Relation between the increase of circulating CD3+ CD57+ lymphocytes and T cell dysfunction in recipients of bone marrow transplantation.
Some patients undergoing bone marrow transplantation (BMT) persistently present increased proportions of circulating CD57+ T cells. We analysed the cell surface phenotype in peripheral blood mononuclear cells (PBMC) from 69 allogeneic and 11 autologous BMT recipients. In parallel samples from 49 patients, the proliferative response to T cell mitogens was assessed, either in the presence or absence of exogenous interleukin-2 (IL-2). PBMC samples from long-term allogeneic BMT patients with increased proportions of CD57+ cells displayed significantly (P less than 0.001) lower proliferative responses, compared with samples from patients with normal proportions of CD57+ cells and from healthy subjects. Elimination of the CD57+ population by C'-dependent lysis did not normalize the proliferative response. After positive selection by cell sorting, CD57+ cells responded poorly, but in the presence of IL-2 the proliferation appeared to be similar to that displayed by the CD57- subset and still suboptimal compared with normal controls. These data suggest that the hyporesponsiveness to mitogenic stimuli in the presence of exogenous IL-2 of PBMC from allogeneic BMT recipients cannot be simply attributed either to the putative suppressor activity of CD57+ cells, or to a poor proliferative capacity of this subset. Supporting this notion we report that PBMC from long-term autologous BMT recipients containing high proportions of CD57+ T cells respond normally to T cell mitogens.


Positive serum crossmatch as predictor for graft failure in HLA-mismatched allogeneic blood stem cell transplantation.
Evaluation of patient sera for complement-fixing anti-donor antibodies (serum crossmatch [XM]) before allogeneic blood stem cell transplantation (BSCT) is routine in most centers. However, in contrast to kidney transplantation, the predictive value of a positive XM for outcome of BSCT is still unclear, and a positive XM is presently not regarded as an absolute contraindication to proceed to transplant. To clarify the role of a positive XM as predictor for overall survival (OS) and graft failure (GF) after BSCT, a retrospective, single-center, matched-pair analysis was performed. Enrolled were all XM-positive BSCT performed at our institution from 1985 to 2000 (n=30). Controls (n=30) were matched for disease, disease stage, patient age, period of transplant, conditioning regimen, protocol for prevention of graft-versus-host disease, and type of donor (related vs. unrelated, HLA-identical vs. HLA-mismatched). Multivariate statistical analysis of all enrolled 60 transplants revealed GF as the all-dominating, independent risk factors for low OS (relative risk [RR]: 59.5, P<0.0001). Univariate (Kaplan-Meier) analysis could attribute inferior OS and high incidence of GF to the subgroup of HLA-mismatched, XM-positive transplants (P=0.01). A XM should always be performed in patients awaiting a BSCT from HLA-mismatched donors, because a positive XM is a predictor for inferior OS due to GF in BSCT.


Geometry-asymmetric photodetectors from metal-semiconductor-metal van der Waals heterostructures.
The functional diversities of two-dimensional (2D) material devices with simple architectures are ultimately limited by immature doping techniques. An alternative strategy is to use geometry-asymmetric metal-semiconductor-metal (GA-MSM) structures, which enable the basic functions of semiconductor junctions such as rectification and photovoltaics. Here, the mixed-dimensional van der Waals heterostructures (MDvdWHs) based on the separation and self-assembly of p-type SnS layered nanosheets (NSs) and n-type SnS2 nanoparticles (NPs) are obtained using an aqueous phase exfoliation (APE) method. Due to the surface charge transfer doping, the carrier transport mechanism of devices based on MDvdWHs turns from thermionic field emission (TFE) to thermionic emission (TE), with the rectification factor (Iforward/Ireverse) changing from 0.7 to 3. To further illustrate the experimental results, the generic current transport models of GA-MSM devices have been established based on the TE and TFE mechanisms in which the TE and TFE mechanisms lead to opposite rectification phenomena in good agreement with the experimental results. The GA-MSM devices show a photovoltaic effect with a high responsivity of 35 A W-1 and detectivity of 3.4 × 1011 cm Hz1/2 W-1. This study not only provides a novel strategy to design photovoltaic devices with MDvdWHs, but more importantly, we have established fundamental models for the rectification behavior of GA-MSM devices.


Simple monitoring technique for muscle flaps.
A simple monitoring technique for the detection of postoperative arterial flow failure in muscle flaps is described. The technique consists of isolating a musculocutaneous perforator on elevation of a muscle flap. This cutaneous perforator is observed for pulsation in the postoperative period. Abrupt cessation prior to 48 hours should be an indicator for prompt clinical evaluation of the muscle flap by an experienced microsurgeon to rule out arterial thrombosis.


Growth abnormalities in genetic syndromes.
The presence of a growth abnormality may be documented by determination of growth velocity, calculation of the upper segment/lower segment ratio or the AF/AT ratio, and measurement of head circumference. Important considerations in differential diagnosis of specific malformation syndromes are birth weight, limb and truck alterations, head size, physical features, and presence or absence of mental retardation. Additional clinical measurements, such as measurement of chest circumference and of finger and hand length, may be useful in selected cases. These data, combined with historical information, can indicate a specific diagnosis and facilitate the choice of confirmatory laboratory studies.


Fast growth rate of a right atrial myxoma.
Primary cardiac tumors are rare, with an incidence between 0.0017 and 0.19%, and are asymptomatic in up to 72% of cases. Approximately 75% of tumors are benign, and nearly 50% of these are myxomas. Concerning location, 75% of myxomas are in the left atrium, 15 to 20% in the right atrium, and more rarely in the ventricles. The finding of cardiac myxomas usually implies immediate surgical excision to prevent embolic events and sudden cardiac death. Reports with documented growth rate are rare, and the actual growth rate remains a controversial issue. We report the rapid growth rate of a right atrial myxoma in an oligosymptomatic 69-year-old patient, with negative previous echocardiographic history in the last two years, who refused surgery upon diagnosis, enabling monitoring of myxoma growth.


[MusicPlayTherapy--a parent-child psychotherapy for children 0-4 years old].
The early stage of building up the parent-child relationship is especially important. It is the basis for the child's development of the ability to relate to others and his or her further emotional, social and cognitive development. In this important early phase various risk factors may alienate parents from their intuitive parental competence towards their children. Such interaction problems indicate an intervention in the form of parent-children psychotherapy. This constitutes an entry point for the concept of MusicPlayTherapy (MPT): The early relationship is characterized mainly by complex communication sequences that address the senses at all levels. Therefore, the MPT concept integrates music as medium to communicate and opens up a playing space for play that allows emotions and experiences to be expressed. The components of music such as rhythm, sound, and melody stimulate babies and toddlers to express, play, and communicate preverbally. We work with the child and a parent in the MusicPlayTherapy sessions. Parents learn again to play and thereby learn to reach their children emotionally and to communicate with them. We complement the therapy sessions by counselling sessions with both parents.


Disarming racial microaggressions: Microintervention strategies for targets, White allies, and bystanders.
Given the immense harm inflicted on individuals and groups of color via prejudice and discrimination, it becomes imperative for our nation to begin the process of disrupting, dismantling, and disarming the constant onslaught of micro- and macroaggressions. For too long, acceptance, silence, passivity, and inaction have been the predominant, albeit ineffective, strategies for coping with microaggressions. Inaction does nothing but support and proliferate biased perpetrator behaviors which occur at individual, institutional and societal levels. This article introduces a new strategic framework developed for addressing microaggressions that moves beyond coping and survival to concrete action steps and dialogues that targets, allies, and bystanders can perform (microinterventions). A review of responses to racist acts, suggest that microaggression reactions/interventions may be primarily to (a) remain passive, retreat, or give up; (b) strike back or hurt the aggressor; (c) stop, diminish, deflect, or put an end to the harmful act; (d) educate the perpetrator; (e) validate and support the targets; (f) act as an ally; (g) seek social support; (h) enlist outside authority or institutional intervention; or (h) achieve any combination of these objectives. We organize these responses into four major strategic goals of microinterventions: (a) make the invisible visible, (b) disarm the microaggression, (c) educate the perpetrator, and (d) seek external reinforcement or support. The objectives and rationale for each goal are discussed, along with specific microintervention tactics to employ and examples of how they are executed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Enantioselective synthesis of spliceostatin E and evaluation of biological activity.
An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.


HSV-1 thymidine kinase negative vaccine: pathogenicity, protection, and perils.
Primary inoculation of mice and rabbits with an avirulent HSV-1 thymidine kinase negative (TK-) mutant reduced keratitis, mortality, and superinfection of the trigeminal ganglion (TG) as measured by cocultivation and iontophoresis-induced ocular shedding following ocular challenge with HSV-1 McKrae and W strains. However species differences were demonstrated; with complete protection in rabbits, and incomplete protection in mice. In mice, BUDR/autoradiography and restriction enzyme analysis identified both HSV-1 McKrae and W strains as having superinfected the TG, established latency and reactivated. Also, the avirulent TK negative inoculating strain was altered to a virulent TK positive strain through possible in vivo selection, mutation &/or host-modification, and possible in vivo recombination with the virulent challenge strains. We conclude that lower species differences require that potential HSV-1 vaccines be tested in non-human primates prior to clinical trials, and that a DNA-free subunit herpes vaccine represents a safer alternative to a live virus vaccine.


Synthesis of a coumarin compound from phenanthrene by a TiO2-photocatalyzed reaction.
Phenanthrene was converted into a coumarin compound by a TiO2-photocatalyzed reaction in an acetonitrile solution containing 8 wt% water and molecular oxygen in 45% yield.


[A press campaign during the last century in order to help women students of medicine as candidates for the "Internat des Hôpitaux de Paris"].
In 1885, towards the end of the last century, young female French medical students were given the right to be "externes des Hôpitaux de Paris" (non-resident students) on a par with male students. Nevertheless they were still denied places at the "Internat des Hôpitaux" entrance examination (houseman or intern resident). Two years afterwards the feminist movement, putting their trust in public opinion, took hold of an opportunity to further their demands and had them published in several daily French newspapers. This successful campaign finally enabled female medical students to sit an open "Internat des Hôpitaux" entrance examination. An American, Augusta Klumpke, became the first graduate in 1886 and went on to be recognised as one of the best neurologists in France a few years later.


A comparison of suicide and undetermined deaths in Cornwall across national and local agencies.
We looked to evaluate the reporting pathways and statistics between relevant stakeholders for reporting suicides and undetermined deaths in Cornwall. We checked on the correlation of the numbers provided for suicides and open verdicts given by different national and regional agencies including the local Coroner's office, Office of National Statistics (ONS), Cornwall Partnership NHS Trust (CPT) and The National Confidential Inquiry (NCI) into suicides for Cornwall. We examined the data of suicides and open verdicts presented by these agencies between the years 2000 and 2002. Our study shows that the data transfer between the relevant agencies (local Coroner, ONS, CPT and NCI) can be inaccurate. These inaccuracies not only prevent establishment of clear records but could also impact on policy decisions. It is also important to recognize that NHS trusts involved in mental health are being evaluated on their record on suicide prevention which in some senses is the most important outcome measure, thus making it important for inspecting bodies to look out for and take account of different figures from different agencies.


Form-Profiling of Optics Using the Geometry Measuring Machine and the M-48 CMM at NIST.
We are developing an instrument, the Geometry Measuring Machine (GEMM), to measure the profile errors of aspheric and free form optical surfaces, with measurement uncertainties near 1 nm. Using GEMM, an optical profile is reconstructed from local curvatures of a surface, which are measured at points on the optic's surface. We will describe a prototype version of GEMM, its repeatability with time, a measurements registry practice, and the calibration practice needed to make nanometer resolution comparisons with other instruments. Over three months, the repeatability of GEMM is 3 nm rms, and is based on the constancy of the measured profile of an elliptical mirror with a radius of curvature of about 83 m. As a demonstration of GEMM's capabilities for curvature measurement, profiles of that same mirror were measured with GEMM and the NIST Moore M-48 coordinate measuring machine. Although the methods are far different, two reconstructed profiles differ by 22 nm peak-to-valley, or 6 nm rms. This comparability clearly demonstrates that with appropriate calibration, our prototype of the GEMM can measure complex-shaped optics.


A Retrospective and Prospective Cohort Study Comparing Pediatric Patients With Cleft Lip and Palate From the United States and Guatemala.
Orofacial clefts (OFC) remain among the most prevalent congenital abnormalities worldwide. In the United States in 2010 to 2014, 16.2 of 10,000 live births are born with OFC compared with 23.6 of 10,000 in Alta Verapaz, Guatemala in 2012. Demographics and cleft severity scores were retrospectively gathered from 514 patients with isolated OFC at the Children's Hospital of Philadelphia scheduled for surgery from 2012 to 2019 and from 115 patients seen during surgical mission trips to Guatemala City from 2017 to 2020. Risk factors were also gathered prospectively from Guatemalan families. The Guatemalan cohort had a significantly lower prevalence of cleft palate only compared with the US cohort, which may be a result of greater cleft severity in the population or poor screening and subsequent increased mortality of untreated cleft palate. Of those with lip involvement, Guatemalan patients were significantly more likely to have complete cleft lip, associated cleft palate, and right-sided and bilateral clefts, demonstrating an increased severity of Guatemalan cleft phenotype. Primary palate and lip repair for the Guatemalan cohort occurred at a significantly older age than that of the US cohort, placing Guatemalan patients at increased risk for long-term complications such as communication difficulties. Potential OFC risk factors identified in the Guatemalan cohort included maternal cooking-fire and agricultural chemical exposure, poor prenatal vitamin intake, poverty, and risk factors related to primarily corn-based diets. OFC patients who primarily rely on surgical missions for cleft care would likely benefit from more comprehensive screening and investigation into risk factors for more severe OFC phenotypes.


A Rare Case of Pregnancy After Surgical Treatment for Stage III Hidradenitis Suppurativa.
Hidradenitis suppurativa is a chronic inflammatory skin condition primarily affecting areas with apocrine glands. It commonly manifests as painful nodules, abscesses, and sinus tracts, significantly impacting the patient's well-being. In this report, we discuss a case of a 32-year-old pregnant woman with Hurley stage III hidradenitis suppurativa who had undergone surgical reconstruction of the vulva before conception. The patient underwent a cesarian section and received topical treatment for her lesions near the genitalia. The importance of early identification, a collaborative approach involving multiple specialists, and individualized treatment strategies for managing this debilitating condition during pregnancy are emphasized in this case study.


Delayed discharges from Oxford city hospitals: who and why?
To determine the extent and characteristics of discharge delays of younger patients from acute hospital beds in Oxford, England. Three-month prospective analysis of patients deemed to have delayed discharge. The primary measure was the number of days from the patient being no longer in need of acute medical inpatient care to eventual discharge. Additional assessments included demographic data, primary diagnosis, Motricity Index, Short Orientation-Memory-Concentration Test (SOMC), Barthel Index and contextual data. The major acute hospitals serving the county of Oxfordshire (560,000 people). Fifty patients aged 18-70 years identified by referrals, delayed discharge lists and ward visits whose discharge from hospital had been delayed. The mean (standard deviation, SD) delay period was 36.1 (26.8) days. The mean prevalence and incidence of discharge delays for each three-day period was 19.7 (SD 1.7) and one (SD 1.7) respectively. Most (88%, n = 44) had a primary neurological diagnosis. Twenty-four (48%) patients had Motricity Index scores of less than 50% in one or more limbs and 16 (32%) in two or more limbs. Twenty-six (52%) patients had cognitive impairment (SOMC <18/28). Thirty-nine (78%) patients had a Barthel Index score of less than 15/20 and 24 (48%) of less than 10/20. The period of discharge delay did not correlate with SOMC, Motricity or Barthel Index scores. Only nine had appropriate accommodation available. Patients whose discharge is delayed were common; most had a neurological disability and cognitive impairment; and accommodation was unsuitable or absent for most. Reorganizing services to give patients access to specialized disability services might both improve the care of these patients and increase the efficiency of the health service.


Does Intervening in the Level of Knowledge About Cervical Cancer Increase Screening and Vaccination in Zambia?
Cancer of the cervix can be prevented by primary and secondary prevention methods. In order for these prevention methods to be practiced it is imperative that women are made aware of cervical cancer and the existing vaccination and cervical screening services available to them. A small intervention study to inquire on the effect of showing a short video about cervical cancer and its prevention proved to be an effective means of increasing awareness and knowledge among Zambian women residing in Lusaka. This brief report follows up on the 2017 intervention study in order to determine to what extent the increased knowledge has led to increased screening and vaccination practices among Zambian women and their daughters after a 3-year period. It is concluded that awareness of prevention services increases women's likeliness to seek screening services when given enough time. Unfortunately, we found no evidence of in an increase of the number of daughters vaccinated in this study.


Mad2 overexpression promotes aneuploidy and tumorigenesis in mice.
Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes.


Malignant lymphoma: an update on diagnosis, staging, and management.
The diagnosis of malignant lymphoma is not difficult. The various subtypes of Hodgkin's disease are easily recognized by the pathologist. The non-Hodgkin's lymphomas can be distinguished from Hodgkin's disease but are more difficult to classify. Staging of the lymphomas has improved. Computerized axial tomography and ultrasonography have assisted in the evaluation of the abdomen. Laparotomy and splenectomy continues to be a useful procedure for the pathologic staging of Hodgkin's disease, but its value will require yearly reassessment as improvements in staging and management are made. The treatment of Hodgkin's disease has been very successful. The majority of patients can be cured of the disease. Therapy has not had a major impact on survival of patients with nodular lymphomas, but has considerably improved the prognosis of patients with diffuse lymphomas.


Pancreatitis with normal lipase and amylase in setting of end-stage renal disease.
Pancreatitis with normal lipase and amylase level is a rare phenomenon. This is especially true in patient with end-stage renal disease as lipase and amylase are renally excreted. Literature review reveals previous case report of pancreatitis with normal lipase and amylase level, however, none of them occurred in the setting of end-stage renal disease. Our case is the first such reported case of pancreatitis in such setting. Here we report a 30year old male with past medical history of end-stage renal disease who presented in emergency department with acute abdominal pain. Laboratory work up revealed normal lipase and amylase level. However, radiological work up was consistent with pancreatitis. This case report highlight the importance of taking the overall clinical picture rather than laboratory work up to rule in or rule out the diagnosis of pancreatitis. Furthermore, this should also serve an important reminder for clinicians to further investigate where clinical suspicion for pancreatitis is high.


Methylotrophy in the thermophilic Bacillus methanolicus, basic insights and application for commodity production from methanol.
Using methanol as an alternative non-food feedstock for biotechnological production offers several advantages in line with a methanol-based bioeconomy. The Gram-positive, facultative methylotrophic and thermophilic bacterium Bacillus methanolicus is one of the few described microbial candidates with a potential for the conversion of methanol to value-added products. Its capabilities of producing and secreting the commercially important amino acids L-glutamate and L-lysine to high concentrations at 50 °C have been demonstrated and make B. methanolicus a promising target to develop cell factories for industrial-scale production processes. B. methanolicus uses the ribulose monophosphate cycle for methanol assimilation and represents the first example of plasmid-dependent methylotrophy. Recent genome sequencing of two physiologically different wild-type B. methanolicus strains, MGA3 and PB1, accompanied with transcriptome and proteome analyses has generated fundamental new insight into the metabolism of the species. In addition, multiple key enzymes representing methylotrophic and biosynthetic pathways have been biochemically characterized. All this, together with establishment of improved tools for gene expression, has opened opportunities for systems-level metabolic engineering of B. methanolicus. Here, we summarize the current status of its metabolism and biochemistry, available genetic tools, and its potential use in respect to overproduction of amino acids.


[Immunopathogeny of pemphigus].
This article reviews recent concepts of pathogenetic mechanisms in pemphigus. We describe the pathogenic effect of the autoantibodies, the animal model for the disease and the ultrastructural alterations which follow the antibody-antigen interaction. The role of complement and protease systems in development of tissue injury are also discussed.


Ultrastructure of Candida parapsilosis endocarditis.
We used light microscopy and scanning and transmission electron microscopy to study the structure of Candida parapsilosis vegetations on five surgically removed porcine bioprosthetic valves. Scanning electron microscopy revealed a "mossy" amorphous surface. In some areas, C. parapsilosis cells could be seen below the surface layer. In areas in which the vegetation had cracked, myriads of healthy C. parapsilosis cells were seen to be loosely adherent to one another. These cells were covered with a flocculent or fibrillar matrix. A compact intercellular matrix was evident by transmission electron microscopy. Hyphal elements were seen invading valvular tissue. The loose matrix that bound large clumps of C. parapsilosis cells explains why large emboli are frequent complications of Candida endocarditis.


Diversity of academic general medicine: A cross-sectional bibliometric study of original English-language research articles in general medicine and cardiology in Japan.
Although research in general medicine is diverse, it has not been compared with research in a different medical specialty. The study aim was to understand the characteristics of research produced at Japanese university departments of general medicine and published in English-language journals, via comparison with another academic specialty, cardiology.In this cross-sectional study, a nationwide survey of the official websites of 82 university-affiliated medical schools in Japan was conducted in April 2020 to identify the heads of general medicine departments. We then surveyed the research output of these individuals in terms of original article output and research field diversity for journals listed in the Web of Science Core Collection of journals from 2010 to 2019. A similar survey of cardiology department publications was also conducted to provide a reference for intergroup comparisons and analysis of covariance.The analysis included 128 researchers from 78 general medicine departments and 96 researchers from 81 cardiology departments. The dominant research field of general medicine was general and internal medicine; that of cardiology was cardiac/cardiovascular systems. Data stratification by research field showed that general medicine researchers published significantly more articles than researchers in cardiology, a field that contains relatively few researchers. Furthermore, a comparison of individual researchers with the same number of published articles showed that researchers in general medicine departments published across a significantly wider range of fields than those in cardiology.This is the first study to describe the research characteristics of general medicine university departments in Japan through comparison with research in a different academic specialty. General medicine researchers in Japan comprise a heterogeneous group that mainly publishes research on general and internal medicine. Some general medicine researchers take a multidisciplinary approach to research and publishing.


Multiplication of Trypanosoma pacifica (Euglenozoa: Kinetoplastea) in English sole, Parophrys vetulus, from Oregon coastal waters.
Multiplication of Trypanosoma pacifica was common in the fish host from observations of live flagellates and Giemsa-stained blood smears. Multiplication began with the elongation of the kinetoplast, thickening of the posterior portion of the body, and appearance of a new flagellum near the kinetoplast. The new flagellum was very rigid when less than 3 microm in length, but it became flexible as it elongated. When the new flagellum was approximately 12 microm in length, cell division began and the kinetoplast also began to divide. The timing of nuclear division was variable. Generally, it did not occur until division of the kinetoplast had begun, but occasionally binucleate individuals were observed before cell or kinetoplast division was apparent. As division continued, 1 nucleus migrated past the dividing kinetoplast into the future daughter trypanosome. Finally, the kinetoplast completed division and the trypanosomes separated. Cell division was unequal, with the daughter trypanosome being smaller than the parent and with a more weakly developed undulating membrane.


Developing a cell line standard for HER2/neu.
Advancements in medical genetics are resulting in the identification of key molecules in the pathways that lead to carcinogenesis. With these discoveries, drugs are developed that target a protein or block a particular molecular pathway with the potential to bring about disease regression. The HER2/neu tyrosine kinase receptor is one such target. Therapy based on the humanised monoclonal antibody, trastuzumab, targets HER-2/neu and inhibits the growth of HER2/neu-overexpressing breast cancer cells. Assays for markers to HER2/neu are forerunners of many more predictive assays that are likely to enter the clinical arena in the near future, many of which will require quantitative analysis. In the field of tissue based assay systems controversies are well documented on the lack of reproducibility in the immunohistochemical analysis HER2/neu. The problems encountered to date lye with the difficulty in reliably standardising the immunohistochemical assay. One of the first steps in addressing this issue is to develop a standard reference material against which the 'variable' of assay sensitivity for HER2/neu can be accurately gauged. Work in the United States and Europe aimed at providing a standard reference material for HER2/neu has already commenced. Preliminary work conducted in Europe shows that development of a standard comprised of cell lines is feasible and when employed as part of an external quality assurance programme, results in significant improvement in the numbers of clinical laboratories achieving appropriate results. In the United States it has been proposed that two standards consisting of well characterized cell lines will be produced, one a National Institute of Standards and Technology (NIST)--certifiable standard, and the other a commercially developed standard for use in all HER2/neu testing. The aim is that this approach will act as a template for other important predictive markers of the future.


A survey of antimicrobial use practices of Tennessee beef producers.
Inappropriate antimicrobial use (AMU) is a key modifiable factor that leads to the development of antimicrobial resistance (AMR). The objectives of this study were to determine the following among Tennessee beef cattle producers: (1) the opinions on factors driving AMU (2) opinions on alternatives to antimicrobials, (3) the knowledge and perceptions regarding AMU and AMR, and (4) the preferred avenues for receiving information on prudent AMU. A survey questionnaire was made available to participants both in print and online from January 26, 2018 through May 11, 2018. The questions targeted the producers' demographics and their AMU practices; factors driving producer's choice of antimicrobials; perceptions, opinions and concerns about AMU and AMR in cattle production. Ordinal logistic regression was used to test for associations between the captured demographic information and producers' degree of concern about AMR. Overall, 231 beef producers responded to all or some of the survey questions. More than 60% of the participants mentioned that they kept up-to-date written records on antimicrobial purchases and AMU. Regarding extra-label use, 169 (84.1%) of the 201 respondents did not practice extra-label AMU. Profitability of the beef operation was a key factor influencing the decisions of many producers to use antimicrobials for disease management and prevention on their farms. Of the 228 producers who completed the question on the rating of their degree of concern about AMR, 50 (21.9%) reported that they were very concerned about AMR, 133 (58.3%) were moderately concerned, and 36 (15.8%) reported that they were not concerned about AMR. Nine producers (4%) did not rate their degree of concern about AMR because they were not familiar with what antimicrobial resistance meant. The inferential analyses suggested that younger beef producers were significantly less concerned about AMR when compared to the older ones (P = 0.019). Regarding avenues for receiving information on prudent AMU, no single medium was most preferred by all the respondents. There is a need to promote the use of written antimicrobial treatment protocols among beef producers in Tennessee. Continued training for beef producers on infection prevention and control and prudent AMU is needed.


ShcB and ShcC activation by the Trk family of receptor tyrosine kinases.
Activation of the neurotrophin Trk receptors is a key process in the survival and development of the nervous system. The signaling adapters ShcB and ShcC, but not ShcA, are thought to be the primary Shc adaptor proteins in neurons as both are highly expressed in both the developing and adult nervous system. Although a previous study suggested that ShcB and ShcC do not strongly interact with the Trk receptors (1), we find that ShcB and ShcC bind the Trk receptors in a phosphotyrosine-dependent manner via their N-terminal phosphotyrosine binding domain at Tyr(499) (TrkA) and Tyr(515) (TrkB), they are tyrosine-phosphorylated in response to neurotrophin stimulation, and they enhance the activation of mitogen-activated protein kinase in Trk-expressing cells. Moreover, neurotrophin treatment of primary cortical neurons stimulates ShcB/ShcC-Trk interaction and the tyrosine phosphorylation of ShcB/ShcC, indicating that they are bona fide targets of the Trk receptors in vivo. Interestingly, two proteins (pp60 and pp75) co-immunoprecipitate with ShcB and ShcC in response to neurotrophin stimulation in primary cortical neurons, suggesting a potential role of these unknown targets in neurotrophin signaling. Collectively, these results demonstrate that ShcB and ShcC, and their co-immunoprecipitating proteins, are activated by the Trk receptors in primary neurons.


Resolution of neurotoxicity and beta-cell toxicity in an islet transplant recipient following substitution of tacrolimus with MMF.
Calcineurin inhibitors such as tacrolimus have well-recognized efficacy in organ transplantation but side effects of nephrotoxicity, neurotoxicity, and beta-cell toxicity that can be particularly detrimental in islet transplantation. Neuro- and nephrotoxicity have been demonstrated in multiple islet transplant recipients despite the relatively low serum maintenance levels typically used (3-5 ng/ml). We describe a single patient in whom symptoms and signs of neurotoxicity necessitated substitution of tacrolimus with mycophenolate mofetil (MMF), which resulted in complete symptom resolution over the subsequent 9 months. Concomitantly noted were an almost immediate improvement in glycemic control and an improved response to stimulation testing, suggesting remission of tacrolimus-induced beta-cell toxicity and insulin resistance. At 18 months post-"switch," 30 months posttransplant, the patient remains insulin independent with good glycemic control. The goal to remove calcineurin inhibitors from regimens of islet transplantation is a worthy one.


Transient changes in milk production efficiency and bacterial community composition resulting from near-total exchange of ruminal contents between high- and low-efficiency Holstein cows.
The objectives of this study were to determine if milk production efficiency (MPE) is altered by near-total exchange of ruminal contents between high- (HE) and low-MPE (LE) cows and to characterize ruminal bacterial community composition (BCC) before exchange and over time postexchange. Three pairs of ruminally cannulated, third-lactation cows were selected whose MPE (energy-corrected milk per unit of dry matter intake) differed over their first 2 lactations. Approximately 95% of ruminal contents were exchanged between cows within each pair. Ruminal pH and volatile fatty acid (VFA) profiles, along with BCC (characterized by sequencing of the variable 4 region of 16S rRNA genes), were assessed just before feeding on d -8, -7, -5, -4, -1, 1, 2, 3, 7, 10, 14, 21, 28, 35, 42, and 56, relative to the exchange date. High-MPE cows had higher total ruminal VFA concentrations, higher molar percentages of propionate and valerate, and lower molar percentages of acetate and butyrate than did LE cows, and re-established these differences 1 d after contents exchange. Across all LE cows, MPE increased during 7 d postexchange but declined thereafter. Two of the 3 HE cows displayed decreases in MPE following introduction of the ruminal contents from the corresponding LE cow, but MPE increased in the third HE cow, which was determined to be an outlier. For all 6 cows, both liquid- and solids-associated BCC differed between individuals within a pair before contents exchange. Upon exchange, BCC of both phases in all 3 pairs was more similar to that of the donor inoculum than to preexchange host BCC. For 5 of 6 cows, the solids-associated community returned within 10 d to more resemble the preexchange community of that host than that of the donor community. Individual variability before the exchange was greater in liquids than in solids, as was the variability in response of bacterial communities to the exchange. Individual cows varied in their response, but generally moved toward re-establishment of their preexchange communities by 10 d after contents exchange. By contrast, ruminal pH and VFA profiles returned to preexchange levels within 1 d. Despite the small number of cows studied, the data suggest an apparent role for the ruminal bacterial community as a determinant of MPE.


Untreated meningomyelocele and squamous cell carcinoma: a case report and literature review.
Early closure of the meningocele, meningomyelocele, is essential to prevent complications such as hypothermia, infection in the postnatal period. But for some reasons, it is not always possible to repair early. The possibility of malign transformation should be considered in long-term due to nonhealing ulcers and cerebrospinal fluid (CSF) fistula and frequent infections in an adult patient with meningomyelocele. The possibility of conversion to malignancy in the control of an untreated meningomyelocele patient with (CSF) drainage should be especially kept in mind. A case is described of a malignant transformation at the site of a myelomeningocele in a 22-year-old woman. The lumbosacral region was deformed by a large meningomyelocele 10 cm in diameter, with areas of scar and ulcer. For 7 years prior to this presentation, the lesion was a large fistula in the roof of the open myelomeningocele. She underwent continuous CSF draining. A biopsy was done which revealed it as squamous cell carcinoma. Early closure of meningocele, meningomyelocele is essential to prevent complications such as hypothermia, infection in the postnatal period. Also, especially if there is continuous CSF exposure, the possibility of malignant change should be kept in mind in neglected cases presenting in an adult.


Localized expression of sloppy paired protein maintains the polarity of Drosophila parasegments.
During germ-band extension in the Drosophila embryo, intercellular communication is required to maintain gene expression patterns initiated at cellular blastoderm. For example, the wingless (wg) single-cell-wide stripe in each parasegment (PS) is dependent on a signal from the adjacent, posterior cells, which express engrailed (eN). This signal is thought to be the hedgehog (hh) gene product, which antagonizes the activity of patched (ptc), a repressor of wg expression. Genetic evidence indicates that the hh signal is bidirectional, but wg transcription is only derepressed on the anterior side of the en/hh stripes. To explain the asymmetric response of the wg promoter to the hh signal, current models predict that each PS is divided into cells that are competent to express either wg or en, but not both. The sloppy paired (slp) locus contains two transcription units, both encoding proteins containing a forkhead domain, a DNA-binding motif. Removal of slp gene function causes embryos to exhibit a severe pair-rule/segment polarity phenotype. We show that the en stripes expand anteriorly in slp mutant embryos and that slp activity is an absolute requirement for maintenance of wg expression at the same time that wg transcription is dependent on hh. The slp proteins are expressed in broad stripes just anterior of the en-positive cells, overlapping the narrow wg stripes. We propose that by virtue of their ability to activate wg and repress en expression, the distribution of the slp proteins define the wg-competent and en-competent groups. Consistent with this hypothesis, ubiquitous expression of slp protein throughout the PS abolishes en expression and, in ptc mutant embryos, results in a near ubiquitous distribution of wg transcripts. In addition to demonstrating the role of slp in maintaining segment polarity, our results suggest that slp works in, or parallel with, the ptc/hh signal transduction pathway to regulate wg transcription.


An Alternative to Moment Closure.
Moment closure methods are widely used to analyze mathematical models. They are specifically geared toward derivation of approximations of moments of stochastic models, and of similar quantities in other models. The methods possess several weaknesses: Conditions for validity of the approximations are not known, magnitudes of approximation errors are not easily evaluated, spurious solutions can be generated that require large efforts to eliminate, and expressions for the approximations are in many cases too complex to be useful. We describe an alternative method that provides improvements in these regards. The new method leads to asymptotic approximations of the first few cumulants that are explicit in the model's parameters. We analyze the univariate stochastic logistic Verhulst model and a bivariate stochastic epidemic SIR model with the new method. Errors that were made in early applications of moment closure to the Verhulst model are explained and corrected.


Np(V) Retention at the Illite du Puy Surface.
In this study, Np(V) retention on Illite du Puy (IdP) was investigated since it is essential for understanding the migration behavior of Np in argillaceous environments. The presence of structural Fe(III) and Fe(II) in IdP was confirmed by Fe K-edge X-ray absorption near-edge structure (XANES) and 57Fe Mössbauer spectroscopy. In batch sorption experiments, a higher Np sorption affinity to IdP was found than to Wyoming smectite or iron-free synthetic montmorillonite. An increase of the relative Np(IV) ratio sorbed onto IdP with decreasing pH was observed by solvent extraction (up to (24 ± 2)% at pH 5, c0(Np) = 10-6 mol/L). Furthermore, up to (33 ± 5)% Np(IV) could be detected in IdP diffusion samples at pH 5. Respective Np M5-edge high-energy resolution (HR-) XANES spectra suggested the presence of Np(IV/V) mixtures and weakened axial bond covalency of the NpO2+ species sorbed onto IdP. Np L3-edge extended X-ray absorption fine structure (EXAFS) analysis showed that significant fractions of Np were coordinated to Fe─O entities at pH 9. This highlights the potential role of Fe(II/III) clay edge sites as a strong Np(V) surface complex partner and points to the partial reduction of sorbed Np(V) to Np(IV) via structural Fe(II).


Taking power, politics, and policy problems seriously: the limits of knowledge translation for urban health research.
Knowledge translation (KT) is a growing movement in clinical and health services research, aimed to help make research more relevant and to move research into practice and policy. This paper examines the conventional model of policy change presented in KT and assesses its applicability for increasing the impact of urban health research on urban health policy. In general, KT conceptualizes research utilization in terms of the technical implementation of scientific findings, on the part of individual decision-makers who can be "targeted" for a KT intervention, in a context that is absent of political interests. However, complex urban health problems and interventions infrequently resemble this single decision, single decision-maker model posited by KT. In order to clarify the conditions under which urban health research is more likely or not to have an influence on public policy development, we propose to supplement the conventional model with three concepts drawn from the social science: policy stages, policy networks, and a discourse analysis approach for theorizing power in policy-making.


Nitric oxide increased interleukin-4 expression in T lymphocytes.
Nitric oxide (NO) is a regulator of many biological functions including T helper 1 (Th1)/T helper 2 cells balance. It has been demonstrated that NO inhibits the secretion of interleukin-2 (IL-2) and interferon-gamma on Th1 cells. Here we showed that, in addition to the suppression of IL-2 production, NO-generating agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) increased the secretion of IL-4 both in Th2 clones and EL4 T cells. The additive effect was dependent on the dose of SNP and SNAP. Augmentation of IL-4 production was detected with 1 microM SNP, and up to threefold increase in IL-4 secretion could be observed with higher concentrations of SNP/SNAP. NO also weakly increased the activation of IL-4 promoter. In contrast, NO markedly inhibited the induction of IL-2 promoter, which could account for most of the reduction in IL-2 production. Analysis of the transcriptional elements on IL-2 and IL-4 promoters revealed a selective inactivation of NF-kappa B and NF-AT. It is suggested that despite the complex feedback network regulating NO production, the enhanced IL-4 expression would lead to the expansion of Th2 cells once NO is generated.


Preventing biological waste: Effective use of viable tissue in traumatized lower extremities.
Severe open lower extremity trauma requires debridement to remove contamination and devitalized tissues. Aggressive debridement should be balanced with preservation of viable tissue. These often damaged but preserved viable tissues are "spare parts" that augment the options available for reconstruction. The long-term goal of reconstruction should be functional limb restoration and optimization. Injury patterns, levels, and patient factors will determine whether this endeavor is better accomplished with limb salvage or amputation. This article reviews the rationale and strategies for preserving spare parts throughout debridement and then incorporating them as opportunistic grafts in the ultimate reconstruction to facilitate healing and maximize extremity function. 5.


[Value of the lateral chest x-ray in the diagnosis of traumatic pleural effusions].
Forty patients were admitted to a hospital emergency department after closed chest injury. Chest X-rays, a-p and lateral, with low and high voltage, were performed in a supine position. The aim of the study was to show the interest of lateral films in the diagnosis of post-traumatic pneumo- and hemothoraces. A special technique, using a double-drawer plate holder, gave a good quality radiograph in emergency conditions without danger for patients with severe trauma. In 30 of the patients, chest radiographs confirmed pleural gas or blood collection. In ten of these, the diagnosis could only be made after radiographic examination. In nine other cases, radiographs showed an absence of hemo- or pneumothorax. Lateral views were very important in confirming a hemothorax and appreciating its volume, as well as in showing up partial pneumothoraces which could not be seen on a-p views. The interest of performing a lateral film in all the cases of chest injury is pointed out.


Mood-altering effects of disulfiram in alcoholics.
The effects of disulfiram on depression and anxiety were examined. In a 3-week double-blind study, 40 inpatients in al alcohol rehabilitation unit (ARU) were randomly assigned to receive placebo, 250 mg/day of disulfiram or 500 mg/day of disulfiram. During their first week in the ARU and prior to beginning medications, all subjects were administered the Zung self-rating depression scale, the Hamilton observer rating scale for depression, the Zung self-rating scale for anxiety and the Hamilton observer rating scale for anxiety. All subjects were rescored on these instruments at the end of their third week in the ARU. Three psychiatrists, blind to the medication condition, sequentially scored the Hamilton items. To evaluate intergroup differences at baseline as well as changes in scale scores during the 3 weeks, scale scores were subjected to analyses of variance. No statistically significant effect attributable to disulfiram was found but significant changes due to a time effect were noted.


The right of elderly patients to refuse life-sustaining treatment.
Some legislation, such as law permitting living wills, has addressed the problem of decisions regarding life-sustaining treatment for the elderly. Most of the developing law on the subject is, however, being made by the courts, often in prospective decisions about treatment. These rulings have followed a variety of approaches to the ends of protecting incompetent patients and enforcing the right of the competent to make their own decisions.


A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil.
Herbal supplements are often regarded as "natural", and are, therefore, considered by many to be safer than pharmaceuticals; however, the adverse effects of these supplements are under-reported in many cases. Many herbal supplements, such as pyrrolizidine alkaloids, kava, chaparral and germander, are known to induce liver injury, which, in general, is one of the main toxicity liabilities observed in the clinic and accounts for about half of total liver failures. One example is the hepatotoxicity of pennyroyal oil, which is ingested as an abortifacient, among other uses. For three decades, the late Professor Sidney Nelson contributed to our understanding of the mechanism of toxicity of pennyroyal and broadened our understanding of chemical toxicology. Here we present the studies and review the findings on acute hepatotoxicity of pennyroyal oil. These studies involved the isolation and characterization of pennyroyal components, determination of the appropriate animal models, identification of the structural requirement for toxicity and determination of the target enzymes and the enzymes involved in the process of bioactivation. Studies with stable isotope labeled pennyroyal metabolites, pulegone and menthofuran, furthered our understanding of the role of cytochrome P450 in the oxidation of these compounds. This review presents the investigational tools used in the study of pennyroyal oil, allowing the reader to not only appreciate these methods but also utilize them to tackle and better understand metabolism-based toxicity in their own projects.


Efficacy of a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate, Delivered in a Single Spray, for the Treatment of Seasonal Allergic Rhinitis: Results from Russia.
The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18-65 years) were randomized to receive MP-AzeFlu (137/50 μg AZE/FP per spray) or AZE (137 μg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: -2.47; 95% confidence interval [CI] -3.65 to -1.30; p < 0.001), rTOSS (difference: -1.62; 95% CI -2.32 to -0.92; p < 0.001), and rT7SS (difference: -4.34; 95% CI -5.98 to -2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.


The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases.
Bortezomib therapy is now indispensable for multiple myeloma, but is associated with patient inconvenience due to intravenous injection and emerging drug resistance. The development of orally active proteasome inhibitors with distinct mechanisms of action is therefore eagerly awaited. Previously, we identified homopiperazine derivatives as a novel class of proteasome inhibitors with a different mode of proteasome binding from bortezomib. In this study, we show that K-7174, one of proteasome inhibitory homopiperazine derivatives, exhibits a therapeutic effect, which is stronger when administered orally than intravenously, without obvious side effects in a murine myeloma model. Moreover, K-7174 kills bortezomib-resistant myeloma cells carrying a β5-subunit mutation in vivo and primary cells from a patient resistant to bortezomib. K-7174 induces transcriptional repression of class I histone deacetylases (HDAC1, -2, and -3) via caspase-8-dependent degradation of Sp1, the most potent transactivator of class I HDAC genes. HDAC1 overexpression ameliorates the cytotoxic effect of K-7174 and abrogates histone hyperacetylation without affecting the accumulation of ubiquitinated proteins in K-7174-treated myeloma cells. Conversely, HDAC inhibitors enhance the activity of K-7174 with an increase in histone acetylation. These results suggest that class I HDACs are critical targets of K-7174-induced cytotoxicity. It is highly anticipated that K-7174 increases the tolerability and convenience of patients by oral administration and has the clinical utility in overcoming bortezomib resistance as a single agent or in combination with HDAC inhibitors.


A Fatal Colchicine Ingestion With Antemortem Blood Concentration.
Although there are multiple therapeutic uses for colchicine, it is particularly dangerous in the setting of overdose due to an irreversible mechanism of action combined with a narrow therapeutic window. Colchicine is an antimitotic agent that binds tubulin and inhibits microtubule polymerization. This produces a predictable sequence of toxicity beginning with gastrointestinal effects with progression to multiorgan system dysfunction. Unfortunately, there are no specific antidotes for colchicine toxicity after organ injury has occurred, which can lead to tragic consequences. Despite the recognized toxicity, it is exceedingly rare to find a case in the medical literature with a confirmed time of ingestion, amount ingested, data from longitudinal examinations, and laboratory assessments, with a quantitative blood colchicine concentration. We present a case of acute colchicine overdose of 18 mg (approximately 0.25 mg/kg) with subsequent multiorgan failure and death with an antemortem blood colchicine concentration of 14 ng/mL at 18.5 hours after ingestion.


Assessing the thermodynamic signatures of hydrophobic hydration for several common water models.
Following the conclusions of an information theory analysis that hydrophobic hydration is dictated by the equation of state of liquid water, we perform simulations of ten different water models to examine the correlation between the fidelity of each model to the experimental density of liquid water and the accuracy of its description of methane hydration. We find that the three- and five-point water models provide an inferior description of both the liquid density and methane solubility compared to the four-point water models. Of the four-point water models, TIP4P/2005 provides the best description of both the aqueous equation-of-state and methane hydration thermodynamics. When the optimized potentials for liquid simulation united-atom description for methane is used, we find that while the entropy and heat capacity of methane hydration are in excellent agreement with experiment, the chemical potential and enthalpy are systematically shifted upwards. We subsequently reoptimize the methane interaction to accurately reproduce the experimental solubilities as a function of temperature by accounting for missing attractive interactions.


The Relation of Q Angle and Anthropometric Measures with Ankle Sprain; a Case-control study.
Since most studies on ankle sprain are medical and sports-related and not much epidemiologic and etiologic data from the general population exist in this field, the present study evaluates the relationship between Q angle and anthropometric measures with ankle sprain in the general population. In the present case-control study, all of the patients over 18 years age presenting to emergency departments (ED) of two educational Hospitals, complaining from ankle sprain, were evaluated during more than 1 year. A checklist consisting of demographic data, height, weight, body mass index (BMI), and history of ankle sprain, as well as degree of Q angle was filled for all participants. The correlation of mentioned variables with incidence of ankle sprain was calculated using SPSS 22. 300 patients with ankle sprain were evaluated (53.5% male). Mean age of the patients was 37.03 ± 14.20 years. Mean weight, height, and BMI were 71.71 ± 11.26 (43 - 114), 168.74 ± 8.63 (143 - 190) and 25.14 ± 3.19 (18.41 - 38.95), respectively. Mean Q angle of the patients was 12.78 ± 3.19 degrees (5 - 23). There was a significant correlation between weight (p < 0.001), BMI (p = 0.001), history of sprain (r: 0.26, p < 0.001) and Q angle (p = 0.002) with incidence of ankle sprain. In addition, there was a significant statistical correlation between weight (p = 0.031), BMI (p = 0.020) and Q angle (p = 0.004) with history of ankle sprain. In patients with a history of ankle sprain, Q angle was wider by about 2 degrees. It seems that the prevalence of ankle sprain directly correlates with high weight, BMI, and Q angle and is more prevalent in those with a history of sprain. Although the findings of the present study show a statistically significant correlation between these factors and ankle sprain, the correlation is not clinically significant.


Gigagauss magnetic field measurements using Zeeman broadening of Ne-like transitions in highly charged ions.
The measurement of gigagauss magnetic fields using Zeeman broadening of Ne-like transitions in highly charged ions in high energy density plasmas is investigated. The transition in Xe44+ from the (2p5 1/23d3/2)J=1 level to the (2p6)J=0 ground level, designated 3C and having 4.858 keV transition energy, is considered in detail. Ne-like Xe spectra were previously recorded from compressed Xe-filled capsules, and the plasma conditions were determined from spectral line ratios and atomic code modeling. Using the Paschen-Back expression for Zeeman broadening produced by strong magnetic fields and the plasma conditions from the compressed Xe-filled capsule experiments to estimate the competing Stark, Doppler, and turbulence broadenings, it is found that >0.34 GG fields can be determined from spectra recorded by a high-resolution spectrometer having 1 eV resolution (5000 resolving power). By scaling the plasma conditions to higher temperatures and densities, the minimum detectable magnetic field is determined for Zeeman broadening of the 3C transition in Ne-like ions up to U82+. Recently developed transmission-crystal spectrometers, employing a cylindrically bent crystal in the Cauchois configuration, have sufficient resolution to determine gigagauss magnetic fields from Zeeman broadening of Ne-like transitions in the 4-18 keV range in Xe44+ to U82+.


Incidence of panic disorder in patients with non-cardiac chest pain and panic attacks.
This study documented the 6-month incidence of panic disorder and its predictors in emergency department patients with panic attacks and non-cardiac chest pain. The assessment included a validated structured interview to identify panic attacks and questionnaires measuring the potential predictors of panic disorder. Presence of panic disorder was assessed 6 months later. The incidence of panic disorder was 10.1 percent (n = 14/138). Anxiety sensitivity was the only significant predictor of the incidence of panic disorder (odds ratio = 1.06; 95% confidence interval = 1.01-1.12). Patients with panic attacks and non-cardiac chest pain are at an elevated risk for panic disorder. This vulnerability appears to increase with anxiety sensitivity.


Dietary nitrate consumption and risk of CHD in women from the Nurses' Health Study.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses' Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.


Three new species of the genera Loxoconcha and Xestoleberis (Crustacea, Ostracoda, Podocopida) from central and southern Vietnam.
The present study reports three new species of Ostracoda, Loxoconcha damensis sp. nov., Xestoleberis vietnamensis sp. nov. and X. munensis sp. nov., from Phu Quoc Island, southwest Vietnam and Nha Trang Bay, central Vietnam. These species inhabit the coral reefs around isolated islands and can be easily distinguished from other known species based on their morphological differences, mainly in the male copulatory organ. Loxoconcha damensis sp. nov. belongs to Loxoconcha Group A, based on the distributional pattern of their pore system below the eye tubercle. Similarly, based on a combination of morphological types of pore systems, the two new Xestoleberis species belong to Xestoleberis Group A, because these species have two types of pore systems, i.e., sieve-type and lip-type. To the best of our knowledge, this study is the first report on Xestoleberididae and the second on Loxoconchidae from the Recent of Vietnam.


[Immunofluorescence study of various constituents of the eyelids in rats before, during and after their closure].
We have brought the evidence for the presence of type I and III collagens and laminin in cultures of eyelid buds removed just before the onset of their junction. The patterns of distribution of laminin (localized in all basement membranes) and of the type III collagen remain constant during all the culture. Type I collagen is distributed homogeneously in the mesenchyma like type III collagen after the twelfth hour of culture. The rapid stabilization of these three distributions would be associated with the persistence of an epithelial seam limited by intact basement membranes between mesenchymal eyelids from the stage of junction to the later stage of disjunction of the eyelids.


Measuring and Predicting the Internal Structure of Semiconductor Nanocrystals through Raman Spectroscopy.
Nanocrystals composed of mixed chemical domains have diverse properties that are driving their integration in next-generation electronics, light sources, and biosensors. However, the precise spatial distribution of elements within these particles is difficult to measure and control, yet profoundly impacts their quality and performance. Here we synthesized a unique series of 42 different quantum dot nanocrystals, composed of two chemical domains (CdS:CdSe), arranged in 7 alloy and (core)shell structural classes. Chemometric analyses of far-field Raman spectra accurately classified their internal structures from their vibrational signatures. These classifications provide direct insight into the elemental arrangement of the alloy as well as an independent prediction of fluorescence quantum yield. This nondestructive, rapid approach can be broadly applied to greatly enhance our capacity to measure, predict and monitor multicomponent nanomaterials for precise tuning of their structures and properties.


Use in 1992 of tranquilizers and smokeless tobacco among Miami's public school students.
This analysis examined tranquilizer use by 466 adolescents in Dade County, Florida public schools in 1992. Significant factors which increased the probability of use include that the adolescents were female, older students, peers' use of tranquilizers, ready access, and they lived alone. Smokeless tobacco use among 468 students was positively and significantly linked to peer influence, students being male, younger, living alone, and the availability of smokeless tobacco.


SCOBY-based bacterial cellulose as free standing electrodes for safer, greener and cleaner energy storage technology.
Bacterial Cellulose (BC) derived from local market or symbiotic culture of bacteria and yeast (SCOBY) was employed as the polymer matrix for hydroxyl multi-walled carbon nanotube (MWCNT-OH)-based electrochemical double-layer capacitor (EDLC). Chitosan (CS)-sodium iodide (NaI)-glycerol (Gly) electrolyte systems were used as the polymer electrolyte. CS-NaI-Gly electrolyte possesses conductivity, potential stability and ionic transference number of (1.20 ± 0.26) × 10-3 S cm-2, 2.5 V and 0.99, respectively. For the electrodes, MWCNT-OH was observed to be well dispersed in the matrix of BC which was obtained via FESEM analysis. The inclusion of MWCNT-OH reduced the crystallinity of the BC polymeric structure. From EIS measurement, it was verified that the presence of MWCNT-OH decreased the electron transfer resistance of BC-based electrodes. Cyclic voltammetry (CV) showed that the shape of the CV plots changed to a rectangular-like shape plot as more MWCNT were added, thus verifying the capacitive behavior. Various amount of MWCNT-OH was used in the fabrication of the EDLC where it was discovered that more MWCNT-OH leads to a better EDLC performance. The EDLC was tested for 5000 complete charge-discharge cycles. The optimum performance of this low voltage EDLC was obtained with 0.1 g MWCNT where the average specific capacitance was 8.80 F g-1. The maximum power and energy density of the fabricated EDLC were 300 W kg-1 and 1.6 W h kg-1, respectively.


Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.
The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.


Evaluation by scintigraphy of hindlimb ischemia in a rat model.
The subject of ischemia-reperfusion has commonly been studied in rat hindlimb models. Unfortunately, in these experiments, the ischemia procedures lack standardization. For this reason, the authors evaluated the reliability of rat ischemia models described in the literature using scintigraphy. The study comprised six groups. Each consisted of ten male Wistar rats; five of them underwent methoxy-isobutyl-isonitrile (MIBI) scintigraphy, which is specific for muscle, and the others underwent methylene diphosphanate (MDP) scintigraphy, which is specific for bone. In Group 1, only the iliac artery was ligated; in Group 2, the iliac artery and its branches, except for the superficial epigastric artery, were ligated; in Group 3, the iliac artery and vein were ligated; in Group 4, the iliac artery and all branches, including the superficial epigastric artery, were ligated; in Group 5, in addition to ligation of the iliac artery and its branches, the skin was incised circumferentially around the pelvic girdle; in Group 6, a tourniquet was applied to the limb at the pelvic level. After 2-hr warm ischemia, a radioactive tracer was injected intravenously. In the MIBI group, images were taken at the twentieth minute and second hour after injection, and in the MDP group, at the fifth minute and third hour after injection. The radioactivity in both hind limbs of the animal was measured, and the ratio of the control to the ischemic limb was calculated. In the first five groups, there was no necrosis in the ischemic limb at the end of 2 weeks. The measured radioactivity in the ischemic limb was lower than that of the control limb in all groups. The ratio of activity obtained from the control limb to that of the ischemic limb in the tourniquet group was significantly higher, compared to other groups in both MIBI and MDP evaluations (p < 0.005). Significant ischemia was also seen in the skin incision group (Group 5). A low-flow state was observed in the ischemic limb in Groups 1-4 using both scintigraphic modalities. The tourniquet method (Group 6) provided almost complete limb ischemia, compared to other arterial ligation methods, and it is practical to use for complete ischemia when studying the physiology of replantation or free flaps.


Nutritional considerations in the treatment of patients with chronic uremia.
Low-protein diets ameliorate uremic symptoms and some of its metabolic complications. These diets can be used successfully to treat patients with chronic renal failure (CRF) because they are able to activate normal compensatory responses when protein intake is restricted and their protein and energy requirements are similar to healthy subjects. However, there has been concern that dietary therapy compromises the nutritional status of CRF patients and that initiating dialysis would be preferable to this type of therapy. Kopple and co-workers have identified the requirements of CRF patients for protein and calories and available evidence indicates that when properly implemented, low-protein diets are safe and can maintain lean body mass even during long-term therapy. Based on the information published by Kopple and co-workers, the strategies for treating CRF patients should include careful analysis of the diet and the nutritional status of the patient.


[Strangulated urethral prolapse. Case report].
We report a case of strangulated urethral prolapse. A 62-year-old female patient presents to the emergency department with complaints of a bleeding vaginal mass, pain referred to the vaginal introitus and dysu-ria. After being diagnosed with a strangulated urethral pro-lapse, surgical excision of the prolapsed urethra was performed. Pathologically, vascular proliferation of the angioma-tous type with thrombosis and focal recanolization (Masson) and inclusion of rare muscular fibers were recognized. Her postoperative course was uneventful, without any recurrence or abnormal micturition. For the treatment of strangulated urethral prolapse, surgical excision has been widely applied with successful results.


[Varicella pneumonia in adult population: review of 21 cases].
Retrospective study of the varicella pneumonia in adults, in order to know incidence, environmental and clinical characteristics and treatments of patients with this diagnosis during the last 9 years in Toledo. Twenty-one adult patients with the diagnosis of varicella pneumonia were studied, using the information of clinical histories and codified data. The backgrounds of pregnancy, smoking habit, concomitant diseases, previous contacts with another patients and the season of the year, were evaluated. Diagnosis was established by clinical and radiologic criteria in the course of varicella infection. 21 patients (10 males and 11 females, between 25 and 73 years) were studied. 17 (81%) were smokers, in 15 (71.4%) there was documented contact with varicella infection and 4 (19%) were immunocompromised. In the first 3-7 days after the development of skin lesions (100%), there was fever in 20 cases (95.2%) and dyspnea in 14 (66.7%). There were 4 patients (33,3%) without respiratory symptoms and in 5 (23,8%) there was important hypoxemia. Evolution was satisfactory in 20 cases (95.2%); three others requiring admission to Intensive Care Unit. Chest X-ray revealed an interstitial pattern in 11 cases (52.4%), nodular in 4 (19%) and a mixed pattern in 5 (23.8%). 20 patients were treated with acyclovir and in one case with foscarnet. In 28.57% cases, corticosteroids were needed. We believe smoking habit could be a risk factor related to an increase of varicella pneumonia. A chest X-ray should be made in every patient, despite the symptoms. Adults with pneumonia have a better prognosis if acyclovir is started early in time. Concomitant treatment with corticosteroids should be used in those cases with respiratory insufficiency.


Magnetic Peripheral Nerve Stimulation (mPNS) for Chronic Pain.
To assess magnetic peripheral nerve stimulation (mPNS) for the treatment of chronic or chronic and intractable neuropathic pain with a retrospective review case series. Twenty-four patients with predominantly neuropathic post-traumatic or postoperative pain were treated as per protocol and followed for 3 months. Data were analyzed as an observational, one-armed, convenience sample. Graphical evidence backed up by a mixed model for repeated measures statistical analysis showed a highly significant reduction of pain at one month out from initial treatment with mPNS. At one month, there was a 3.8 average reduction in pre-pain scores using a visual analogue scale (VAS), and that relief was generally durable measured out to three months. Two-thirds of patients, deemed responders, showed an 87% reduction in pain. Opioid reduction was seen in 58.3% of responders as well. mPNS appears promising for the treatment of chronic or chronic and intractable neuropathic pain for many of the same indications as traditional electrical peripheral nerve stimulation (PNS). No invasive techniques or implants are needed for mPNS.


Binding interaction of a novel fluorophore with serum albumins: steady state fluorescence perturbation and molecular modeling analysis.
Fluorescence emission and anisotropy are widely used to measure the binding parameters and kinetic behavior of reactions that cause a change in the rotational time of a fluorescent molecule. We report here fluorescence emission and anisotropy behavior of a newly synthesized novel naphthalene base fluorophore (methyl 3-[(6-{[2-(tert-butoxy)-2-oxoethyl] (4-methoxyphenyl)amino}naphthalen-2-yl)formamido]propanoate) in several solution conditions including its binding to human and bovine serum albumin proteins both in their native and denatured states. The fluorescence yield of the compound substantially increased inside hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to aqueous solution, was observed. Shift in fluorescence excitation peak position from the absorption peak of the molecule was ~8 nm in protein solution. This indicated possible alteration of excited state geometry of the compound by the globular fold of albumins. In addition, we measured the steady state fluorescence anisotropy of the molecule to evaluate several thermodynamic parameters and the results suggested the binding was energetically favorable. The measured ΔG° was ~-30 kJ mol(-1) and the derived dissociation constant was ~10(-6) M. The molecular docking analysis further highlighted the nonspecific association of the compound with the proteins and hydrophobic forces may have a significant role in the binding processes. Under the denatured condition of the protein, the compound lost its binding efficacy and reduction in fluorescence intensity was observed. Thus, the molecule appears as a new fluorescence probe to report the nature of its binding site in terms of increased fluorescence quantum yield and decreased Stokes' shift. It can also report the changes in the binding site due to global change in protein structure such as unfolding/misfolding often linked to several human disorder. Further it could be useful to detect and study the drug binding site of specific protein of interest.


[Renal amyloidosis. An echographic study of 7 cases].
Seven patients suffering from renal amyloidosis (2 primitive and 5 secondary) underwent US examination. The results show a strict correlation between US findings and the pathologic changes produced by this condition. US proves to be especially useful in the early stages of the disease: its results, together with the clinical data, may in fact be highly suggestive of the correct diagnosis. On the contrary, in the late stages of renal amyloidosis, when pathologic changes lead to progressive nephrosclerosis, US findings appear aspecific, since they are undistinguishable from the patterns observed in other renal medical disorders.


MicroED structure of the human vasopressin 1B receptor.
The small size and flexibility of G protein-coupled receptors (GPCRs) have long posed a significant challenge to determining their structures for research and therapeutic applications. Single particle cryogenic electron microscopy (cryoEM) is often out of reach due to the small size of the receptor without a signaling partner. Crystallization of GPCRs in lipidic cubic phase (LCP) often results in crystals that may be too small and difficult to analyze using X-ray microcrystallography at synchrotron sources or even serial femtosecond crystallography at X-ray free electron lasers. Here, we determine the previously unknown structure of the human vasopressin 1B receptor (V1BR) using microcrystal electron diffraction (MicroED). To achieve this, we grew V1BR microcrystals in LCP and transferred the material directly onto electron microscopy grids. The protein was labeled with a fluorescent dye prior to crystallization to locate the microcrystals using cryogenic fluorescence microscopy, and then the surrounding material was removed using a plasma-focused ion beam to thin the sample to a thickness amenable to MicroED. MicroED data from 14 crystalline lamellae were used to determine the 3.2 Å structure of the receptor in the crystallographic space group P 1. These results demonstrate the use of MicroED to determine previously unknown GPCR structures that, despite significant effort, were not tractable by other methods.


Effective Modulation of Optical and Photoelectrical Properties of SnS2 Hexagonal Nanoflakes via Zn Incorporation.
Tin sulfides are promising materials in the fields of photoelectronics and photovoltaics because of their appropriate energy bands. However, doping in SnS2 can improve the stability and robustness of this material in potential applications. Herein, we report the synthesis of SnS2 nanoflakes with Zn doping via simple hydrothermal route. The effect of doping Zn was found to display a huge influence in the structural and crystalline order of as synthesized SnS2. Their optical properties attest Zn doping of SnS2 results in reduction of the band gap which benefits strong visible-light absorption. Significantly, enhanced photoresponse was observed with respect to pristine SnS2. Such enhancement could result in improved electronic conductivity and sensitivity due to Zn doping at appropriate concentration. These excellent performances show that Sn1-xZnxS2 nanoflakes could offer huge potential for nanoelectronics and optoelectronics device applications.


Study on the effect of sodium-nanoparticle in rice root development.
Micro-nanoparticles can enter the root tissue of plant cells along with the multiple lanes, and then accumulate in the tissue. But the plant physiological effect is still less studied. In this study, rice seedlings at germination stage were treated with 100 µM NaBiF4 and BiF3. We found that exogenous application of NaBiF4 treatment inhibited the elongation of rice roots and promoted the generation of adventitious roots, but treated BiF3 did not mediate obvious phenotype. Further analysis of the peroxidase activity in related tissues showed that NaBiF4 induced the activity of SOD and CAT decreased, and POD increased, while BiF3 only induced the activity of SOD to reduced, but the activity of CAT and POD were no changed. Further analysis of the sodium element and potassium element concentration in tissues showed that only the NaBiF4 treatment reduced content of potassium, but not sodium. Finally, stress-related genes OsMT1, OsMT2, OsOVP1, OsNIP2;1, and OsMT2b were analyzed by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). These results showed that NaBiF4 induced the expression of OsMT2, OsOVP1, OsNIP2;1 decreased, and OsMT2b increased. However, BiF3 only induced expression of OsMT1 increased. These results provide a physiological basis for further analysis of the effects of sodium salt-nanoparticles in crop plants.


Resistance to fatigue of individual Xenopus single skeletal muscle fibres is correlated with mitochondrial volume density.
The purpose of the present study was to compare the individual fatigue characteristics of isolated single skeletal muscle fibres with their mitochondrial volume density (MVD), using direct histological morphometry. Single muscle fibres (n= 14) were microdissected from lumbrical muscle of adult female Xenopus laevis, and force was measured while fibres were stimulated (tetanic contractions of 200 ms trains with 70 Hz stimuli at 9 V) at progressively increasing frequencies (2 min each at 0.25, 0.33, 0.5 and 1 contractions s(-1)) until fatigue (<50% initial maximal force) had been established. Following the end of the fatigue protocol, MVD was determined by electron microscopy. Time to fatigue varied among the individual fibres from 3.3 to 10 min. MVD of individual fibres ranged from 3.0 to 9.2% and was positively correlated (r= 0.93) with time to fatigue of corresponding fibres. These results, using direct histological measurements of MVD: (1) support on a single cell basis the notion that oxidative capacity is a major determinant of muscle fatigue resistance; and (2) show that the fatigue profile of a single cell can be used to predict oxidative capacity.


Megaesophagus was complicated with Billroth I gastroduodenostomy in a cat.
A seven-year-old, female, domestic short hair cat was presented with a history of chronic anorexia. Radiographic examination revealed a large space-occupying calcified mass in the abdominal cavity. The mass was located in pylorus and did not extend into the duodenum and surrounding tissues. Billroth I gastroduodenostomy was conducted to remove the mass. Histopathological examination of the mass showed a lymphoma. Although Recovery following the operation was excellent, the patient showed intermittent vomiting unrelated to feeding. Radiographical examination revealed a megaesophagus, which was assumed to be a complication of the Billroth I procedure, since the condition was not observed before the procedure.


Primary Immunodeficiency Diseases in Highly Consanguineous Populations from Middle East and North Africa: Epidemiology, Diagnosis, and Care.
Middle East and North Africa region (MENA) populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance. Studies of PIDs in the region had contributed into the discovery and the understanding of several novel immunodeficiency disorders. Few MENA countries have established national registries that helped in estimating the prevalence and defining common PID phenotypes. Available reports from those registries suggest a predominance of combined immunodeficiency disorders in comparison to antibody deficiencies seen in other populations. Access to a comprehensive clinical immunology management services is limited in most MENA countries. Few countries had established advanced clinical immunology service, capable to provide extensive genetic testing and stem cell transplantation for various immunodeficiency disorders. Newborn screening for PIDs is an essential need in this population considering the high incidence of illness and can be implemented and incorporated into existing newborn screening programs in some MENA countries. Increased awareness, subspecialty training in clinical immunology, and establishing collaborating research centers are necessary to improve patient care. In this review, we highlight some of the available epidemiological data, challenges in establishing diagnosis, and available therapy for PID patients in the region.


High-flexion rotating-platform knees: rationale, design, and patient selection.
High flexion in total knee arthroplasty (TKA) is any flexion beyond 125 degrees. High-flexion activities such as kneeling or praying are done with internal rotation, external rotation, and in neutral. Therefore, maximum flexion TKA requires a rotating platform. Superior range of motion (ROM) and fluoroscopic kinematics of femoral roll-back have been shown with the P.F.C. Sigma RP posterior-stabilized knee. This knee was modified to reduce the P.F.C. Sigma RP-F, a maximum flexion knee, by adding a third contact area at the post-cam mechanism to significantly increase bearing conformity and decrease polyethylene stresses in the range of 125 degrees-155 degrees. Clinical experience is reported with statistically significant increases in postoperative ROM in patients with the P.F.C. Sigma RP-F. Patient selection criteria for the P.F.C. Sigma RP-F include patients with high-flexion lifestyles, younger, more active patients demanding a better ROM, and those patients with less than 100 degrees preoperative ROM. This knee system shows significant promise in providing maximum flexion, and system longevity is expected.


Metabolomics of a superorganism.
The human can be thought of as a human-microbe hybrid, and the health of this superorganism will be affected by intrinsic properties such as human genetics, diurnal cycles, and age and by extrinsic factors such as lifestyle choices (food and drink, drug intake) and the acquisition of a stable "healthy" gut microflora (the so-called microbiome). Alterations in this superorganism will be manifest in the metabolite complement within its serum and urine samples. The unraveling of this metabolic compartmentalization in this complex ecosystem will certainly be a challenge for systems biology and necessary for defining human health at the molecular level. Within the systems biology framework, functional analyses at the level of gene expression (transcriptomics), protein translation (proteomics), and, more recently, the metabolite network (metabolomics) have become increasingly popular. Metabolomics experiments aim to quantify all metabolites in a cellular system (cell or tissue) under defined states and at different time points so that the dynamics of any biotic, abiotic, or genetic perturbation can be accurately assessed. This article provides an overview of metabolomics and discusses how data are generated and analyzed within a systems biology framework. The role of metabolomics in nutrigenomics is also discussed, as are the concepts of the human being a superorganism and the complexities required to be overcome to understand human health and disease.


The alpha1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells: is HLA-G the public ligand for natural killer cell inhibitory receptors?
We have investigated the protective role of the membrane-bound HLA-G1 and HLA-G2 isoforms against natural killer (NK) cell cytotoxicity. For this purpose, HLA-G1 and HLA-G2 cDNAs were transfected into the HLA class I-negative human K562 cell line, a known reference target for NK lysis. The HLA-G1 protein, encoded by a full-length mRNA, presents a structure similar to that of classical HLA class I antigens. The HLA-G2 protein, deduced from an alternatively spliced transcript, consists of the alpha1 domain linked to the alpha3 domain. In this study we demonstrate that (i) HLA-G2 is present at the cell surface as a truncated class I molecule associated with beta2-microglobulin; (ii) NK cytolysis, observed in peripheral blood mononuclear cells and in polyclonal CD3(-) CD16(+) CD56(+) NK cells obtained from 20 donors, is inhibited by both HLA-G1 and HLA-G2; this HLA-G-mediated inhibition is reversed by blocking HLA-G with a specific mAb; this led us to the conjecture that HLA-G is the public ligand for NK inhibitory receptors (NKIR) present in all individuals; (iii) the alpha1 domain common to HLA-G1 and HLA-G2 could mediate this protection from NK lysis; and (iv) when transfected into the K562 cell line, both HLA-G1 and HLA-G2 abolish lysis by the T cell leukemia NK-like YT2C2 clone due to interaction between the HLA-G isoform on the target cell surface and a membrane receptor on YT2C2. Because NKIR1 and NKIR2, known to interact with HLA-G, were undetectable on YT2C2, we conclude that a yet-unknown specific receptor for HLA-G1 and HLA-G2 is present on these cells.


Association of single nucleotide polymorphisms in FGF-RAS/MAP signalling cascade with breast cancer susceptibility.
The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein (RAS/MAP) signalling cascades are the main molecular pathways involved in breast carcinogenesis. This study aims to determine the association between FGF10 (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene polymorphisms and breast cancer, to analyse the discriminative ability of each SNP and to test the accuracy of the predictive breast cancer risk model which includes all SNPs. We conducted a case-control study of 170 women (57.06 ± 11.60 years) with histologically confirmed breast cancer and 146 controls (50.24 ± 10.69 years). High resolution melting (HRM) method with Sanger sequencing validation was used in analyses. We have revealed significant association of FGFR2 and MAP3K1 polymorphisms with breast cancer. The odds ratio of FGFR2 T allele was 1.897 (95% CI 1.231-2.936, p = 0.004) and MAP3K1 C allele 1.804 (95% CI 1.151-2.845, p = 0.012). FGFR2 polymorphism achieved the best discriminative ability (41.95%). The Random Forest algorithm selected FGFR2, MAP3K1 and age as important breast cancer predictors. The accuracy of this prediction model approached moderate accuracy (70%), with 35.9% sensitivity and 88.6% specificity.


Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes.
To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval time significantly impacts the pathological complete response (pCR) rate and long-term survival. One hundred and seventy-six patients with gastric cancer undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NACT-surgery interval time (< 4 wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS). The NACT-surgery interval time and clinician T stage were independent predictors of pCR. The interval time > 6 wk was associated with a 74% higher odds of pCR as compared with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of clinical T3vs clinical T4 stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041). In Cox regression analysis of long-term survival, post-neoadjuvant therapy pathological N (ypN) stage significantly impacted OS (N0vs N3: HR = 0.16, 95%CI: 0.37-0.70, P = 0.015; N1vs N3: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and disease-free survival (DFS) (N0vs N3: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005; N1vs N3: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36-0.44, P = 0.001) for DFS. The NACT-surgery interval time is associated with pCR but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pCR.


Importance of monovalent ions for the fast axonal transport of proteins.
Proteins labeled with [35S]methionine or [3H]leucine were generated in vitro in bullfrog dorsal root ganglia and their fast axonal transport in the spinal nerves was followed during a subsequent incubation period. Incubation of the ganglia in a medium where sucrose, choline chloride, or sodium isethionate replaced NaCl caused respectively an 88, a 37, or a 76% reduction in the quantity of proteins carried by the fast axonal transport system; no decrease in synthesis of labeled proteins was observed and protein transport followed the usual time course. Incubation of desheathed spinal nerves in a medium where sucrose replaced NaCl reduced by 67% the quantity of labeled proteins which were transported past the desheathed region. Although both the axons and the dorsal root ganglia exhibit the requirement for monovalent ions to maintain fast axonal transport, the possibility that the ionic requirements of the ganglia pertain to the somal portion of the nerve cell is discussed.