Assisted reproductive technology and risk of asthma and allergy in the offspring: protocol for a systematic review and meta-analysis.
The use of assisted reproductive technology (ART) procedures has increased globally over the last three decades. Recent observational studies suggest that children conceived through ART may be at increased risk of asthma and atopic disease compared with children conceived naturally, but findings are mixed. We aim to synthesise the evidence on the impact of ART on the risk of asthma and atopic disease in the offspring. We will identify relevant studies by searching MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, CINAHL, Scopus, Google Scholar, AMED, Global Health, PsychINFO, CAB International and the WHO Global Health Library from 1978 to 2016. We will locate additional studies through searching databases of the proceedings of international conferences, contacting international experts in the field, and searching the references cited in identified studies. We will include analytic observational studies (cohort studies, case-control studies and cross-sectional studies) that have investigated the impact of any type of ART on offspring's asthma and atopic disease. Screening of identified records, data extraction from eligible studies and risk of bias assessment of eligible studies will be independently undertaken by two reviewers, with arbitration by a third reviewer. The Effective Public Health Practice Project will be employed for risk of bias assessment. Estimates from studies judged to be clinically, methodologically and statistically homogeneous will be synthesised using random-effects meta-analysis. As this study is based solely on the published literature, no ethics approval is required. We will publish our findings in a peer-reviewed scientific journal and present the results at national and international scientific conferences. We will register a detailed protocol for the review with the International Prospective Register of Systematic Reviews (PROSPERO) prior to starting the review.


TNF-alpha inhibits flow and insulin signaling leading to NO production in aortic endothelial cells.
Endothelial cells release nitric oxide (NO) acutely in response to increased "flow" or fluid shear stress (FSS), and the increase in NO production is correlated with enhanced phosphorylation and activation of endothelial nitric oxide synthase (eNOS). Both vascular endothelial growth factor and FSS activate endothelial protein kinase B (PKB) by way of incompletely understood pathway(s), and, in turn, PKB phosphorylates eNOS at Ser-1179, causing its activation. In this study, we found that either FSS or insulin stimulated insulin receptor substrate-1 (IRS-1) tyrosine and serine phosphorylation and increased IRS-1-associated phosphatidylinositol 3-kinase activity, phosphorylation of PKB Ser-473, phosphorylation of eNOS Ser-1179, and NO production. Brief pretreatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) inhibited the above described FSS- or insulin-stimulated protein phosphorylation events and almost totally inhibited FSS- or insulin-stimulated NO production. These data indicate that FSS and insulin regulate eNOS phosphorylation and NO production by overlapping mechanisms. This study suggests one potential mechanism for the development of endothelial dysfunction in disease states with alterations in insulin regulation and increased TNF-alpha levels.


Prevalence and Impact of Adverse Childhood Experiences on Chicago Public School Students in the Youth Risk Behavior Survey.
Adverse Childhood Experiences (ACEs) can impair health and other outcomes. To obtain district-level data about the prevalence and impact of ACEs in Chicago Public Schools (CPS), we advocated for CPS to add a short ACE screener to the 2017 Youth Risk Behavior Survey (YRBS) and analyzed the results. Responses to the screener were scored zero, one, or two ACEs. Student scores for violence and victimization, substance use, sexual health risk, mental health, housing insecurity, physical health, grades, and multiple risk/high vulnerability (those students in the top 20% of affirmative responses) were correlated with ACE scores for categories and individual items. Among 1883 student respondents (response rate 73%), there were 17.8% affirmative responses for experiencing physical abuse and 19.8% for witnessing domestic violence; 20% reported at least one ACE and 8% both. A significant dose-response was found for behaviors, experiences, and sleep by ACE scores. ACEs were common among CPS high school students and associated with many negative behavior and health-related outcomes. Increased awareness of ACEs and their impact among all school personnel can inform and strengthen the development of safer, more supportive, and trauma-informed schools that help all students and families thrive.


FRAGILE X SYNDROME: PSYCHIATRIC MANIFESTATIONS, ASSESSMENT AND EMERGING THERAPIES.
Fragile X Syndrome (FXS), the most common inherited cause of intellectual disabilities, is an X-linked dominant disorder caused by the amplification of a CGG repeat in the 5' untranslated region of the fragile X mental retardation gene 1 (FMR1). Prevalence estimates of the disorder are approximately 1/3600. Psychiatric manifestations of the disorder include anxiety, attention deficit hyperactivity disorder, autism, mood instability and aggression. In this article we review the above psychiatric manifestations and challenges to accurate assessment. We also discuss how the neurobiological underpinnings of these symptoms are beginning to be understood and can help guide treatment.


Methods in Nutrition & Gut Microbiome Research: An American Society for Nutrition Satellite Session [13 October 2022].
The microbial cells colonizing the human body form an ecosystem that is integral to the regulation and maintenance of human health. Elucidation of specific associations between the human microbiome and health outcomes is facilitating the development of microbiome-targeted recommendations and treatments (e.g., fecal microbiota transplant; pre-, pro-, and post-biotics) to help prevent and treat disease. However, the potential of such recommendations and treatments to improve human health has yet to be fully realized. Technological advances have led to the development and proliferation of a wide range of tools and methods to collect, store, sequence, and analyze microbiome samples. However, differences in methodology at each step in these analytic processes can lead to variability in results due to the unique biases and limitations of each component. This technical variability hampers the detection and validation of associations with small to medium effect sizes. Therefore, the American Society for Nutrition (ASN) Nutritional Microbiology Group Engaging Members (GEM), sponsored by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), hosted a satellite session on methods in nutrition and gut microbiome research to review currently available methods for microbiome research, best practices, as well as tools and standards to aid in comparability of methods and results. This manuscript summarizes the topics and research discussed at the session. Consideration of the guidelines and principles reviewed in this session will increase the accuracy, precision, and comparability of microbiome research and ultimately the understanding of the associations between the human microbiome and health.


Temperature-driven evolution of ceria-zirconia-supported AuPd and AuRu bimetallic catalysts under different atmospheres: insights from IL-STEM studies.
The evolution of the structure and composition of the system of particles in two Ce0.62Zr0.38O2-supported bimetallic catalysts based on Au and a 4d metal (Ru or Pd) under high temperature conditions and different reducing and oxidizing environments has been followed by means of Identical Location Scanning Transmission Electron Microscopy (IL-STEM). As an alternative to in situ microscopy, this technique offers valuable insights into the structural modifications occurring in chemical environments with the characteristics of a macro-scale reactor. By tracking exactly the same areas on a large number of metallic entities, it has been possible to reveal the influence of particle size and the nature of the redox environment on the temperature-driven mobilization of the different metals involved. Thus, oxidizing environments evidenced a much higher capacity to mobilize the three metals, preferentially Au. Moreover, the typical storage conditions (under air) of catalysts during the prolonged exposure time has been proved to induce significant modifications in these bimetallic systems, even at room temperature. Regardless of the type of redox environment, bimetallic systems showed better thermal resistance, which demonstrates a beneficial effect of the second metal. In summary, IL-STEM is an invaluable and complementary methodology for characterizing heterogeneous catalysts under realistic reaction conditions and is within the reach of most laboratories.


Life-threatening allergic vasculitis after clipping an unruptured aneurysm: Case report, weighing the risk of nickel allergy.
This case report represents one of the estimated 17,000 aneurysms clipped annually in the United States, often with nickel-containing clips. The authors highlight the development of life-threatening allergic vasculitis in a 33-year-old woman after aneurysm clipping. After suffering subarachnoid hemorrhage, the patient had coil embolization at another facility for rupture of a right internal carotid artery (ICA) aneurysm. An incidental finding, an unruptured left posterior communicating artery aneurysm unamenable to coiling, was then successfully clipped via a left pterional craniotomy. Arriving in our emergency department 11 days later, she progressively declined during the next weeks, facing deteriorating clinical status (i.e. seizures) and additional infarctions in the left frontal lobe, midline shift, and new infarctions in the bilateral frontal lobe, right sylvian, right insular regions, and posterior cerebral artery distribution. During decompressive surgery, biopsy findings raised the possibility of lymphocytic vasculitis; consultations with rheumatology, allergy, and immunology specialists identified that our patient had a nickel allergy. After reoperation to replace the nickel-containing clip with one of a titanium alloy, the patient had an uncomplicated postoperative course and was discharged 6 days later to a rehabilitation facility. Nickel-related allergies are more common than appreciated, affecting up to 10% of patients. Fortunately, severe reactions are rare; nevertheless, vascular neurosurgeons should be aware of this potential complication when using cobalt alloy aneurysms clips. The use of titanium alloy clips eliminates this risk.


HDR interstitial perineal implant for locally advanced or recurrent uterine cervix cancer.
To evaluate whether high-dose-rate (HDR) interstitial perineal implants can effectively eradicate residual tumor or recurrent tumor in uterine cervix cancer after complete radiation treatment. This method of treatment was commenced in January 2002, and four advanced stage and four uterine cervix cancer (UCC) recurrences were admitted for this study. All untreated stage II bulky mass and IIIB patients received 50 Gy external beam radiotherapy (EBR) to the whole pelvis prior to the interstitial perineal implant. No EBR was given to recurrent UCC. Brachytherapy was delivered using Martinez Universal Perineal Interstitial Template (MUPIT) and 192Ir HDR. This implant will only be done if residual disease on the parametria was bimanually palpable or was proven by CT scan or MRI. The dose of interstitial brachytherapy boost to the parametria was 17 to 30 Gy, and treatment days ranged from 42 to 64 days. Uterine recurrences were found on the uterine cervix and/or parametria. The dose delivered by this implant ranged from 6 to 16 Gy and encompassed either uterus or vaginal stump and both parametria. Total treatment days ranged from 1 to 2 days. This short-term study showed that almost all tumors were locally controlled when the study was closed (1 to 15 months). One distant metastasis was found. No significant morbidity has been identified until now. HDR 192Ir interstitial perineal implants were proven to be effective in eradicating tumor cells in advanced stage UCC and recurrent disease with no significant morbidity.


Dissociation energies and potential energy functions for the ground X (1)Σ(+) and "avoided-crossing" A (1)Σ(+) states of NaH.
A direct-potential-fit analysis of all accessible data for the A (1)Σ(+) - X (1)Σ(+) system of NaH and NaD is used to determine analytic potential energy functions incorporating the correct theoretically predicted long-range behaviour. These potentials represent all of the data (on average) within the experimental uncertainties and yield an improved estimate for the ground-state NaH well depth of 𝔇e = 15797.4 (±4.3) cm(-1), which is ∼20 cm(-1) smaller than the best previous estimate. The present analysis also yields the first empirical determination of centrifugal (non-adiabatic) and potential-energy (adiabatic) Born-Oppenheimer breakdown correction functions for this system, with the latter showing that the A-state electronic isotope shift is -1.1(±0.6) cm(-1) going from NaH to NaD.


Anti-Bordetella bronchiseptica effects of targeted bacteriophages via microbiome and metabolic mediated mechanisms.
Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the impact of a novel targeted bacteriophage in controlling B. bronchiseptica challenge (BBC) in an experimental design involving five distinct treatment groups: NC (no challenge), PC (BBC challenge), BF (108 pfu bacteriophage/kg diet + BBC), BN (2 × 107 pfu/day bacteriophage by nasal spray + BBC), and AT (antibiotic + BBC). The experiment was conducted for 2 weeks. The highest turbinate score was observed in the PC. The BF treatment showed higher plasma IL (interleukine)-1β and IL-6 compared with the BN and AT treatments. Plasma concentrations of IL-1β were increased in the BF pigs compared with the BN, AT, and NC. Among the BBC groups, the PC treatment exhibited a higher abundance of Staphylococcus. aureus and B. bronchiseptica in the lung. A lower S. aureus, Streptococcus. suis, and B. bronchiseptica colonization was detected in the AT compared with the BF and BN treatments. The BF showed lower plasma zonulin compared with the BN and AT. A higher plasma concentration of superoxide dismutase was observed in the BF and AT compared with PC and BN. The BN influenced the glycine, serine-threonine metabolism; glycerolipid metabolism; glyoxylate-dicarboxylate metabolism; and arachidonic acid metabolism compared with the NC. In conclusion, nasal-sprayed bacteriophage effectively controlled B. bronchiseptica infection, however, their efficiency was lower than the antibiotic.


Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group.
Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months. Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001). Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.


The unlikelihood effect: When knowing more creates the perception of less.
People face increasingly detailed information related to a range of risky decisions. To aid individuals in thinking through such risks, various forms of policy and health messaging often enumerate their causes. Whereas some prior literature suggests that adding information about causes of an outcome increases its perceived likelihood, we identify a novel mechanism through which the opposite regularly occurs. Across seven primary and six supplementary experiments, we find that the estimated likelihood of an outcome decreases when people learn about the (by- definition lower) probabilities of the pathways that lead to that outcome. This "unlikelihood" bias exists despite explicit communication of the outcome's total objective probability and occurs for both positive and negative outcomes. Indeed, awareness of a low-probability pathway decreases subjective perceptions of the outcome's likelihood even when its addition objectively increases the outcome's actual probability. These findings advance the current understanding of how people integrate information under uncertainty and derive subjective perceptions of risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Reduced cerebral vascularization in experimental neuronopathic Gaucher disease.
The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates, and the non-acylated congener β-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here, we report strikingly diminished cerebral microvascular density in a murine model of disease, and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β-glucosylsphingosine. Further in vitro studies confirmed a concentration-dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of β-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Effect of supplementing rumen-protected methionine on production and nitrogen excretion in lactating dairy cows.
Two 4 x 4 Latin square trials (4-wk periods; 16 wk total) were conducted to see whether supplementing rumen-protected Met (RPM; fed as Mepron) would allow feeding less crude protein (CP), thereby reducing urinary N excretion, but without losing production. In trial 1, 24 Holsteins were fed 4 diets as total mixed rations containing [dry matter (DM) basis]: 18.6% CP and 0 g of RPM/d; 17.3% CP and 5 g of RPM/d; 16.1% CP and 10 g of RPM/d; or 14.8% CP and 15 g of RPM/d. Dietary CP was reduced by replacing soybean meal with high-moisture shelled corn. All diets contained 21% alfalfa silage, 28% corn silage, 4.5% roasted soybeans, 5.8% soyhulls, 0.6% sodium bicarbonate, 0.5% vitamins and minerals, and 27% neutral detergent fiber. There was no effect of diet on intake, weight gain, or yields of protein, lactose, and solids-not-fat. However, production was greater at 17.3% CP plus RPM and 16.1% CP plus RPM than on the other 2 diets. Apparent N efficiency (milk N:N intake) was greatest on the lowest CP diet containing the most RPM. Linear reductions in milk urea N and urinary N excretion were observed with lower dietary CP. In trial 2, 32 Holsteins were fed 4 diets as total mixed rations, formulated from ingredients used in trial 1 and containing 16.1 or 17.3% CP with 0 or 10 g of RPM/d. On average, cows were calculated to be in negative N balance on all diets because of lower than expected DM intake. There was no effect of RPM supplementation on any production trait. However, higher CP gave small increases in yields of milk, protein, and solids-not-fat and tended to increase DM intake and lactose yield. Apparent N efficiency was greater, and milk urea nitrogen was lower, on 16.1% CP. In trial 1, feeding lower CP diets supplemented with RPM resulted in improved N efficiency and reduced urinary N excretion. However, in trial 2, reducing dietary CP from 17.3 to 16.1% reduced milk secretion, an effect that was not reversed by RPM supplementation at low DM intakes when cows were apparently mobilizing body protein.


Digital quasi-phase-matched two-color nonvolatile holographic storage.
Unwanted erasure during readout of holographic data can be reduced or eliminated by use of a different wavelength for reading than that which was used for writing. To prevent distortion and Bragg mismatch that would be unacceptable for digital data storage, one can format data to account for the wavelength difference. Techniques to format data and the results of this formatting are presented. Varying the formatting parameters is investigated to optimize diffraction efficiency.


Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL).
Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12 mg/kg, n = 5), and (c) VRC-TEMPOL treatment (250 mg/kg, n = 5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning.


Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual-Stage Activity.
Increasing reports of multidrug-resistant malaria parasites urge the discovery of new effective drugs with different chemical scaffolds. Protein kinases play a key role in many cellular processes such as signal transduction and cell division, making them interesting targets in many diseases. Protein kinase 7 (PK7) is an orphan kinase from the Plasmodium genus, essential for the sporogonic cycle of these parasites. Here, we applied a robust and integrative artificial intelligence-assisted virtual-screening (VS) approach using shape-based and machine learning models to identify new potential PK7 inhibitors with in vitro antiplasmodial activity. Eight virtual hits were experimentally evaluated, and compound LabMol-167 inhibited ookinete conversion of Plasmodium berghei and blood stages of Plasmodium falciparum at nanomolar concentrations with low cytotoxicity in mammalian cells. As PK7 does not have an essential role in the Plasmodium blood stage and our virtual screening strategy aimed for both PK7 and blood-stage inhibition, we conducted an in silico target fishing approach and propose that this compound might also inhibit P. falciparum PK5, acting as a possible dual-target inhibitor. Finally, docking studies of LabMol-167 with P. falciparum PK7 and PK5 proteins highlighted key interactions for further hit-to lead optimization.


Hepatic Injury in Patients With COVID-19.
Coronavirus disease 2019 (COVID-19) has infected over 2 million people worldwide over the course of just several months. Various studies have highlighted that patients infected with COVID-19 may develop various degrees of liver injury. Here, we discuss the impact of underlying liver disease and manifestations of hepatic injury with COVID-19. We also review mechanisms of hepatic injury. We searched the database PubMed for all studies focused on hepatic injury in COVID-19. We identified 13 studies that assessed the impact of underlying liver disease in patients infected with COVID-19 (N=3046). Underlying liver disease was one of the most common known comorbid categories in patients infected with COVID-19. Overall, 25% of the patients identified from the 13 studies had hepatic injury. Twenty-one percent and 24% had elevated alanine transaminase and aspartate transaminase values, respectively. Nine percent of the patients had elevated total bilirubin values. Ten of the 13 studies assessed COVID-19 acuity with severity of hepatic injury. In 9 of the 10 studies, clinical outcomes were worse with hepatic injury. Liver injury is highly prevalent in patients that present with COVID-19. Since the liver is one of the most affected organs outside of the respiratory system in COVID-19, more intensive surveillance is warranted for severe cases, particularly among those with pre-existing advanced liver disease.


Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas.
The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor- and cell line-derived global histone modification analyses and epigenetic drug treatment in vitro We found that DNA methylation patterns identify divergent patient subgroups with respect to survival and clinicobiologic variables, including amplified MYCN Transcriptome integration and histone modification-based definition of enhancer elements revealed intragenic enhancer methylation as a mechanism for high-risk-associated transcriptional deregulation. Furthermore, in high-risk neuroblastomas, we obtained evidence for cooperation between PRC2 activity and DNA methylation in blocking tumor-suppressive differentiation programs. Notably, these programs could be re-activated by combination treatments, which targeted both PRC2 and DNA methylation. Overall, our results illuminate how epigenetic deregulation contributes to neuroblastoma pathogenesis, with novel implications for its diagnosis and therapy. Cancer Res; 76(18); 5523-37. ©2016 AACR.


The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure.
The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR.


The efficacy of endoscopic third ventriculostomy in children 1 year of age or younger: A systematic review and meta-analysis.
Hydrocephalus is a major cause of morbidity in the pediatric population, with potentially severe consequences if left untreated. Two viable strategies for management of non-communicating hydrocephalus are endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting. However, there is uncertainty over the safety and efficacy of ETV in younger infants aged 1 year or below. In this systematic review, we aim to elucidate the success rate and procedural risks of ETV in this age group. A multi-database (PubMed, Embase, Web of Science) literature search between January 1990 and April 2018 was performed in accordance with PRISMA guidelines. Eligible studies were included if they (i) examined non-communicating hydrocephalus; (ii) quantified the success/failure rates of ETV; and (iii) assessed outcomes in children 1 year of age or younger. A total of 19 articles with 399 patients were eligible for inclusion. Mean age at procedure was 4.2 months (range 34 weeks gestation to 12 months), with 116 females and 143 males. Commonest underlying aetiology was congenital aqueductal stenosis (AS) (60.4%). Remaining causes included post-haemorrhagic, post-infection, Chiari malformations, malignancies and others. Overall and AS mean success rates were 51.6% and 56.5% respectively. Overall complication rate was 10.0%, consisting mainly of CSF leak, infection, and haemorrhage. Younger age was significantly associated with poorer ETV success rate when divided into <6 months and 6-12 months of age (44.4 vs 66.7%; p = 0.0007). Underlying pathology had no significant association with ETV outcome when divided into AS and other pathologies (p = 0.53). Age is significantly associated with ETV success rates. Pathology-dependent effects were not found in this age group. Despite a lower ETV success rate at younger ages (44.4 vs 66.7%), it offers a comparable safety profile that is independent of age. ETV remains a viable treatment option for non-communicating hydrocephalus for infants aged 1 year or younger.


[Usefulness of bone scintigraphy for staging in a case of histiocytosis of the temporal bone].
We present the case of a 43-year-old man diagnosed of insipid diabetes and hypogonadotropic hypogonadism in whom a right temporal bone lesion was observed in the control MRI, thus leading to his admission. A bone scintigraphy with 99mTc-HMDP showed increased uptake in the right temporal region with sphenoidal extension, coinciding with the MRI. In addition, increased uptake having less intensity and size was observed in the left temporal region. A biopsy on the newly appearing mouth ulcers in the jugal mucous was performed and showed Langerhan's cells, the diagnosis of histiocytosis X being confirmed. Six months later a new MRI indicated disease progression with bilateral temporal involvement. The bone scan findings in this case provided a more exact extension diagnosis of the disease than the MRI.


Interference from multiple trapped colloids in an optical vortex beam.
Laguerre-Gaussian (LG) beams are important in optical micromanipulation. We show that optically trapped microparticles within a monochromatic LG beam may lead to the formation of unique intensity patterns in the far field due to multiple interference of the forward scattered light from each particle. Trapped colloids create far field interference that exhibits distinct spiral wave patterns that are directly correlated to the helicity of the LG beam. Using two trapped particles, we demonstrate the first microscopic version of a Young's slits type experiment and detect the azimuthal phase variation around the LG beam circumference. This novel technique may be implemented to study the relative phase and spatial coherence of two points in trapping light fields with arbitrary wavefronts.


Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment.
Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.


Efficacy of an internet-based learning module and small-group debriefing on trainees' attitudes and communication skills toward patients with substance use disorders: results of a cluster randomized controlled trial.
To examine whether an Internet-based learning module and small-group debriefing can improve medical trainees' attitudes and communication skills toward patients with substance use disorders (SUDs). In 2011-2012, 129 internal and family medicine residents and 370 medical students at two medical schools participated in a cluster randomized controlled trial, which assessed the effect of adding a two-part intervention to the SUDs curricula. The intervention included a self-directed, media-rich Internet-based learning module and a small-group, faculty-led debriefing. Primary study outcomes were changes in self-assessed attitudes in the intervention group (I-group) compared with those in the control group (C-group) (i.e., a difference of differences). For residents, the authors used real-time, Web-based interviews of standardized patients to assess changes in communication skills. Statistical analyses, conducted separately for residents and students, included hierarchical linear modeling, adjusted for site, participant type, cluster, and individual scores at baseline. The authors found no significant differences between the I- and C-groups in attitudes for residents or students at baseline. Compared with those in the C-group, residents, but not students, in the I-group had more positive attitudes toward treatment efficacy and self-efficacy at follow-up (P<.006). Likewise, compared with residents in the C-group, residents in the I-group received higher scores on screening and counseling skills during the standardized patient interview at follow-up (P=.0009). This intervention produced improved attitudes and communication skills toward patients with SUDs among residents. Enhanced attitudes and skills may result in improved care for these patients.


[Simultaneous quantification of soluble fibrin and D-dimer in blood plasma for the assessment of the threat of thrombosis].
Soluble fibrin and D-dimer are the most specific markers of blood coagulation cascade and the threat of thrombosis. Two immunoassay test systems were designed using the fibrin-specific and D-dimer-specific monoclonal antibodies. The clinical trials of the test systems were carried out in Ukraine. The high informative value of soluble fibrin quantification as a prognostic indicator of the threat of thrombosis associated with hip replacement and endoprosthetics of the abdominal aorta was shown. Independent D-dimer quantification is less informative. Simultaneous quantification of soluble fibrin and D-dimer before operation and at different time intervals after it is required for the prediction of postoperative thrombotic complications and monitoring the efficiency of antithrombotic therapy. Only in this case it is possible to get information about the state of the balance between blood coagulation and fibrinolytic systems, and determine the degree of the threat of thrombosis.


Differences in clinical experiences of ADN and BSN students.
Prior research has suggested that clinical experience for nursing students is stressful. Concern about making an error and harming the patient, limited knowledge and skills for practice, and difficulties in interacting with the teacher and others in the clinical setting are some of the stressors reported by students. Few studies have compared these stresses and the clinical experiences in general between students in associate degree (ADN) and baccalaureate (BSN) nursing programs. The purposes of this research were to compare the clinical experiences of ADN and BSN students at different levels in the programs and describe these experiences from the students' perspectives. As such, both quantitative and qualitative data were collected from 415 students in ADN and BSN programs in the Midwest. The ADN students reported significantly higher stress in clinical practice than BSN students (t = 2.16, p < .05). The stress experienced by ADN and BSN students in clinical practice increased as they progressed through the programs. The semester prior to graduation was the most stressful time in terms of clinical practice for both ADN and BSN students. The instructor was the predominant stressor reported by students in ADN programs across all levels of the curriculum. Among BSN students, the most prevalent stresses were coping with demands associated with patient care and the clinical teacher. The findings highlight the important role of the clinical faculty in both types of nursing programs.


Femtosecond Nd:glass oscillator operating in normal dispersion regime.
A diode-pumped, prismless Nd:glass laser oscillator, mode-locked by a semiconductor saturable absorber, was stabilized against self-Q-switching by using a phase-mismatched second harmonic crystal. Furthermore, negative-index cascaded second-order nonlinearity provided the soliton shaping mechanism with normal intracavity dispersion. Nearly Fourier-limited pulses as short as 520 fs were obtained.


Mechanism of choline O-sulphate utilization in fungi.
1. The position of the enzyme blocks in a number of parathiotrophic mutants of Aspergillus nidulans A 69 and mutants A and C of a biotinless mutant of Aspergillus nidulans were examined by nutritional and heterokaryosis experiments and by assay in vitro of enzyme systems and specific enzymes. 2. The mutants were in five groups: A and C blocked at sulphate transport; gamma at ATP sulphurylase; iota at adenosine 5'-sulphatophosphate kinase; eta at the adenosine 3'-phosphate 5'-sulphatophosphate reductase system; alpha, beta and zeta between sulphite and thiosulphate. 3. The ability of the various mutants to synthesize choline O-sulphate in vivo and in vitro and to utilize choline O-sulphate as a source of sulphur indicated that the utilization of endogenously formed choline O-sulphate involved the splitting off of inorganic sulphate, which was then reduced. 4. Choline O-sulphate acted as a source of choline for cholineless strains of Neurospora crassa, suggesting that choline O-sulphate breakdown occurred by simple hydrolysis involving a choline sulphatase. 5. After de-repression of mycelia by growing for a period on a sulphur-free medium the presence of choline sulphatase in physiologically significant amounts was demonstrated in all the A. nidulans strains tested. 6. Choline O-sulphate is transported across the mycelial wall by a mechanism different to that responsible for inorganic sulphate transport.


Controversies and advances in adrenal venous sampling in the diagnostic workup of primary aldosteronism.
Adrenal venous sampling (AVS) is a key part of the diagnostic workup of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. Although AVS is a well-established procedure, many aspects remain controversial, including optimal patient selection for the procedure and exactly how AVS is performed and interpreted. Despite the controversies, a growing body of evidence supports the use of AVS in most patients with primary aldosteronism, though some specific patient groups may be able to forego AVS and proceed directly to treatment. Although AVS remains a difficult procedure, success rates may be improved with the use of advanced CT imaging techniques and/or rapid cortisol assays. New advances in nuclear imaging and steroid profiling may also offer alternatives or adjuncts to AVS in the future.


Cricothyrotomy technique using gum elastic bougie is faster than standard technique: a study of emergency medicine residents and medical students in an animal lab.
The objective was to compare time to completion, failure rate, and subjective difficulty of a new cricothyrotomy technique to the standard technique. The new bougie-assisted cricothyrotomy technique (BACT) is similar to the rapid four-step technique (RFST), but a bougie and endotracheal tube are inserted rather than a Shiley tracheostomy tube. This was a randomized controlled trail conducted on domestic sheep. During a 3-month period inexperienced residents or students were randomized to perform cricothyrotomy on anesthetized sheep using either the standard technique or the BACT. Operators were trained with an educational video before the procedure. Time to successful cricothyrotomy was recorded. The resident or student was then asked to rate the difficulty of the procedure on a five-point scale from 1 (very easy) to 5 (very difficult). Twenty-one residents and students were included in the study: 11 in the standard group and 10 in the BACT group. Compared to the standard technique, the BACT was significantly faster with a median time of 67 seconds (interquartile range [IQR] = 55-82) versus 149 seconds (IQR = 111-201) for the standard technique (p = 0.002). The BACT was also rated easier to perform (median = 2, IQR = 1-3) than the standard technique (median = 3, IQR = 2-4; p = 0.04). The failure rate was 1/10 for the BACT compared to 3/11 for the standard method (p = NS). This study demonstrates that the BACT is faster than the standard technique and has a similar failure rate when performed by inexperienced providers on anesthetized sheep.


Obstructive sleep apnoea causes transient and sustained systemic hypertension.
Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy.


Accessing the +IV Oxidation State in Molecular Complexes of Praseodymium.
Out of the 14 lanthanide (Ln) ions, molecular complexes of Ln(IV) were known only for cerium and more recently terbium. Here we demonstrate that the +IV oxidation state is also accessible for the large praseodymium (Pr) cation. The oxidation of the tetrakis(triphenysiloxide) Pr(III) ate complex, [KPr(OSiPh3)4(THF)3], 1-PrPh, with [N(C6H4Br)3][SbCl6], affords the Pr(IV) complex [Pr(OSiPh3)4(MeCN)2], 2-PrPh, which is stable once isolated. The solid state structure, UV-visible spectroscopy, magnetometry, and cyclic voltammetry data along with the DFT computations of the 2-PrPh complex unambiguously confirm the presence of Pr(IV).


Synchronized oscillations in swarms of nematode Turbatrix aceti.
There is a recent surge of interest in the behavior of active particles that can at the same time align their direction of movement and synchronize their oscillations, known as swarmalators. While theoretical and numerical models of such systems are now abundant, no real-life examples have been shown to date. We present an experimental investigation of the collective motion of the nematode Turbatrix aceti that self-propel by body undulation. We discover that these nematodes can synchronize their body oscillations, forming striking traveling metachronal waves, which produces strong fluid flows. We uncover that the location and strength of this collective state can be controlled through the shape of the confining structure; in our case the contact angle of a droplet. This opens a way for producing controlled work such as on-demand flows or displacement of objects. We illustrate this by showing that the force generated by this state is sufficient to change the physics of evaporation of fluid droplets, by counteracting the surface-tension force, which allow us to estimate its strength. The relatively large size and ease of culture make Turbatrix aceti a promising model organism for experimental investigation of swarming and oscillating active matter capable of producing controllable work.


The impact of a multidisciplinary safety checklist on adverse procedural events during bedside bronchoscopy-guided percutaneous tracheostomy.
Bedside procedures are seldom subject to the same safety precautions as operating room (OR) procedures. Since July 2013, we have performed a multidisciplinary checklist before all bedside bronchoscopy-guided percutaneous tracheostomy insertions (BPTIs). We hypothesized that the implementation of this checklist before BPTI would decrease adverse procedural events. A prospective study of all patients who underwent BPTI after checklist implementation (PostCL, 2013-2014, n = 63) at our Level I trauma center were compared to all patients (retrospectively reviewed historical controls) who underwent BPTI without the checklist (PreCL, 2010-2013, n = 184). Exclusion criteria included age less than 16 years, OR, and open tracheostomy. The checklist included both a procedural and timeout component with the trauma technician, respiratory therapist, nurse, and surgeon. Demographics and variables focusing on BPTI risk factors were compared. Variables associated with the primary end point, adverse procedural events, during univariate analysis were used in the multiple variable logistic regression model. A p ≤ 0.05 was significant. Of 247 study sample patients, no difference existed in body mass index, baseline mean arterial pressure, duration or mode of mechanical ventilation, cervical spine or maxillofacial injury, or previous neck surgery between PreCL and PostCL BPTI patients. PreCL patients were younger (48 [20] years vs. 57 [21] years, p < 0.01) but more often had adverse procedural events compared with PostCL patients (PreCL,14.1% vs. PostCL,3.2%, p = 0.020). After adjusting for age, vitals, BPTI risk factors, and intensive care unit duration after BPTI, multiple variable logistic regression determined that performing the safety checklist alone was independently associated with a 580% reduction in adverse procedural events (odds ratio, 5.8; p = 0.022). Our results suggest that the implementation of a multidisciplinary safety checklist similar to those used in the OR would benefit patients during invasive bedside procedures. Therapeutic/care management study, level IV.


Association Between Mental Health Burden and Coronary Artery Disease in U.S. Women Veterans Over 45: A National Cross-Sectional Study.
The women Veteran population accessing Veterans Health Administration (VA) care has grown rapidly. Women Veterans exhibit high rates of mental health conditions that increase coronary artery disease (CAD) risk; however, the relationship between specific conditions and increasing mental health burden to CAD in this population is unknown. Using VA National Patient Care Data for 2009, we identified women Veterans over 45 (N = 157,195). Logistic regression models examined different mental health diagnoses and increasing mental health burden (number of diagnostic clusters) as predictors of CAD. CAD prevalence was 4.16%, and 36% of women Veterans were current smokers. Depression exhibited the strongest association with CAD (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.50-1.71]), similar to that of current smoking (OR 1.68 [1.58-1.78]). Controlling for demographic variables, smoking, diabetes, and obesity, each additional mental health diagnosis increased the odds of CAD by 44%. Women Veterans over age 45 accessing VA care exhibited a high degree of mental health burden, which is associated with elevated odds of CAD; those with depression alone had 60% higher odds of CAD. For women Veterans using VA, mental health diagnoses may act as CAD risk factors that are potentially modifiable. Novel interventions in primary care and mental health are needed to address heart disease in this growing and aging population.


Postoperative pulmonary complications with high versus standard fiO2 in adult patients undergoing major abdominal surgery: A noninferiority trial.
Despite the possible clinical benefit of high intraoperative oxygen therapy on surgical site infection, the effect on postoperative respiratory function is debatable. However, it remains yet to be elucidated whether hyperoxia due to a high fraction of inspired oxygen used in conjunction with lung protective ventilation can lead to increased incidence of postoperative pulmonary complications. In this noninferiority randomized trial, an intraoperative high fraction of inspired oxygen of 0.8 (group H) was compared to a standard fraction of inspired oxygen of 0.3 to 0.4 (group S) in adult patients undergoing major elective or emergency surgery. A lung protective ventilation strategy was employed in all patients, including volume control ventilation with a tidal volume of 6 to 8 mL/kg of predicted body weight, respiratory rate of 12 beats per minute, and positive end-expiratory pressure of 5 to 8 cm H2O. Postoperative pulmonary complications were assessed on postoperative days 3 and 5 by the Melbourne group scale. In this trial, n = 226 patients were randomized; among them, 130 patients underwent routine surgery, and 96 patients underwent emergency surgery. The median (interquartile range) of the patients was 48 (35-58) years, and 47.3% were female. Melbourne group scale scores at postoperative day 3 (median [interquartile range] 2 [1-4] in group S vs 2 [1-3] in group H; the difference in median [95% confidence interval] 0 [0, -1]; P = .13) and day 5 (median [interquartile range] 1 (0-3) in group S vs 1 [0-3] in group H; the difference in median [95% confidence interval] 0 [0, 0.5]; P = .34) were statistically similar in both the groups and the upper margin was within the predefined margin of 1. Incidence of surgical site infection (P = .46), postoperative hospital stay (P = .29), and days alive without antibiotic therapy at postoperative day 28 (P = .95) were similar in both groups. High intraoperative fiO2 was noninferior to standard fiO2 in postoperative pulmonary complications in adult patients undergoing major surgery.


Occurrence and removal efficiency of parasitic protozoa in Swedish wastewater treatment plants.
Giardia intestinalis, Cryptosporidium spp., Entamoeba histolytica and Dientamoeba fragilis are parasitic protozoa and causative agents of gastroenteritis in humans. G. intestinalis and Cryptosporidium spp. in particular are the most common protozoa associated with waterborne outbreaks in high-income countries. Surveillance of protozoan prevalence in wastewater and evaluation of wastewater treatment removal efficiencies of protozoan pathogens is therefore imperative for assessment of human health risk. In this study, influent and effluent wastewater samples from three wastewater treatment plants in Sweden were collected over nearly one year and assessed for prevalence of parasitic protozoa. Quantitative real-time PCR using primers specific for the selected protozoa Cryptosporidium spp., G. intestinalis, E. histolytica, Entamoeba dispar and D. fragilis was used for protozoan DNA detection and assessment of wastewater treatment removal efficiencies. Occurrence of G. intestinalis, E. dispar and D. fragilis DNA was assessed in both influent (44, 30 and 39 out of 51 samples respectively) and effluent wastewater (14, 9 and 33 out of 51 samples respectively) in all three wastewater treatment plants. Mean removal efficiencies of G. intestinalis, E. dispar and D. fragilis DNA quantities, based on all three wastewater treatment plants studied varied between 67 and 87%, 37-75% and 20-34% respectively. Neither E. histolytica nor Cryptosporidium spp. were detected in any samples. Overall, higher quantities of protozoan DNA were observed from February to June 2012. The high prevalence of protozoa in influent wastewater indicates the need for continued monitoring of these pathogens in wastewater-associated aquatic environments to minimise the potential risk for human infection.


High density scaffolding of functional polymer brushes: surface initiated atom transfer radical polymerization of active esters.
In this Article, we describe a method for the polymerization of active esters based on N-hydroxysuccinimide 4-vinyl benzoate (NHS4VB) using surface initiated atom transfer radical polymerization (SI-ATRP). Poly(NHS4VB) brushes have high grafting density and a uniform and smooth morphology, and film thickness increases linearly with reaction time. Block copolymer brushes with 2-hydroxyethyl acrylate, tert-butyl acrylate, and styrene were synthesized from surface bound poly(NHS4VB) macroinitiators. The active ester brushes show rapid and quantitative conversion under aminolysis conditions with primary amines, which was studied using grazing incidence attenuated total reflection Fourier transform infrared (GATR-FTIR) and UV-vis spectroscopy. UV-vis was also used to quantify the amount of reactive groups in polymer brush layers of differing thickness. Functionalization of the active ester pendant groups with chromophores containing primary amines showed a linear correlation between the amount of chromophore incorporated into the brush layer and brush thickness. Grafting densities as high as 25.7 nmol/cm(2) were observed for a 50 nm brush. Block copolymer brushes with buried active ester functional moieties also undergo quantitative conversion with primary amines as confirmed by GATR-FTIR. We discuss the potential of activated ester brushes as universal scaffolds for sensor and microarray surfaces, where the twofold control of functionalizable active ester polymer and block copolymers provides well-ordered, tunable microenvironments.


Successful Montelukast Treatment in an Infant with Steroid-Resistant Eosinophilic Colitis.
Eosinophilic colitis (EC) belongs to a group of idiopathic diseases called eosinophilic gastrointestinal disorders, which are characterized by eosinophil-predominant inflammation in the gastrointestinal tract. Corticosteroids is the first-line pharmacotherapy for EC refractory to diet therapy. We report an infant with steroid-resistant EC, who successfully returned to a healthy growth trajectory under the combined therapy of montelukast and ketotifen. An 8-month-old boy presented with bloody diarrhea, anemia, and failure to thrive (FTT) that started 6 days after birth. The patient has no known allergies. A trial of elementary diet was unsuccessful. The results of several stool cultures were unremarkable. Similarly, lower gastrointestinal series failed to identify anything significant. At 3 months of age, an esophagogastroduodenoscopy with biopsies from the distal duodenum and proximal jejunum were unremarkable. The diarrhea and FTT persisted. A rectosigmoidoscopy with biopsies was performed; the results led to the diagnosis of EC at 5 months of age. Oral prednisolone 1 mg/kg/day was prescribed; however, 3 months into the treatment, persistent bloody diarrhea and FTT were still noted. Montelukast and ketotifen were added, after which diarrhea and weight gain started to improve. Prednisolone and montelukast/ketotifen were tapered off 6 months after. He remains symptom free and has normal growth and development in a 5-year follow-up.


Osteoporosis and osteoarthritis (osteoarthrosis). Anthropometric distinctions.
Anthropometric and skin-fold characteristics were studied in 27 women with symptomatic osteoporosis of the postmenopausal type and in 25 women with generalized osteoarthritis. In several aspects, important and significant differences were found between both groups. It was shown that the osteoporotic women were shorter, more slender, and had less fat, muscle girth, and strength, while the women with osteoarthritis, although of comparable age and skeletal size, were more obese and had more fat, muscle mass, and strength. These findings support the idea that osteoarthritis and osteoporosis are two different disease entities and not simple phenomena of aging and wear and tear.


Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis.
Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown. To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses. English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches. Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included. Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations. When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant). A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome.


Laser plasma jet driven microparticles for DNA/drug delivery.
This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength) ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval) in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles) was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications.


Miniaturized electrochemical biosensor based on whole-cell for heavy metal ions detection in water.
The heavy metals pollution represents one of the important issues in the environmental field since it is involved in many pathologies from cancer, neurodegenerative, and metabolic diseases. We propose an innovative portable biosensor for the determination of traces of trivalent arsenic (As(III)) and bivalent mercury (Hg(II)) in water. The system implements a strategy combining two advanced sensing modules consisting in (a) a whole cell based on engineered Escherichia coli as selective sensing element towards the metals and (b) an electrochemical miniaturised silicon device with three microelectrodes and a portable reading system. The sensing mechanism relies on the selective recognition from the bacterium of given metals producing the 4-aminophenol redox active mediator detected through a cyclic voltammetry analysis. The miniaturized biosensor is able to operate a portable, robust, and high-sensitivity detection of As(III) with a sensitivity of 0.122 µA ppb-1 , LoD of 1.5 ppb, and a LoQ of 5 ppb. The LoD value is one order of magnitude below of the value indicated to WHO to be dangerous (10 μg/L). The system was proved to be fully versatile being effective in the detection of Hg(II) as well. A first study on Hg(II) showed sensitivity value of 2.11 µA/ppb a LOD value of 0.1 ppb and LoQ value of 0.34 ppb. Also in this case, the detected LOD was 10 times lower than that indicated by WHO (1 ppb). These results pave the way for advanced sensing strategies suitable for the environmental monitoring and the public safety.


[Pegfilgrastim in hematopoietic stem cell transplantation].
Pegylation implies progress in filgrastim therapy. The addition of one molecule of polyethylene glycol (PEG) increases the drug's half-life by reducing renal excretion. A single dose of pegfilgrastim is equivalent to a daily administration of G-CSF for recovering from neutropenia after cancer chemotherapy. Pegfilgrastim is also useful to mobilize hematopoietic stem cells. Several studies have researched its efficacy in this context, in patients with myeloma or lymphoma. Outcomes suggest that it has an efficacy similar to daily G-CSF. In allogeneic donors, a single 12-mg dose of pegfilgrastim produces sufficient increase of CD34+ in peripheral blood, with acceptable toxicity. There is interest on the data about the various functional and biologic properties of hematopoietic stem cells mobilized with pegfilgrastim compared to G-CSF, and on the effect that these differences may have on the graft composition. The administration of a single dose of pegfilgrastim after autologous transplantation has been shown to shorten the time for leukocyte recovery in a manner similar to G-CSF


[Septic syndrome with a pulmonary focus].
After acute pharyngitis a 21 year old patient developed signs of severe bacteremia with a well demarcated infiltrate in the left lung. The typical course and a prompt response to antibiotic therapy with Imipenem (Tienam) led to the diagnosis of Lemierre's syndrome (post-anginal sepsis)--in spite of negative blood cultures. The patient recovered quickly, a chest radiogram after two weeks showing but pleural scarring and restitution ad integrum after four weeks.


Incidence of hypertension among persons living with HIV in China: a multicenter cohort study.
Life expectancy among persons living with HIV (PLWH) has improved with increasing access to antiretroviral therapy (ART), however incidence of chronic comorbidities has simultaneously increased. No data are available regarding the incidence of hypertension among Chinese PLWH. We analyzed data collected from patients enrolled in two prospective longitudinal multicenter studies of PLWH initiating ART in China. Incidence rate of hypertension per 100 person-years (PYs) among PLWH was calculated, and Cox proportional hazards models was used to evaluate the association between incident hypertension and traditional and HIV-associated risk factors. Of 1078 patients included in this analysis, 984 ART-naïve patients were hypertension-free at baseline, and contributed 2337.7 PYs of follow up, with a median follow-up period of 1.8 years (range: 1.2-3.2) after initiation of ART. Incidence of hypertension was 7.6 [95% confidence interval (CI): 6.5-8.7] per 100 PYs. In the Cox regression analysis, incidence of hypertension was positively associated with body mass index [adjusted hazard ratio (aHR) 1.07 (1.01,1.13), p = 0.02] and recent viral load (aHR 1.28, 95% CI:1.08-1.51, p < 0.01), and negatively associated with recent CD4+/CD8+ ratio (aHR 0.14, 95% CI:0.06-0.31, p < 0.001), zidovudine exposure (aHR 0.15, 95% CI: 0.10-0.24, p < 0.001) and tenofovir disoproxil fumarate exposure (aHR 0.13, 95% CI: 0.08-0.21, p < 0.001). The incidence of hypertension was relatively high among Chinese PLWH initiating ART. Recent low CD4+/CD8+ ratio and detectable HIV viremia were associated with incident hypertension, whereas receipt of ART was associated with reduced risk. Hypertension may be mitigated, in part, by excellent HIV care, including viral suppression with ART. ClinicalTrials.gov Identifier: NCT00872417 registered on 31 March, 2009, and NCT01844297 registered on 1 May, 2013.


Microorganisms Associated with Mosquito Oviposition Sites: Implications for Habitat Selection and Insect Life Histories.
Mosquitoes are considered one of the most important threats worldwide due to their ability to vector pathogens. They are responsible for the transmission of major pathogens such as malaria, dengue, zika, or chikungunya. Due to the lack of treatments or prophylaxis against many of the transmitted pathogens and an increasing prevalence of mosquito resistance to insecticides and drugs available, alternative strategies are now being explored. Some of these involve the use of microorganisms as promising agent to limit the fitness of mosquitoes, attract or repel them, and decrease the replication and transmission of pathogenic agents. In recent years, the importance of microorganisms colonizing the habitat of mosquitoes has particularly been investigated since they appeared to play major roles in their development and diseases transmission. In this issue, we will synthesize researches investigating how microorganisms present within water habitats may influence breeding site selection and oviposition strategies of gravid mosquito females. We will also highlight the impact of such microbes on the fate of females' progeny during their immature stages with a specific focus on egg hatching, development rate, and larvae or pupae survival.


Strategies for enhancing computer system availability.
Lack of access to a healthcare facility's computer system can contribute to several problems: low employee productivity, reduced revenues, increased expenses, cash flow difficulties, and poor quality patient care. Three potential strategies that can improve system access are disk shadowing, clustered processors, and protection from environmental factors.


Activity limitations and subjective well-being after stroke.
As limitations in activities of daily living are major components of many stroke outcome scales, we examined how well activity limitations predicted subjective well-being among stroke survivors in a nationally representative survey. Individuals with a self-reported history of stroke were identified from the National Health and Aging Trends Study. Subjective well-being (primary outcome) was assessed with a validated 7-item measure (higher = greater well-being) assessing emotions (cheerful, bored, full of life, and upset) and self-realization (purpose in life, self-acceptance, and environmental mastery). Activity limitations were defined by the receipt of help in any of 11 activities of daily living/instrumental activities of daily living. Multivariable linear regression assessed predictors of well-being including medical, physical, cognitive, psychological, and environmental factors. A total of 738 stroke survivors age 65 or older were included (57% female, 9% African American, 6% Hispanic). Activity limitations were modestly associated with well-being after adjusting for demographic characteristics and availability of assistance (estimate -0.49, 95% confidence interval -0.61 to -0.37). However, in the fully adjusted model (R2 = 0.28), neither activity limitations nor physical capacity was associated with subjective well-being. Predictors of lower well-being in the final model included depressive symptoms, chewing/swallowing problems, pain that limited activity, and restricted participation in valued life activities. Income and executive function were modestly associated with improved well-being, while comorbidities and communication technology access were not associated. Activity limitations were not associated with stroke survivors' subjective well-being after adjustment for other factors. While some predictors of well-being after stroke were identified, the determinants of well-being remained largely unexplained.


Metabolomics and 16S rRNA sequencing of human colorectal cancers and adjacent mucosa.
Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis.


ADNP/NAP dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy.
Activity-dependent neuroprotective protein (ADNP), vital for brain formation and cognitive function, is mutated in autism and linked to neurodegenerative/psychiatric diseases. An eight-amino-acid peptide snippet of ADNP, NAP (NAPVSIPQ), identified as a smallest active fragment, includes the SxIP microtubule (MT) end-binding protein (EB) association motif, and enhances ADNP-EB3 interaction. Depletion of EB1 or EB3 abolishes NAP protection against zinc intoxication. Furthermore, NAP enhances Tau-MT interaction, and Tau regulates the localization and function of EB1 and EB3 in developing neuronal cells. Here, we asked how NAP (ADNP) enhances Tau-MT interactions and whether this is mediated by EBs. We showed, for we believe the first time, that NAP augmented endogenous EB1 comet density in the N1E-115 neuroblastoma neuronal model. This finding was substantiated by cell transfection with fluorescent EB1 and live cell imaging. NAP increased comet amounts, length and speed. At the molecular level, NAP enhanced EB3 homodimer formation, while decreasing EB1-EB3 heterodimer content and driving EB1- and EB3-Tau interactions (dramatic 20-fold increases), leading to recruitment of EB1/EB3 and Tau to MTs under zinc intoxication. Our previous results showed that while NAP protected neuronal-like cells against oxidative stress, it did not protect NIH3T3 fibroblasts. Here, NAP did not protect NIH3T3 cells against zinc intoxication, unless these cells were transfected with Tau. Interestingly, other MT associated proteins (MAPs) may replace Tau, thus, EB-Tau (MAPs) interaction is identified as a novel target for endogenous ADNP neuroprotection, and a future target for drug development, with NAP as a prototype.


Adsorption and sensing performance of air pollutants on a β-TeO2 monolayer: a first-principles study.
Two-dimensional (2D) β-TeO2 is a novel semiconductor with potential applications in electronic circuits due to its air-stability and ultra-high carrier mobility. In this study, we explore the possibility of using a 2D β-TeO2 monolayer for the detection of gaseous pollutants including SO2, NO2, H2S, CO2, CO, and NH3 gas molecules based on first-principles calculations. The adsorption properties including the adsorption energy, adsorption distance and charge transfer indicate that the interaction between 2D β-TeO2 and the six gases is via a physisorption mechanism. Among the six gas adsorption systems, the SO2 adsorption system has the most negative adsorption energy and the largest charge transfer. In addition, the adsorption of SO2 obviously changes the electrical conductivity of the β-TeO2 monolayer because the band gap decreases from 2.727 eV to 1.897 eV after adsorbing SO2. Our results suggest that the 2D β-TeO2 should be an eminently promising SO2 sensing material.


Effects of Fenofibrate on the Expression of Small Heterodimer Partner (SHP) and Cytochrome P450 (CYP) 2D6.
Cytochrome P450 (CYP) 2D6 is a major drug-metabolizing enzyme, responsible for eliminating 25% of marketed drugs. We recently identified SHP as a negative regulator of CYP2D6 expression and showed that factors that alter SHP expression influence CYP2D6 expression. Fenofibrate, an agonist of peroxisome proliferator-activated receptor α(PPARα), has been previously reported to upregulate SHP expression in the mouse liver. The objective of this study was to determine whether fenofibrate decreases CYP2D6 expression via upregulating SHP expression. CYP2D6-humanized transgenic mice were administered with fenofibrate (100 mg/kg/day intraperitoneally for 5 days) or vehicle control. Hepatic mRNA and protein expression levels of CYP2D6 and SHP were measured. Results showed that while mRNA levels of SHP did not differ between the groups, protein levels of SHP increased by 2-fold in fenofibrate-treated mice. Despite the increased SHP protein levels, CYP2D6 expression did not decrease at the mRNA or protein levels. Similar results were observed in human hepatocytes treated with fenofibrate. Results from transient transfection and promoter reporter assays indicate that PPARα can transactivate CYP2D6 promoter, suggesting that the lack of CYP2D6 downregulation by fenofibrate may be in part due to the activation of CYP2D6 promoter by PPARα. These results indicate that fenofibrate has minimal effects on CYP2D6 expression despite increased SHP expression.


The aqueous stability of bupropion.
In this study the aqueous stability of bupropion was determined and the pH-degradation profile was obtained. The effects of hydrogen ion, solvent and hydroxide ion concentration are discussed with particular emphasis on the kinetics of degradation of bupropion. Kinetics and degradation of bupropion were determined by HPLC-UV and LC-MS analysis both utilising high pH chromatographic methods. Degradation of bupropion in aqueous solutions follows first-order reaction kinetics. The pH-degradation profile was determined using non-linear regression analysis. The micro- and macro-reaction constants for degradation are presented. Bupropion was most stable in aqueous solutions below pH 5. Degradation was catalyzed by water but mainly by hydroxide ion on the unionised form of bupropion. The energy of activation for decomposition in aqueous solution pH 10.7 I=0.055 was determined to be 53 kJ mol(-1) with a frequency factor of 6.43 x 10(10)s(-1). The degradants of bupropion were positively identified and a mechanism of degradation is proposed. The inherent instability of bupropion above pH 5 has implications for its therapeutic use, formulation, pharmacokinetics and use during analysis and storage.


Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases.
We report the cloning, expression, and characterization of a new family of cyclic nucleotide phosphodiesterase (PDE) that has unique kinetic and inhibitor specificities. A clone corresponding to the C terminus of this PDE was initially identified by a bioinformatic approach and used to isolate a cDNA that is likely full-length. This novel PDE, designated as MMPDE9A1, shows highest mRNA expression in kidney with lower levels in liver, lung, and brain. The mRNA size by Northern blot analysis is approximately 2.0 kilobases, and the cDNA encoding PDE9A1 is 1929 base pairs in length. The largest open reading frame predicts a protein of 534 amino acids with a molecular mass of 62,000 Da. When expressed in COS-7 cells, PDE9A1 activity was not inhibited well by either the nonselective inhibitor 3-isobutyl-1-methyl-xanthine or the new selective PDE5 inhibitor, sildenafil, but it is inhibited by the PDE1/5 inhibitor (+)-cis-5,6a, 7,8,9 hyl] phenylmethyl]-5-methyl-cylopent[4,5]imidao[2, 1-b]purin-49(3H)one (SCH51866) with an IC50 of 1.55 microM. This new phosphodiesterase is highly specific for cGMP. Its Km of approximately 0.07 microM for cGMP is the lowest yet reported for a PDE, being at least 40-170 times lower than that of PDE5 and PDE6, respectively.


Evaluation of the EVIGENE VRE detection kit for detection of vanA and vanB genes in vancomycin-resistant enterococci.
The aim of this study was to evaluate the performance of the EVIGENE VRE Detection kit and compare it with PCR, considered the gold standard for detection of vancomycin-resistant enterococci (VRE). The correlation between the MIC values of vancomycin and teicoplanin using the epsilon test was also determined. In the EVIGENE VRE Detection kit, DNA probes specific for bacterial target DNA sequences are bound to microwell plates. A hundred and ten VRE (104 Enterococcus faecium and six Enterococcus faecalis) and 45 vancomycin-susceptible E. faecium were tested. All VRE strains were found to be positive for the vanA genotype using the EVIGENE VRE Detection kit. All results obtained with the EVIGENE VRE Detection kit were confirmed by PCR. MIC results for the strains also correlated highly with the PCR and kit results. The EVIGENE VRE Detection kit should be used in preference to other methods for detecting resistance genes in all strains, since it is less time-consuming, does not require the handling of hazardous chemicals and has the same specificity as PCR.


Associations between chronic caregiving stress and T cell markers implicated in immunosenescence.
Chronic psychological stress is associated with accelerated biological aging, immune dysfunction, and premature morbidity and mortality. Changes in the relative proportions of T cell subpopulations are thought to be a characteristic of immunological aging; however, understanding of whether these changes are associated with chronic psychological stress is incomplete. This study investigated associations between chronic caregiving stress and distributions of T cell phenotypes in a sample of high stress mothers of children with Autism Spectrum Disorder (caregivers; n = 91) and low stress mothers of neurotypical children (controls; n = 88). Immune markers assessed were naïve (CD45RA + CD62L+), central memory (CD45RA-CD62L+), and effector memory (CD45RA-CD62L-) CD4+ and CD8+ T cells. We also examined the ratio of effector to naïve (E:N) CD4+ and CD8+ T cells. In models adjusted for age, body mass index, race/ethnicity, and antidepressant use, caregivers displayed higher percentages of effector memory CD8+ and CD4+ T cells as well as lower percentages of naïve CD8+ T cells and central memory CD8+ and CD4+ T cells compared to controls. Caregivers also displayed significantly higher E:N ratios for both CD4+ and CD8+ T cells. These findings were also independent of cytomegalovirus infection status. Furthermore, higher parental stress, across both groups, was related to several immune parameters. These findings provide preliminary evidence that chronic parental caregiving stress is associated with changes in relative proportions of T cell subpopulations that are consistent with accelerated immunological aging.


Engineered design of theranostic upconversion nanoparticles for tri-modal upconversion luminescence/magnetic resonance/X-ray computed tomography imaging and targeted delivery of combined anticancer drugs.
Upconversion nanoparticles (UCNPs) are ideal building blocks for fabricating multifunctional theranostic agents for simultaneous diagnosis and therapy. We develop multifunctional nanoparticles based on NaGdF4:Yb/Er@NaGdF4 core-shell UCNPs, which are not only endowed with upconversion luminescence (UCL), magnetic resonance (MR) and X-ray computed tomography (CT) imaging ability, but also could be applied as nanocarriers for targeted drug delivery. We systematically investigate their upconversion luminescent, magnetic and X-ray attenuation properties. Importantly, for the first time, we report the controlled loading and delivery of a mixture of chemotherapeutic anticancer drugs, camptothecin (CPT) and doxorubicin (DOX), through UCNPs-based nanocarriers considering that the combined use of two or more drugs usually exhibits much better therapeutic efficacy than that of a single drug. By conjugating nanoparticles with folic acid (FA), which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted tri-modal UCL/MR/CT cell imaging and drug delivery with UCNPs. Our results suggest the as-prepared nanocomposites are highly versatile and could potentially be used for simultaneous imaging and therapeutic applications.


[Spontaneous peritonitis induced by Campylobacter spp in patients with liver cirrhosis. Report of 2 cases and review of the literature].
Campylobacter spp is not usual as the aetiology agent for spontaneous bacterial peritonitis. We report two cases of spontaneous peritonitis due to Campylobacter jejuni diagnosed in our hospital and review the literature trough MEDLINE data base. We found 13 cases of spontaneous peritonitis in which Campylobacter sp was isolated from ascitic fluid. The main characteristics of these cases were: the existence of an evolved alcoholic cirrhosis, a high positivity of blood cultures as well as a high relapse index and letality.


Assessment of dehydrothermally cross-linked collagen membrane for guided bone regeneration around peri-implant dehiscence defects: a randomized single-blinded clinical trial.
The aim of this study was to determine the clinical feasibility of using dehydrothermally cross-linked collagen membrane (DCM) for bone regeneration around peri-implant dehiscence defects, and compare it with non-cross-linked native collagen membrane (NCM). Dehiscence defects were investigated in twenty-eight patients. Defect width and height were measured by periodontal probe immediately following implant placement (baseline) and 16 weeks afterward. Membrane manipulation and maintenance were clinically assessed by means of the visual analogue scale score at baseline. Changes in horizontal thickness at 1 mm, 2 mm, and 3 mm below the top of the implant platform and the average bone density were assessed by cone-beam computed tomography at 16 weeks. Degradation of membrane was histologically observed in the soft tissue around the implant prior to re-entry surgery. Five defect sites (two sites in the NCM group and three sites in the DCM group) showed soft-tissue dehiscence defects and membrane exposure during the early healing period, but there were no symptoms or signs of severe complications during the experimental postoperative period. Significant clinical and radiological improvements were found in all parameters with both types of collagen membrane. Partially resorbed membrane leaflets were only observed histologically in the DCM group. These findings suggest that, compared with NCM, DCM has a similar clinical expediency and possesses more stable maintenance properties. Therefore, it could be used effectively in guided bone regeneration around dehiscence-type defects.


Increased Ca++, Mg++, and Na+ + K+ ATPase activities in erythrocytes of sickle cell anemia.
To determine whether diminished activity of the Ca++ extrusion pump could account for the high levels of red blood cell (RBC) Ca++ in sickle cell anemia (SS), we measured calmodulin-sensitive Ca++ ATPase activity in normal and SS RBC. Hemolysates prepared with saponin were compared, since such preparations expressed maximum ATPase activities, exceeding isolated membranes or reconstituted systems of membranes plus cytosol, SS RBC hemolysates had greater Ca++ ATPase activity than normal hemolysates; they exhibited higher Mg++ and Na+ + K+ ATPase activities as well. Assays on density (age) fractions of SS and normal red cells demonstrated that all ATPase activities were highest in low density (young) cells, and activities in SS red cells exceeded those in normals in all fractions studied. Thus, when studied under conditions that maximize enzyme activity, Ca++ ATPase activity, like Mg++ and Na+ + K+ ATPase, is actually increased in SS RBC, probably due to the young red cell population present. The elevated Ca++ levels in these cells are more likely due to an increased Ca++ leak or abnormal calcium binding than to defective extrusion by the ATPase pump.


Melatonin and its day and night rhythm of alterations in familial mediterranean Fever: a brief research letter.
The pineal hormone melatonin plays a crucial role in immunomodulation, mainly by effecting T cells. The aims of the present study were to compare the melatonin levels in patients with Familial Mediterranean Fever (FMF) and healthy controls and to find out if it associates with interferon(IFN)γ and interleukin(IL)-10. Twenty five patients with FMF and 16 healthy donors were enrolled into the study. Melatonin, IFN γ and IL-10 measurements were assayed by using enzyme immunoassay (EIA) method. Serum melatonin levels at 03.30 am in both patients during attack-free phase and healthy controls were significantly higher than those levels of corresponding groups measured at 10.00 am. The melatonin levels at 03.30 and 10.00 am in patients during attack-free phase were higher than those levels measured in healthy controls at the same time points. IFNγ and IL-10 did not show any day and night rhythm in both patients and healthy controls. In addition, there was no association among day and night levels of melatonin, IFNγ and IL-10. We conclude that melatonin may play a role in FMF pathogenesis. However, its modulatory effect on immune response most likely does not depend on T cells. Further comprehensive studies should be performed in order to reveal the role of melatonin in the pathogenesis of this disease.


[Streptococcal abscesses of the liver: diagnosis and therapy using ultrasound controlled puncture].
Three male patients without accompanying diseases, 27, 47, and 52 years of age, were admitted with fever of unknown origin. Focal liver disease was seen on ultrasound and the diagnosis of an abscess was confirmed by sonographically-guided fine-needle puncture. Microaerophilic streptococci were found in two cases, streptococcus viridans once. Two patients had cryptogenic abscesses; one had previously undergone surgery for a rectal abscess. All three patients were cured of their condition by appropriate antibiotic coverage and evacuation of the abscess by needle aspiration.


Prolongation and enhancement of gamma-aminobutyric acid receptor mediated excitation by chronic treatment with estradiol in developing rat hippocampal neurons.
GABA(A) receptor activation during brain development is a critical source of excitation. This is due to the positive equilibrium potential for chloride relative to resting membrane potential, resulting in membrane depolarization sufficient to open voltage sensitive calcium channels. The gonadal steroid estradiol has pronounced trophic effects on the developing hippocampus, promoting cell survival and synaptogenesis. In the current study, we investigated the effect of estradiol on GABA(A) receptor-mediated calcium transients in cultured neonatal hippocampal neurons, from Sprague-Dawley rats, using the calcium sensitive dye, Fura-2-AM. Treatment of hippocampal neurons with physiological levels of estradiol significantly increased the peak amplitude of calcium transients, increased the number of cells responding to the GABA(A) agonist muscimol with membrane depolarization, and delayed the rate of clearance of free intracellular calcium. These effects were significantly attenuated by pretreatment with the oestrogen receptor antagonist ICI-182,780. This suggests that estradiol, via its action on the oestrogen receptor, prolongs the developmental duration of depolarizing GABA. Estradiol likely maintains GABA-mediated excitation by promoting increased protein levels of the active/phosphorylated form of the chloride cotransporter Na+K+2CL- and L-type voltage sensitive calcium channels containing the alpha1C subunit. We propose that a component of the trophic effects of estradiol on hippocampal development results from enhanced calcium influx subsequent to GABA(A) receptor activation.


Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer.
Pure and mixed isoprenoid end products of plant mevalonate metabolism trigger actions that suppress 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity. These actions modulate HMG CoA reductase mRNA translation and the proteolytic degradation of HMG CoA reductase. Such post-transcriptional events, we propose, are activated directly by acyclic isoprenoids and indirectly by cyclic isoprenoids. Isoprenoids, acting secondarily to the dominant transcriptional effector of sterologenesis, modestly lower cholesterol levels, if and only if, sterologenesis is not repressed by a saturating imput of dietary cholesterol. An anomaly associated with tumor growth-a sterol feedback-resistant HMG CoA reductase activity-ensures a pool of sterologenic pathway intermediates. Such intermediates provide lipophilic anchors essential for membrane attachment and biological activity of growth hormone receptors, nuclear lamins A and B, and oncogenic ras. Tumor HMG CoA reductase retains high sensitivity to the isoprenoid-mediated secondary regulation. Repression of mevalonate synthesis by plant-derived isoprenoids reduces ras and lamin B processing, arrests cells in G1, and initiates cellular apoptosis. This unique tumor cell-specific sensitivity allows isoprenoids to be used for tumor therapy, an application emulating that of the statins, but one free of adverse effects. When evaluated at levels provided by a typical diet, isoprenoids individually have no impact on cholesterol synthesis and tumor growth. Nonetheless, isoprenoid-mediated activities are additive, and, sometimes synergistic. Therefore, the combined actions of the estimated 23,000 isoprenoid constituents of plant materials, acting in concert with other chemopreventive phytochemicals, may explain the lowered cancer risk associated with a diet rich in plant products. In contrast, that lowering of cancer risk does not correspond to supplemental intake of other dietary factors associated with fruits, vegetables, and cereal grains, namely fiber, beta-carotene, vitamin C, and vitamin E, and only weakly to supplemental folate.


Alterations in lipoprotein homeostasis during human experimental endotoxemia and clinical sepsis.
Cell wall constituents of bacteria are potent endotoxins initiating inflammatory responses which may cause dramatic changes in lipid metabolism during the acute phase response. In this study, the sequential changes in lipoprotein composition and lipid transfer and binding proteins during clinical sepsis and during low-dose experimental endotoxemia were followed. In addition, the effect on (phospho)lipid homeostasis by administration of reconstituted HDL (rHDL) prior to low-dose LPS administration was investigated. Changes in (apo)lipoprotein concentrations typical of the acute phase response were observed during clinical sepsis and experimental endotoxemia with and without the rHDL intervention. During clinical sepsis negative correlations between the acute phase marker C-reactive protein (CRP) and lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer protein (CETP) activities were seen, whereas positive correlations between plasma phospholipid transfer protein (PLTP) activity and acute phase markers such as CRP and LPS binding protein were observed. Plasma lipid changes upon rHDL/LPS infusion were comparable with the control group (low-dose LPS only). PLTP activity decreased upon LPS infusion and transiently increased during rHDL infusion, whereas LCAT activity slightly decreased upon both LPS infusion and LPS/rHDL infusion. However, long-lasting increases of circulating HDL cholesterol, apo A-I and a high initial processing of both phosphatidylcholine (PC) and lyso-PC, were indicative for extensive rHDL and LDL remodelling. Both sepsis and experimental endotoxemia lead to a disbalance of lipid homeostasis. Depending on the magnitude of the inflammatory stimulus, LCAT and PLTP activities reacted in divergent ways. rHDL infusion did not prevent the lipid alterations seen during the acute phase response. However profound changes in both HDL and LDL phospholipid composition occurred upon rHDL infusion. This may be explained, at least in part, by the fact that PLTP as a positive acute phase protein, can accelerate the alterations in (phospho)lipid homeostasis thereby playing a role in the attenuation of the acute phase response.