Benchmarking medical laboratory performance: survey validation and results for Europe, Middle East, and Africa.
Medical laboratory performance is a relative concept, as are quality and safety in medicine. Therefore, repetitive benchmarking appears to be essential for sustainable improvement in health care. The general idea in this approach is to establish a reference level, upon which improvement may be strived for and quantified. While the laboratory community traditionally is highly aware of the need for laboratory performance and public scrutiny is more intense than ever due to the SARS-CoV-2 pandemic, few initiatives span the globe. The aim of this study was to establish a good practice approach towards benchmarking on a high abstraction level for three key dimensions of medical laboratory performance, generate a tentative snapshot of the current state of the art in the region of Europe, Middle East, and Africa (EMEA), and thus set the stage for global follow-up studies. The questionnaire used and previously published in this initiative consisted of 50 items, roughly half relating to laboratory operations in general with the other half addressing more specific topics. An international sample of laboratories from EMEA was approached to elicit high fidelity responses with the help of trained professionals. Individual item results were analyzed using standard descriptive statistics. Dimensional reduction of specific items was performed using exploratory factor analysis and assessed with confirmatory factor analysis, resulting in individual laboratory scores for the three subscales of "Operational performance", "Integrated clinical care performance", and "Financial sustainability". Altogether, 773 laboratories participated in the survey, of which 484 were government hospital laboratories, 129 private hospital laboratories, 146 commercial laboratories, and 14 were other types of laboratories (e.g. research laboratories). Respondents indicated the need for digitalization (e.g. use of IT for order management, auto-validation), automation (e.g. pre-analytics, automated sample transportation), and establishment of formal quality management systems (e.g. ISO 15189, ISO 9001) as well as sustainably embedding them in the fabric of laboratory operations. Considerable room for growth also exists for services provided to physicians, such as "Diagnostic pathways guidance", "Proactive consultation on complex cases", and "Real time decision support" which were provided by less than two thirds of laboratories. Concordantly, the most important kind of turn-around time (TAT) for clinicians, sample-to-result TAT, was monitored by only 40% of respondents. Altogether, the need for stronger integration of laboratories into the clinical care process became apparent and should be a main trajectory of future laboratory management. Factor analysis confirmed the theoretical constructs of the questionnaire design phase, resulting in a reasonably valid tool for further benchmarking activities on the three aimed-for key dimensions.


Delivery of trifluridine to human cornea and aqueous using collagen shields.
We investigated the ability of collagen shields to deliver trifluridine (trifluorothymidine [TFT]) to human cornea and aqueous humor. 24-hour porcine collagen shields were soaked in commercially prepared TFT (Viroptic). Patients undergoing penetrating keratoplasty wore a pre-soaked collagen shield for at least 30 minutes preoperatively. Control patients received drops of TFT only. Cornea and aqueous samples were obtained. TFT levels were measured using high performance liquid chromatography. Among the four patients with intact corneal epithelium, TFT was detected in only one patient (0.13 microgram/g in the aqueous). In seven patients with poor epithelium, corneal levels ranged from 0 to 635.34 micrograms/g, and aqueous levels ranged from 0.06 to 11.17 micrograms/g. Collagen shields do not enhance delivery of TFT to corneas with intact epithelium. In corneas with poor epithelium, drug penetration was higher but variable. The role of collagen shields as a drug delivery system for the treatment of herpes simplex keratitis remains to be determined.


The Accelerated Medical Program and the Liberal Arts at Boston University.
Since September 1961, fifteen classes have matriculated in Boston University's Six- Year College of Liberal Arts--Medical Education Combined Degree Program. The applicant pool is approximately three to four times larger now than in the earlier years, with classes averaging 50 students. Academic qualifications (high-school class rank and Scholastic Aptitude Test and College Board Achievement Test results) of the entering classes have been at a consistently high level. Fifty percent or more of the graduates receive the BA degree with honors; 10% or more receive the MD degree with honors. The degree of flexibility in the liberal arts component of the program has increased and currently exceeds that of the traditional four-year premedical curriculum. These data, together with additional information concerning postgraduate professional activities, indicate that the combined accelerated program has been successful.


SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.
Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.


Adolescent substance abuse. Confidentiality and consent.
Although all states have laws that allow minors to consent to substance abuse treatment, there is variability from state to state. Health care providers need to be aware of laws within their states. When providing health care to adolescents, many situations arise in which the provider must make a determination of the patient's competence to consent and whether parental notification would be in the patient's best interest. Confidentiality should be honored when possible, with limitations of the extent of confidentiality explained. Adolescents are able to consent for alcohol and drug treatment in most states, but involvement of the family is optimal in most cases. Physicians and other medical care providers also need to manage confidentiality issues in drug testing, billing of services, and medical records and need to work with clinical administrative staff to clarify and implement policies to maintain confidentiality. Proposed changes to medical privacy regulations may compromise confidentiality for medical care of adolescents. Medical providers should continue to work with their professional societies and legislators to ensure that appropriate consent and confidentiality statues exist to provide optimal health care to adolescents.


KV7 but not dual small and intermediate KCa channel openers inhibit the activation of colonic afferents by noxious stimuli.
In numerous subtypes of central and peripheral neurons, small and intermediate conductance Ca2+-activated K+ (SK and IK, respectively) channels are important regulators of neuronal excitability. Transcripts encoding SK channel subunits, as well as the closely related IK subunit, are coexpressed in the soma of colonic afferent neurons with receptors for the algogenic mediators ATP and bradykinin, P2X3 and B2, highlighting the potential utility of these channels as drug targets for the treatment of abdominal pain in gastrointestinal diseases such as irritable bowel syndrome. Despite this, pretreatment with the dual SK/IK channel opener SKA-31 had no effect on the colonic afferent response to ATP, bradykinin, or noxious ramp distention of the colon. Inhibition of SK or IK channels with apamin or TRAM-34, respectively, yielded no change in spontaneous baseline afferent activity, indicating these channels are not tonically active. In contrast to its lack of effect in electrophysiological experiments, comparable concentrations of SKA-31 abolished ongoing peristaltic activity in the colon ex vivo. Treatment with the KV7 channel opener retigabine blunted the colonic afferent response to all applied stimuli. Our data therefore highlight the potential utility of KV7, but not SK/IK, channel openers as analgesic agents for the treatment of abdominal pain.NEW & NOTEWORTHY Despite marked coexpression of small (Kcnn1, Kcnn2) and intermediate (Kcnn4) conductance calcium-activated potassium channel transcripts with P2X3 (P2rx3) or bradykinin B2 (Bdkrb2) receptors in colonic sensory neurons, pharmacological activation of these channels had no effect on the colonic afferent response to ATP, bradykinin or luminal distension of the colon. This is in contrast to the robust inhibitory effect of the KV7 channel opener, retigabine.


Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other neuromuscular blocking agents: a survey.
BACKGROUND: Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. MATERIAL AND METHODS: The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned. RESULTS: Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. CONCLUSION: Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice.


[The gene responsible for Huntington's disease in Spanish families: its diagnostic value and the relation between trinucleotide expansion and the clinical characteristics].
We have studied 77 patients from 38 families with Huntington's disease (HD) analyzing the genes trinucleotide repeats (CAG)n; we have compared the results with those of 154 chromosomes from control population. Patients with HD range from 39 to 70 repeats while healthy patients have between 12 and 36 repeats. These results show the great feasibility of this genetic test. We do not have found a correlation between expansion's repeats and age of onset except for young people with the disease; in these cases we have found high level of expansions (more than 65) that could be a prognostic parameter of the disease.


Uterine artery pseudoaneurysm: a rare cause of secondary postpartum haemorrhage following caesarean section.
A 30-year-old woman, para 2, who underwent an uneventful repeat elective lower segment caesarean section with sterilisation presented on the 23rd postnatal day to our Obstetric Emergency department with profuse bleeding per vaginum. She had a similar bout of bleeding on the 19th postnatal day and was treated elsewhere with blood transfusion and uterotonics. On ultrasonography, she was diagnosed to have few retained adherent placental bits in the lower part of the uterus with a small left broad ligament haematoma and hence was injected with a single dose of methotrexate. A communication of uterine artery was suspected as the mass was close to the uterus and few pulsations were felt on per vaginal examination while attempting aspiration of haematoma. Uterine artery pseudoaneurysm was diagnosed by Doppler studies and confirmed by contrast enhanced CT. She was treated successfully by bilateral internal iliac artery ligation as facilities for embolisation are not available.


Severe ascites with hypothyroidism and elevated CA125 concentration: a case report.
Ascites caused by hypothyroidism is rare and the pathogenesis is unclear. Several reports have presented cases of progressive ascites with hypothyroidism and elevated tumor markers. We report a 31-year-old female case with massive ascites and elevated serum CA 125 concentrations. The patient had no typical feature of hypothyroidism except an accumulation of ascitic fluid which showed elevated total protein concentration and a high serum-ascites albumin gradient (SAAG). There was no finding of malignancy. Following thyroid hormone replacement, the ascites was completely resolved accompanied by reduced concentrations of serum CA125. In general, primary hypothyroidism with ascites presents with coexisting massive pericardial or pleural effusion. The massive ascites and increased serum CA125 concentrations may have led us to make the incorrect diagnosis of ovarian malignancy. The evaluation of thyroid function is useful to determine the pathology of high-protein ascites or elevated tumor markers, and ascites may be treatable by thyroid replacement therapy.


The relationship of intracranial infrared light absorbance to fetal oxygenation. I: Methodology.
Current clinical methods for assessing fetal oxygenation in labor are indirect and remain somewhat imperfect. Since infrared light passes through the cranium and infrared light absorbance by tissues has been shown in adult animals to vary with oxygenation, monitoring of infrared light absorbance may serve as the basis for a new, more direct technique for the assessment of fetal condition. Described here is the application of infrared reflectance spectrophotometry to a fetal sheep model and the precision of the relationship between fetal arterial or venous PO2 and infrared light absorbance at selected wavelengths. A very strong, linear correlation (r = 0.915) was found between fetal arterial PO2 and intracranial infrared light absorbance according to an algorithm developed for selective monitoring of the state of hemoglobin oxygenation in tissue. With further development, this method holds promise for a more direct, noninvasive assessment of fetal condition in labor than is currently available.


Prevalence and factors associated with overweight and central obesity among adults in the Eastern Sudan.
A global epidemic of obesity has been documented, particularly among African countries. While central obesity and overweight have been reported for many countries, very limited information exists about the prevalence of these health problems in Sudan, and these data are nonexistent for Eastern Sudan. The present study aimed to determine the prevalence of obesity and central obesity, as well as the factors associated with both, among adults in Gadarif, Eastern Sudan. A cross-sectional study was conducted in Gadarif, Eastern Sudan, during the period of January through May 2018. Sociodemographic and health characteristics data were collected through a questionnaire. Body mass index (BMI) and waist circumference (WC) were measured using the standard methods. Both descriptive and inferential statics were applied to analyze the data. A total of 594 adults participated in the study; 70.4% of them were female. The mean (standard deviation) age was 44.98 (16.64) years. Of the 594 enrolled participants, 33.7%, 7.4%, 26.8%, and 32.2% were normal weight, underweight, overweight, and obese, respectively. The prevalence of central obesity was (67.8%). Approximately, one-third of the participants (29.29%) were obese and had central obesity. In the multinomial regression, being married was the main risk factor associated with overweight, and older age, female sex, being married and hypertension were significantly associated with obesity. In the binary regression, the main risk factors associated with central obesity were female sex and being married. The prevalence rates of both obesity and central obesity among the study participants were high. Older age and hypertension were only associated with obesity. Obesity and central obesity were significantly associated with female sex and being married. This study provided valuable baseline information to develop appropriate strategies for the prevention and control of obesity in Eastern Sudan.


Mild postnatal anemia: is it a problem?
Mild postnatal anemia is common. However, determination of postnatal hemoglobin level or iron supplementation are not routine in many obstetric units. This study was designed to evaluate the impact of mild postnatal anemia and iron supplementation on women. One hundred fifty women who had postnatal hemoglobin levels between 80 and 99 g/L were randomly assigned into two groups with iron tablets or placebo provided from the time of diagnosis until reassessment at 6 weeks. The patients' general well-being, hemoglobin levels, iron status, side effects, and compliance were assessed. One hundred twenty-two women returned for reassessment. Twelve (9.8%) of the 122 women recruited and four (3.2%) of 122 nonanemic matched controls complained of dizziness 2 days after delivery; the difference was statistically significant (chi2 test, p<0.05). At 6 weeks postpartum, significantly more women were anemic (chi2 test, p<0.05) and iron deficient (chi2 test, p<0.01) in the placebo group. The score of general well-being as assessed by a 4-point scale was significantly higher in the iron supplementation group (Mann-Whitney test, p<0.05). The amounts of drugs consumed in both groups were comparable and the incidences of side effects were similar.


An investigation into the effect of alcohol consumption on health status and health care utilization in Ireland.
This paper presents a study of the effect of alcohol consumption on individual health status and health care utilization in Ireland using the 2007 Slán National Health and Lifestyle Survey, while accounting for the endogenous relationship between alcohol and health. Drinkers are categorized as those who never drank, non-drinkers, moderate drinkers, or heavy drinkers, based on national recommended weekly drinking levels in Ireland. The drinking-status equation is estimated using an ordered probit model. Predicted values for the inverse mills ratio are generated, which are then included in the health and health-care utilization equations. Differences in health status for each category of drinker are examined, and the relationship between both alcohol consumption and health with a host of other personal and socio-economic variables is also identified. Given that the measure of health status available is self-assessed, the effect of alcohol consumption on health-care utilization is also analyzed as an alternative measure of health. Findings show that in Ireland, moderate drinkers enjoy the best health status. More moderate drinkers report having very good or excellent health compared with heavy drinkers, non-drinkers, or those who never drank. While heavy drinkers do not report having as good a health status as moderate drinkers, they are better off in terms of health when compared with non-drinkers and those who are lifetime abstainers.


Minor spliceosome inactivation causes microcephaly, owing to cell cycle defects and death of self-amplifying radial glial cells.
Mutation in minor spliceosome components is linked to the developmental disorder microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Here, we inactivated the minor spliceosome in the developing mouse cortex (pallium) by ablating Rnu11, which encodes the crucial minor spliceosome small nuclear RNA (snRNA) U11. Rnu11 conditional knockout mice were born with microcephaly, which was caused by the death of self-amplifying radial glial cells (RGCs), while intermediate progenitor cells and neurons were produced. RNA sequencing suggested that this cell death was mediated by upregulation of p53 (Trp53 - Mouse Genome Informatics) and DNA damage, which were both observed specifically in U11-null RGCs. Moreover, U11 loss caused elevated minor intron retention in genes regulating the cell cycle, which was consistent with fewer RGCs in S-phase and cytokinesis, alongside prolonged metaphase in RGCs. In all, we found that self-amplifying RGCs are the cell type most sensitive to loss of minor splicing. Together, these findings provide a potential explanation of how disruption of minor splicing might cause microcephaly in MOPD1.


Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: an 18-month prospective follow-up.
Our objective was to determine the prevalence and incidence of human immunodeficiency virus (HIV) infection and related risk behaviors among opiate-abusing intravenous drug users (IVDUs) either in or out of methadone treatment. The subjects, 152 in-treatment and 103 out-of-treatment intravenous opiate users, were followed prospectively for 18 months. Behavioral and serologic assessments were made at 6-month intervals, with complete information available on 89% of the sample. Subjects were recruited from a single methadone maintenance program and the surrounding neighborhood in north-central Philadelphia. At baseline, the HIV seroprevalence rate for the total sample was 12%: 10% for the methadone-maintained group and 16% for the out-of-treatment group. Out-of-treatment subjects were injecting drugs, sharing needles, visiting shooting galleries, and practicing unsafe sex at significantly higher rates than in-treatment subjects. Follow-up of HIV-negative subjects over the next 18 months showed conversion rates of 3.5% for those who remained in methadone maintenance versus 22% for those who remained out of treatment. The sixfold difference in rate of seroconversion between the two groups suggests that although rapid transmission of HIV still occurs, opiate-abusing IVDUs who enter methadone treatment are significantly less likely to become infected. In contrast, those opiate addicts who do not enter treatment are at significantly higher risk of contracting and spreading the disease. Implications for developing additional risk interventions for out-of-treatment IVDUs are discussed.


Facilitating culturally integrated behaviors among allied health students.
This article offers a perspective on why culturally integrated behaviors are important for allied health education and suggestions of methods to facilitate such behaviors. Literature and theory are used to support cultural integration in allied health curricula. Examples of learning experiences from students in cross-cultural environments and reflections on those experiences further elucidate facilitation methods.


[Results and reliability of stereotactic and endoscopic biopsies in brain tumors].
Stereotactic neurosurgery was the first "minimal invasive method" in the field of neurosurgery, later followed and partly replaced by endoscopic techniques. One reason for such an approach is sampling of small tissue probes for diagnosis, e.g. in brain tumours not accessible to open surgery. The appropriate method in the hands of the experienced is the "Quetsch" or smear technique. Its reliability is limited by the fact, that the "architectural" or "tissular" components of tumours lack in those purely cytological preparations. Tissue architecture however is crucial for the assessment of different grades in glial tumour progression. The grade of a glial tumour is the most critical information for the patient and the therapist; grading of the supratentorialf gliomas of the adult by means of cellular and tissue pleomorphism therefore forms the basis of Zülchs system of classification and grading of all intracranial tumours by comparison of postoperative survival. The resulting four grade system--slightly modified--is part of the old and new issue of the WHO classification of brain tumours. In order to specify the possibility of correct diagnosis and grading in probes gained by the minimal invasive techniques, we present results of three diagnostic approaches: First: We report results of a study performed during the last twelve years in which a diagnosis of smear preparations had been made on neurosurgical specimens prior to conventional handling. The "blind" cytological diagnosis was then compared with the final diagnosis of the tumour using light and electron microscopy and immunohistochemistry. Second: We report results and estimates of tissue probes gained by the so called sandwich technique in which the removal of material for cytological analysis is done stepwise. By doing so, material representative for different compartments of the neoplasm is obtained. This implies collaboration between neurosurgeon and neuropathologist not only during the time of stereotactic action but also in the planing period; the correct interpretation of the different compartments delivered by imaging methods in this context is essential. Third: We present selected cases of probe sampling under direct visual control by endoscopy. This method is especially useful for tumours bordering the ventricular system. Surface structures and cyst linings can be visualized directly if the endoscopist is familiar with normal and pathological tissue appearance. The specimen for analysis may therefore be taken from the most relevant tumour region and the sandwich technic which means tissue damaging in multiple localisations can be partly or fully avoided.(ABSTRACT TRUNCATED AT 400 WORDS)


A tribute to Leif Hertz: The historical context of his pioneering studies of the roles of astrocytes in brain energy metabolism, neurotransmission, cognitive functions, and pharmacology identifies important, unresolved topics for future studies.
Leif Hertz, M.D., D.Sc. (honōris causā) (1930-2018), was one of the original and noteworthy participants in the International Conference on Brain Energy Metabolism (ICBEM) series since its inception in 1993. The biennial ICBEM conferences are organized by neuroscientists interested in energetics and metabolism underlying neural functions; they have had a high impact on conceptual and experimental advances in these fields and on promoting collaborative interactions among neuroscientists. Leif made major contributions to ICBEM discussions and understanding of metabolic and signaling characteristics of astrocytes and their roles in brain function. His studies ranged from uptake of K+ from extracellular fluid and its stimulation of astrocytic respiration, identification, and regulation of enzymes specifically or preferentially expressed in astrocytes in the glutamate-glutamine cycle of excitatory neurotransmission, a requirement for astrocytic glycogenolysis for fueling K+ uptake, involvement of glycogen in memory consolidation in the chick, and pharmacology of astrocytes. This tribute to Leif Hertz highlights his major discoveries, the high impact of his work on astrocyte-neuron interactions, and his unparalleled influence on understanding the cellular basis of brain energy metabolism. His work over six decades has helped integrate the roles of astrocytes into neurotransmission where oxidative and glycogenolytic metabolism during neurotransmitter glutamate turnover are key aspects of astrocytic energetics. Leif recognized that brain astrocytic metabolism is greatly underestimated unless the volume fraction of astrocytes is taken into account. Adjustment for pathway rates expressed per gram tissue for volume fraction indicates that astrocytes have much higher oxidative rates than neurons and astrocytic glycogen concentrations and glycogenolytic rates during sensory stimulation in vivo are similar to those in resting and exercising muscle, respectively. These novel insights are typical of Leif's astute contributions to the energy metabolism field, and his publications have identified unresolved topics that provide the neuroscience community with challenges and opportunities for future research.


Aortoiliac occlusive disease and gastrointestinal malignancy: changing therapeutic options.
Treatment of gastrointestinal malignancy encountered unexpectedly during procedures involving the abdominal aorta continues to be debated. Previously, simultaneous vascular procedures with intra-abdominal malignancy were rare. Most underwent vascular reconstruction followed by a delayed aortic procedure. With recent improvement in axillobifemoral graft patency, a one-stage procedure for aortoiliac disease should be entertained. We recently encountered a small bowel lymphoma while beginning an aortic replacement for aortic occlusion. Resection of a near-obstructing small bowel tumor immediately after axillofemoral reconstruction provided treatment of both entities at one time. Since the early description of axillofemoral bypass in 1963, varying success with extra-anatomic bypass has been reported. Early data for axillofemoral bypass were dismal, but with recent technical and graft improvements patency has been improved. Occult malignancy during aortic procedures is uncommon, about 2 to 4 per cent, but when met is usually dealt with after the patient recovers from the vascular procedure. With improvements in extra-anatomic bypass results, a single operative period can be entertained.


Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats.
BACKGROUND We aimed to investigate the role of PDCD4-mediated Akt signaling pathway in vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities. MATERIAL AND METHODS Ten rats were used as control, while 50 rats were used for creating disease models and were assigned to 5 groups: model group (no injection), NC group (injected with vectors containing PDCD negative control sequence), sh-PDCD4 group (injected with vectors containing sh-PDCD4 sequence), IGF-1 group (injected with IGF-1), and sh-PDCD4+IGF-1 group (injected with IGF-1 and vectors containing sh-PDCD4 sequence). RESULTS Compared with the control group, the expression levels of PDCD4 mRNA and protein, as well as levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, increased in the other 5 groups, while the mRNA and protein expression levels of Akt and eNOS, the protein expression levels of p-Akt and p-eNOS, and superoxide dismutase content decreased in these groups (all P<0.05). Compared with the model group, the sh-PDCD4 and sh-PDCD4+1GF-1 groups had lower mRNA and protein expressions of PDCD4 (all P<0.05), whereas the IGF-1 group had similar levels (all P>0.05). These 3 groups had lower levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, and higher mRNA and protein expressions of Akt and eNOS, protein expressions of p-Akt and p-eNOS, and superoxide dismutase content (all P<0.05). The NC group did not differ from the model group (all P>0.05). CONCLUSIONS PDCD4 gene silencing can activate the Akt signaling pathway and attenuate vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities in rats.


Reassessment of Clostridium difficile susceptibility to metronidazole and vancomycin.
Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea. The drugs most commonly used to treat diseases associated with C. difficile are metronidazole and vancomycin. Most clinical laboratories assume that all C. difficile isolates are susceptible to metronidazole and vancomycin. We report on the antimicrobial susceptibilities of 415 C. difficile isolates to metronidazole and vancomycin over an 8-year period (1993 to 2000). The overall rate of resistance to metronidazole at the critical breakpoint (16 microg/ml) was 6.3%. Although full resistance to vancomycin was not observed, the overall rate of intermediate resistance was 3.1%. One isolate had a combination of resistance to metronidazole and intermediate resistance to vancomycin. Rates of resistance to metronidazole and vancomycin were higher among isolates from human immunodeficiency virus-infected patients. Molecular typing methods proved the absence of clonality among the isolates with decreased susceptibilities to the antimicrobials tested.


Further reflections on the "watched" play state and the role of "watched play" in analytic work.
This paper expands upon the concept of "watched play," a play state in which the mother silently but attentively watches her child play. The regulatory presence of the "watching mother" is introjected and internalized through the child's development of mental representations of mother's latently interactive presence, contributing to the development of self-regulatory mechanisms. By contrast, the consequences of failed "watched play" are disorganizing play disruptions which foster ambivalence and affect disregulation. The introjection of the "watching mother" during play contributes to the child's growing capacity to mentalize others' behaviors. Finally, "watched play" is consistent with the paradigm of the passive, albeit attentive analyst in both the adult and child analytic modes.


Effect of double bonds in the formation of sodium dodecanoate and sodium 10-undecenoate mixed micelles in water.
The micellization of an aqueous mixture of sodium dodecanoate (SDD) and sodium 10-undecenoate (SUD) was studied with the theory of mixed micellization. A strong nonideality was found, with a preferential composition of mixed micelles. This phenomenon was interpreted on the basis of the interaction between the vinyl group and water by hydrogen bonding. The importance of the aliphatic pi electrons and water was stated.


Gene regulatory network reconstruction using conditional mutual information.
The inference of gene regulatory network from expression data is an important area of research that provides insight to the inner workings of a biological system. The relevance-network-based approaches provide a simple and easily-scalable solution to the understanding of interaction between genes. Up until now, most works based on relevance network focus on the discovery of direct regulation using correlation coefficient or mutual information. However, some of the more complicated interactions such as interactive regulation and co-regulation are not easily detected. In this work, we propose a relevance network model for gene regulatory network inference which employs both mutual information and conditional mutual information to determine the interactions between genes. For this purpose, we propose a conditional mutual information estimator based on adaptive partitioning which allows us to condition on both discrete and continuous random variables. We provide experimental results that demonstrate that the proposed regulatory network inference algorithm can provide better performance when the target network contains coregulated and interactively regulated genes.


A Novel Chimeric Endolysin with Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus.
Cysteine/histidine-dependent amidohydrolase/peptidase (CHAP) and amidase are known as catalytic domains of the bacteriophage-derived endolysin LysK and were previously reported to show lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). In the current study, the in silico design and analysis of chimeric CHAP-amidase model was applied to enhance the stability and solubility of protein, which was achieved through improving the properties of primary, secondary and tertiary structures. The coding gene sequence of the chimeric CHAP-amidase was synthesized and subcloned into the pET-22(+) expression vector, and the recombinant protein was expressed in E. coli BL21 (DE3) strain. Subsequent affinity-based purification yielded ~12 mg soluble protein per liter of E. coli culture. Statistical analysis indicated that concentrations of ≥1 μg/mL of the purified protein have significant antibacterial activity against S. aureus MRSA252 cells. The engineered chimeric CHAP-amidase exhibited 3.2 log reduction of MRSA252 cell counts at the concentration of 10 μg/mL. A synergistic interaction between CHAP-amidase and vancomycin was detected by using checkerboard assay and calculating the fractional inhibitory concentration (FIC) index. This synergistic effect was shown by 8-fold reduction in the minimum inhibitory concentration of vancomycin. The chimeric CHAP-amidase displayed strong antibacterial activity against S. aureus, S. epidermidis, and enterococcus. However, it did not indicate any significant antibacterial activity against E. coli and Lactococcus lactis. Taken together, these findings suggest that our chimeric CHAP-amidase might represent potential to be used for the development of efficient antibacterial therapies targeting MRSA and certain Gram-positive bacteria.


MK-801 reinstates drug-seeking behaviour in cocaine-trained rats.
We evaluated the incentive motivational properties of MK-801 by determining its priming effect on drug-seeking behaviour following extinction of cocaine self-administration, an animal model for drug craving. Rats were allowed to self-administrate cocaine (0.5 mg/kg) or saline during 10 daily sessions. MK-801 (0.1-0.25 mg/kg, i.p.) dose-dependently reinstated responding for cocaine following an extinction period of 3 weeks. Responding was selectively enhanced in the previously drug-paired hole and was completely absent in rats with a history of saline self-administration. These data provide evidence for a possible role of NMDA receptors in the incentive motivation underlying cocaine-seeking behaviour. In addition, the ability of MK-801 to elicit drug-seeking behaviour may prove to be a serious drawback for the proposed use of NMDA antagonists in the treatment of drug addiction.


Functionally selective signaling for morphine and fentanyl antinociception and tolerance mediated by the rat periaqueductal gray.
Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance.


Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7.
It is well documented that B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), widely overexpressed in the vast majority of malignancies, plays an essential role in the occurrence and development of several different tumors. Here, we report Bmi-1 siRNA-mediated cell proliferation inhibition and cell apoptosis in vitro and in vivo in the human breast carcinoma cell line MCF-7. Our results demonstrated that Bmi-1 siRNA effectively down-regulated the expression of Bmi-1, inhibited cell proliferation in vitro and in vivo, evoked cell cycle arrest in the G0/G1 phase and induced cell apoptosis in MCF-7 cells, coupled with decrease in cyclin D1, cyclin E, cdk2, bcl-2 and Ki-67 expression and Akt phosphorylation levels and an increase of p21 and bax expression and activities of caspase-3/-9. Taken together, our results suggest that Bmi-1 may be a potential molecular target for the therapy of breast carcinoma.


The state of the reward comparison hypothesis: theoretical comment on Huang and Hsiao (2008).
Rats avoid intake of a gustatory cue following pairings with a drug of abuse, such as morphine or cocaine. Despite the well-established rewarding properties of these drugs, the reduction in intake of the taste cue has been interpreted as a conditioned taste aversion for decades. In 1997, I proposed the reward comparison hypothesis suggesting that rats avoided intake of the drug-associated taste cue because the value of the taste cue pales in comparison to the highly rewarding drug of abuse expected in the near future. In this issue of Behavioral Neuroscience, A. C. W. Huang and S. Hsiao challenge the reward comparison hypothesis by showing parallels between amphetamine and LiCl-induced suppression of CS intake. This commentary addresses the current state of the reward comparison hypothesis in the context of the experiments completed by Huang and Hsiao and their new task-dependent drug effects hypothesis.


Challenges and predictors of exclusive breastfeeding among mothers attending the child welfare clinic at a regional hospital in Ghana: a descriptive cross-sectional study.
The challenges and predictors of exclusive breastfeeding (EBF) have been examined in many parts of the world. Considering the socio-cultural dynamics and the few research studies in Ghana, the factors that hinder and predict EBF practice in other countries may be different in the Ghanaian setting. The study therefore sought to assess the challenges and predictors of EBF among mothers attending a child welfare clinic at a regional hospital in Ghana. A descriptive cross-sectional study was carried out between January and March, 2015 to elicit information from 240 mothers who were sampled using simple random sampling technique. A validated structured questionnaire was used in collecting data on participants' socio-demographic characteristics and reported breastfeeding practices. Participants' breastfeeding challenges were rated on a Likert scale from 1 (not at all), 2 (mild), 3 (moderate), 4 (severe) to 5 (unbearable). In this study, EBF refers to birth of the infants up to six months. The top three breastfeeding challenges of mothers were: belief that breast milk alone was not sufficient in meeting their babies' nutritional needs [mean 3.43 (standard deviation {SD} 1.35)], short maternity leave period [mean 3.41 (SD 1.29)], and socio-cultural pressure to introduce water and artificial feeds [mean 3.39 (SD 1.28)]. Independent predictors of EBF were: infant's age [Adjusted Odds Ratio (AOR) 0.82 (95% Confidence Interval [CI] 0.71, 0.95)], and self-employment [AOR 2.67 (95% CI 1.11, 6.41)]. Mothers are confronted with numerous EBF challenges both at the individual and societal levels, and stakeholders need to consider these in order to support breastfeeding mothers to maximize outcomes. Reviewing the labour laws on Ghana's maternity leave to accommodate an extended maternity leave in addition to the employee's annual leave could further improve EBF practice rates.


PHBHHx Facilitated the Residence, Survival and Stemness Maintain of Transplanted Neural Stem Cells in Traumatic Brain Injury Rats.
Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a polyhydroxyalkanoate (PHA) with broad application prospects in various biomedical fields. Our previous study demonstrated the great biocompatibility of PHBHHx with neural stem cells (NSCs) in vitro. In this study, we went a step further and implanted the NSC-carrying PHBHHx film to in vivo into the lesion region in a rat traumatic brain injury (TBI) model. The in vivo biocompatibility of PHBHHx, as well as the survival, migration and differentiation of the transplanted NSCs were investigated. The results showed that PHBHHx did not induce additional reactive gliosis and supported the in vivo survival and growth of the transplanted stem cells. The transplanted NSCs were able to migrate into the brain tissue and differentiated into both neurons and astrocytes. Moreover, PHBHHx seemed to be able to maintain the stemness of the attached NSCs both in vitro and in vivo. The major monomer of PHBHHx, 3-hydroxybutyrate (3-HB), might contribute to this bioactivity because the addition of low concentrations of 3-HB facilitated the self-renewal of NSCs by shortening the G1 phase, promoted their proliferation, and enhanced the expression of a key regulatory transcription factor which helped to keep the stemness of NSCs. These results highlight the application of PHBHHx as a promising bioactive material for NSC transplantation in the brain and open up a wide space for further studies on functional recovery following the transplantation of NSCs attached to PHBHHx.


Hot water dipping of olives (Olea europaea) for virgin oil debittering.
Olives (Olea europaea L.) of the Manzanilla, Picual, and Verdial varieties harvested at the green mature stage of ripening were dipped in hot water at a range of temperatures between 60 and 72 degrees C for 3 min. Immediately after treatment, oils were physically extracted from the olives. Olive heating promotes a reduction of oil bitterness in direct relationship to the temperature used. Fruit heating at > or =60 degrees C for 3 min did not cause significant changes in acidity, UV absorption, peroxide index, and panel test score of the oils obtained but decreased its oxidative stability. Oils extracted from heated fruit showed higher concentrations of chlorophylls and carotenes and lower total phenol content.


Resistance of TNF/LT alpha double deficient mice to bleomycin-induced fibrosis.
In order to evaluate the role and mode of action of TNF in bleomycin-induced lung fibrosis, mice deficient for TNF and LT alpha (delta TNF/LT alpha) were examined at 2 months of age and after 3 weekly i.v. injections of bleomycin. The body weight of the delta TNF/LT alpha mice was 88 +/- 11% of that of the wild type littermates. Lung collagen, evaluated by its hydroxyproline content, was also lower (81 +/- 9%) in mutant than in wild type littermates. Bleomycin induced a diffuse alveolitis with focal areas of alveolar remodelling in wild type but not in delta TNF/LT alpha, mice. Lymphoid infiltration was also prominent in wild type, but absent from delta TNF/LT alpha, mice. Bleomycin injections increased collagen deposition, as evaluated by the lung hydroxyproline content, more markedly in wild type, than in delta TNF/LT alpha, mice. Cell trapping in the alveolar capillaries was evaluated by semi-quantitative electron microscopy. Bleomycin markedly increased platelet trapping in the alveolar capillaries of wild type, but not of delta TNF/LT alpha, mice. This study indicates that the expression of TNF/LT alpha genes increases the deposition of collagen in both untreated and inflamed lung and that these genes may act, at least in part, by promoting platelet trapping.


Phase variable changes in genes lgtA and lgtC within the lgtABCDE operon of Neisseria gonorrhoeae can modulate gonococcal susceptibility to normal human serum.
The alpha-chain of the core oligosaccharide of the lipo-oligosaccharide (LOS) produced by Neisseria gonorrhoeae can undergo reversible and rapid changes in structure due to phase-variable production of certain enzymes employed in the biosynthesis of the lacto-N-neotetraose structure. Five of these enzymes are encoded by the lgtABCDE operon, and polynucleotide tracts within three of these genes (lgtA, lgtC and lgtD) can be substrates for slipped-strand mispairing events that lead to nucleotide insertions or deletion events which result in variable production of their respective gene products. We now report that phase-variable synthesis of the lgtA and lgtC gene products in strain FA19 results in the production of elongated LOS alpha-chains and that the presence of these LOS species can result in gonococci being sensitive to the bacteriolytic action of serum-antibody and complement. Hence, phase variation within the lgtABCDE operon can significantly impact the ability of gonococci to subvert this important host defense system.


Pituitary glycoprotein hormone beta subunits in the Australian lungfish and estimation of the relative evolution rate of these subunits within vertebrates.
The beta subunits of the two pituitary gonadotropins LH and FSH and of thyroid-stimulating hormone (TSH) were cloned from Australian lungfish (Neoceratodus forsteri) pituitary glands. These three glycoprotein hormone beta subunits possess the main characteristics common to their counterparts in other vertebrates. Taking advantage of the phylogenetic position of the lungfish, close to the root of tetrapods, a maximum parsimony tree was inferred from these new sequences and sequences from representatives of the diversity of vertebrates. The topology of the tree was imposed so that it reflected as closely as possible the real evolutionary history of the subunits. This tree was used to estimate the relative evolution rate of the three subunits in vertebrates. Cumulated amino acid substitutions from the basal subunit node (ancestral subunit sequence) to the species node were calculated and compared. It showed that a burst in evolutionary rate occurred for the LHbeta subunit in the tetrapod lineage sometime after the emergence of amphibians. The rate of evolution of the LHbeta subunit was particularly high throughout the radiation of mammals while FSH and TSHbeta subunits kept quite stable in this lineage. A burst in evolutionary rate was also observed for the FSHbeta subunit in the lineage leading to teleosts sometime after the emergence of chondrosteans and the dynamic of evolution was high throughout the radiation of teleosts. These results were consistent with data obtained from pairwise comparisons.


Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.
Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging.


The Drosophila Dead end Arf-like3 GTPase controls vesicle trafficking during tracheal fusion cell morphogenesis.
The Drosophila larval tracheal system consists of a highly branched tubular organ that becomes interconnected by migration-fusion events during embryonic development. Fusion cells at the tip of each branch guide migration, adhere, and then undergo extensive remodeling as the tracheal lumen extends between the two branches. The Drosophila dead end gene is expressed in fusion cells, and encodes an Arf-like3 GTPase. Analyses of dead end RNAi and mutant embryos reveal that the lumen fails to connect between the two branches. Expression of a constitutively active form of Dead end in S2 cells reveals that it influences the state of actin polymerization, and is present on particles that traffic along actin/microtubule-containing processes. Imaging experiments in vivo reveal that Dead end-containing vesicles are associated with recycling endosomes and the exocyst, and control exocyst localization in fusion cells. These results indicate that the Dead end GTPase plays an important role in trafficking membrane components involved in tracheal fusion cell morphogenesis and lumenal development.


Cancer-related tasks involving employment: opportunities for clinical assistance.
Many cancer survivors experience unmet psychosocial needs related to their jobs, and women often fare worse than men in this regard. However, little research exists on ways to assist patients with cancer in preventing or managing common job problems. We conducted focus groups and a survey among 73 women who were employed at the time of presentation of a gynecologic cancer. We compared the findings with existing recommendations and professional standards for occupational rehabilitation. Participants described different cancer-related employment tasks in three time periods: just after diagnosis, during primary treatment, and after primary treatment is completed. The more difficult tasks included communicating with supervisors and coworkers, determining company policies, applying for employer-sponsored benefits, handling finances, managing symptoms on returning to work, finding effective solutions to cancer-related job problems, leaving the job with dignity if too sick or if the job ended, and making career plans. The cancer care team may be able to help meet the psychosocial needs of employed cancer survivors by screening for job concerns, providing information, formulating a return-to-work plan, treating symptoms, consulting with professionals who have employment-related expertise, and giving other forms of assistance.


Hepatic photopenia in gallium imaging.
Although Ga-67 has been used extensively in imaging many different conditions, much is yet unknown about the mechanisms by which gallium concentrates preferentially in tissues such as the liver. This paper reports three patients with markedly diminished hepatic uptake of gallium. The cases are examined in light of published data demonstrating such factors as transferrin levels, radiation, and chemotherapeutic agents as altering the hepatic uptake of gallium. Of the many factors believed to influence the biodistribution of gallium, none can definitively account for the lack of hepatic uptake in these patients.


Costs and outcomes of AIDS care: comparing a health maintenance organization with fee-for-service systems in the Boston Health Study.
A 4-month observational cohort study was performed to compare the performance of one health maintenance organization (HMO) with two fee-for-service (FFS) systems in Boston, Massachusetts in treating 255 patients with AIDS. Total 4-month costs; cost subcomponents, including inpatient, outpatient, home care, and zidovudine costs; functional status (difficulties with activities of daily living); and satisfaction with care. Compared with FFS patients, HMO patients were better educated, more often white, less often on Medicaid, and more often reported homosexual or bisexual behaviors as HIV risk factors (all factors, p = .001). Both groups had similar duration of AIDS, baseline hemoglobin levels, and leukocyte counts. Total 4-month costs at the HMO were significantly lower than those in the FFS settings ($4799 U.S. versus $8540 U.S.; p = .013), as were outpatient costs ($1131 U.S. versus $1614 U.S.; p = .001), after adjustment for sociodemographic factors, baseline functioning, main HIV risk factor, and other clinical variables. Adjusted physical functioning (p = .32) and patient satisfaction (p = .82). were similar between systems. The HMO had significantly lower total costs without any observable decrement in functional outcomes or patient satisfaction. The largest component of these cost savings came from reduced spending on inpatient care, but the HMO also spent less on outpatient and home care. Better coordination of care at the HMO may have been responsible for these lower costs.


Patterns of complementary and alternative medicine (CAM) use among dental patients.
Complementary and alternative medicine (CAM) is a diverse collection of approaches used to prevent or treat diseases. The goal of this study was to examine relationships between dental patient characteristics and current usage of CAM therapies. The CAM definition encompassed 24 therapies excluding prayer. Associations and trends in usage were assessed for gender, income, education, and age. Multivariable logistic and negative binomial models were used to identify factors impacting the use and number of CAM therapies used. In dental patients (n = 402), nearly 67 percent of subjects reported at least one CAM treatment. Gender was significantly associated with recent utilization of CAM, biological, manipulative (all P < 0.01), and mind-body (P = 0.04) therapies, as well as the number (P < 0.01) of therapies used. Higher education levels were significant in usage of any CAM, biological, and mind-body therapies (P < 0.01). A large proportion of dental patients reported use of CAM therapies. While CAM therapies and those who use them are diverse, given their widespread use, they clearly have potential impacts on the oral health of the public. Knowledge of the characteristics of dental patients who use CAM therapies is a first step in developing a broader understanding how CAM therapies and associated beliefs may affect oral health and public health programs.


The role of the microenvironment and intercellular cross-talk in tumor angiogenesis.
The expression of angiogenic factors in tumors is controlled by intrinsic factors in the tumor and by the host microenvironment. Endothelial cells within particular tumor microenvironments interact not only with tumor cells but also with immune cells, fibroblasts, pericytes, and the extracellular matrix (ECM). The relationship and cross-talk among these cells determine gene expression, phenotypic distinction, and ultimately whether endothelial cells survive, proliferate, or undergo apoptosis. The diversity of angiogenic factor expression in tumors at different sites, combined with the fact that endothelial cells in different organs and tumors are phenotypically distinct, constitutes a formidable challenge for the development of effective anti-angiogenic therapies.


Cytokinins - regulators of de novo shoot organogenesis.
Plants, unlike animals, possess a unique developmental plasticity, that allows them to adapt to changing environmental conditions. A fundamental aspect of this plasticity is their ability to undergo postembryonic de novo organogenesis. This requires the presence of regulators that trigger and mediate specific spatiotemporal changes in developmental programs. The phytohormone cytokinin has been known as a principal regulator of plant development for more than six decades. In de novo shoot organogenesis and in vitro shoot regeneration, cytokinins are the prime candidates for the signal that determines shoot identity. Both processes of de novo shoot apical meristem development are accompanied by changes in gene expression, cell fate reprogramming, and the switching-on of the shoot-specific homeodomain regulator, WUSCHEL. Current understanding about the role of cytokinins in the shoot regeneration will be discussed.


D-cycloserine augmentation of behavior therapy for anxiety and obsessive-compulsive disorders: A meta-analysis.
The present meta-analysis investigates whether the antibiotic D-cycloserine (DCS), a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, can augment the effect of behavior therapy in humans with anxiety and obsessive-compulsive disorders. A keyword-based computer search was conducted using common electronic databases. Only studies investigating the effect of DCS in humans with anxiety and obsessive-compulsive disorders were included, resulting in 23 studies with a combined sample size of 1314 patients. Effect sizes were coded as Hedges' g and SMCC, the latter also incorporating differences in pre-treatment values. Bayesian multilevel meta-analysis was applied to take dependencies of effect sizes obtained from the same study into account. While previous meta-analyses found small to moderate improvements, the current results including the most recent research indicate that the overall effect of DCS is very small and almost indistinguishable from zero (g = -0.12, CI = [-0.27, 0.02]; SMCC = -0.10, CI = [-0.29, 0.07]). Slightly larger effects were found for social anxious patients. Further, study quality and year of publication were relevant moderators, with higher quality / more recent studies reported smaller effects of DCS. These findings raise the question of the usefulness of DCS as an augmentation of exposure therapy for anxiety and obsessive-compulsive disorders. At least, it seems to be less promising than initially thought. The fact that study quality was inversely related to the reported effect sizes underlines the importance of high quality primary research in order to avoid over-estimation of treatment effects in clinical psychology.


X-ray triple refraction and triple absorption in a cobalt-complex crystal.
X-ray triple refraction and triple absorption have been quantitatively measured for the first time. The samples were (100)-, (010)- and (001)-oriented plates of a cobalt-complex monoclinic crystal. The apparatus used was an energy-tunable X-ray polarimeter with a phase retarder. The X-ray energy was scanned over a range of 150 eV near the cobalt K-absorption edge. Both the spectra of ellipticity and rotation of polarization were completely different for each crystal plate, which revealed that the biaxial crystal had three refractive indices and three absorption coefficients in the X-ray region. The Kramers-Kronig relation between the real and imaginary parts of the dielectric anisotropy has been quantitatively confirmed for all three different orientations.


High contrast and homogeneous staining of paraffin sections of whole human brains for three dimensional ultrahigh resolution image analysis.
The gallocyanin chromalum stain belongs to the classical DNA-RNA staining techniques in histochemistry. It has some important features for successful object orientated image analysis of whole sections of the human brain. To obtain reproducible staining results with these large sections, the method of Einarson was adapted to image analytical requirements. We discuss staining in a warm staining solution, pH adjustment, and optimal stain composition. The embedding procedure for whole human brains is considered as well.


Appendiceal tie syndrome.
Intestinal knot syndromes such as ileosigmoid knots, ileal-ileal knots have been described in the literature. We describe a case of a long inflamed appendix wrapping around a loop of ileum causing an appendico-ileal knot, a rare form of closed loop obstruction with only five cases reported previously. The use of CT scanning prior to surgery is discussed and literature reviewed.


An explanation for camera perspective bias in voluntariness judgment for video-recorded confession: Suggestion of cognitive frame.
Three experiments were conducted to test the hypothesis that difference in voluntariness judgment for a custodial confession filmed in different camera focuses ("camera perspective bias") could occur because a particular camera focus conveys a suggestion of a particular cognitive frame. In Experiment 1, 146 juror eligible adults in Korea showed a camera perspective bias in voluntariness judgment with a simulated confession filmed with two cameras of different focuses, one on the suspect and the other on the detective. In Experiment 2, the same bias in voluntariness judgment emerged without cameras when the participants were cognitively framed, prior to listening to the audio track of the videos used in Experiment 1, by instructions to make either a voluntariness judgment for a confession or a coerciveness judgment for an interrogation. In Experiment 3, the camera perspective bias in voluntariness judgment disappeared when the participants viewing the video focused on the suspect were initially framed to make coerciveness judgment for the interrogation and the participants viewing the video focused on the detective were initially framed to make voluntariness judgment for the confession. The results in combination indicated that a particular camera focus may convey a suggestion of a particular cognitive frame in which a video-recorded confession/interrogation is initially represented. Some forensic and policy implications were discussed.


Osteogenic differentiated periodontal ligament stem cells maintain their immunomodulatory capacity.
Periodontal ligament stem cells (PDLSCs) have great potential for regenerating periodontal ligament tissue, which is involved in attaching teeth to the underlying alveolar bone. Recently, PDLSCs were characterized as having both low immunogenicity and profound immunomodulation abilities. Further, transplanted PDLSCs differentiate into osteoblasts in vivo. In the present study, we investigated the immunological characteristics of osteogenic differentiated PDLSCs. We found that PDLSCs expressed mesenchymal stem cells markers, including STRO-1 and CD146, but were negative for CD14, CD34 and CD45. RT-PCR indicated that NCAM1, MSX1 and S100A4 were expressed in PDLSCs. The cells underwent osteogenic and adipogenic differentiation when cultured in defined medium. Osteogenic differentiated PDLSCs failed to stimulate allogeneic T cell proliferation and suppressed phytohaemagglutinin-triggered T cell proliferation. Indomethacin, an inhibitor of prostaglandin E2 (PGE2) production, restored the T cell proliferation inhibited by osteogenic differentiated PDLSCs. These data confirm that osteogenic differentiated PDLSCs have low immunogenicity and demonstrate that they suppress T cell proliferation in vitro through secretion of PGE2.


[Cellular transport mechanisms for 57Co-bleomycin].
The cell-specific absorption mechanism for 57Co bleomycin and the transport behavior was examined under various parameters in an in vitro tumor cell system. The 57Co bleomycin absorption of vital Ehrlich-ascites tumor cells showed a positive time-dose-temperature correlation plus a definite indication of an active intracellular transport mechanism. Because erythrocytes, as compared to Ehrlich-ascites tumor cells, absorb almost no 57Co bleomycin, it could be concluded indirectly that active transport of 57Co bleomycin into the intracellular space is controlled by endocytosis. The additional 57Co bleomycin absorption in membrane structures was also demonstrated in examinations of an Ehrlich-ascites tumor cell membrane preparation.


Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin.
Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.


Two new species of the genus Chibiraga Matsumura, 1931 (Lepidoptera: Limacodidae) from China.
Two new species in the genus Chibiraga, C. houshuaii sp. nov. and C. yukei sp. nov., are described based on specimens collected in Yunnan Province and Sichuan Province, respectively. Illustrations depicting male adults and male genitalia are provided, along with venation patterns and a distribution map of the genus Chibiraga. COI DNA fragments of C. yukei sp. nov. and both sexes of C. banghaasi (Hering Hopp, 1927) are also depicted.


Effect of ticlopidine on the cutaneous circulation in peripheral vascular disease.
To assess the effect of ticlopidine on the cutaneous circulation, 25 patients with lower limb ischemia were investigated just before and at two hours after being given a 200 mg oral dose of ticlopidine. The transcutaneous partial pressure of oxygen (PtcO2) and the skin temperature were determined at 35 limb sites and 9 chest walls sites. Both the PtcO2 and the skin temperature were significantly increased at two hours after the administration of ticlopidine (p < 0.01). The findings suggest that ticlopidine can improve the cutaneous microcirculation in patients with peripheral vascular disease.


Prevalence and sport-related predictors of disturbed eating attitudes and behaviors: Moderating effects of sex and age.
Very few studies examined the prevalence and sport-related predictors of disturbed eating attitudes and behaviors (DEABs) among adolescents involved in sport practice, and their results are mixed and inconclusive. These inconsistencies are most likely due to their methodological heterogeneity and to the fact that none of these studies took into consideration the potentially relevant characteristics of the sport practice context. This study attempts to answer this limitation among French adolescents not involved or involved in various sports contexts defined based on their organization, leanness-centration, and competitive level. Participants were 335 adolescents involved in sport practice, and 435 adolescents not involved in any form of regular sport practice. The DEABs were measured using the Eating Attitudes Test-26. Global results do not showed any significant association between the status of the participants and DEAB. However, these results drastically changed when we considered the potential moderating role of sex and age on these relations. Indeed, sports involvement in general, and involvement in leanness and competitive sports were found to exert sex- and age-differentiated effects on the risks of presenting clinically significant levels of DEAB. This study suggests the importance of monitoring, preventive, and early intervention mechanisms within the context of practice, particularly for adolescent girls.


Bacteremic nosocomial pneumonia. Analysis of 172 episodes from a single metropolitan area.
We studied 172 episodes of bacteremia attributed to nosocomial pneumonia in 168 patients, observed in the 4 major hospitals of a single metropolitan area over a 5-yr period. Overall mortality for these patients was 58%. Deaths attributed directly to nosocomial pneumonia occurred almost exclusively in patients with serious and largely irreversible underlying diseases. These data confirm the high mortality associated with endemic hospital-acquired pneumonia. Although some deaths appear to be preventable, primarily by measures designed to reduce the risk of aspiration, analysis of the data herein raises doubts whether overall mortality can be significantly reduced by currently available measures.


[Assessment of criminal responsibility for perpetrators of homicide: analysis of 105 cases].
To explore the main factors that most influence the psychiatrists in the process of assessing the capacity for criminal for perpetrators of homicide. 105 homicide cases were retrospectively analyzed. The number of cases for no responsibility, reduced responsibility and full responsibility is 41 (39.0%), 28 (26.7%) and 36 (34.3%) respectively. The assessment of capability for criminal responsibility was significantly correlated with three major factors, they are: whether the homicide was driven by psychopathological factors (Gamma = 0.906, P = 0.000), whether the perpetrator was suffering a severe mental disorders (Gamma = 0.761, P = 0.000) and, whether the victim is the perpetrator's family member or relative (Gamma = 0.412, P = 0.000). Forensic psychiatrists take three major aspects into account in their process in assessing capacity for criminal responsibility, in a descending order, they are: was the homicide driven by pathological motivation? Was the perpetrator suffering from a severe mental disorder? Was the victim a family member or stranger?


Association between free sugars intake and early psychopathological problems.
Mental health problems are highly prevalent in childhood and adolescence and may be associated with nutritional intake. It has recently been shown that a high percentage of infants and children consume large amounts of free sugars. In this paper, we analyse the relationship between free sugar consumption at 12 and 30 months and the risk of developing psychological problems at 30 months in a community sample of 86 children evaluated longitudinally. Socio-family and anthropometric data, and the amount of free sugars consumed were collected at both ages. At 30 months, the Child Behavior Checklist 1.5-5 was administered to parents and an interview was conducted to identify psychological disorders in accordance with DC: 0-3's classification. We report a relationship between high free sugar consumption at 30 months and the concurrent presence of sleeping problems, ADHD and anxiety symptoms. However, no significant association was observed between free sugar consumption at 12 months and the subsequent development of psychological problems. Early detection of emotional and behavioural manifestations and high sugar consumption in children may help to prevent the persistence of psychological problems.


Finishing and Polishing Procedures and Glaze Application on Physical Properties of a Fine-Structure Feldspathic Ceramic.
The aim of this study was to verify the effect of finishing and polishing procedures and glaze application on biaxial strength and surface properties of milled feldspathic ceramic blocks. Forty disc-shaped samples (14 mm diameter, 1.2 mm thickness) were divided in four groups (n = 10): C (control): no finishing and polishing; FP: finishing and polishing; G: glaze; and GFP: finishing and polishing + glaze. The specimens were subject to surface gloss (glossmeter) and roughness (profilometer) tests followed by biaxial flexural strength (universal testing machine) and Vickers hardness (microhardness tester) tests. The surface morphological analysis was performed by scanning electron microscopy (n = 3). Data were submitted to normality tests with Shapiro-Wilk, and one-way ANOVA followed by Tukey's post hoc test (α = 0.05). Group C showed the lowest gloss. For the hardness test, groups C, FP, and GFP obtained the highest values without significant differences between them. Regarding the biaxial strength test, group C showed the lowest mean value. Both finishing and polishing methods (FP and GFP) showed surface properties similar or better than the control, and with higher biaxial strength.


Pathogenic Yersinia enterocolitica O:3 isolated from a hunted wild alpine ibex.
Occurrence of Yersinia spp. in wild ruminants was studied and the strains were characterized to get more information on the epidemiology of enteropathogenic Yersinia in the wildlife. In total, faecal samples of 77 red deer, 60 chamois, 55 roe deer and 27 alpine ibex were collected during 3 months of the hunting season in 2011. The most frequently identified species was Y. enterocolitica found in 13%, 10%, 4% and 2% of roe deer, red deer, alpine ibex and chamois, respectively. Interestingly, one Y. enterocolitica O:3 strain, isolated from an alpine ibex, carried the important virulence genes located on the virulence plasmid (yadA and virF) and in the chromosome (ail, hreP, myfA and ystA). Most of the Y. enterocolitica strains belonged to biotype 1A of which 14 were ystB positive. Further studies are needed to clarify the importance of alpine ibex as a reservoir of pathogenic Y. enterocolitica.


Autism, Asperger's and other oddities ... thoughts about treatment approaches.
The etiology of the Autistic Spectrum Disorders is discussed with a focus on Asperger's disorder. The manifestation of the triad of social impairment, communication impairment, and restricted repetitive behaviors and interests is discussed in terms of the various symptom phenotypes comprising these three domains. Clinical case material is used to illustrate how the treatment modality utilized should be fitted to an individual child's needs. A multimodal treatment plan is considered optimal in order to achieve a successful therapeutic outcome.


Occupational mercury vapour exposure and testicular, pituitary and thyroid endocrine function.
We have investigated the pituitary-testicular axis in a well-characterized population which was occupationally exposed to mercury vapour. Thyroid stimulating hormone and prolactin were also measured as indices of thyroid and pituitary endocrine function. We found no relation between blood or urine mercury levels or length of occupational exposure with any measurement of endocrine function. A small, but statistically significant negative correlation between serum sex-hormone binding globulin and the duration of occupational exposure to mercury was found. The physiological significance of this result is unclear.


[A Case of Advanced Gastric Cancer Presenting as Multiple Colonic Lymphoid Hyperplasia].
Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.


Probing the Interaction of Selonsertib with Human Serum Albumin: In silico and In vitro Approaches.
Selonsertib, the most recently developed selective inhibitor of apoptosis signal-regulating kinase 1. We elucidated the binding characteristics, mechanism of interaction, and dynamic behaviors of selonsertib with human serum albumin (HSA), a major circulatory transport protein. Different biophysical approaches (fluorescence quenching and isothermal titration calorimetry (ITC) were combined with various in silico techniques to examine the binding of selonsertib to HSA. Molecular docking results, analysis of molecular dynamics trajectories, and essential dynamics investigations indicated the stable binding of selonsertib to HSA. Further in vitro studies were performed to validate the observed interaction. ITC results confirmed the robust binding and high affinity of selonsertib and HSA. Likewise, the fluorescence quenching results highlighted the binding affinity of selonsertib and HSA. Collectively, our findings offer deeper insight into the binding mechanism of selonsertib and HSA, emphasizing the selonsertib-mediated structural changes within HSA, along with a comprehensive rationale for the biological transport and accumulation of selonsertib in the blood plasma. Therefore, considering the bioavailability and effectiveness of selonsertib, assessing the interactions of this inhibitor with carrier proteins is crucial to elucidate its biological processes at the molecular level. This evidence carries the considerable scientific potential for future drug design.


Adenovirus-Based Gene Therapy for Bone Regeneration: A Comparative Analysis of In Vivo and Ex Vivo BMP2 Gene Delivery.
Adenovirus-mediated gene therapy is a promising tool in bone regenerative medicine. In this work, gene-activated matrices (GAMs) composed of (1) polylactide granules (PLA), which serve as a depot for genetic constructs or matrices for cell attachment, (2) a PRP-based fibrin clot, which is a source of growth factors and a binding gel, and (3) a BMP2 gene providing osteoinductive properties were studied. The study aims to compare the effectiveness of in vivo and ex vivo gene therapy based on adenoviral constructs with the BMP2 gene, PLA particles, and a fibrin clot for bone defect healing. GAMs with Ad-BMP2 and MSC(Ad-BMP2) show osteoinductive properties both in vitro and in vivo. However, MSCs incubated with GAMs containing transduced cells showed a more significant increase in osteopontin gene expression, protein production, Alpl activity, and matrix mineralization. Implantation of the studied matrices into critical-size calvarial defects after 56 days promotes the formation of young bone. The efficiency of neoosteogenesis and the volume fraction of newly formed bone tissue are higher with PLA/PRP-MSC(Ad-BMP2) implantation (33%) than PLA/PRP-Ad-BMP2 (28%). Thus, ex vivo adenoviral gene therapy with the BMP2 gene has proven to be a more effective approach than the in vivo delivery of gene constructs for bone regeneration.


A portable electrochemiluminescence bipolar electrode array for the visualized sensing of Cas9 activity.
CRISPR/Cas9 has become a powerful tool for genomic manipulation, and the evaluation of the Cas9 activity is essential for the precise control of the CRISPR system. Herein, we develop a point-of-care platform for the rapid and visible determination of the Cas9 activity. A bipolar electrochemiluminescence (ECL) biosensor platform comprises an Au electric circuit fabricated on a glass substrate and the PDMS layer acts as a reservoir. DNA probes are then modified on electrodes and hybridization chain reaction (HCR) is applied to introduce ferrocene-labeled DNA. The CRISPR/Cas9 system can recognize the immobilized DNA probes and cleave them from the electrode surface as well as the labeled H1 and H2. Therefore, the cleavage activity is closely related to the labeled ferrocene. The modified electrode is then embodied in a closed bipolar system such that the oxidation reaction on sensing poles could be detected by the anodic ECL reactions on isolated luminescent poles due to charge balance, leading to the changes in ECL signals. This portable, integrated and convenient platform may become a meaningful tool for the discovery of a new CRISPR/Cas9 system or additional Cas9 inhibitors.


Magnetoelectric properties of A2[FeCl5(H2O)] with A = K, Rb, Cs.
The compounds A(2)[FeCl(5)(H(2)O)] with A = K, Rb, Cs are identified as new linear magnetoelectric (non-multiferroic) materials. We present a detailed investigation of their linear magnetoelectric properties through measurements of pyroelectric currents, dielectric constants and magnetization. The anisotropy of the linear magnetoelectric effect of the K-based and Rb-based compound is consistent with the magnetic point group m'm'm', already reported in literature. A symmetry analysis of the magnetoelectric effect of the Cs-based compound allows us to determine the magnetic point group mmm' and to develop a model for its magnetic structure. In addition, magnetic-field versus temperature phase diagrams are derived and compared to the closely related multiferroic (NH(4))(2)[FeCl(5)(H(2)O)].


Adherence to the Mediterranean diet in young male soccer players.
Nutrition is vital in health and sports performance by improving anthropometric-related parameters and dietary habits, especially in the youngest ages. The Mediterranean diet (MD) has been highly recognized for its positive health effects and low adverse environmental impact. We aimed to characterize adherence to the MD and analyze its association with anthropometric parameters in young soccer players. In the present study, 132 male young soccer players from under 9 to under 15 categories (aged 7 to 15 years) from a Portuguese football club participated. The Mediterranean Diet Quality Index for Children and Adolescents (KIDMED) questionnaire was applied to assess adherence to the MD. Anthropometric-related parameters, including body mass, height, triceps skinfold thickness (TSKF), suprailiac skinfold thickness (SISKF), body mass index (BMI) and body fat percentage (%BF), were determined. The differences between groups were performed accordingly to normal and non-normal distribution. Spearman's correlations were performed to analyze the hypothetical correlation between KIDMED and BMI. Players reached an average KIDMED score of 8.36 ± 1.92, showing that 68.2% (n = 90) reached high adherence to the MD, 31.1% (n = 41) had moderate adherence to the MD, and 0.78% (n = 1) had poor adherence to the MD. When the analysis was made for age group and BMI classification, no significant differences were observed in adherence to the MD. Considering the main characteristics of the MD, 50.8% consumed fruit (vs. 49,2%), 52.3% consumed vegetables (vs. 47,7%), and only 20% consumed oleaginous dried fruits (vs. 80%). Dairy consumption throughout the day was 49,2% (vs. no: 50,8%). Data from the present study showed that many soccer players adhered to the MD, and no differences were observed for age group or BMI classification.


Does Preoperative Statin Exposure Reduce Prosthetic Joint Infections and Revisions Following Total Joint Arthroplasty?
The pleiotropic effects of statins extend beyond managing cardiovascular health and are suggested to modulate Staphylococcus aureus biofilm formation with prosthetic joint infection (PJI) reduction. However, a large analysis of statin use prior to total joint arthroplasty (TJA) to determine infection and revision risk is lacking. We specifically evaluated: 90-day to two-year (1) prosthetic joint infection (PJIs); (2) revisions; and (3) respective risk factors. We queried a national, all-payer database for patients undergoing either TKA or THA between 2010-2020. Chronic statin exposure was defined as >3 prescriptions filled within one-year prior to TJA (statin users). A control cohort of patients undergoing TJA without history of statin use prior was identified (statin naïve). Cohorts were matched 1:1 based on demographics and comorbidities (TKA: n=579,136; THA: n=202,092). Multivariate logistic regression was performed to evaluate risk factors for PJIs and revisions. Among TKA recipients, statin users had lower incidence of PJIs at one year (0.36 vs. 0.39%) to two years (0.45 vs. 0.49%) compared to the statin naïve (all, p≤0.007). Similarly, statin users had lower incidence of one- to two-year revisions (all, p≤0.048). Among THA recipients, statin users had lower incidence of PJIs at 90 days (0.37 vs. 0.45%) to two years (2% vs. 2.14%) (all, p<0.001). Similar trends were observed for 90-day to two-year revisions (all, p≤0.022). Statin use was independently associated with decreased odds of PJIs and revisions by one year. Statin use is associated with a reduced risk of PJIs and revisions from one to two years following TJA. It may be worthwhile to ensure patients take statin therapy if indicated for previously established cardiovascular guidelines.


Shape and Dynamics of Adhesive Cells: Mechanical Response of Open Systems.
Cell adhesion is an essential biological process. However, previous theoretical and experimental studies ignore a key variable, the changes of cellular volume and pressure, during the dynamic adhesion process. Here, we treat cells as open systems and propose a theoretical framework to investigate how the exchange of water and ions with the environment affects the shape and dynamics of cells adhered between two adhesive surfaces. We show that adherent cells can be either stable (convex or concave) or unstable (spontaneous rupture or collapse) depending on the adhesion energy density, the cell size, the separation of two adhesive surfaces, and the stiffness of the flexible surface. Strikingly, we find that the unstable states vanish when cellular volume and pressure are constant. We further show that the detachments of convex and concave cells are very different. The mechanical response of adherent cells is mainly determined by the competition between the loading rate and the regulation of the cellular volume and pressure. Finally, we show that as an open system the detachment of adherent cells is also significantly influenced by the loading history. Thus, our findings reveal a major difference between living cells and nonliving materials.


The Epidermal Environment's Influence on the Dermal Environment in Response to External Stress.
The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.


Comparison of methods for determining probenecid in tablets and flavored oral suspensions containing ampicillin.
Several methods for quantitating probenecid were compared: USP XIX method for probenecid in tablets, a modified USP extraction method for probenecid in tablets, a new column extraction method for probenecid in tablets and oral suspensions containing ampicillin, and a high pressure liquid chromatographic (HPLC) method for probenecid in tablets and oral suspensions containing antibiotics. The first 3 methods were satisfactory for probenecid in bulks and tablets but proved unsatisfactory for oral suspeonsions containing flavors. The flavors gave positive interference for probenecid in oral suspensions. The HPLC method, although more time-consuming, separated probenecid from excipients, thus eliminating positive interference from flavors.


[Studies on DNA-protein interactions in the HS3 of the human beta-LCR].
Upstream of the human epsilon-globin gene is the Locus Control Region (LCR) of the human beta-globin cluster, which consists of four DNase-I hypersensitive sites(HS1-HS4). It has been reported in transgenic experiments that HS3 preferentially regulates epsilon-globin gene expression. In order to elucidate the regulatory function of HS3 in the expression of globin gene, nuclear extracts from mouse hematopoietic tissues at several developmental stages were prepared and the binding of the nuclear factors to HS3 was analysed by using electrophoresis mobility shift assay(EMSA). Our results showed that the binding patterns of HS3 with nuclear extracts of mouse hematopoietic tissues at day 13 and day 18 of gestation were completely different; furthermore, by Southwestern Blot, the distinction between both stages was also demonstrated. It has been known that GATA and CACCC binding motifs are contained within HS3 core region. Using competitive gel-retardation assay, we found that no shift bands could be competed by using CACCC motif as a competitor. However one shift band at day 13 and day 18 of gestation could be competed respectively by using GATA motif as a competitor. We suggested that the shift bands, which could not be competed by both motifs, might be novel and stage-specific factors. In addition, by using Western Blot, we demonstrated that the two shift bands at day 13 and day 18 of gestation, competed by GATA motif, were GATA-2 and GATA-1 respectively: GATA-1 was expressed in mouse hematopoietic tissues at day 18 of gestation and not expressed at day 13 of gestation; however, GATA-2 was only expressed in mouse hematopoietic tissues at day 13 of gestation. According to these results, we speculated that HS3 might play an important role in regulation of stage-specific expression of globin genes through interaction between stage-specific nuclear factors and HS3.


Organizational commitment to professional practice models.
Magnet hospitals must show evidence of professional practice models. A professional practice organizational environment is necessary, but not sufficient, to create professional practice models. The authors analyze the relationship between a professional practice environment and a professional practice and explore organizational commitments required to ensure professional practice at the unit level.


Long-term hemodialysis at reduced dialysate flow rates.
20 stable hemodialysis patients were maintained on a dialysate flow rate of 300 ml/min (QD 300) to determine the safety of prolonged reductions in dialysate flow rate. After 24 months, QD 300 compared to QD 500 resulted in no change in weight, blood pressure, BUN, hematocrit, creatinine, bicarbonate, potassium, cholesterol, or calcium. Serum phosphate concentration increased between month 13 and month 17 but then stabilized. No adverse symptoms developed. EEGs and motor nerve conduction studies following 24 months at QD 300 were normal. We conclude that QD 300 does not impair dialysis efficiency for most small molecules and saves $1.38 per patient per dialysis.