of IL-1 circulating in the bloodstream.


Acetaminophen administration and the risk of acute kidney injury: a self-controlled case series study.
Acetaminophen (APAP) is frequently used for analgesia and is considered safer than nonsteroidal anti-inflammatory drugs (NSAIDs) for the kidneys. However, there is little epidemiological evidence of the association between APAP and acute kidney injury (AKI). To examine the association between APAP and AKI using the self-controlled case series (SCCS) method, which is a novel strategy to control between-person confounders by comparing the risk and reference periods in each patient. We performed SCCS in 1,871 patients (39.9% female) who were administered APAP and subsequently developed AKI, by reviewing electronically stored hospital information system data from May 2011 to July 2016. We used conditional Poisson regression to compare each patient's risk and reference period. As a time-varying confounder, we adjusted the status of liver and kidney functions, systemic inflammation, and exposure to NSAIDs. We identified 5,650 AKI events during the 260,549 person-day observation period. The unadjusted incidences during the reference and exposure periods were 2.01/100 and 3.12/100 person-days, respectively. The incidence rate ratio adjusted with SCCS was 1.03 (95% confidence interval [CI]: 0.95-1.12). When we restricted endpoints as stage 2 AKI- and stage 3 AKI-level creatinine elevations, the incidence rate ratios were 1.20 (95% CI 0.91-1.58) and 1.20 (95% CI 0.62-2.31), respectively, neither of which was statistically significant. Our findings added epidemiological information for the relationship between APAP administration and AKI development. The results indicated scarce association between APAP and AKI, presumably supporting the general physicians' impression that APAP is safer for kidney.


Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.
Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. One patient developed a benign clonal dominance that could not be attributed to insertional mutagenesis and instead likely resulted from expansion of a transduced natural killer clone in response to chronic Epstein-Barr virus viremia. Clonal diversity and T-cell repertoire, measured by vector integration site sequencing and T-cell receptor β-chain rearrangement sequencing, correlated significantly with the amount of busulfan preconditioning delivered to patients and to CD34+ cell dose. These data, in combination with results of other ADA-SCID gene therapy trials, suggest that disease background may be a crucial factor in leukemogenic potential of retroviral gene therapy and underscore the importance of cytoreductive conditioning in this type of gene therapy approach.


Urodynamic and continence assessment of orthotropic neobladder reconstruction following radical cystectomy in bladder cancer; a prospective, blinded North Indian tertiary care experience.
The aim of this study is to compare urodynamic and continence parameters among patients undergoing orthotropic neo-bladder substitution with sigmoid or ileal segments. Variations in the Urodynamic parameter between the continent and incontinent patients were also evaluated. From January 2008 to March 2012, 44 patients underwent ileal neobladder (IN) reconstruction and 36 patients underwent sigmoid neobladder (SN) reconstruction. Evaluation of Urodynamic and Continence parameters was performed at 12 months after surgery. The average capacity of IN and SN was 510 ml and 532 ml respectively. The voiding pressure, mean peak flow rates and post void residual urine (PVRU) for IN and SN were 27.5 cm H2O versus 37 cm H2O, 15ml/s versus 17ml/s and 36 ml versus 25 ml respectively. Daytime continence for IN and SN was 93% (41/44) and 89% (32/36), and night-time continence was 91% (40/44) and 78% (28/36) respectively. The compliance, maximum cystometric capacity and PVRU in the daytime continent (versus incontinent) were 61 (versus 41), 471 (versus 651) and 22 (versus 124) and in the night-time continent (versus incontinent) were 57 (versus 43), 437 (versus 654) and 18 (versus 105) respectively. A neobladder constructed from detubularized ileum or sigmoid achieves urodynamically proven adequate capacity and compliance with 89-93% daytime and 78-91% night time continence. Continent men when compared with incontinent (both daytime and night time) were more likely to have comparatively higher compliance, lower maximum cystometric capacity and lower PVRU. Urodynamic study could predict which incontinent men would improve with pelvic floor exercises and clean intermittent catheterization (CIC).


Drug interactions--friend or foe?
An explosion of knowledge about interactions of drugs with other drugs and with foods threatens to inundate clinicians. This review provides a better understanding of the cytochrome P450 system with a focus on those enzymes most involved in drug metabolism. Emphasis is placed on antidepressant medications, how they are metabolized by the P450 system, and how they alter the metabolism of other drugs. The role of antidepressants in precipitating the serotonin syndrome is also discussed.


Follow-up Care Education and Information: Identifying Cancer Survivors in Need of More Guidance.
Cancer survivors engage in cancer screenings and protective health behaviors at suboptimal rates despite their increased risk for future illness. Survivorship care plans and other educational strategies to prepare cancer survivors to adopt engaged roles in managing long-term follow-up care and health risks are needed. In a sample of cancer survivors, we identified patient characteristics and psychosocial predictors associated with increased follow-up care informational needs. Cross-sectional surveys were administered to early-stage breast and prostate survivors (N = 278; 68 % breast) at least 2 years post treatment from four community hospital programs in New Jersey between May 2012 and July 2013. Patient demographics, medical history, psychosocial characteristics (i.e., worries about the future, fear of disease recurrence, and patient activation), and perceptions of oncology and primary care were assessed. African-American survivors (AOR = 2.69, 95 % confidence interval [CI] 1.27-5.68) and survivors with higher comorbidity (AOR =1.16, CI 1.01-1.33) were more likely to want additional information to guide follow-up care. Adjusting for race and comorbidities, survivors who wanted more information to guide their follow-up care reported greater worries about the future (p < 0.05) and fears about disease recurrence (p < 0.05) compared to those who did not want additional information. Results emphasize the need to develop cancer survivorship educational strategies that are both responsive to the needs of specific populations (e.g., African-American survivors and patients with multiple comorbidities) and the psychosocial profiles that motivate requests for more extensive follow-up guidance.


[Exercise can be an addiction].
Exercise is normally a healthy activity, which leads to enjoyment and wellness. But some people appear to become addicted and continue to exercise even to the detriment of their social lives and health. The symptoms are e.g. increasing exercise amounts, withdrawal symptoms, euphoria and relapse. The Exercise Addiction Inventory is a screening tool validated in Danish, which identifies 3-10% of the exercisers at risk of addiction. Exercise addiction can be a symptom of an eating disorder, but it seems to exist independently though it is not recognized as a diagnosis.


Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6.
Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.


Electromyography of the paravertebral muscles in idiopathic scoliosis. Measurements of amplitude and spectral changes under load.
The myoelectric activity of the paraspinal muscles was recorded in girls with idiopathic scoliosis and in healthy controls. The muscles of the back were loaded isometrically and the signals recorded at the T8 and L3 levels were analysed as regards amplitude and frequency. A comparatively higher signal amplitude was found on the convex side of the scoliosis curve. This was found to be due to a lower amplitude on the concave side when the scoliosis group was compared to the controls. The amplitude difference was correlated to the degree of scoliosis. A shift in the myoelectric spectrum toward lower frequencies occurred during the loading period. There were no differences in this respect between the sides of the scoliosis, nor were there differences between the scoliosis patients and the controls. Secondary adaptation to the higher load demand by the muscles on the convex side in scoliosis is the most probable explanation for our observations.


Respiratory effects of low-level photochemical air pollution in amateur cyclists.
A group of male amateur cyclists was studied in the summer of 1991 in the east of the Netherlands. Lung function was measured before and after training sessions or competitive races on a number of occasions. Continuous heart rate monitors were employed to document exercise levels. Heart rate averaged 161 beats/min during training, and 176 beats/min during races. Exercise duration averaged 75 min. Ozone concentrations during exercise were obtained from the nearest stations of the National Monitoring Network. The difference between pre- and postexercise lung function values was related to these ozone concentrations. Ozone concentrations were low on most occasions with an average of 87 micrograms/m3 and a maximum of 195 micrograms/m3. The difference between pre- and postexercise lung function was found to be negatively related to the ozone concentration during exercise. When all observations obtained at ozone concentrations higher than 120 micrograms/m3 were removed from the analysis, the relationship with ozone was still significant. The data also suggested that effects of ozone on lung function were stronger in midsummer than in the late summer. The difference between pre- and postexercise acute symptoms was positively related to ozone, for shortness of breath, chest tightness, and wheeze. Cough and eye irritation were not related to ozone. These results indicate that in healthy young men vigorously exercising outdoors, ozone is related to lung function changes and acute respiratory symptom changes at low levels of exposure.


Comparative repellent activities of some plant extracts against Simulium damnosum complex.
The root and leaf extracts of four plants, Occimum gratissimum, Azadirachta indica, Pterocarpus santalinoides, and Pistia hyptis, were studied for repellent activities against the adults of Simulium damnosum sensu lato. The leaves and roots were extracted with 95% ethanol and the stocks were diluted with paraffin. The repellent activities of the extracts were investigated using human baits along the banks of River Oyan and River Ogun in southwestern Nigeria. The results showed that the root extract of O. grattissium and leaf extract of P. hyptis had highest repellent potentials with 78% and 78.1% protection against S. damnosum sensu lato, respectively, whereas the root and leaf of P. santalinoides recorded the least. Although there were significant differences in the percentage of protection of the extracts of the plants (p < 0.05), the variations in the percentage of protection of the leaf and root extracts were not statistically significant (p > 0.05). The study concludes that there exist some repellent efficacies in the extracts of the plants, most importantly O. grattissimum and P. hyptis. The plant extracts can further be developed in the prevention of man-vector contact in onchocerciasis endemic communities.


Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients.
We evaluated the effect of botulinum toxin type A (BTX-A) injections in the trigone on the antireflux mechanism and evaluated its short-term efficacy. Between April and December 2006, 21 patients (10 men and 11 women) were prospectively evaluated. All were incontinent due to refractory NDO and underwent detrusor injection of 300 units of BTX-A, including 50 units into the trigone. Baseline and postoperative evaluation after eight weeks included cystogram, urinary tract ultrasound and urodynamics. At baseline, 20 patients had no vesicoureteral (VUR) and one had grade II unilateral VUR. Postoperative evaluation revealed no cases of de novo VUR and the patient with preinjection VUR had complete resolution of the reflux. Ultrasound showed 5 (23.8%) patients with hydronephrosis before BTX-A injection and only one (4.8%) at the followup evaluation (p=0.066). After treatment, 9 (42.8%) patients became dry, 11 (52.4%) were improved and one (4.8%) had no improvement. Improved patients received antimuscarinic treatment and 8 (38.1%) became dry, with a final total continence rate of 80.1%. Cystometric capacity increased from 271+/-92 to 390+/-189 ml (p=0.002), reflex volume varied from 241+/-96 to 323+/-201 ml (p=0.020) and maximum detrusor pressure reduced from 66+/-39 to 38+/-37 cm H(2)O (p<0.001). Our results confirm the safety of trigone injections of BTX-A in terms of development of VUR and upper urinary tract damage. Whether they are beneficial for patients with NDO or other causes of voiding dysfunction will need further studies.


[Introduction to geriatric oncology].
The demographic changes will result in a profound increase of the number of elderly people within the next years. As a consequence of the age dependent increase of the incidence and mortality rate of cancer these changes will bring an increase in the number of elderly people with cancer. There is a number of differences between young and old patients diagnosed with cancer. This must result in an adaption of standardised oncological procedures, mainly designed for younger patients, to the special situation of elderly patients. The differences between young and old patients with cancer may be depicted by a structured geriatric assessment. Suggestions for the structure of such an assessment exist. Ongoing clinical trials have to demonstrate, whether or not the inclusion of a geriatric oncological assessment in the decision making process will result in an improvement of treatment results in elderly cancer patients diagnosed with cancer.