View-based organization and interplay of spatial working and long-term memories.
Space perception provides egocentric, oriented views of the environment from which working and long-term memories are constructed. "Allocentric" (i.e. position-independent) long-term memories may be organized as graphs of recognized places or views but the interaction of such cognitive graphs with egocentric working memories is unclear. Here we present a simple coherent model of view-based working and long-term memories, together with supporting evidence from behavioral experiments. The model predicts (i) that within a given place, memories for some views may be more salient than others, (ii) that imagery of a target square should depend on the location where the recall takes place, and (iii) that recall favors views of the target square that would be obtained when approaching it from the current recall location. In two separate experiments in an outdoor urban environment, pedestrians were approached at various interview locations and asked to draw sketch maps of one of two well-known squares. Orientations of the sketch map productions depended significantly on distance and direction of the interview location from the target square, i.e. different views were recalled at different locations. Further analysis showed that location-dependent recall is related to the respective approach direction when imagining a walk from the interview location to the target square. The results are consistent with a view-based model of spatial long-term and working memories and their interplay.


Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis.
The metabolism of cells in inflammatory and noninflammatory arthritic joint diseases is subject to complex environmental controls. The aim of the present study was to investigate the total antioxidant capacity (TAC), levels of lipid peroxidation (LPO), and antioxidant enzyme activities in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Plasma levels of TAC, malondialdehyde (MDA), the activities of some erythrocyte antioxidant enzymes, as well as erythrocyte sedimentation rates (ESR) were estimated in patients with RA and OA and compared with controls. The plasma TAC levels were significantly lower in the RA group than the OA and control group (P < 0.05). Plasma MDA concentrations were significantly higher in patients with RA than those with OA and healthy subjects (P < 0.05). Erythrocyte GSH-Px and CAT activities were found to be significantly lower in patients with RA than those with OA and healthy subjects (P < 0.05, P < 0.05, respectively). However, there were no significant differences in erythrocyte SOD activities between the groups (P > 0.05). ESR were significantly higher in RA patients than in healthy subjects and patients with OA (P < 0.01). Moreover, there were significant negative correlations between TAC vs. MDA, ESR vs. TAC, and a positive correlation between ESR vs. MDA in the RA group (r = -0.398, P < 0.05; r = -0.422, P < 0.05; r = 0.530, P < 0.05, respectively). Our results demonstrated that levels of LPO are increased in patients with RA compared to patients with OA. In addition, plasma TAC levels are decreased in RA due to its inflammatory character. We conclude that detecting plasma TAC levels with this novel method may be used as a routine and rapid test to verify the levels of oxidative stress in RA. Furthermore, correlating TAC and LPO levels with acute phase reactants such as ESR may give some clues about disease activity in RA.


Iodine deficiency disorders in Sarawak, Malaysia.
The state of Sarawak in Malaysia has a high prevalence of iodine deficiency disorders (IDD). This has been revealed through a review of goitre surveys that were carried out in the State from the early 1970s to the 1990s. The primary cause was low iodine intake. Contributory factors were low iodine content in the soil and water as well as high cassava consumption. Virtual elimination of IDD is one of the nutritional goals of the IDD prevention and control programs. The strategies adopted include the iodination of coarse salt, which is sold in the market by shopkeepers and also provided free from government health clinics; legislation requiring that salt sold in IDD-gazetted areas must be iodised; and the use of iodinators to iodise water supplied by the gravity-feed system to villages and boarding schools in rural areas. The indicators used in the monitoring and evaluation of the program include the availability of iodised salt in the market and households, iodine levels in water supply that had been fitted with iodinators, goitre volume measured by ultrasound, and urinary iodine excretion among school children.


Impact of resolved early major complications on 2-year follow-up outcome following adult spinal deformity surgery.
Major complications are a concern following ASD surgery. Even when properly managed and resolved, they may still have a relevant impact on HRQL. We aimed to investigate the impact of resolved early major complications on 2-year outcome after ASD surgery. Two groups of consecutive surgical patients were extracted from a prospective multicentre database. Major complication group (MCG) included patients with any major complication, resolved within 6 months after surgery. Patients with further major complications during follow-up were excluded. Control group (CG) included patients with no major complications over the entire follow-up. Analysis of covariance adjusting for preoperative baseline values was used to compare improvements in HRQL measures at 2 years. One hundred and seventy-five patients met the inclusion criteria and had complete HRQL data at 2 years (24 MCG, 151 CG). MCG patients were older and had more severe deformity and poorer baseline HRQL. There were 27 resolved major complications at 6 months needing 19 additional surgeries (18 revisions, 1 cholecystectomy). At 2 years, and after adjusting for preoperative data, outcome in MCG patients was as follows: scores were 5.98 (SE 3.03) points higher for the ODI (p = 0.05), 0.36 (SE 0.13) lower SRS-22 function (p = 0.01), 4.07 (SE 1.93) lower SF-36 PCS (p = 0.04), and 0.16 (SE 0.13) lower SRS-22 subtotal (p = 0.22). The results indicate that patients experiencing major complications after ASD surgery have significantly less functional improvement (SRS-22 function, ODI, SF-36 PCS) than their complication-free counterparts, even when complications were considered resolved, and the outcome was measured after an 18-month complication-free period. These slides can be retrieved under Electronic Supplementary Material.


[Radiofrequency ablation for liver metastases from colorectal cancer after systemic chemotherapy].
To evaluate the effectiveness and safety of radiofrequency ablation(RFA)for liver metastases from colorectal cancer after chemotherapy. From January 2006 to June 2012, 27 tumors in 17 patients with liver metastases from colorectal cancer were treated using RFA after systemic chemotherapy. The median tumor diameter after chemotherapy was 12(range: 3-35)mm, and the mean number of tumors was 1.6(range: 1-4).The median time without local recurrence was 21.3(range: 2.2-61.9)months, and the median overall survival time was 38.0(range: 5.9-66.3)months. One patient had a complication(liver abscess).Of the 27 tumors, 9 were larger than 20 mm in diameter, and 4 of these 9 tumors showed local recurrence after RFA. In tumors smaller than 20 mm in diameter, only 1 showed local recurrence. The local recurrence rate was significantly higher for tumors larger than 20 mm than for tumors smaller than 20 mm(44.4% vs 5.6%,p=0.030). RFA was an effective and safe method for treating liver metastases from colorectal cancer, especially for tumors smaller than 20 mm and in cases of less than 3 tumors after systemic chemotherapy.


The winding path towards symbiotic autonomous systems.
Over the next 10 years, we are likely to see the convergence of two independent evolutionary paths: one leading to an augmentation of machine capabilities; the other with the augmentation of human capabilities. This convergence will not happen at a specific point in time; instead, it will be the result of progressive overlapping, to the point that it might be difficult to identify a defining moment. The following decade will likely be quite different from the present one. 5G will probably be remembered as a transitional system, artificial intelligence (AI) as a misplaced objective. We are looking forward to a communications fabric created by autonomous systems that will exist both in the physical world as well as in cyberspace, determining a continuum that gives rise to digital reality and where intelligence is an emerging property of the ambient. Hence, the dichotomy between AI and natural intelligence will no longer exist and AI will be considered as a tool for human augmentation and as the glue connecting minds and machines. This article is part of the theme issue 'Towards symbiotic autonomous systems'.


Effects of a TAFI-inhibitor combined with a suboptimal dose of rtPA in a murine thromboembolic model of stroke.
Since thrombolysis is the only approved intervention for ischemic stroke, improving its efficacy and safety is a therapeutic aim of considerable interest. The activated form of thrombin activatable fibrinolysis inhibitor (TAFI) has antifibrinolytic effects, and inhibition of TAFI might thus favor recanalization. The present study compared efficacy between TAFI inhibition alone and TAFI inhibition in combination with rtPA at a suboptimal dose, in a murine model of thromboembolic stroke. Focal ischemia was induced in mice by thrombin injection in the middle cerebral artery. Animals were placed within the magnet immediately after surgery for baseline MRI (H0). MRI examination comprised diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and T2-weighted imaging (T2-WI). Animals were randomly assigned to 1 of 5 treatment groups: saline, rtPA 5 mg/kg (tPA(5): suboptimal or low dose), rtPA 10 mg/kg (tPA(10): standard dose), TAFI-I 100 mg/kg (TAFI-I), and rtPA 5 mg/kg + TAFI-I 100 mg/kg (tPA(5) + TAFI-I). Treatments were administered inside the magnet, via a catheter placed in the tail vein, using a power injector, as 10% bolus and 90% infusion over a period of 20 min. MRI examination was repeated at 3 h (H3) and 24 h (H24) after surgery. Therapeutic benefit was evaluated by: (1) improvement of reperfusion and (2) reduction in final lesion size. Microhemorrhages were assessed as black spots on T2-WI at H24. Animals were sacrificed after the last MR examination. The surgeon and all investigators were blinded to treatment allocation. A total of 104 mice were operated on. Forty four of these were excluded from the study and 27 from the analysis, according to a priori defined criteria (no lesion or no mismatch), leading to the following distribution: saline (n = 6), tPA(5) (n = 8), tPA(10) (n = 7), TAFI-I (n = 7), and TAFI-I + tPA(5) (n = 5). Standard-dose rtPA treatment (tPA(10)) significantly improved lesion regression between H0 and H24 compared to saline (-57 ± 18% vs. -36 ± 21%, p = 0.03), which treatment with rtPA(5) or TAFI-I alone did not. On the other hand, combined treatment with tPA(5) + TAFI-I showed only a trend toward lesion regression (-49 ± 26%), similarly to treatment with tPA(10), but not significantly different from saline (p = 0.46). Nine animals showed microhemorrhage on T2-WI at H24. These animals were evenly distributed between groups. The present study showed that the combination of TAFI-I with a suboptimal dose of rtPA is not as effective as the standard dose of rtPA, while TAFI inhibition alone is not effective at all. The thromboembolic model is of particular interest in assessing rtPA association to improve thrombolysis, especially when coupled with longitudinal MRI assessment.


Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial.
To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE). An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry. IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration. IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.


["Freud and fetichism": previously unpublished minutes of the Vienna Psychoanalytic Society].
On the occasion of this session held by the Viennese Psychoanalytic Society on the 24th of February 1909, Freud made a presentation on fetchism that was the point of departure for a reflection that led him to the theorization of the article of 1927. Being careful to differentiate his position from that of other authors having shown an interest for the subject, he clearly stressed the role of infantile sexuality as an etiological factor, and in particular the link between fetichism and repression. The discussion that followed the presentation shows that Freud and Adler's positions were beginning to diverge, the latter replacing the notion of instincts that Freud held to be involved in the mechanism of repression, by that of "fear of degradation" and of "sensitivity". These Minutes that had been thought to have disappeared are studied within the more general framework of the meetings of the Viennese Psychoanalytic Society.


Enzymes and Metabolites in Carbohydrate Metabolism of Desiccation Tolerant Plants.
Resurrection plants can tolerate extreme water loss. Substantial sugar accumulation is a phenomenon in resurrection plants during dehydration. Sugars have been identified as one important factor contributing to desiccation tolerance. Phylogenetic diversity of resurrection plants reflects the diversity of sugar metabolism in response to dehydration. Sugars, which accumulate during dehydration, have been shown to protect macromolecules and membranes and to scavenge reactive oxygen species. This review focuses on the performance of enzymes participating in sugar metabolism during dehydration stress. The relation between sugar metabolism and other biochemical activities is discussed and open questions as well as potential experimental approaches are proposed.


Characteristics of the phagocytically induced respiratory burst in leukocytes from young adult and aged beagle dogs.
Phagocytically stimulated canine leukocyte suspensions obtained from 12 young adult and 43 aged individuals were examined for several physiological manifestations of the phagocytically induced respiratory burst. There was considerable variation in levels of oxygen consumption, glucose oxidation via the hexose monophosphate shunt (HMPS), and chemiluminescence response by both resting and phagocytically stimulated leukocytes from different individual animals in each age-group. Leukocyte suspensions from specific individuals in each age-group exhibited a weakly responsive respiratory burst. Chronological age could not be used as a predictor of either the specific (oxygen consumption and HMPS activity) or nonspecific (chemiluminescence response) manifestations of the respiratory burst. The kinetics of the chemiluminescence response were similar for all age-groups. Collectively, the results suggest that there is not an age-related alteration in the phagocytically induced respiratory burst of canine neutrophils and that cells from young adult and aged dogs have a comparable capacity to generate levels of highly reactive antimicrobial oxidizing agents. The increased relative susceptibility of aging dogs to microbial agents is apparently not related to an absent, abbreviated, or reduced leukocyte respiratory burst.


Human pathogenic bacteria, fungi, and viruses in Drosophila: disease modeling, lessons, and shortcomings.
Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.


A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity.
To date, human peripheral blood mononuclear cells (PBMCs) have been used mainly in immune stimulation assays and the interpretation of data can be influenced by the previous immunological history of donors and cross reactivity with other infectious agents. Resolving these limitations requires an alternative in vitro model to uncover the primary response profiles. A novel in vitro model of mononuclear cells (MNCs) generated from haematopoietic stem cells (HSCs) was developed and these cells were then co-cultured with various antigens from Plasmodium falciparum and Plasmodium vivax to investigate the response of naïve immune cells to malaria antigens by flow cytometry. In vitro stimulation of naïve lymphocytes showed that CD4+ and CD8+ T lymphocytes were significantly reduced (P < 0.01) by exposure to lysates of infected erythrocytes or intact erythrocytes infected with P. falciparum. The depletion was associated with the expression of CD95 (Fas receptor) on the surface of T lymphocytes. Maturation of T lymphocytes was affected differently, showing elevated CD3+CD4+CD8+ and CD3+CD4-CD8- T lymphocytes after stimulation with cell lysates of P. falciparum and P. vivax, respectively. In addition, antigen presenting monocytes and dendritic cells derived from haematopoietic stem cells showed impaired HLA-DR expression as a consequence of exposure to different species of malaria parasites. These results suggest that naïve mononuclear cells differentiated in vitro from HSCs could provide a valid model for the assessment of immunity. P. falciparum and P. vivax malaria parasites could modulate various populations of immune cells starting from newly differentiated mononuclear cells.


MICROSATELLITE LOCI REVEAL SEX-DEPENDENT RESPONSES TO INBREEDING AND OUTBREEDING IN RED DEER CALVES.
Mean d2 is a recently devised microsatellite-based measure that is hypothesised to allow the detection of inbreeding depression and heterosis in free-living populations. Two studies that have investigated the measure have both demonstrated an association between mean d2 and traits related to fitness. Here we present an association between mean d1 and an important component of fitness, first-year overwinter survival, in a population of red deer on the Isle of Rum, Scotland. The association between survival and mean d2 differed between males and females. As predicted, outbred female calves (high mean d2 ) survived better than those that were inbred (low mean d2 ). However, the association was in the opposite direction in male calves. We suggest that this difference is due to different early growth strategies between the sexes. The association between mean d2 and survival was not significantly influenced by any single locus. Decomposition of mean d2 into a recent inbreeding component and an outbreeding component showed that it was the degree of outbreeding that influenced survival in males and both the degree of outbreeding and recent inbreeding that influenced survival in females. Our analyses suggest that mean d2 is an easy-to-calculate measure of inbreeding and degree of outbreeding that can reveal interesting interactions between genetics and ecology.


Quantitative analysis of auxin sensing in leaf primordia argues against proposed role in regulating leaf dorsoventrality.
Dorsoventrality in leaves has been shown to depend on the pre-patterned expression of KANADI and HD-ZIPIII genes within the plant shoot apical meristem (SAM). However, it has also been proposed that asymmetric auxin levels within initiating leaves help establish leaf polarity, based in part on observations of the DII auxin sensor. By analyzing and quantifying the expression of the R2D2 auxin sensor, we find that there is no obvious asymmetry in auxin levels during Arabidopsis leaf development. We further show that the mDII control sensor also exhibits an asymmetry in expression in developing leaf primordia early on, while it becomes more symmetric at a later developmental stage as reported previously. Together with other recent findings, our results argue against the importance of auxin asymmetry in establishing leaf polarity.


Position of the American Dietetic Association: ethical and legal issues in nutrition, hydration, and feeding.
It is the position of the American Dietetic Association that the development of clinical and ethical criteria for the nutrition and hydration of persons through the life span should be established by members of the health care team. Registered dietitians should work collaboratively to make nutrition, hydration, and feeding recommendations in individual cases. Registered dietitians have an active role in determining the nutrition and hydration requirements for individuals throughout the life span. When patients choose to forgo artificial nutrition and hydration, or when patients lack decision-making capacity, and others must decide whether or not to provide artificial nutrition and hydration, the registered dietitian has an active and responsible professional role in the ethical deliberation around that decision. There is strong clinical, ethical, and legal support both for and against the administration of food and water when issues arise regarding what is or is not wanted by the patient and what is or is not warranted by empirical clinical evidence. When a conflict arises, the decision to administer or withhold nutrition and hydration requires ethical deliberation. The registered dietitian's understanding of nutrition and hydration within the context of nutritional requirements and cultural, social, psychological, and spiritual needs provides an essential basis for ethical deliberation on issues of nutrition and hydration.


Content and Communication of Inpatient Family Visitation Policies During the COVID-19 Pandemic: Sequential Mixed Methods Study.
Inpatient health care facilities restricted inpatient visitation due to the COVID-19 pandemic. There is no existing evidence of how they communicated these policies to the public nor the impact of their communication choices on public perception. This study aims to describe patterns of inpatient visitation policies during the initial peak of the COVID-19 pandemic in the United States and the communication of these policies to the general public, as well as to identify communication strategies that maximize positive impressions of the facility despite visitation restrictions. We conducted a sequential, exploratory, mixed methods study including a qualitative analysis of COVID-19 era visitation policies published on Pennsylvania-based facility websites, as captured between April 30 and May 20, 2020 (ie, during the first peak of the COVID-19 pandemic in the United States). We also conducted a factorial survey-based experiment to test how key elements of hospitals' visitation policy communication are associated with individuals' willingness to seek care in October 2020. For analysis of the policies, we included all inpatient facilities in Pennsylvania. For the factorial experiment, US adults were drawn from internet research panels. The factorial survey-based experiment presented composite policies that varied in their justification for restricted visitation, the degree to which the facility expressed ownership of the policy, and the inclusion of family-centered care support plans. Our primary outcome was participants' willingness to recommend the hypothetical facility using a 5-point Likert scale. We identified 104 unique policies on inpatient visitation from 363 facilities' websites. The mean Flesch-Kincaid Grade Level for the policies was 14.2. Most policies prohibited family presence (99/104, 95.2%). Facilities justified the restricted visitation policies on the basis of community protection (59/104, 56.7%), authorities' guidance or regulations (34/104, 32.7%), or scientific rationale (23/104, 22.1%). A minority (38/104, 36.5%) addressed how restrictive visitation may impair family-centered care. Most of the policies analyzed used passive voice to communicate restrictions. A total of 1321 participants completed the web-based survey. Visitation policy elements significantly associated with willingness to recommend the facility included justifications based on community protection (OR 1.44, 95% CI 1.24-1.68) or scientific rationale (OR 1.30, 95% CI 1.12-1.51), rather than those based on a governing authority. The facility expressed a high degree of ownership over the decision (OR 1.16, 95% CI 1.04-1.29), rather than a low degree of ownership; and inclusion of family-centered care support plans (OR 2.80, 95% CI 2.51-3.12), rather than no such support. Health systems can immediately improve public receptiveness of restrictive visitation policies by emphasizing community protection, ownership over the facility's policy, and promoting family-centered care.


Tibial Onlay Posterior Cruciate Ligament Reconstruction: Surgical Technique and Results.
The posterior cruciate ligament (PCL) is a fundamental structure in knee kinematics. PCL tears may lead to adverse consequences, such as impaired functional performance and an increased risk of osteoarthritis. Although surgical treatment is a well-established option for the patients of PCL rupture, many surgeons opt for conservative treatment because of the lack of consensus in the orthopedic literature concerning the best surgical method with less risk of iatrogenic lesions to the neurovascular structures in the popliteal region. Here, we describe an onlay technique for PCL reconstruction, which has some advantages over the traditional transtibial and over inlay techniques. The technique described in this study avoids the "killer angle"-frequently considered the cause of laxity of the reconstructed ligament-while simultaneously permitting safe retraction of the neurovascular structures without the need for a change in the patient's position. This technique has been used at our institution for approximately 10 years with very satisfactory results. The aim of this study is to describe the technique and perform a retrospective evaluation of the results of a case series.


Differential gene expression and alternative splicing between diploid and tetraploid watermelon.
The exploitation of synthetic polyploids for producing seedless fruits is well known in watermelon. Tetraploid progenitors of triploid watermelon plants, compared with their diploid counterparts, exhibit wide phenotypic differences. Although many factors modulate alternative splicing (AS) in plants, the effects of autopolyploidization on AS are still unknown. In this study, we used tissues of leaf, stem, and fruit of diploid and tetraploid sweet watermelon to understand changes in gene expression and the occurrence of AS. RNA-sequencing analysis was performed along with reverse transcription quantitative PCR and rapid amplification of cDNA ends (RACE)-PCR to demonstrate changes in expression and splicing. All vegetative tissues except fruit showed an increased level of AS in the tetraploid watermelon throughout the growth period. The ploidy levels of diploids and the tetraploid were confirmed using a ploidy analyser. We identified 5362 and 1288 genes that were up- and downregulated, respectively, in tetraploid as compared with diploid plants. We further confirmed that 22 genes underwent AS events across tissues, indicating possibilities of generating different protein isoforms with altered functions of important transcription factors and transporters. Arginine biosynthesis, chlorophyllide synthesis, GDP mannose biosynthesis, trehalose biosynthesis, and starch and sucrose degradation pathways were upregulated in autotetraploids. Phloem protein 2, chloroplastic PGR5-like protein, zinc-finger protein, fructokinase-like 2, MYB transcription factor, and nodulin MtN21 showed AS in fruit tissues. These results should help in developing high-quality seedless watermelon and provide additional transcriptomic information related to other cucurbits.


Detection of tumor cells in bone marrow, peripheral blood and lymph nodes by automated imaging devices.
The presence of tumor cells in bone marrow, peripheral blood and lymph nodes has proven its clinical and prognostic value. Since the frequency of these cells in bone marrow and blood is sometimes as low as 1 per million and due to the fact that for the analysis of lymph nodes many sectioning levels have to be analyzed, automated imaging devices have been suggested as an useful alternative to conventional manual screening of specimens. The aim of this paper is to review the performance of current equipment that is commercially available, based on literature published so far. Requirements for introducing this equipment for routine clinical practice are discussed.


1H-NMR analysis of turkey egg-white lysozyme and comparison with hen egg-white lysozyme.
The complete main chain and approximately 75% of the side chain 1H-NMR assignments of the 129-residue protein, turkey egg-white lysozyme, are presented. NOE data, hydrogen-exchange rates, chemical shifts and coupling constants are reported and are indicative of a structure in solution that is essentially identical to that of the homologous hen egg-white lysozyme. The NH-alpha CH coupling constants of turkey lysozyme are compared to torsion-angle data from three crystal structures of the protein and the results are interpreted in terms of crystal-structure resolution and refinement.


Association between Serum Irisin and Leptin Levels and Risk of Depressive Symptoms in the Diabetic Elderly Population.
Adipokines are considered to be involved in the pathogenesis of diabetes and depression. The associations of serum levels of leptin and irisin with depressive symptoms were investigated in elderly patients with type 2 diabetes (T2DM). 189 elderly diabetics were assessed with the 30-item Geriatric Depression Scale (GDS-30), and 57 patients with depressive symptoms and 132 controls were selected. Blood biochemical parameters, including serum irisin and leptin, were measured. Serum irisin levels were decreased and leptin concentrations were significantly higher in T2DM patients with depressive symptoms compared to controls. In all subjects, the irisin level was inversely correlated with the leptin level and the GDS-30 score, whereas the leptin level was highly correlated with BMI and the GDS-30 score. Higher levels of leptin and lower concentrations of irisin are, among other factors, variables indicative of predictive capacity for depressive symptoms in elderly patients with T2DM. The results indicated that irisin and leptin levels may be used as diagnostic markers of depressive symptoms in diabetic, elderly patients and as potential therapeutic targets for the treatment. Further prospective and more extensive studies are needed to clarify the role of these adipokines in the common pathogenesis of depression and diabetes.


Will brain cells derived from induced pluripotent stem cells or directly converted from somatic cells (iNs) be useful for schizophrenia research?
The reprogramming of nonneuronal somatic cells to induced pluripotent stem cells and their derivation to functional brain cells as well as the related methods for direct conversion of somatic cells to neurons have opened up the possibility of conducting research on cellular disease models from living schizophrenia patients. We review the published literature on schizophrenia that has used this rapidly developing technology, highlighting the need for specific aims and reproducibility. The key issues for consideration for future schizophrenia research in this field are discussed and potential investigations using this technology are put forward for critical assessment by the reader.


Notes from the taxonomic disaster zone: Evolutionary drivers of intractable species boundaries in an Australian lizard clade (Scincidae: Ctenotus).
Genomic-scale datasets, sophisticated analytical techniques, and conceptual advances have disproportionately failed to resolve species boundaries in some groups relative to others. To understand the processes that underlie taxonomic intractability, we dissect the speciation history of an Australian lizard clade that arguably represents a "worst-case" scenario for species delimitation within vertebrates: the Ctenotus inornatus species group, a clade beset with decoupled genetic and phenotypic breaks, uncertain geographic ranges, and parallelism in purportedly diagnostic morphological characters. We sampled hundreds of localities to generate a genomic perspective on population divergence, structure, and admixture. Our results revealed rampant paraphyly of nominate taxa in the group, with lineages that are either morphologically cryptic or polytypic. Isolation-by-distance patterns reflect spatially continuous differentiation among certain pairs of putative species, yet genetic and geographic distances are decoupled in other pairs. Comparisons of mitochondrial and nuclear gene trees, tests of nuclear introgression, and historical demographic modelling identified gene flow between divergent candidate species. Levels of admixture are decoupled from phylogenetic relatedness; gene flow is often higher between sympatric species than between parapatric populations of the same species. Such idiosyncratic patterns of introgression contribute to species boundaries that are fuzzy while also varying in fuzziness. Our results suggest that "taxonomic disaster zones" like the C. inornatus species group result from spatial variation in the porosity of species boundaries and the resulting patterns of genetic and phenotypic variation. This study raises questions about the origin and persistence of hybridizing species and highlights the unique insights provided by taxa that have long eluded straightforward taxonomic categorization.


High-resolution image workstation for intensive care units.
Despite their potential for improving patient management and decreasing costs, picture archiving and communication systems (PACS) are not being absorbed rapidly into clinical practice because of their technical immaturity and because the cost-effectiveness of the technology has not been established. Workstations and archives need to be significantly improved before they can be useful. This report describes the authors' experiences with a high-resolution image workstation for a medical intensive care unit. The workstation has been designed around a standard computer platform and is equipped with two high-resolution image displays. The user interface stresses speed and simplicity. Image manipulation is simplified by providing empirical preset window and level values. Images are displayed in less than 2 seconds. The workstation also displays radiologic reports as soon as they become available. Future work will focus on using the workstation to improve communication between the physician and the radiologist.


Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve.
During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of radiotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subjected to radiotherapy (40 Gy) for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no obvious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echinococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve.


Phenotypes and genotypes in a cohort of children with single-ventricle CHD.
CHD is known to be associated with increased risk for neurodevelopmental disorders. The combination of CHD with neurodevelopmental disorders and/or extra-cardiac anomalies increases the chance for an underlying genetic diagnosis. Over the last 15 years, there has been a dramatic increase in the use of broad-scale genetic testing. We sought to determine if neurodevelopmental disorders in children with single-ventricle CHD born prior to the genetic testing revolution are associated with genetic diagnosis. We identified 74 5-12-year-old patients with single-ventricle CHD post-Fontan procedure. We retrospectively evaluated genetic testing performed and neurodevelopmental status of these patients. In this cohort, there was an overall higher rate of neurodevelopmental disorders (80%) compared to the literature (50%). More of the younger (5-7-year-old) patients were seen by genetic counsellors compared to the older (8-12-year-old) cohort (46% versus 19% p value = 0.01). In the younger cohort, the average age of initial consultation was 7.7 days compared to 251 days in the older cohort. The overall rate of achieving a molecular diagnosis was 12% and 8% in the younger and older cohorts, respectively; however, the vast majority of did not have broad genetic testing. The minority of patients in our cohort achieved a genetic diagnosis. Given a large increase in the number of genes associated with monogenic CHD and neurodevelopmental disorders in the last decade, comprehensive testing and consultation with clinical genetics should be considered in this age range, since current testing standards did not exist during their infancy.


Clarifying the molecular mechanism associated with carfilzomib resistance in human multiple myeloma using microarray gene expression profile and genetic interaction network.
Carfilzomib is a Food and Drug Administration-approved selective proteasome inhibitor for patients with multiple myeloma (MM). However, recent studies indicate that MM cells still develop resistance to carfilzomib, and the molecular mechanisms associated with carfilzomib resistance have not been studied in detail. In this study, to better understand its potential resistant effect and its underlying mechanisms in MM, microarray gene expression profile associated with carfilzomib-resistant KMS-11 and its parental cell line was downloaded from Gene Expression Omnibus database. Raw fluorescent signals were normalized and differently expressed genes were identified using Significance Analysis of Microarrays method. Genetic interaction network was expanded using String, a biomolecular interaction network JAVA platform. Meanwhile, molecular function, biological process and signaling pathway enrichment analysis were performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Totally, 27 upregulated and 36 downregulated genes were identified and a genetic interaction network associated with the resistant effect was expanded basing on String, which consisted of 100 nodes and 249 edges. In addition, signaling pathway enrichment analysis indicated that cytokine-cytokine receptor interaction, autophagy, ErbB signaling pathway, microRNAs in cancer and fatty acid metabolism pathways were aberrant in carfilzomib-resistant KMS-11 cells. Thus, in this study, we demonstrated that carfilzomib potentially conferred drug resistance to KMS-11 cells by cytokine-cytokine receptor interaction, autophagy, ErbB signaling pathway, microRNAs in cancer and fatty acid metabolism pathways, which may provide some potential molecular therapeutic targets for drug combination therapy against carfilzomib resistance.


Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells.
Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.


Landscape of genomic imprinting and its functions in the mouse mammary gland.
Genomic imprinting is an epigenetic modification of DNA, whereby gene expression is restricted to either maternally or paternally inherited alleles. Imprinted genes (IGs) in the placenta and embryo are essential for growth regulation and nutrient supply. However, despite being an important nutrition delivery organ, studies on mammary gland genomic imprinting remain limited. In this study, we found that both the number of IGs and their expression levels decreased during development of the mouse mammary gland. IG expression was lineage-specific and related to mammary gland development and lactation. Meta-analysis of single-cell RNA sequencing data revealed that mammary gland IGs were co-expressed in a network that regulated cell stemness and differentiation, which was confirmed by our functional studies. Accordingly, our data indicated that IGs were essential for the self-renewal of mammary gland stem cells and IG decline was correlated with mammary gland maturity. Taken together, our findings revealed the importance of IGs in a poorly studied nutrition-related organ, i.e. the mammary gland, thus providing a reference for further studies on genomic imprinting.


Good acceptability of HIV, HBV, and HCV screening during immigration medical check-up amongst migrants in France in the STRADA study.
The prevalence of HIV, hepatitis B, and hepatitis C amongst migrants in France is high. Thus, effective screening and follow-up is needed. The mandatory medical check-up for residency application is an opportunity to offer rapid HIV and hepatitis testing. The main objective of the STRADA study is to create a feasible and acceptable screening strategy for migrants. Within the STRADA study, this qualitative research examined the acceptability of conducting screening tests in the context of residency application. We conducted a qualitative study amongst legal migrants over 18 years of age with sufficient knowledge of the French, English, or Arabic language. Interviews were performed following a semi-structured interview guide of open-ended questions. Interviews were transcribed verbatim and subsequently analyzed through thematic analysis. We interviewed 34 migrants. Mean age was 32.6 (min-max: 19, 59) years. The participants' region of origin was mostly Sub-Saharan Africa and the main reason for migrating to France was family reunification. Migrants' acceptability of HIV and hepatitis testing was high. Participants who accepted testing indicated a benefit for individual health and to avoid transmission. Most preferred rapid tests; reluctance was related to anxiety about the immediate results and the perceived reliability of rapid tests. Migrants' knowledge about HIV was satisfactory, but inadequate for hepatitis. Screening in the context of a compulsory medical visit did not present an obstacle for acceptability. Some expressed concern in the case of HIV but when explained, the independence between obtaining the residence permit along with screening and access to medical care was well understood. Medical check-ups at immigration centers is an opportunity to screen for HIV and hepatitis which is considered acceptable by migrants. Informing migrants that test results do not affect residency applications, and incorporating their preferences, are all important to optimize the acceptability of screening.


Organizational and provider characteristics fostering smoking cessation practice guideline adherence: an empirical look.
We examined the relationship between physician adherence with a smoking cessation guideline and organizational structures, policies, leadership support, and physician knowledge and attitudes. A random sample of 844 physicians practicing in 127 VHA hospitals was surveyed. Survey results were aggregated to the hospital level and linked with data on organizational characteristics from the 1998 annual survey of hospitals by the American Hospital Association. Significant predictors of adherence included organizational policies related to nicotine replacement prescriptions, the timing and effectiveness of guideline implementation, physicians' knowledge of VHA clinical guidelines generally, and physicians' beliefs about the receptiveness of patients to smoking cessation.


Responsivity/nonresponsivity in psychosomatic disorders.
Tested the hypothesis that gastrointestinal and dermatological symptoms are associated with differing psychological styles. Specifically, it was predicted that tendencies toward heightened environmental responsiveness and heightened experiences of urges and affects would be associated with gastrointestinal diseases, whereas affectively reduced environmental responsiveness and muted experiences of urges and affects would be associated with dermatological diseases. Forty adult male Ss, 20 in each disease category, were given an open-ended interview--the basis for the main test of the hypothesis, the Mayman Early Memory Test, and the TAT. Based on the interview material, coders classified the Ss as predicted at levels well beyond chance. Though the data from the other tests did not provide clear-cut evidence, they did offer tentative support for the hypothesis. S responses are presented that highlight the contrast between the two styles.


Efficacy of telerehabilitation exercise in patients with chronic neck pain: a protocol for a non-inferiority randomized controlled trial.
The aim of this study is to investigate if telerehabilitation is just as effective as the same face-to-face exercise program in patients with chronic neck pain (NP). 140 participants will participate in this non-inferiority randomized controlled trial. Primary outcomes will be pain intensity and disability, and secondary outcomes will be kinesiophobia, catastrophizing, fear avoidance beliefs, anxiety and depression symptoms, self-efficacy for pain and global perceived effect. It will be collected at baseline, 6 weeks and 6 months after intervention. The analysis of non-inferiority will be calculated by mixed linear models considering the non-inferiority margin. The results of this clinical trial will be able to overcome the barriers that physiotherapists face for the success of their therapies. In addition, it may reduce the high demands and public health costs with NP. Brazilian Clinical Trials Registry (RBR-6VBSMB). Clinical Trial Registration: REBEC (Brazilian Registry of Clinical Trials) RBR-6VBSMB (ClinicalTrials.gov).


Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps.
Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be further validated with larger sample size cohort to produce a panel of biomarkers for CRC and P patients. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.


Synthesis of a novel slow-release potassium fertilizer from modified Pidgeon magnesium slag by potassium carbonate.
A novel slow-release potassium fertilizer (SPF) was synthesized using Pidgeon magnesium slag (PMS) and potassium carbonate, which could minimize fertilizer nutrient loss and PMS disposal problems. Orthogonal experiments were conducted to determine the optimum conditions for synthesis. The potassium (K)-bearing compounds of SPF existed mainly in the form of crystalline phases Ca1.197K0.166SiO4, K2MgSiO4, and K4CaSi3O9, and in the noncrystalline phase. The active silicon content of SPF was 2.09 times as much as that of magnesium slag, and the slow-release character of SPF met the requirement for partly slow-release fertilizer in the national standard (GB/T23348-2009). The best models for describing the K release kinetics in water and 2% citric acid were the Elovich model and the first-order model, respectively. The heavy metal contents of SPF conformed to the national standard for organic-inorganic compound fertilizers, and the leaching mass concentrations of heavy metals and Fluorine were far lower than the limit values of the identification standard for hazardous waste identification for extraction toxicity (GB5085.3-2007), and also met the class II quality standard for ground water. The environmental risk of SPF is therefore very low, but because SPF is alkaline, its effect on soil pH should be taken into account. PMS is the solid waste resulting from the production of magnesium metal by Pidgeon's reduction process. Utilization of PMS in the high-technology and high-value areas may promote the high-efficiency development of worldwide collection metallic magnesium industry and contribute to the reduction of emissions of fine dust to air. This paper presents one of the new techniques in the use of PMS as a slow-release fertilizer by adding K2CO3. The product can serve as a very cost-effective and reliable artificial fertilizer.


Dry eye clinical practice patterns of UK optometrists.
In light of the increased roles of optometrists working in primary care in the UK, this research study aimed to gain an insight into perceptions of dry eye disease (DED), knowledge and confidence in diagnosis and management, and satisfaction with currently available treatment options. Links to an online survey were distributed to optometrists across the UK via optometry websites newsletters, conferences, and local optical committee data bases, between October 2021 and July 2022. The anonymous questionnaire contained a variety of question types including multiple choice, likert-type scale, and free text questions. The survey was completed by 131 optometrists, with a broad range of experience, who reported examining 33.3 ± 31.0 dry eye patients per month. Forty-eight percent of respondents were involved in the provision of an extended service. Fluorescein tear breakup time, corneal fluorescein staining, and anterior lid assessment were the most used clinical procedures, both for diagnosis and monitoring purposes. Sixty percent of respondents reported that they believed their patients were satisfied/managed with artificial tear alone, with the availability of a preservative free option being the top consideration, particularly with increasing severity. Of the 18.7% of respondents who held Independent prescriber status, 68% felt this had widened their ability to diagnose and treat DED. This was evidenced by an increase in steroid recommendation for moderate and severe disease. Although dry eye disease was perceived to be an important condition, opinions varied widely regarding knowledge and confidence in diagnosis and management. Involvement in an extended service did not alter patient management. However, an increase in therapeutic management and the employment of a stepwise approach to management has been identified.


Ultrastructure of cultured adult myocardial cells during anoxia and reoxygenation.
Cultured heart cells from adult rats were exposed to anoxia in a substrate-free Tyrode's solution at constant pH. In this system the metabolic and the morphologic pattern can be investigated simultaneously. Anoxic changes develop gradually above 2 mumol adenosine triphosphate (ATP)/ gww . Morphometry reveals that the morphologic changes are closely related to the energetic state: creatine phosphate (CP) decay is accompanied by the loss of small mitochondrial matrix granules (r = 0.97). The fall of ATP is coincident with sarcomere shortening (r = 0.95) and, below 4 mumol/ gww , with mitochondrial swelling (r = -0.88). The number of lipid droplets correlates with the ATP level during anoxia and reoxygenation (r = -0.92). The early energetic depletion is accompanied by a moderate release of cytosolic enzymes and morphologic changes: the appearance of sarcolemmal microblebs and an increase in subsarcolemmal vesicles. Below an average ATP level of 2 mumol/ gww an increasing number of individual cells fail to recover when reoxygenated . However, that failure is accompanied neither by massive enzyme release nor by ultrastructural damage regarded as typical for the "oxygen paradox."


Stimulatory effect of lysophosphatidic acids on uterine smooth muscles of non-pregant rats.
Lysophosphatidic acids stimulated isolated uterine smooth muscle dose-dependently. The contractions were not reduced by pretreatment with atropine or an anti-5-hydroxytryptaminic agent. The potency depended on the nature of the acyl chain in the molecule. Of the compounds with a saturated fatty acyl group tested, the most effective were myristoyl- and lauroyl-lysophosphatidic acid. In a series of unsaturated lysophosphatidic acids, the potency increased with the number of cis double bonds in the acyl chain, and linolenoyl-lysophosphatidic acid was the most active. When injected intravenously, these compounds induced an immediate rise in blood pressure and intrauterine pressure, like prostaglandin F2 alpha: The order of potency of their effects on the intact uterus was consistent with that of their effects on isolated uterine smooth muscle, but not with that of their hypertensive effects in rats.


Growth hormone secretion in insulin-independent pregnant diabetics.
A study was initiated to determine whether hypersecretion of growth hormone (HGH) was involved in the inhibition of normal glucose metabolism in pregnant insulin-independent diabetic (IID). A total of 25 patients was studied, of whom 13 had normal glucose tolerance and 12 were recently diagnosed IIDs. Hgh secretion was stimulated by insulin-induced hypoglycemia. The mean basal HGH levels and the plasma HGH pattern following the insulin stimulus were similar in the study group and the normal controls. Although it is unlikely that HGH participates to any significant degree in the diabetogenicity of normal and diabetic pregnancy, final proof depends on the assessment of the biologically active inhibitory polypeptide fraction of HGH and the growth-promoting protein, somatomedin.


Cytotoxic T-cell response and in vivo protection against tumor cells harboring activated ras proto-oncogenes.
Activated forms of the ras proto-oncogene have been found in approximately 30% of human malignancies, including pancreatic, colon, and lung adenocarcinomas. Ras oncoproteins arise by somatic mutation and contain amino acid changes at residues 12, 13, or 61, thus generating unique tumor-specific proteins that are attractive targets for cancer therapy. The goal of this study was to determine whether vaccination with mutant Ras protein could lead to the generation of cytotoxic T lymphocytes (CTLs) specific for the mutant epitope and to protection against challenge with tumor cells expressing the mutant oncoprotein. To determine a methodology for generating CTL responses following immunization with soluble protein, ovalbumin was used as a model tumor antigen. C57BL/6 mice were immunized with soluble ovalbumin administered intraperitoneally at 2-week intervals or with intravenous injection of ovalbumin or osmotically loaded splenocytes. Immunized mice were challenged with E.G7 cells (which express a transfected ovalbumin gene), and tumor growth was monitored. Generation of ovalbumin-specific CTLs was determined by 51Cr release assays. Purified wild-type or mutant H-Ras proteins (containing single amino acid substitutions at position 12 converting Gly to Arg or Val) were used to immunize BALB/c mice intraperitoneally. Ras-immunized mice were challenged with tumor cells containing Arg 12 or Val 12 mutations or not harboring mutant forms of Ras. Cytolytic and proliferative responses to mutant forms of Ras were studied, and the effects of in vivo depletion of CD4+ or CD8+ T lymphocytes were determined. In vivo challenge with E.G7 showed that intraperitoneal immunization with soluble ovalbumin was as effective as osmotic loading, resulting in long-term disease-free survival of some mice and the development of ovalbumin-specific CTLs. Immunization with Arg 12 Ras led to disease-free survival in nine of 10 animals challenged with tumor cells containing an Arg 12 mutation, while no protection was afforded against tumors expressing other forms of Ras or other oncogenes. Splenocytes from BALB/c mice immunized with Arg 12 Ras demonstrated cytolytic activity specific against tumor cells expressing Arg 12 Ras, with most of this activity residing in the CD8+ subset. Mutation-specific proliferation to Arg 12 Ras peptides was also observed. Immunization with Val 12 Ras did not elicit detectable Val 12-specific immunity. Antigen-specific CTLs can be induced following intraperitoneal immunization of mice with purified, soluble proteins. For both ovalbumin and Arg 12 Ras, specific in vivo protection against tumor cell challenge was observed.


Neural regulation of the interrelation between haustral and taenial motility in the rabbit proximal colon.
Neural regulation of the motility between the haustra and taenia coli was studied in the isolated rabbit proximal colon. Four types of haustral and taenial preparations were used: the haustral strip without the taenia coli (type 1), the haustral strip including the taenia coli (type 2), the L-shaped (taenia-haustra) preparations for recording the haustral (circular) response to taenial stimulation (type 3) and the L-shaped (haustra-taenia) preparation for recording the taenial (longitudinal) response to haustral stimulation (type 4). Field electrical stimulation induced a contractile response in the haustra and taenia coli. Hexamethonium reduced the contraction in type 2, 3 and 4 preparations. The desensitization to serotonin reduced the response in type 2 and 3 preparations. After atropinization, the response in types 1 and 4 was reversed to relaxation, and the response in types 2 and 3 was reversed to relaxation followed by contraction which was reduced or abolished by indomethacin. The responses remaining after atropinization in all types of preparations were not affected by other blocking agents tested or desensitization to neuropeptides. Tetrodotoxin abolished all relaxation and contractile responses in all types of preparations. These results suggest that the indirect contractile response to field stimulation is induced mainly via cholinergic and serotonergic neurons, and that the relaxation is mainly mediated by nonadrenergic noncholinergic neurons. The late haustral contractions after atropine may be caused by endogenous prostaglandin.


Relative validity of a non-quantitative 33-item dietary screener with a semi-quantitative food frequency questionnaire among young adults.
The objective of the study was to assess the concordance and ranking ability of a non-quantitative 33-item dietary screener developed to assess the diet of young adults in Norway, 'MyFoodMonth 1.1', compared to a semi-quantitative food frequency questionnaire (FFQ). Data were collected in a cross-sectional dietary survey evaluating the diets of students at the University of Agder, in southern Norway. The students were asked to complete both a dietary screener and an FFQ. Data collection was carried out from September to December 2020. Participants were first-year university students aged ≥18 years familiar with Scandinavian language. Almost half of the eligible sample (n 344) was excluded due to not completing the FFQ, compared to 1⋅7 % not completing the dietary screener, resulting in 172 (66 % female) participants with a median age of 21 years. For most items of the dietary screener (n 27/33, 82 %), all aspects of diet quality and components of the Diet Quality Score showed moderate-to-strong concordance with the FFQ evaluated using Kendall's tau-b analyses (t > 0⋅31), supported by visual inspection of box and whisker plots and descriptive ranking ability in a cross-tabulation. There was little evidence to suggest that concordance was dependent on sex. The concordance and ranking ability of 'MyFoodMonth 1.1' is considered satisfactory compared to a semi-quantitative FFQ. This rapid dietary assessment instrument presents a valuable addition to traditional instruments and a possible solution to recruit hard-to-reach parts of the population.


Clinical Evaluation After Peripheral Nerve Repair With Caprolactone Neurotube.
Background: Peripheral nerve injuries with substance loss are challenges to surgeons because direct suture repair may result in malfunction due to nerve suture tension. Autologous nerve grafts are alternatives for treating those lesions; however, harvesting grafts adds morbidity at donor sites. Synthetic substitutes are options to bridge the gaps in these situations. The caprolactone neurotubes are used to assist nerve regeneration, but the literature lacks studies that evaluate their results. Methods: This research was designed to clinically evaluate patients undergoing repair of peripheral nerves with that conduit. We described results of 12 case series consisting of operations with Neurolac®. All nerves severed were sensory and had small gaps (ie, less than 25 mm). Subjective and objective clinical evaluations were performed and registered. Results: Physical examination by monofilament testing and 2-point discrimination showed results rated as good or excellent. However, the patients had complaints regarding sensory changes. Conclusions: Synthetic bioabsorbable guides for nerve repair are promising. The caprolactone conduits were demonstrated to be a safe option treatment and with a simple technique. Although in our study there were some operative complications, they were in line with previous descriptions in the literature. This case series added information about the treatment prognosis, but a higher evidence level study is necessary for decision making.


Comparison of the Prognostic Value of Inflammation-Based Scores in Patients with Hepatocellular Carcinoma After Anti-PD-1 Therapy.
Inflammatory response is related to cancer progression and patient survival. However, the value in predicting survival in hepatocellular carcinoma (HCC) patients who received anti-PD-1 therapy has not been elucidated. This study aimed to compare the predictive ability of inflammation-based scores for the prognosis of HCC patients after anti-PD-1 therapy. A total of 442 patients who received anti-PD-1 therapy were included in the study. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan-Meier survival curves, time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses. All the inflammation-based prognostic scores exhibited good discriminatory ability in overall survival (OS) (all P < 0.01), while the PNI score was a unique independent predictor for OS in multivariate analysis (hazard ratio, 1.770; confidence interval, 1.309-2.393; P < 0.001). The areas under the ROC curves at 6, 12, 18 and 24 months and the C-index (0.65) demonstrated that the predictive accuracy of the PNI score was superior to that of the other inflammation-based scores. The PNI score is a discriminatory prognostic indicator for OS in HCC patients with anti-PD-1 therapy and is superior to the other inflammation-based prognostic scores in terms of predictive ability.


Influence of porcine somatotropin administration and sex on glucose and endocrine responses in obese pigs.
The endocrine and hyperglycemic responses to chronic administration of exogenous porcine somatotropin (pST) were investigated in genetically obese intact and castrate male (boars and barrows) and female (gilts) swine. Somatotropin was administered at a dose of 4 mg.pig-1/day by daily im injection. After a 26-hr fast on Day 22 of treatment, a loading dose of glucose (0.5 g/kg body wt) was administered iv, and blood samples were collected to determine parameters of glucose clearance and responses to a glucose bolus. Blood samples were assayed for glucose, insulin, insulin-like growth factor (IGF)-I, IGF-II, and pST. On Day 24 of treatment, blood samples were similarly collected every 15 min for 8 hr, to examine metabolic and endocrine measures in the fed state. After collection of the 6-hr sample, porcine growth hormone-releasing factor (pGHRF, 0.5 microgram/kg body wt) was administered iv. Administration of pST reduced feed consumption, increased gain, and resulted in 50% greater efficiency of gain. Plasma glucose was increased with pST treatment in both fasted (44%) and fed (64%) pigs. After administration of glucose bolus, glucose distribution volume and half-life (t1/2) were approximately doubled and MCR was reduced 75% in pST-treated pigs. Peak glucose-induced insulin concentrations were increased in pST-treated gilts and barrows but not boars. Concentrations of IGF-I were increased with pST treatment. Concentrations of pST during the sampling periods were influenced by sex and pST treatment. Control pigs responded to GHRF administration with increased plasma concentrations of pST, whereas, no pST response to GHRF administration was observed in the pST-treated pigs. The glucose and insulin results indicate chronic administration of pST to gilts and barrows induces insulin insensitivity and enhances insulin responses to a glucose challenge. The differences among the sexes in pST concentrations in the pST-treated pigs suggest differences in sexual differentiation or activation of the mechanisms of pST clearance.


Data fabrication and other reasons for non-random sampling in 5087 randomised, controlled trials in anaesthetic and general medical journals.
Randomised, controlled trials have been retracted after publication because of data fabrication and inadequate ethical approval. Fabricated data have included baseline variables, for instance, age, height or weight. Statistical tests can determine the probability of the distribution of means, given their standard deviation and the number of participants in each group. Randomised, controlled trials have been retracted after the data distributions have been calculated as improbable. Most retracted trials have been written by anaesthetists and published by specialist anaesthetic journals. I wanted to explore whether the distribution of baseline data in trials was consistent with the expected distribution. I wanted to determine whether trials retracted after publication had distributions different to trials that have not been retracted. I wanted to determine whether data distributions in trials published in specialist anaesthetic journals have been different to distributions in non-specialist medical journals. I analysed the distribution of 72,261 means of 29,789 variables in 5087 randomised, controlled trials published in eight journals between January 2000 and December 2015: Anaesthesia (399); Anesthesia and Analgesia (1288); Anesthesiology (541); British Journal of Anaesthesia (618); Canadian Journal of Anesthesia (384); European Journal of Anaesthesiology (404); Journal of the American Medical Association (518) and New England Journal of Medicine (935). I chose these journals as I had electronic access to the full text. Trial p values were distorted by an excess of baseline means that were similar and an excess that were dissimilar: 763/5015 (15.2%) trials that had not been retracted from publication had p values that were within 0.05 of 0 or 1 (expected 10%), that is, a 5.2% excess, p = 1.2 × 10-7 . The p values of 31/72 (43%) trials that had been retracted after publication were within 0.05 of 0 or 1, a rate different to that for unretracted trials, p = 1.03 × 10-10 . The difference between the distributions of these two subgroups was confirmed by comparison of their overall distributions, p = 5.3 × 10-15 . Each journal exhibited the same abnormal distribution of baseline means. There was no difference in distributions of baseline means for 1453 trials in non-anaesthetic journals and 3634 trials in anaesthetic journals, p = 0.30. The rate of retractions from JAMA and NEJM, 6/1453 or 1 in 242, was one-quarter the rate from the six anaesthetic journals, 66/3634 or 1 in 55, relative risk (99%CI) 0.23 (0.08-0.68), p = 0.00022. A probability threshold of 1 in 10,000 identified 8/72 (11%) retracted trials (7 by Fujii et al.) and 82/5015 (1.6%) unretracted trials. Some p values were so extreme that the baseline data could not be correct: for instance, for 43/5015 unretracted trials the probability was less than 1 in 1015 (equivalent to one drop of water in 20,000 Olympic-sized swimming pools). A probability threshold of 1 in 100 for two or more trials by the same author identified three authors of retracted trials (Boldt, Fujii and Reuben) and 21 first or corresponding authors of 65 unretracted trials. Fraud, unintentional error, correlation, stratified allocation and poor methodology might have contributed to the excess of randomised, controlled trials with similar or dissimilar means, a pattern that was common to all the surveyed journals. It is likely that this work will lead to the identification, correction and retraction of hitherto unretracted randomised, controlled trials.


Do we need colonoscopy in patients with gastric adenomas? The risk of colorectal adenoma in patients with gastric adenomas.
Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes occur in gastric adenomas and colorectal adenomas. However, it is unknown whether patients with gastric adenomas are at higher risk for colorectal adenomas. To investigate the prevalence rate of colorectal adenoma in patients with gastric adenomas and to determine the association between the presence of gastric adenomas and synchronous colorectal adenomas. A retrospective, cross-sectional, case-control study. Single center: Center for Health Promotion of Samsung Medical Center. This study involved 87 patients with gastric adenomas and 174 sex-matched and age-matched controls among 19,019 participants who underwent EGD and colonoscopy simultaneously or within 6 months of each other from January 2001 to December 2008 at the Center for Health Promotion of Samsung Medical Center. EGD and colonoscopy. The prevalence rate of colorectal adenoma in patients with gastric adenomas. The 87 gastric adenoma patients included 72 men and 15 women. Colorectal adenomas were identified in 42 (48.3%) of 87 cases and in 58 (33.3%) of 174 controls (P = .022). The prevalence of colorectal adenoma was significantly higher in the gastric adenoma group than in the control group. The mean size and number of colorectal adenomas were not significantly different between the two groups. The majority of colorectal adenomas were located in distal colonic segments in the gastric adenoma group in contrast with proximal colonic segments in the control group. Multivariate logistic regression analysis revealed that independent risk factors for colorectal adenoma were the presence of gastric adenomas (odds ratio [OR], .915; 95% confidence interval [CI], 1.044-3.513) and increasing age over 55 years (OR, 2.943; 95% CI, 1.558-5.560). Lack of data on previous colorectal adenomas and possible confounding factors such as hyperlipidemia or diabetes mellitus. The risk of colorectal adenoma increases significantly in patients with gastric adenomas and in patients over age 55. A screening colonoscopy may be necessary for patients with gastric adenomas to detect colorectal adenomas.


BMP2 and VEGF165 transfection to bone marrow stromal stem cells regulate osteogenic potential in vitro.
An exogenous supply of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factors 165 (VEGF165) will synergize to promote bone regeneration in vivo. The aim of this study was to confirm the role of VEGF165 on the osteogenesis potential of bone mesenchymal stem cells (BMSCs) transduced by adenovirus vector containing BMP2 gene in vitro.Rabbit BMSCs were isolated and transfected with various adenovirus vectors: Ad-BMP2-VEGF165 (BMP2+VEGF165 group), Ad-BMP2 (BMP2 group), Ad-VEGF165 (VEGF165 group), and Ad-green fluorescent protein (GFP group). The multiplicity of infection was detected by GFP expression. Expression of BMP2 and VEGF165 was detected by Western blot and ELISA, and the osteogenic biological activity of BMP2 and VEGF165 by osteogenic assay. Meanwhile, the osteogenic biological activity of BMP2 and VEGF165 was evaluated by detection of Col I (collagen type I), OC (osteocalcin), and ALP (alkaline phosphatase) activity using OC staining, ALP activity assay, and real-time PCR assay.Expression of target genes and proteins reached peak values at 5 days and then gradually declined. The OC staining, ALP activity, and real-time PCR assay of ColI, OC, and ALP were all increased in cells transfected with Ad-BMP2-VEGF165, Ad-BMP2, Ad-VEGF165, and Ad-GFP. However, the osteogenic biological activity in cells transfected with Ad-BMP2 was higher compared to cells transfected with other vectors after transfection at 14 and 21 days. We also found that BMP2 +VEGF165 group showed more osteogenic activity effect than the VEGF165 or control group. Furthermore, osteogenic assays in VEGF165 showed that a slightly lower osteogenic effect when compared to controls at 21 days.VEGF165 might be a potent inhibitor of BMSCs differentiation into osteoblasts. The strategies to use BMP2 and VEGF165 in bone regeneration and the molecular mechanism of their interaction require further investigation.


Care of elderly patients with chronic symptomatic coronary artery disease: is it TIME to be more offensive?
Young patients with coronary artery disease usually benefit from revascularization in terms of symptom relief and outcome. There are no prospective data available, however, for patients older than age 75 years, for whom quality of life might be more of an issue than quantity of life and for whom risk profiles and comorbidities make treating physicians more reluctant to prescribe an invasive procedure. The recently published Trial of Invasive vs. Medical therapy in Elderly patients (TIME) was the first to address patients > or =75 years of age with chronic angina despite standard medical therapy. The authors discuss the benefits and risks of interventional vs. medical management of chronic, symptomatic coronary artery disease in elderly patients in view of the TIME results and their clinical implications.


[Two case mimicking cerebral tuberculoma in MRI diffusion weighted-images with difficult preoperative diagnosis].
Two cases with a high signal intensity core with laminar structure based on diffusion weighed-images (DWI) mimicking intracerebral tuberculoma were herein reported. Both patients were suspected to have pulmonary tuberculosis in their past history and/or based on chest X-ray findings. DWI demonstrated a high signal intensity core with laminar structure, thus suggesting the presence of an intracerebral tuberculoma. As initial therapy, both patients received anti-tuberculous drugs, however, their symptoms did not improve, and the lesions were observed to have increased in MRI. As a result, a biopsy was carried out to clarify the nature of the disease. A pathological examination showed the former to be a brain abscess while the latter was metastatic carcinoma. In such cases mimicking intracerbral tuberculoma based on DWI, anti-tuberculous drugs are first treatment of choice, however, a biopsy should be performed as early as possible if the medication dose not show a significant response.


Interfering with different steps of protein synthesis explored by transcriptional profiling of Escherichia coli K-12.
Escherichia coli responses to four inhibitors that interfere with translation were monitored at the transcriptional level. A DNA microarray method provided a comprehensive view of changes in mRNA levels after exposure to these agents. Real-time reverse transcriptase PCRanalysis served to verify observations made with microarrays, and a chromosomal grpE::lux operon fusion was employed to specifically monitor the heat shock response. 4-Azaleucine, a competitive inhibitor of leucyl-tRNA synthetase, surprisingly triggered the heat shock response. Administration of mupirocin, an inhibitor of isoleucyl-tRNA synthetase activity, resulted in changes reminiscent of the stringent response. Treatment with kasugamycin and puromycin (targeting ribosomal subunit association as well as its peptidyl-transferase activity) caused accumulation of mRNAs from ribosomal protein operons. Abundant biosynthetic transcripts were often significantly diminished after treatment with any of these agents. Exposure of a relA strain to mupirocin resulted in accumulation of ribosomal protein operon transcripts. However, the relA strain's response to the other inhibitors was quite similar to that of the wild-type strain.


Freeze-drying of tert-butyl alcohol/water cosolvent systems: effects of formulation and process variables on residual solvents.
The objective of this study was to identify significant formulation and processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems. The variables examined were the physical state of the solute (crystalline vs amorphous), initial TBA concentration, freezing rate, cake thickness, and the temperature and duration of secondary drying. Sucrose and glycine were used as models for noncrystallizing and crystallizing solutes, respectively. The TBA concentration above which eutectic crystallization takes place was determined by differential scanning calorimetry. Model formulations were subjected to extremes of freezing rate by either dipping in liquid nitrogen or by slowly freezing on the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was determined by withdrawing samples as a function of time at different shelf temperatures using a thief system. On the basis of these studies, the most important determinant of residual TBA level is the physical state of the solute. Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%) regardless of freezing rate or initial TBA concentration. For freeze-dried sucrose, residual TBA levels were approximately 2 orders of magnitude higher and were significantly affected by initial TBA concentration and freezing rate. For the sucrose/TBA/water system, relatively low residual TBA levels were obtained when the initial TBA level was above the threshold concentration for eutectic crystallization of TBA, whereas samples freeze-dried from solutions containing TBA concentrations below this threshold contained significantly higher levels of TBA. Residual IPA levels increased continuously with initial concentration of TBA in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were frozen rapidly contained residual TBA levels which were approximately twice those measured in the same formulation after slow freezing and drying under the same conditions. For the sucrose/TBA/water system, the temperature and time of secondary drying had only minimal influence on residual TBA in the freeze-dried solid. At low initial TBA concentrations (2%), residual TBA increases with increased cake thickness, perhaps because of the influence of depth of fill on effective freezing rate.


Development of quality indicators and data assessment strategies for the prevention of central venous catheter-related bloodstream infections (CRBSI).
The number of catheter related bloodstream infections (CRBSI) could be reduced and the outcome improved if specific standards in the quality of care were maintained. Therefore, the development of quality assurance (QA) procedures was commissioned to be included in the national mandatory QA programme in Germany. Indicators representing quality deficiencies and potential for improvement of quality in relation to prevention and management of central venous catheters (CVC) were developed by (1) evidence-based literature searches and the compiling of an indicator register; (2) a multi-professional expert panel including patient representatives who selected indicators from this register by using a modified RAND/UCLA Appropriateness Method; (3) defining methods for data assessment, risk adjustment and feedback of indicator results to service providers; and (4) consulting all relevant medical societies and other stakeholders with regard to the QA procedures that had been developed. Thirty-two indicators for CRBSI prevention and management were eventually approved by the expert panel. These indicators represent quality of care at predefined points with regard to indication, insertion and care of CVCs, management of sepsis, general hygiene and training of health care personnel. Fourteen indicators represent processes, together with 7 representing structures and 11 outcomes. For assessing these indicators, data was obtained from four sources: claims data from health insurance funds, routine claims data from hospital electronic information systems, case specific longitudinal documentation from service providers and cross-sectional annual assessment of structures. It was possible to develop indicators for mandatory QA procedures on CRBSI that take into account the different perspectives of all stakeholders involved. Despite efforts to use routine data for documentation wherever possible, most indicators required extra documentation.


Feasibility Study of Low-dose Prostate CT Perfusion on Third-generation Dual-source CT.
Objective To investigate the feasibility of using low-dose prostate CT perfusion (pCTP)on a third-generation dual-source CT. Methods Nine patients with elevated prostate-specific antigen underwent pCTP before having prostate biopsy. We measured the blood flow (BF),blood volume (BV),mean transit time (MTT),permeability surface (PS),and time to peak(TTP)of both lesions and normal prostate tissue. The effective dose (ED)was calculated. Results Of the 9 cases,6 were prostate cancers and 3 were prostate hyperplasia with chronic inflammation. The average ED of the 9 pCTPs was (3.5±0.3)mSv. The BF (t=4.64,P<0.001),BV (t=3.27,P<0.001),and PS (t=3.58,P=0.004)of prostate cancer were significantly higher than those of normal prostate tissue and TTP (t=-1.26,P<0.001)of prostate cancer was significantly lower than that of normal prostate tissue. BF (t=3.96,P=0.001)and PS (t=2.91,P=0.021)of prostate hyperplasia with chronic inflammation were also significantly higher and TTP (t=-1.19,P<0.001)was significantly lower than those of normal prostate tissue. TTP of prostate cancer was significantly lower than that of prostate hyperplasia with chronic inflammation (t=-2.56,P=0.049). Conclusion sLow-dose pCTP is feasible on third-generation dual-source CT. The BF,PS,and TTP differ among prostate cancer,prostate hyperplasia with chronic inflammation,and normal prostate tissue.


[Mechanisms, prevention, and treatments of prosthetic aseptic loosening].
To introduce the occurrence mechanisms, prevention, and treatment measures of prosthetic aseptic loosening. The recent original articles about prosthetic aseptic loosening were extensively reviewed and analyzed. Prosthetic aseptic loosening was a very complex process involving many mechanical and biological aspects. The main mechanical factors included prosthetic materials, shapes and sizes, implant fixation methods (including surface treatments), clinical installation, interface micromotion, stress shielding, implant wear, interface integrity, and peri prosthetic high hydraulic pressure, etc.; the main biological factors included the types and sizes of wear particles, cell-activated responses, cytokine release, enzyme activation and allergic reactions to wear particles, etc.. Many measures should be adopted to effectively prevent and treat it, including improving materials and designs of prostheses, fixation techniques, surgical techniques, and drug treatments. Prosthetic aseptic loosening is still a troublesome complication after joint replacements in orthopaedics, and more attention should be paid for its effective prevention and treatment.


Resolution of bilateral ptosis after reduction of unilaterally elevated intraocular pressure in a child with Axenfeld-Reiger spectrum disorder.
We report a 9-month-old boy with bilateral pseudoptosis associated with elevated IOP. The patient had previously undergone bilateral trabeculectomies and Ahmed tube placement and right cataract extraction and penetrating keratoplasty. At presentation, the right eye IOP was 24 mm Hg and the left eye IOP was 32 mm Hg. Approximately 2 weeks after dorzolamide was added to the treatment regimen for the left eye, the mother reported that the ptosis had resolved. We suggest several explanations for the resolution of the ptosis.


The Study on the Performance of Carbon Supported PtSnM (M = W, Pd, and Ni) Ternary Electro-Catalysts for Ethanol Electro-Oxidation Reaction.
PtSn/C and Pt5Sn4M/C (M = W, Pd, Ni) electrocatalysts were prepared by impregnation method using NaBH4 as a reducing agent. Chemical composition, crystalline size, and alloy formation were determined by EDX, XRD and TEM. The average particle sizes of the synthesized catalysts were approximately 3.64-4.95 nm. The electro-chemical properties were measured by CO stripping, cyclic voltammetry, linear sweep voltammetry, and chronoamperometry. The maximum specific activity of the electro-catalysts for ethanol electro-oxidation was 406.08 mA m(-2) in Pt5Sn4Pd/C. The poisoning rate of the Pt5Sn4Pd/C (0.0017% s(-1)) was 4.5 times lower than that of the PtSn/C (0.0076% s(-1)).


Bidirectional Regulation of AdpAch in Controlling the Expression of scnRI and scnRII in the Natamycin Biosynthesis of Streptomyces chattanoogensis L10.
AdpA, an AraC/XylS family protein, had been proved as a key regulator for secondary metabolism and morphological differentiation in Streptomyces griseus. Here, we identify AdpAch, an ortholog of AdpA, as a "higher level" pleiotropic regulator of natamycin biosynthesis with bidirectional regulatory ability in Streptomyces chattanoogensis L10. DNase I footprinting revealed six AdpAch-binding sites in the scnRI-scnRII intergenic region. Further analysis using the xylE reporter gene fused to the scnRI-scnRII intergenic region of mutated binding sites demonstrated that the expression of scnRI and scnRII was under the control of AdpAch. AdpAch showed a bi-stable regulatory ability where it firstly binds to the Site C and Site D to activate the transcription of the two pathway-specific genes, scnRI and scnRII, and then binds to other sites where it acts as an inhibitor. When Site A and Site F were mutated in vivo, the production of natamycin was increased by 21% and 25%, respectively. These findings indicated an autoregulatory mechanism where AdpAch serves as a master switch with bidirectional regulation for natamycin biosynthesis.


Positive fEMG Patterns with Ambiguity in Paintings.
Whereas ambiguity in everyday life is often negatively evaluated, it is considered key in art appreciation. In a facial EMG study, we tested whether the positive role of visual ambiguity in paintings is reflected in a continuous affective evaluation on a subtle level. We presented ambiguous (disfluent) and non-ambiguous (fluent) versions of Magritte paintings and found that M. Zygomaticus major activation was higher and M. corrugator supercilii activation was lower for ambiguous than for non-ambiguous versions. Our findings reflect a positive continuous affective evaluation to visual ambiguity in paintings over the 5 s presentation time. We claim that this finding is indirect evidence for the hypothesis that visual stimuli classified as art, evoke a safe state for indulging into experiencing ambiguity, challenging the notion that processing fluency is generally related to positive affect.


[A CASE OF RIGHT PYONEPHROSIS DUE TO URETERAL STONES IN A HEMODIALYSIS PATIENT].
We report a case of a 64-year-old male with right pyonephrosis due to ureteral stones in association with chronic renal failure. The patient had been treated with hemodialysis for fourteen years. He was admitted to the Department of Internal Medicine of Kurobe City Hospital with chief complaints of fever and lumbago in January 2013. CT demonstrated a right pyonephrosis accompanied by right ureteral stones positioned in the middle and lower ureter. The stones could not be detected by KUB. He was consequently referred to the Department of Urology. Firstly, percutaneous nephrostomy for the right kidney was performed, and 200 ml of pyuria was discharged at that time. Urine culture demonstrated Escherichia coli. Secondly, rigid transurethral ureterolithotripsy (TUL) for the right ureteral stones was performed using Lithoclast, and a ureteral stent was indwelled on day 15 after nephrostomy construction. The nephrostomy catheter and ureteral stent were removed 10 and 21 days after the operation, respectively. The constituents of the stone were CaOx (26%) and CaP (74%). Right hydronephrosis improved and the patient showed no pyelonephritis for 1 year postoperatively.


Screening for retinopathy of prematurity: is it painful?
Screening programmes for retinopathy of prematurity have shown to reduce unfavourable visual outcome and to be cost-effective. Following present recommendations, almost 1% of all newborn babies should therefore be screened and undergo at least one ophthalmologic examination. This is a skilled procedure that requires drug instillation and manipulation of the ocular globe with scleral indentation. The objective of this study is to describe the side effects of this ophthalmic exam with special focus on the occurrence of pain. This was an observational study with a before-after analysis where all neonates undergoing an ophthalmologic exam during a 4-month period in a third level hospital were included. CRIES pain score was determined before the exam, 5 min after and 24 h after the screening manoeuvre. Blood pressure and pulse rate were determined in addition to the mentioned measurements 30 min after the ophthalmologic examination. Minimum oxygen saturation, apnoeas, gastrointestinal side effects (like vomiting and gastric aspirates), the need for respiratory assistance or for intensive care unit admission were recorded within 24 h before and after the procedure. 27 preterm neonates underwent an ophthalmologic examination and were included in the study. CRIES pain score was significantly higher 5 min after and 24 h after the screening procedure than before. This difference was also observed after stratification for birth weight and gestational age. No other study variable modified this time effect. No significant changes in blood pressure and pulse rate were shown after the ophthalmic exam. Vomiting was present in 4% of the newborns, gastric aspirates in 22% and apnoeas in 41% after the examination. Ten percent of the explored preterm babies needed increased respiratory assistance and 4% had to be transferred from the intermediate care unit to the intensive care because of severe apnoeas. An increase in pain score was shown after retinopathy of prematurity screening examination. Physiologic variable changes do not last long enough to evaluate the impact of certain procedures. Multivariate pain scores (like CRIES) should be used in everyday practice. It seems that the ophthalmologic examination in preterm babies might be painful and further studies should identify the best strategy to prevent pain during the retinopathy of prematurity screening manoeuvre.