Delay in the diagnosis of paediatric brain tumours: a systematic review.
A delay in obtaining a diagnosis has been associated with inferior outcomes across several cancer types, including paediatric brain tumours. However, no clear evidence exists in this population. We aimed to quantify the reported pre-diagnostic symptom interval (PSI) as the time from onset of first symptoms to diagnosis in the literature, in addition to evaluating the relationship between delay and outcomes, including survival. A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Wiley Online Library, Web of Science and EMBASE databases were searched. We considered all sources published between 1st January 2010 and 5th November 2022. Children and adolescents aged under 21 years, with new symptomatic primary brain tumour diagnoses, were included. Of 3123 studies identified, 11 were included for analysis. Owing to study heterogeneity, a quantitative meta-analysis was not feasible; however, a narrative synthesis was performed. The median reported PSI varied widely, ranging between 28 and 760.8 days. We failed to identify a significant association between prolonged PSI and inferior overall survival. Few factors were consistently associated with prolonged PSI, amongst them only tumour grade and patient age. Delayed diagnosis of paediatric brain tumours was not associated with inferior survival within this review. This 'waiting time' paradox appears to result from several confounding factors including tumour biology, patient population and key systematic factors that were inconsistently reported. Diagnostic interval clearly presents a complex variable, reflected further by disparity in the reporting of delay within the literature. Ultimately diagnostic interval is unlikely to provide a meaningful representation for all tumour types and should not detract from sharp clinical acumen and prompt diagnosis.


30-Day Outcomes With the Portico Transcatheter Heart Valve: Insights From a Multi-Centre Australian Observational Study.
Transcatheter aortic valve implantation (TAVI) is an established therapy for the treatment of aortic valve disease in appropriately selected patients. Previous studies using the self-expanding Portico transcatheter heart valve (THV), (Abbott Structural Heart, St Paul, MN, USA) have demonstrated the technical feasibility of this system albeit in the hands of relatively inexperienced Portico users. The objective of this study was to assess the real-world safety and efficacy of the Portico THV (with and without the FlexNav delivery system, Abbott Structural Heart) at the 30-day timepoint in an Australian cohort. This study was a retrospective real-world cohort analysis of 269 consecutive patients with severe aortic valve disease who underwent TAVI at multiple centres within Australia between February 2015 and April 2021. Of the 269 patients, 51.7% were female, mean Society of Thoracic Surgeons (STS) score was 5.2 (±6.8) and 98.5% had successful implantations. Thirty (30)-day post-implantation all-cause mortality was observed in one (0.4%) patient, major vascular complications in two (0.7%) patients, more-than-mild paravalvular leak in six (2.2%) patients and requirement for new permanent pacemaker implantation in 27 (10.2%) patients. Haemodynamic parameters at 30 days included mean effective orifice area (EOA) of 2.3 (±0.9) cm2 and mean aortic valve gradient (AVG) of 9.6 (±6.2) mmHg. This analysis of the Portico THV in a real-world setting suggested that the system is associated with satisfactory safety and efficacy parameters. Previously published datasets may not have found similar findings owing to lower operator experience with the Portico THV system.


Acute-phase inflammatory process contributes to malnutrition, anemia, and possibly other abnormalities in dialysis patients.
The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.


[Quantitative parameters to evaluate the publication of scientific papers].
The assessment of the publication of scientific works is a hard challenge when it is necessary to classify a curriculum vitae or even to verify the performance of an institution, such as a medical school, a postgraduate program or a research department. Most of time, the evaluation is based on personal feelings and experience, without established standard pattern. To present a guideline to evaluate the publications of scientific papers, without foreign influence. The guideline to assess the value of each publication is based on the multiplication of three factors. The first factor is the value of the author corresponding to his place among the authors in the authorship of the work. The second factor is the classification of the type of publication. Finally, the product of these two factors is multiplied by ten times the "impact factor" of the journal. When the "impact factor" is zero, 0.1 should substitute it. This method has been used by us since 1994, with good results and without any problem related to the judgment. This criterion prevents subjective interference. Conflicts of interest are avoided when clearly presented from the beginning of the judgment process.


Reduction of oxaloacetate by pig liver isocitrate dehydrogenase.
Pure isocitrate dehydrogenase from pig liver cytoplasm catalyses the reduction of oxaloacetate by NADPH at a rate comparable with that observed for the usual substrates. The products are NADP and D-malate, the 'unatural' isomer. High concentrations of magnesium (25 mM) are necessary for maximal activity, and the reaction is not appreciably reversible. These results are discussed in connection with the inhibition of the enzyme by mixtures of glyoxylate and oxaloacetate. The reduction is not thought to be of physiological importance.


Regulation and tissue distribution of the human sodium iodide symporter gene.
Iodide uptake by the thyroid gland is mediated by the sodium iodide symporter (NIS). In the present report, we have analysed the factors that modulate human NIS mRNA expression and iodide uptake in primary thyroid follicular cell (TFC) cultures. In addition, NIS mRNA tissue distribution was investigated. Primary thyroid follicular cell cultures were treated with human recombinant TSH with or without cytokines for 72 h. Subsequently, NIS gene expression and iodide uptake were analysed using reverse transcription-polymerase chain reaction (RT-PCR) and 125I uptake, respectively. Human tissue samples were investigated for NIS gene expression using both RT-PCR and Northern blotting. Human TSH increased both NIS gene expression and iodide uptake in TFC cultures in a dose-dependent manner. Using concentrations of 0.1 U/l of hTSH, a minor increase in NIS gene expression was detected without a detectable increase in iodide uptake. IL-1 alpha, TNF alpha and IFN gamma at concentrations of 10(5) U/l all inhibited TSH-induced NIS gene expression and iodide uptake. In these experiments, there was a good correlation between NIS mRNA expression and iodide uptake. Using RT-PCR higher levels of NIS mRNA were detected in Graves' disease (GD) compared to multi-nodular goitre tissue samples. Stomach and salivary gland tissue also expressed NIS mRNA, whereas low levels were found in the mammary gland and extraocular muscle tissue. No expression was detected in the ovary, oesophagus, colon, extraocular fat or skin. In contrast, Northern blot analysis failed to detect NIS in stomach, salivary gland, intestinal fat or non-toxic multi-nodular goitre tissue samples, although this was present in GD thyroid tissue. TSH upregulates sodium iodide symporter gene expression and iodide uptake in primary thyroid follicular cell cultures, and this induction is modulated by cytokines. Variable levels of sodium iodide symporter mRNA are present in different tissue samples, with high expression evident in Graves' disease thyroid tissue.


Abnormal dermatoglyphics in arthrogryposis multiplex congenita.
Dermatoglyphic abnormalities have been found in patients with arthrogryposis multiple congenita. These unusual features, which appear to be pathognomonic, indicate an early prenatal pathogenesis and may aid in differential diagnosis.


Neuroprotective effects of virally delivered HSPs in experimental stroke.
Heat shock proteins (HSPs) are molecular chaperones with essential roles in modulating the proteolytic machinery and accelerating cell repair. Heat shock protein overexpression has been observed in vivo and in vitro under stresses including heat, nutrient deprivation and ischemia. Experiments in in vivo models of stroke indicate that transgenically overexpressed or virally delivered HSPs can enhance cell survival, but cannot always reduce lesion size. This study aims to assess the effects of virally delivered HSPs in a rat middle cerebral artery occlusion model of reversible focal cerebral ischemia using noninvasive magnetic resonance imaging. Attenuated herpes simplex virus carrying HSP27, HSP70, or a LacZ control was microinjected into the striatum 3 days before ischemia. Multislice T(2)-weighted images at 24 h after ischemia indicated that lesion volume was reduced by 44% in HSP27-treated animals compared with controls (P = 0.019). No significant differences were found between HSP70-treated and control animals (P = 0.88). Immunohistochemistry and Western blots revealed that HSP27 and HSP70 expression levels were equally high in injected hemispheres, but only the former had an effect on lesion size. This is the first evidence of the efficacy of gene therapy with any viral vector expressing HSP27 in an experimental model of stroke.


Usefulness of three-dimensional computed tomography venography differentiating calvarium subperiosteal hematoma crossing the suture lines due to hair pulling from subgaleal hematoma: case report and review of the literature.
This case showed a 13-year-old boy presented with calvarium subperiosteal hematoma crossing the suture lines caused by hair pulling, and 3D-CTV can differentiate calvarium subperiosteal hematoma crossing the suture lines from subgaleal hematoma. He was treated successfully.


The neurobiological underpinning of the circadian wake signal.
The circadian wake drive is a mathematic representation of the observed increased propensity to stay awake late in the day, peaking in the hours just before anticipated bed time. It has been called the "forbidden zone" due to the difficulty in initiating sleep during this time and is responsible for the problems initiating sleep when traveling eastward, for maintaining daytime sleep in shift workers, and for initiating sleep in some individuals with insomnia. Evidence culled from studies in individuals with narcolepsy, who lack production of hypocretin (orexin) neuropeptides, as well as a primate model of human wake consolidation and pharmacologic studies of hypocretin antagonists indicate that hypocretin-1 may be the physiologic instantiation of the circadian wake drive. This review will discuss the evidence in support of this hypothesis.


Headache in cerebral hemorrhage is associated with inflammatory markers and higher residual cavity.
The mechanisms responsible for headache in patients with intracerebral hemorrhage (ICH) are not completely understood. The present study was undertaken to analyze the headache-associated factors, the possible related biochemical mechanisms, and the headache potential predictors of outcome in spontaneous ICH. We prospectively studied 189 patients from a large cohort of 266 consecutive patients with supratentorial ICH admitted within the first 12 hours of symptoms onset. The presence of headache at stroke onset was evaluated in these patients. The volumes of the initial ICH, peripheral edema at 48 hours, and the residual cavity at 3 months were measured on CT scan. Glutamate, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha levels were measured in blood samples obtained on admission. The Canadian Stroke Scale (CSS) and the modified Rankin Scale were used to evaluate stroke severity and neurological outcome, respectively. Headache at onset of stroke was observed in 65 patients (34.4%). Patients who experienced headache had a significantly higher frequency of history of infection (P= .009) or inflammation (P= .045), as well as higher body temperature (P= .021), leukocyte count (P= .038), ESR (P= .011), and mass effect (P= .017) on admission. Plasma concentrations of IL-6 and TNF-alpha were significantly higher in patients with headache than in those without. Headache was an independent predictor of the residual cavity volume in patients with spontaneous ICH (odds ratio 6.49; 95% CI 2.51 to 16.78; P= .0001). Headache at ICH onset is associated with clinical and biochemical markers of inflammation and is an independent predictor of higher residual cavity volume after spontaneous ICH.


Differential contributions of occipitotemporal regions to person perception.
Downing and Peelen have produced an excellent review synthesizing the current literature on the processing of body stimuli in visual cortex. However, while they consider the Extrastriate Body Area (EBA) and Fusiform Body Area (FBA) in combination, these regions are physically separate in cortex and must contribute differentially to person perception. Here, we evaluate the hierarchical view of processing in EBA and FBA and highlight the visual field biases in these regions, which may provide insight into their origin and functional roles.


Molecular dynamics study of the behavior of nitromethanes enclosed inside carbon nanotube containers.
We utilized molecular dynamics (MD) to investigate the behavior of nitromethane molecules (NMs) enclosed inside carbon nanotube (CNT) containers sealed with buckybowl caps. Two different sizes of CNT containers, i.e., (10,10) and (20,20), were employed to contain the energetic NMs. After loading the NMs into these containers, MD simulations were carried out at different loading densities. The loading density was changed from 0.4 to 2.0 g/cc. At low loading densities, NMs preferentially resided near the surface of the CNT wall (orienting themselves in the cylindrical direction) and near the buckybowl caps (orienting themselves in the principal-axis direction). This behavior suggests the buckybowl caps and the CNT wall have attractive interactions with the NMs. The distribution of the NMs inside the containers did not change upon increasing the temperature from ambient to 100 °C. However, the positional preference of the NMs found at ambient temperature to 100 °C was not the same as that observed at 1000 °C due to the increased thermal motions of the NMs. The size of the CNT container had a significant effect on the fluidity of the NMs. From 25 to 100 °C, the NMs inside the (10,10) CNT container were only mobile at low loading densities. On the other hand, in the (20,20) CNT container, the NMs showed good mobility up to a loading density of 1.6 g/cc. Graphical Abstract Attractive interactions between the nitromethanes and the buckybowl caps as well as the carbon nanotube wall.


Lichens as a useful mapping tool?--an approach to assess atmospheric N loads in Germany by total N content and stable isotope signature.
To assess whether nitrogen (N) content and δ(15)N ratios in nitrophytic lichen species (Xanthoria parietina (L.) Th. Fr. (1860) and Physcia spp. (Schreb.) Michaux (1803)) reflect the quantity and quality of atmospheric N loads, 348 lichen samples from 174 sampling grid cells were investigated in the western part of Germany. The analysed lichen N content ranged between 0.98 and 4.28 % and δ(15)N ratios between -15.2 and -1.3 ‰. Based on the N concentrations and the δ(15)N ratios of lichens, different landscape categories and coupled N deposition rates could be inferred for different regions of Germany. By analysing environmental variables like altitude, ammonia emission density, livestock unit and different defined deposition types, a direct relationship was found between lichen chemistry and N compounds produced from agricultural activity. The results support the development of a monitoring method which could be used nationally or even internationally to support current N deposition measurements, by providing reliable information on the quantity and quality of N deposition in high N environments.


Nonpsychiatric consultations within a general hospital psychiatric unit: characteristics and concordance.
Nonpsychiatric consultations to a general hospital psychiatric unit were investigated for concordance with diagnostic testing advice, drug recommendations, and representation of the medical diagnoses in the discharge summary. Those patients who received consultations were older and had less social support but did not have more severe medical illnesses. The level of concordance with medical consultants' recommendations was far greater than previous reports of psychiatric consultants' advice to nonpsychiatric colleagues.


A rapid and reliable in vivo method for anti-GPLA (class I and class II antigens) antibody titration and GPLA typing.
A reverse Arthus reaction (RAR) may be successfully used in guinea pigs to detect histocompatibility alloantigens of the GPLA type. Epidermal cells carry class I GPLA antigens, and Langerhans cells also bear class II alloantigens. It is therefore possible to elicit an RAR by intradermal injection of relevant alloimmune sera in the skin of guinea pigs of known GPLA haplotype. RAR is detected by increased vascular permeability due to IgG1 antibody and hemorrhage due to IgG2 antibody. Compared with an in vitro protein A-rosetting method RAR is easier and quicker. It proved more sensitive for class II antigens in which Langerhans cells are the target for anti-class II antibody and rather less sensitive for class I antigens. RAR is a convenient method for following the course of GPLA alloimmunization, allowing titration of antibodies against both classes of antigen. It may also be used to type guinea pigs of unknown GPLA haplotype.


Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts.
Cytotoxic and mutagenic effects of aphidicolin (APC), an inhibitor of DNA polymerases alpha and delta, were studied in human diploid VH-10 fibroblasts. The cells were treated (2 or 4h) with APC at concentration ranges of 10-40 microM. The effect of APC on cell survival after 4 h treatment was significantly higher than after 2 h treatment. The mutagenicity of APC was investigated at the HPRT locus, and the frequency of HPRT mutants was estimated by selection in medium containing 6-thioguanine (6-TG). Treatment of fibroblast cells with 20 microM of APC for 2 or 4 h resulted approximately in 5 or 10 times increase of 6-TG resistant mutant frequencies, respectively, compared to untreated control cells. The cell cycle analyses performed during the expression time (9-12 days) have shown that after 2 and 4h treatment with APC the cells were blocked in G2 phase during the majority of the expression period, compared to control cells. Four days after the treatment, the amount of cells in G2 phase increased about two-fold (28.6-31.8% compared to 13.5% in the untreated cells). The mode of cell death during the expression time was via necrosis, rather than apoptosis, which was demonstrated by fluorescein-diacetate (FDA)-staining and terminal dUTP nick end labeling (TUNEL)-method.


Mismatch negativity to single and multiple pitch-deviant tones in regular and pseudo-random complex tone sequences.
To determine whether the process responsible for the mismatch negativity (MMN) might be involved in the analysis of temporal sound patterns for information. Synthesized musical instrument tones of 'clarinet' timbre were delivered in a continuous sequence at 16 tones/s, such that there was virtually no N1 potential to each individual tone. The standard sequence comprised 4 or 5 adjacent notes of the diatonic scale, presented either as a regularly repeated, rising pattern or pseudo-randomly. The deviant stimuli were 1-5 consecutive tones of higher pitch than the standards. A MMN was evoked by a single deviant tone, 1 or 5 semitones above the pitch range of the standards. The response to the 5-semitone deviant was significantly larger (mean of 7.3 microV) when the standard pattern was regular as compared with pseudo-random. The MMN latency, on the other hand, was only influenced by the magnitude of pitch deviation. A second MMN was evoked by a second deviant tone, immediately (SOA 62.5 ms) following the first. Further consecutive MMNs were not consistently evoked. The large amplitude of these MMNs can be attributed to the use of complex tones, continuous presentation and a rapid rate of pitch changes, such that no waveform subtraction was required. Over and above the probability with which each individual tone occurs in the standard sequence, the mismatch process is influenced by its temporal structure, i.e. can be regarded as a temporal pattern analyzer. Contrary to the findings of some other groups, we found that two consecutive deviants can evoke an MMN, even at high rates of presentation such that both occur within the postulated 'temporal window of integration' of ca. 170 ms. These findings suggest that the mismatch process might be involved in the extraction of sequential information from repetitive and non-repetitive sound patterns.


Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic female patients.
The incidence of cardiovascular disease in patients with type 2 diabetes mellitus is approximately twice as high as in the non-diabetic population. To investigate the hypoglycemic and hypocholesterolemic effects of Daflon(®) 500 mg (DF) administration together with its tolerability and efficacy in reducing the cardiovascular metabolic risk factors in female patients with type 2 diabetes. In a well-adequate controlled single-blinded randomized parallel design the tolerability and the efficacy of Daflon(®) (500 mg) either alone or with oral hypoglycemic, twice daily for 45 days, was studied in 36 female patients with type 2 diabetes. None of the patients in the studied groups were reported to have any adverse events throughout the treatment period (45 days), liver and kidney function tests were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 45) values. Female patients receiving Daflon(®) either alone or with oral hypoglycemic showed significant decrease in serum glucose; fructosamine; total cholesterol; LDL-cholesterol; triglycerides; malondialdehydes (as index of lipid peroxidation) and C-reactive protein (CRB) levels along with increase in the levels of nitric oxide and blood glutathione. This study has shown that Daflon(®) (500 mg, twice daily for 45 days) is helpful in reducing glucose level and the risk of cardiovascular disease in type 2 diabetic patients. Further clinical trials are essential for strengthening the evidence base on the role of this drug in the cardiovascular risk in diabetic patients.


[Historical investigation of meridian theory vicissitude in the initial period of People's Republic of China(1949─1959)].
The years from 1949 to 1959, in the process of exploring the " scientific acupuncture and moxibustion" , the Chinese medicine community experienced three historical stages in the understanding of meridian theory, namely, the initial " de-meridianization of meridians" , the mid-term " Pavlovization " and the final "back to the origin" . The academic status of the meridian theory also has ups and downs. This was influenced by the political and social environment at that time and the vitality of the discipline itself. The history has finally proved that the meridian theory is one of the important components of TCM theory which cannot be neglected.


Psychological Issues of Patient Transition from Intensive Care to Palliative Care.
End-of-life care in the intensive care unit is fraught with complicated psychological responses by patients, families, and staff. Empathic and mindful communication, inclusion of all integral staff in decision-making meetings, and multidimensional support of patients and families can ease the transition away from aggressive life-prolonging to comfort-oriented end of life care. Primary palliative care communication strategies can help clarify goals of care and facilitate transitions. Early integration of specialist palliative care is recommended.


Cytokines, receptors, and inhibitors.
Cytokines are endogenous mediators in inflammatory and immunologic host defense reactions. In various diseases cytokines produced in excess cause systemic or local toxic effects. Cytokines therefore are tightly controlled by regulation of their biosynthesis and release and by counteracting mechanisms which limit their activities. Two new cytokine inhibitory mechanisms have recently been discovered. First, the generation of soluble receptors which compete with cellular receptors for cytokine binding has been recognized as a general phenomenon. Second, a receptor antagonist polypeptide binding to the receptor but not eliciting biological activity has been discovered in the IL-1 system. These polypeptides, when expressed in various recombinant forms, are not only research tools but may find also direct clinical use.


Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.
Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.


Successful treatment of severe bleeding with recombinant factor VIIa after kidney transplantation.
Recombinant factor VIIa (rFVIIa, NovoSeven) has been registered for the treatment of bleeding episodes in patients with inherited or acquired hemophilia A or B with inhibitors. Furthermore, rFVIIa has been used successfully for the treatment of bleeding in patients with thrombocytopenia, and acquired and congenital platelet dysfunction. The definite spectrum of indications for rFVIIa has not yet been established. We describe a case of severe intra-abdominal bleeding 3 days after non-heart beating kidney transplantation in a patient with severe coronary artery disease in which rFVIIa (a single intravenous bolus injection 70 microg/kg bodyweight) was successfully used. No thrombotic complications occurred. This report demonstrates that rFVIIa might be safe and effective after recent renal transplantation.


Peripheral blood mononuclear cells stimulate prostacyclin levels of human synovial fibroblast-like cells.
Fibroblast-like synovial cells, isolated from intact joints of non-arthritic human donors and from explants of rheumatoid and non-rheumatoid synovial tissue, released prostacyclin (PGI2) when incubated in conditioned medium from human peripheral blood mononuclear cells (MCCM). The effect of MCCM on the rate of PGI2 synthesis (measured by radioimmunoassay as the stable product, 6-keto-PGF1 alpha) was clearly established within 2 h and appeared to require RNA and protein synthesis as judged by inhibition with actinomycin D and cycloheximide, respectively. Low concentrations of dexamethasone suppressed the increase in PGI2 levels. Prostaglandin E2 (PGE2) levels were also raised by the MCCM and reduced by dexamethasone. All-trans retinoic acid did not stimulate the levels of either prostanoid. These findings offer an explanation for some of the inflammatory events occurring in rheumatoid lesions.


Recognizing the Relationship Between Disorders in the Oral Cavity and Systemic Disease.
Oral health is integral to general health. The oral cavity may harbor manifestations of systemic disease and can be the harbinger of early onset. Primary care providers (PCPs) can therefore use the oral cavity to support working diagnoses. Conversely, systemic diseases and treatments can affect oral health and require interactions between PCPs and dental providers. Acute oral manifestations of systemic disease may involve teeth and/or gums. This article reviews oral and systemic disease connections for some diseases, identifies issues that benefit patients through medical-dental collaboration, and highlights some nondental oral injuries that might confront PCPs or emergency medical providers.


Long-term stability of Class II malocclusion treatment with the cantilever bite jumper.
This study aimed to assess the long-term stability of Class II malocclusion treatment with the Cantilever Bite Jumper (CBJ) after 13 years of follow-up. The treatment group comprised 10 Class II Division 1 malocclusion patients treated with the CBJ, followed by fixed appliances, analyzed at 3 stages: pretreatment (aged 11.56-14.32 years), posttreatment (aged 16.34-19.58 years), and long-term posttreatment (aged 29.04-32.33 years). The control group included 15 subjects with normal occlusion. Intragroup treatment changes comparison was performed with repeated measures and analysis of variance followed by Tukey tests. Intergroup comparisons regarding the long-term posttreatment changes were performed with t tests. No statistically significant relapse was observed during the follow-up period. Morever, the treated group presented a significantly smaller increase in lower anterior facial height and greater retrusion of the lower lip than the control group in the posttreatment period. Treatment with the CBJ, followed by fixed appliances, is a stable alternative for Class II Division 1 malocclusion correction. The dentoskeletal and soft-tissue changes obtained during treatment remained stable in the long-term posttreatment follow-up.


Youth involvement in anti-gay and anti-lesbian bias crimes.
There is currently little information available about youth who commit bias crimes. This article contributes to the literature by highlighting the similarities and differences between sexual orientation-motivated bias crimes committed by adult and youth suspects. Among 894 reported sexual orientation-motivated incidents in Los Angeles County between 2002 and 2008, this study found that, when compared to adult suspects, youth suspects were more likely to target other youths, were more likely to be in mixed-gender groups, were less likely to commit crimes against person, and were most likely to be reported as committing the crime at school. These preliminary findings highlight the need for additional research into bias-motivation among youth and to clarify the links between bullying and bias crimes.


Global inventory of natural and anthropogenic emissions of trace metals to the atmosphere.
FEW (if any) recent studies on the atmospheric cycle of trace metals have considered the flux of the metals into the atmosphere on a global scale. Information on worldwide emissions is needed to assess the transboundary movement of pollutant metals and to validate models of the global atmospheric circulation patterns. The worldwide inventories of the natural and anthropogenic sources and emissions of airborne cadmium, copper, lead, nickel and zinc are presented here. The data summarised here are taken from very detailed studies published elsehwere(1-5).


Decreased urokinase receptor expression on granulocytes in HIV-infected patients.
Pericellular proteolysis initiated by receptor-bound urokinase-type plasminogen activator (uPA) is considered important for directed migration of granulocytes to inflammatory sites. Using flow cytometry and whole-cell binding of radiolabelled-uPA, we found a high level of uPA-receptor (uPAR) expression in granulocytes (3.9 x 104 +/- 0.9 x 104 sites/cell). Modulation of uPAR expression was assessed in the presence of chemoattractant gradients. Our findings demonstrate that interleukin (IL)-8, leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine (f MLP) caused a dose-dependent upregulation of uPAR on granulocytes in healthy controls. Modulation of uPAR expression is known to regulate chemotactic response. As determined by flow cytometry, uPAR expression by granulocytes from human immunodeficiency virus (HIV)-infected patients was distinctly lower than that of healthy control cells (P < 0.001). However, upregulation of uPAR in response to chemoattractants was similar to that observed in healthy controls. In HIV-infected patients, the uPAR expression on granulocytes correlated (P < 0.001, n = 10) with the number of CD4+ blood cells. In contrast, the expression of IL-8 receptor, CD11b, CD18 and CD62 was not significantly altered in HIV-patients compared with healthy controls.


Degradation of chemical substances using wet peroxide oxidation under mild conditions.
The objectives of this study are to clarify the degradation mechanism of chemical substances using wet peroxide oxidation (WPO) under mild condition (150 degrees C) and to confirm the removal of polychlorinated biphenyls (PCBs) in soil using this oxidation process. Acetic and oxalic acids were mineralized using WPO. TOC removal rate of acetic acid was highest in the solution of pH 2.5. However, TOC removal rate was decreased with the increase in pH and TOC were hardly removed in the solution of pH 7 and 10. The decomposition rate of isobutyric acid by WPO decreased in the presence of radical scavenger (t-BuOH). The results suggested that the decomposition of chemical substances using WPO proceeded by hydroxyl radical (OH radical). PCBs in soil were also decomposed by performing WPO at 150 degrees C.


Advance Care Planning in the United Kingdom - A snapshot from the four UK nations.
The United Kingdom (UK) as a whole has a long-established decades-old history as an early adopter of the concepts of Advance Care Planning (ACP), with significant integration into mainstream national policy and widespread implementation. The ACP term itself, its processes, means, inclusions and implementations vary considerably within the UK and between its four nations, but the overall impression is of a strongly uniting consensus on the positive impact, value and vital importance of ACP in enabling better care for people in the final years of life, and at earlier life stages. Though there is always more work to do and more lessons to learn, those of us who have watched this world-wide movement grow over recent decades, find the overall direction of travel of commitment to mainstreaming ACP in the UK to be inspiring and encouraging, and gives us hope for the future. Across the UK, there is much shared history, policy, objectives, and regulation related to ACP, and at the same time, many variations in approach, tone, emphasis and detail within and between the four nations of the UK. The 2022 Office of National Statistics reports that the four nations of the UK have a combined population of 67 million (England 56.5 million, Scotland 5.5 million, Wales 3.1 million, Northern Ireland 1.9 million). All four nations are prioritising ACP as part of national policy, aiming to deliver more personalised care, particularly but not exclusively for those nearing the end of life, with a wide variety of best practice examples. Here we describe some common areas and variations across the UK history, policy and legal perspectives, some examples of best practice, resources, and exciting developments across all four nations which, although not exhaustive and within the limitations of our brief, reflect the flavour of our shared commitment. We are most grateful to all the contributing authors.


Fetal echocardiography in the diagnosis of congenital heart disease.
Fetal echocardiography provides an opportunity to diagnose congenital heart disease as early as the midtrimester of pregnancy, allowing for proper planning of perinatal care and counselling of the parents. This paper reviews the accuracy and outcomes of fetal cardiac ultrasound studies at The Prince Charles Hospital over the past 4 years. A total of 43 fetuses, of gestational ages 16-39 weeks, were studied. The indications for these were: previous sibling with cardiac anomaly (16 cases); abnormal heart on obstetric ultrasound scan (USS) (13 cases); abnormalities found on obstetric USS with normal appearing heart (one case); fetal bradycardia (seven cases); fetal tachycardia (four cases); irregular fetal heart beat (two cases). At birth all fetuses assessed because of a previously affected sibling were normal. Of the 13 referred because of structural heart lesions suspected on obstetric USS, eight were abnormal, four were normal and one was terminated without autopsy. Important rhythm disturbances occurred in nine of the 11 referred because of abnormal heart rates. One false positive diagnosis of a possible coarctation was made, and in four cases an abnormality was noted on USS but the diagnosis was not completely correct. Nine of the 19 infants with abnormalities detected have died. Fetal echocardiography is an accurate and useful method of diagnosing congenital heart disease in utero. Although the mortality of affected fetuses is high, antenatal diagnosis allows planning of medical care and offers the greatest chance of a successful outcome.


Metabolic effects of four intravenous nutritional regimens after elective surgery. I. Clinical data and biochemistry.
Biochemical variables have been determined in 28 patients before and after resection of carcinoma of colon or rectum. A synthetic oral diet was given for four days before operation, (0.1 gN.kg/day and 165 kJ.kg/day) and four isocaloric intravenous regimens with different amounts and proportions of amino acids were given for six days after operation. During the preoperative diet the serum urea, glucose, urate, inorganic phosphate and cholesterol concentration decreased while those of triglyceride, iron and alanine amino-transferase increased. After operation the serum triglyceride, protein, albumin, iron, TIBC and urate concentrations decreased. The serum calcium fell in all groups receiving amino acids after operation while magnesium increased in all groups except the one receiving the highest amount of amino acids. The urea concentration decreased when no amino acids were given but increased when amino acids were administered whereas the reverse situation occurred with cholesterol. The highest increase in glucose level was observed when the highest amount of amino acids were given.


The moving emission features in SS433 require a dynamical interpretation.
New spectrophotometry of SS433 shows that the variable-wavelength emission features discovered by Margon et al. are due to the simultaneous presence of material having a substantial redshift and a substantial blueshift. A magnetic interpretation for the features is also ruled out by polarimetric measurements. Implications for dynamical models are discussed.


Physical activity and screen time in outside school hours care services across Australia: current versus best practice.
Outside school hours care (OSHC) is accessed by millions of children internationally. Recently, physical activity and screen time guidelines in OSHC were developed. This study described the current physical activity and screen time scheduling in Australian OSHC, obtained sector feedback on the guidelines and compared current- with best-practice. A cross-sectional online survey was administered to n = 3551 Australian OSHC directors. Participants reported scheduling for physical activity and screen time opportunities in before- and after-school care. Feedback was sought on the new guidelines, including barriers and enablers for implementation. Scheduling data were used to evaluate whether services were currently meeting the new guidelines; that is if time allocated matched with time recommended. Five hundred and sixty-six directors participated (response rate 16%). Physical activity and screen time practices varied widely (e.g., after-school physical activity opportunity ranged from 15 to 150 min, mean 74, SD 28; after-school screen time opportunity ranged from 15 to 195 min, mean 89, SD 43), with state (p = 0.002) and socioeconomic (based on postcode; p < 0.001) differences. Most participants (54-81%) agreed that the guideline's recommended physical activity and screen time durations were appropriate, however, only 40% of participants' OSHC services' programs actually met the guidelines. Physical activity and screen time scheduling in OSHC is highly variable. Despite support for the guidelines, current scheduling practice in the majority of OSHC services surveyed do not meet best practice guidelines.


Preparation and bioevaluation of 166Ho labelled hydroxyapatite (HA) particles for radiosynovectomy.
The preparation of 166Ho labeled hydroxy apatite (HA) particles for radiosynovectomy applications is described in this paper. 166Ho was prepared by the irradiation of Ho2O3 at a flux of 1.8 x 10(13) neutrons/cm2/s for about 7 days. The irradiation resulted in the production of approximately 17 GBq of 166Ho activity at the end of six hours post end of bombardment and the corresponding specific activity was approximately 3-4 GBq/mg of Ho. The irradiated target was dissolved in 0.1 N HCl solution. Radionuclidic purity was ascertained by high resolution gamma ray spectrometry. HA particles were synthesized and characterized by X-ray diffractometry. Labeling studies were carried out with and without citric acid as a transchelating agent. Radiochemical yield and purity of the 166Ho-HA particles were ascertained by paper chromatography and by paper electrophoresis techniques. Labeling yield of >98% could be achieved at pH 7, with 40 mg of HA particles and 8.6 microg of Ho. 166Ho-HA particles prepared were stable for 72 h. Bio-evaluation of the 166Ho -HA particles were carried out by injecting approximately 74 MBq dose in 200 microL (approximately 8 mg of 166Ho-HA particles) directly into the arthritis induced knee joints as well as into the healthy knee joints of white New Zealand rabbits. Images of the injected joints of the animals recorded using a gamma camera at regular intervals showed good retention. Blood samples were collected from the animals and activity assayed in a scintillation detector. Experiments were also carried out under identical conditions in normal rabbits. In both the cases, it was observed that there was no significant extra articular leakage of the injected activity over the study period of 96 h post injection.


Human TRPV5 and TRPV6: key players in cadmium and zinc toxicity.
TRPV5 and TRPV6 are two major calcium transport pathways in the human body maintaining calcium homeostasis. TRPV5 is mainly expressed in the distal convoluted and connecting tubule where it is the major, regulated pathway for calcium reabsorption. TRPV6 serves as an important calcium entry pathway in the duodenum and the placenta. Previously, we showed that human TRPV6 (hTRPV6) transports several heavy metals. In this study we tested whether human TRPV5 (hTRPV5) also transports cadmium and zinc, and whether hTRPV5 together with hTRPV6 are involved in cadmium and zinc toxicity. The hTRPV5 mRNA and protein were expressed in HEK293 cells transiently transfected with pTagRFP-C1-hTRPV5. The overexpression of the hTRPV5 protein at the plasma membrane was revealed by cell surface biotinylation and immunofluorescence techniques. We observed that both cadmium and zinc permeate hTRPV5 in ion imaging experiments using Fura-2 or Newport Green DCF. Our results were further confirmed using whole-cell patch clamp technique. Transient overexpression of hTRPV5 or hTRPV6 sensitized cells to cadmium and zinc. Toxicity curves of cadmium and zinc were also shifted in hTRPV6 expressing HEK293 cells clones. Our results suggest that TRPV5 and TRPV6 are crucial gates controlling cadmium and zinc levels in the human body especially under low calcium dietary conditions, when these channels are maximally upregulated.


NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy.
An increasing number of clinical and animal model studies indicate that activation of the innate immune system and inflammatory mechanisms are important in the pathogenesis of diabetic nephropathy. Nucleotide-binding oligomerization domain containing 2 (NOD2), a member of the NOD-like receptor family, plays an important role in innate immune response. Here we explore the contribution of NOD2 to the pathogenesis of diabetic nephropathy and found that it was upregulated in kidney biopsies from diabetic patients and high-fat diet/streptozotocin-induced diabetic mice. Further, NOD2 deficiency ameliorated renal injury in diabetic mice. In vitro, NOD2 induced proinflammatory response and impaired insulin signaling and insulin-induced glucose uptake in podocytes. Moreover, podocytes treated with high glucose, advanced glycation end-products, tumor necrosis factor-α, or transforming growth factor-β (common detrimental factors in diabetic nephropathy) significantly increased NOD2 expression. NOD2 knockout diabetic mice were protected from the hyperglycemia-induced reduction in nephrin expression. Further, knockdown of NOD2 expression attenuated high glucose-induced nephrin downregulation in vitro, supporting an essential role of NOD2 in mediating hyperglycemia-induced podocyte dysfunction. Thus, NOD2 is one of the critical components of a signal transduction pathway that links renal injury to inflammation and podocyte insulin resistance in diabetic nephropathy.


Rapid, automated nerve histomorphometry through open-source artificial intelligence.
We aimed to develop and validate a deep learning model for automated segmentation and histomorphometry of myelinated peripheral nerve fibers from light microscopic images. A convolutional neural network integrated in the AxonDeepSeg framework was trained for automated axon/myelin segmentation using a dataset of light-microscopic cross-sectional images of osmium tetroxide-stained rat nerves including various axonal regeneration stages. In a second dataset, accuracy of automated segmentation was determined against manual axon/myelin labels. Automated morphometry results, including axon diameter, myelin sheath thickness and g-ratio were compared against manual straight-line measurements and morphometrics extracted from manual labels with AxonDeepSeg as a reference standard. The neural network achieved high pixel-wise accuracy for nerve fiber segmentations with a mean (± standard deviation) ground truth overlap of 0.93 (± 0.03) for axons and 0.99 (± 0.01) for myelin sheaths, respectively. Nerve fibers were identified with a sensitivity of 0.99 and a precision of 0.97. For each nerve fiber, the myelin thickness, axon diameter, g-ratio, solidity, eccentricity, orientation, and individual x -and y-coordinates were determined automatically. Compared to manual morphometry, automated histomorphometry showed superior agreement with the reference standard while reducing the analysis time to below 2.5% of the time needed for manual morphometry. This open-source convolutional neural network provides rapid and accurate morphometry of entire peripheral nerve cross-sections. Given its easy applicability, it could contribute to significant time savings in biomedical research while extracting unprecedented amounts of objective morphologic information from large image datasets.


Retrospective study of prognostic importance of DNA flow cytometry of urinary bladder carcinoma.
Cellular DNA content was determined by flow cytometry on routinely processed paraffin sections of 61 primary and untreated transitional cell carcinomas of the urinary bladder, and correlated with tumour grade and stage and clinical follow up. All 16 (25%) grade 1 carcinomas were diploid and all 11 (20%) grade 3 tumours were aneuploid. The 34 (55%) grade 2 carcinomas comprised 13 (40%) diploid and 21 (60%) aneuploid cases. Among the 37 superficial carcinomas (stage Ta and T1), 25 (65%) were diploid; 20 (85%) of the 24 advanced tumours (stage T2 to T4) had aneuploid tracings. Ploidy was a significant prognostic indicator (p: 0.006) of five year survival. The initial presence of aneuploidy in superficial bladder carcinoma (stage Ta and T1) is a strong argument for more aggressive treatment than is customary.


Effects of an individualised exercise programme plus Behavioural Change Enhancement (BCE) strategies for managing fatigue in frail older adults: a cluster randomised controlled trial.
To the best of our knowledge, although ageing-induced fatigue could cause adverse outcomes such as frailty, there is currently no intervention for it. This study evaluated the effects of an individualised exercise programme with/without BCE strategies on reducing fatigue in older adults. A three-armed cluster-randomised controlled trial (RCT) was conducted with 184 participants (mean age: 79.1 ± 6.4; mean frailty score: 2.8 + 0.8) from 21 community centres (ClinicalTrials.gov: NCT03394495). They were randomised into either: the COMB group (n = 64), receiving 16 weeks of exercise training plus the BCE programme; the EXER group (n = 65), receiving exercise training and health talks; or the control group (n = 55), receiving only health talks. Fatigue was assessed using the Multi-dimensional Fatigue Inventory (range: 20 to 100, with higher scores indicating higher fatigue levels) at baseline, and immediately, 6 months, and 12 months post-intervention. The GEE analyses showed significant interaction (time x group) between the COMB and control groups immediately (p < 0.001), 6 months (p < 0.001), and 12 months (p < 0.001) post-intervention. Comparing the COMB and EXER groups, there was a significant interaction immediately (p = 0.013) and at 12 months post-intervention (p = 0.007). However, no significant difference was seen between the EXER group and control group at any time point. The COMB intervention showed better immediate and sustainable effects (i.e., 12 months after the intervention) on reducing fatigue in frail older adults than exercise training or health education alone. ClinicalTrials.gov (NCT03394495), registered on 09/01/2018.


Measuring Participation for Children and Youth With Power Mobility Needs: A Systematic Review of Potential Health Measurement Tools.
To identify and critically appraise potential participation measurement tools for children aged 18 months to 17 years with power mobility (PM) needs. Searches in 9 electronic databases identified peer-reviewed publications in English to January 2015, along with hand-searching included bibliographies. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed with inclusion criteria set a priori. Keywords and subject headings included participation and measurement terms with descriptors of young people who are potential PM candidates. Publications describing measurement properties of English-language tools were included if the items included ≥ 85% content related to participation and described at least 2 participation dimensions. Two reviewers reached consensus after independently screening titles and abstracts, identifying full-text articles meeting criteria, extracting data, and conducting quality ratings. Tool descriptions, clinical utility, and measurement properties were extracted. Study quality and measurement properties were evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments checklist and the McMaster Outcome Measures Rating Form. Of 1330 titles identified, 138 peer-reviewed publications met study inclusion criteria. Fifty tools were identified, of which 20 met inclusion criteria. Evidence supporting reliability and validity varied considerably. Two tools had responsiveness evidence, an important measurement property when evaluating change. Quality ratings were strongest for internal consistency and content validity. Ratings were downgraded because of small sample sizes and a limited description of missing data or study conditions. While potential tools emerged (Assessment of Preschool Children's Participation, Preferences for Activities of Children, Child and Adolescent Scale of Participation, Child Engagement in Daily Life, Canadian Occupational Performance Measure, Questionnaire of Young People's Participation), none were judged best suited for use with children having PM needs. Further empirical studies with this population are needed before recommending use for PM applications.


Environmental contamination by eggs of Toxocara species.
A study was conducted to determine the level of contamination with Toxocara spp. eggs in parks and playgrounds in several central Illinois communities. A total of 135 composite 50-g soil samples were collected from 23 parks and public places in three cities in central Illinois. Of these soil samples, 22 (16.3%) contained from one to thirteen Toxocara spp. eggs. A total of 40 fecal samples were collected from the same parks. Toxocara spp. eggs were found in two (5%) of the samples.


Local inhibitory effects of dynorphin A-(1-17) on capsaicin-induced thermal allodynia in rhesus monkeys.
Although dynorphin A-(1-17) has been characterized in vitro as a high efficacy kappa-opioid receptor agonist, functional studies of dynorphin A-(1-17) following central or systemic administration indicate the involvement of both opioid and non-opioid components. The aim of this study was to investigate whether local administration of dynorphin-related analogs can attenuate capsaicin (8-methyl-N-vanillyl-6-nonenamide)-induced nociception and what type of opioid receptor mediates the local action of dynorphin A-(1-17) in monkeys. Capsaicin (100 microg) was used to evoke a nociceptive response, thermal allodynia, which was manifested as a reduced tail-withdrawal latency in normally innocuous 46 degrees C warm water. Co-administration of dynorphin A-(1-17) (0.3-10 microg) with capsaicin in the tail dose-dependently inhibited thermal allodynia; however, both non-opioid fragments dynorphin A-(2-17) (10-300 microg) and dynorphin A-(2-13) (10-300 microg) were ineffective. Local antiallodynia of dynorphin A-(1-17) was antagonized by a small dose (100 microg) of an opioid receptor antagonist, quadazocine, applied s.c. in the tail. Pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), s.c. 320 microg in the tail also reversed local antiallodynia of dynorphin A-(1-17). Both locally effective doses of antagonists, when applied s.c. in the back, did not antagonize local dynorphin A-(1-17), indicating that peripheral kappa-opioid receptors selectively mediated the local action of dynorphin A-(1-17) in the tail. In addition, a much larger dose of dynorphin A-(1-17) (1000 microg), when administered s. c. in the back or i.m. in the thigh, did not cause sedative or diuretic effects. These results suggest that in vivo opioid actions of dynorphin-related peptides can be differentiated locally in this procedure. They also indicate that local application of peptidic ligands may be a useful medication for localized pain.


Connective tissue disorders in dissections of the carotid or vertebral arteries.
Dissections of the carotid or vertebral arteries are a significant cause of ischemic stroke. Their etiology includes not only mechanical forces but also underlying arteriopathies such as Ehlers-Danlos syndrome type IV and other connective tissue disorders. Furthermore, dissections often occur spontaneously or after minor trauma in otherwise healthy individuals without clinically evident underlying aberrations. However, in some of these patients ultrastructural connective tissue changes can be detected. An overview of connective tissue disorders associated with dissections of the carotid or vertebral arteries is presented.


Synthesis of Multiply Substituted Polycyclic Aromatic Hydrocarbons by Iridium-Catalyzed Annulation of Ring-Fused Benzocyclobutenol with Alkyne through C-C Bond Cleavage.
The first iridium-catalyzed intermolecular cyclization between alkynes and ring-fused benzocyclobutenols (RBCB) through C-C bond cleavage is described. A variety of elusive polycyclic aromatic hydrocarbons (PAHs) with multiple substituents are obtained in good yields under mild conditions. This procedure provides a unique and expeditious tool for the synthesis of PAHs.


Flow cytometry applications in the evaluation of sperm quality: semen analysis, sperm function and DNA integrity.
Flow cytometry (FCM) has been extensively used to study mammalian sperm in the areas of reproductive toxicology (to monitor effects from environmental, occupational and therapeutic exposures), veterinary science (to preselect the gender of offspring by sorting X- and Y-chromosome-bearing sperm) and clinical andrology (to assess individual fertility potential). Using FCM, a variety of sperm features can now be rapidly measured on a cell-by-cell basis such as sperm count, viability, acrosomal integrity, mitochondrial function and DNA integrity; the last one is involved in postfertilization failure and embryo toxicity. It is foreseen that only a multiplex approach, which includes FCM assays together with the new genomics/proteomics methods, could increase the predictive power of fertility status and help identify susceptible subpopulations of men at risk for infertility, spontaneous abortions and birth defects.


Correction to: GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data.
An amendment to this paper has been published and can be accessed via the original article.


Epigenome-wide association analyses of active injection drug use.
Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized. 401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics. We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10-8) and injection intensity (cg13117953, p = 4.30 × 10-8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03). Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.


Ontogeny of unconjugated estriol in fetal blood and the relation of estriol levels at birth to the development of respiratory distress syndrome.
Unconjugated estriol (E3) was quantified in serum of umbilical cord blood of 533 newborn infants, 360 of whom were delivered between 23 and 37 wk of gestation. Serum E3 levels rose (F = 7.71, p less than 0.0001) as a function of gestational age; the mean concentration of E3 at 37.5-42 wk of gestation (105 ng/ml, n = 173) was significantly higher than that in serum of newborns delivered at 23-28 wk of gestation (63 ng/ml, n = 33). Umbilical cord serum levels of E3 were significantly higher among newborns delivered vaginally between 31.5 and 42 wk of gestation than among newborns delivered by cesarean section (p less than 0.005). Although serum E3 levels correlated highly (p less than 0.0001) to newborn weight throughout the entire period of gestation, there was no relationship of newborn weight to umbilical serum E3 levels within a given gestational period. Also, the umbilical serum levels of E3 in male infants were similar to those of female infants at each gestational age. Significant changes in umbilical serum levels of E3 as a function of gestational age were not observed among newborns (n = 90) who developed respiratory distress syndrome (RDS). The mean umbilical serum concentration of E3 in newborns delivered at 34.5-37 wk of gestation who developed RDS were significantly lower (p less than 0.01) than that in similar aged newborns whose lung function was normal.(ABSTRACT TRUNCATED AT 250 WORDS)


Pharmacokinetic and pharmacodynamic profiles of CS-518, a selective, long-lasting thromboxane synthase inhibitor, after single and multiple oral administration to healthy volunteers.
A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were examined. The production of TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in serum during whole blood coagulation ex vivo also were examined. In the single-dose study (50, 100, and 200 mg), plasma concentrations of the drug were well fitted to a one-compartment open model with first-order absorption. The area under plasma concentration curve (AUC) and maximum plasma concentration (Cmax) showed dose-related increases, whereas the mean elimination half-lives remained rather constant (.68-.92 hour). The drug was recovered in urine by 32 to 37% and 62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively, showing almost complete absorption of CS-518. The effect of food intake on the pharmacokinetics of CS-518 was determined at the dose of 100 mg. The time to reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by about 66%, whereas the AUC and urinary recovery showed no significant changes. The platelet aggregation in plasma induced by AA was markedly inhibited, whereas the secondary aggregation induced by ADP was inhibited to a much less degree. Platelet aggregation by AA was almost completely inhibited 2 hours after administration of any dose and the duration for maintaining the significant inhibition tended to depend on the dose ranging from 48 to 72 hours after administration, which was much longer than expected from the plasma concentration of drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of the chemical composition of urinary calculi by computerized tomography.
The clinical management of renal calculi would be aided if a direct in vivo determination of stone chemical composition could be made. We investigated the possibility of obtaining this information by a quantitative analysis of the computerized tomography scan images of 80 urinary calculi. Our results show that by using an appropriately calibrated computerized tomography scanner the differentiation of stone chemical composition can be made on the basis of 3 parameters, namely, absolute computerized tomography value at a single x-ray energy, the difference between computerized tomography values measured at 2 different x-ray energies, and computerized tomography value-frequency histograms (pixel patterns) of the stones. Uric acid stones were differentiated from all other stones at a significance level of p less than 0.001. Cystine was differentiated from calcium oxalate and brushite at the same significance level. Using pixel patterns cystine and struvite were separated from each other correctly with 70 per cent accuracy. Struvite stones of low or moderate calcium phosphate content were identified correctly with 80 per cent accuracy. Struvite stones of high calcium phosphate content could not be differentiated from calcium oxalate or brushite. Calcium oxalate and brushite could not be separated. The minimum stone size that allowed chemical identification was established for each stone type. In addition, we demonstrated that all the urinary calculi examined were visible on computerized tomography scan regardless of chemical composition or size.


Intra-parotid facial nerve multiple plexiform neurofibroma in patient with NF1.
Primary neurogenic tumours of facial nerve are uncommon with the majority found intra-temporally. Intracranial and intra-parotid neoplastic involvement of cranial nerve VII is much less common. There are 11 reported cases, in the English-language literature, of intra-parotid facial nerve plexiform neurofibromas with eight of them associated with NF1. A child, 10 years old, with NF1, reached us for a cheek swelling, slowly increased in previous 8 years. At the age of 3 years, a plexiform neurofibroma was diagnosed by biopsy of the lesion. Clinical examination and NMR showed in the sub-cutaneous tissue of the right cheek, two contiguous nodular lesions, about 2 cm x 1.5 cm in diameter; a third neoformed lesion, about 1cm in diameter, was located above the ipsilateral labial commissure. No facial nerve impairment was seen. The patient underwent superficial parotidectomy with removal of the lesions and preservation of the facial nerve. The patient had a considerable regional swelling in the immediate post-operative course; no facial nerve impairment was observed. The swelling of the cheek did not show a fully regression in the post-operative course. Ultrasonography at 3 months showed a recurrence of disease. Plexiform neurofibromas should be distinguished due to their risk of malignant transformation seen in up to 15% of patients affected by NF1. Surgery is the only effective option currently available for the treatment of PNF. However, success of surgical intervention is limited by the infiltrating nature of the tumours, resulting in a high rate of tumour re-growth. Facial nerve preservation during surgery is unlikely and significant morbidity can result from their excision. The age of the patient at surgical resection seemed to influence outcome: tumours resected before age 10 years recurred in 60% of cases compared with only 30% recurrence in patients older than the age of 10 years. Indication and timing of surgery, in paediatrics patients with NF1, are complex. To avoid eventual physical and psychological consequences, it seems prudent to delay surgery as long as it is feasible for otherwise asymptomatic paediatric patients with facial plexiform neurofibroma.


Improving Pediatric Neuro-Oncology Survival Disparities in the United States-Mexico Border Region: A Cross-Border Initiative Between San Diego, California, and Tijuana, Mexico.
Treatment of children with CNS tumors (CNSTs) demands a complex, interdisciplinary approach that is rarely available in low- and middle-income countries. We established the Cross-Border Neuro-Oncology Program (CBNP) between Rady Children's Hospital, San Diego (RCHSD), and Hospital General, Tijuana (HGT), Mexico, to provide access to neuro-oncology care, including neurosurgic services, for children with CNSTs diagnosed at HGT. Our purpose was to assess the feasibility of the CBNP across the United States-Mexico border and improve survival for children with CNSTs at HGT by implementing the CBNP. We prospectively assessed clinicopathologic profiles, the extent of resection, progression-free survival, and overall survival (OS) in children with CNSTs at HGT from 2010 to 2017. Sixty patients with CNSTs participated in the CBNP during the study period. The most common diagnoses were low-grade glioma (24.5%) and medulloblastoma (22.4%). Of patients who were eligible for surgery, 49 underwent resection at RCHSD and returned to HGT for collaborative management. Gross total resection was achieved in 78% of cases at RCHSD compared with 0% at HGT (P < .001) and was a predictor of 5-year OS (hazard ratio, 0.250; 95% CI, 0.067 to 0.934; P = .024). Five-year OS improved from 0% before 2010 to 52% in 2017. The CBNP facilitated access to complex neuro-oncology care for underserved children in Mexico through binational exchanges of resources and expertise. Survival for patients in the CBNP dramatically improved. Gross total resection at RCHSD was associated with higher OS, highlighting the critical role of experienced neurosurgeons in the treatment of CNSTs. The CBNP model offers an attractive alternative for children with CNSTs in low- and middle-income countries who require complex neuro-oncology care, particularly those in close proximity to institutions in high-income countries with extensive neuro-oncology expertise.


Tumor-Free Resection Margin Distance in the Surgical Treatment of Node-Negative Squamous Cell Cancer of the Vulva Has No Impact on Survival: Analysis of a Large Patient Cohort in a Tertiary Care Center.
The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. The patients were subclassified into three resection margin category groups: "1 to 3 mm" (n = 42), ">3 to 8 mm" (n = 47) or ">8 mm" (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62-0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71-0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.


Acrylamides and methacrylamides as alternative monomers for dental adhesives.
Synthesize and characterize a methacrylamide monomer for adhesive system and evaluate the physicochemical properties of the adhesive resin. The liquid methacrylamide monomer N,N',N″-(nitrilotris(ethane-2,1-dyil)tris(2-methylacrylamide) (TMA) was prepared by reaction of methacrylic anhydride and tris(2-aminoethyl)amine with 60% yields. The TMA structure was analyzed by 1H NMR, 13C NMR, ATR-FTIR and UHPLC-QTOF-MS. Experimental adhesive resin containing bisphenol-A glycidyl methacrylate (BISGMA), 2-hydroxyethylacrylamide (HEAA), 2-hydroxyethylmethacrylate (HEMA) and TMA were formulated. Polymerization kinetics of neat TMA and experimental adhesive resin (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA/HEAA/TMA and BisGMA/HEMA) were evaluated using Differential Scanning Calorimetry. Physiochemical properties for BisGMA/HEAA/TMA and BisGMA/HEMA adhesives were evaluated by cytotoxicity, ultimate tensile strength (UTS), softening in solvent (ΔKHN), contact angle (θ), microtensile bond strength (μTBS) and failure analysis. A primer was also formulated with H2O/HEAA/AMPS (2-acrylamido-2-methylpropane sulfonic acid) and the pH value was verified and compared to commercial primer. Adhesive resin with only HEAA and TMA (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) showed lower conversion and polymerization rate after 40s of light activation. Conversion up to 60% was found for BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin without significant difference between groups, p>0.05. Cytotoxicity, UTS, μTBS, ΔKHN and θ showed no statistical difference, p>0.05, between BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin. In this study, the proposed synthetic route resulted in a tris(methacrylamide). A new primer composed without acrylates or methacrylates was formulated for 3-step etch-and-rinse adhesive system without the presence of HEMA monomer. Physicochemical properties and cell viability of BisGMA/HEAA/TMA adhesive resin represents an alternative adhesive resin without HEMA monomer.


No further decrease in blood pressure when the interval between readings exceeds one hour.
The assessment of blood pressure (BP) in individuals is traditionally based on a few BP readings obtained at intervals of just a few minutes. We examined if increasing intervals between BP readings on one visit would have an impact on the BP estimates. We conducted an examination survey of cardiovascular risk factors in the general population aged 25-64 years in Seychelles (Indian Ocean), attended by 1255 of 1565 eligible participants. BP was measured once shortly after participants' arrival to the study centers (BP1) and twice before discharge, 15-351 min later (BP2, BP3; separated by 2 min). Mean (standard error) BP1 was 135.1 (0.7)/87.9 (0.4) mmHg, BP2: 130.7 (0.6)/85.1 (0.4) mmHg and BP3: 128.4 (0.6)/83.9 (0.3) mmHg. The difference in BP between the first and the last measurements (DeltaBP1-BP3) was, respectively, 5.8 (1.3)/2.6 (0.9) mmHg for a time interval between BP1 and BP3 of 15-60 min, 6.3 (0.5)/3.9 (0.3) mmHg for 61-120 min, 6.9 (0.6)/4.1 (0.4) mmHg for 121-240 min and 7.4 (0.7)/4.3 (0.5) mmHg for 241-351 min (P-trend for systolic/diastolic BP: 0.15/0.49). In multivariate analysis, both systolic and diastolic DeltaBP were associated with the initial BP level and the female sex but not with time (in minutes) between BP readings (for systolic/diastolic BP, P=0.12/0.34). The decrease in subsequent BP readings obtained did not differ whether the time interval between BP measurements was larger or smaller than 1 h. This indirectly suggests that extending the time interval between repeated BP readings on one single visit is unlikely to be a valid, alternative strategy to the recommendation of gathering BP readings on several, separate visits to define hypertension.


Therapeutic options for advanced prostate cancer: 2011 update.
Up to 40% of male patients diagnosed with prostate cancer develop metastatic disease that generally responds to initial chemical or surgical castration, but this eventually progresses despite castrate levels of testosterone, termed castration-resistant prostate cancer (CRPC). A large phase 3 trial of abiraterone acetate in patients who have progressed following docetaxel based chemotherapy were published in 2011 and dramatically proved that CRPC is still androgen-dependant and responds to CYP17 inhibition. Overall survival benefits were also reported for a novel tubulin-binding drug, cabazitaxel, tested as second-line chemotherapy after docetaxel failure; for sipuleucel-T, an autologous dendritic cell therapy, in chemotherapy-naive patients; for MDV3100, a novel antiandrogen, and for radium-223, which is a bone-seeking α-irradiation-emitting radioisotope. Denosumab, a monoclonal antibody against receptor activator of nuclear factor-kB ligand, was shown to be superior to zoledronic acid for prevention of skeletal-related events in prostate cancer patients with metastatic bone disease. This review will focus on the recent developments in the field of CRPC.


Integrated neuroimmune processing of threat, injury, and illness: An ecological framework mapping social alienation onto lifetime health vulnerability.
Social alienation is a pre-eminent ecological threat for humans. In clinical and social care settings its impact is acknowledged in conditions as diverse as severe mood disturbance, chronic pain, and metabolic non-communicable diseases. An integrated psychoneuroimmune perspective shows how threat, injury, healing, and recovery follow through as a continuous process, but accepted cultural and clinical paradigms separating mental from physical illness provide little common ground on which to analyse and apply this continuum in practice. By reviewing the ecological relationships between emotional threat, tissue dyshomeostasis and injury, infection, pain, and mood this article explores not only how primeval somatic responses underpin the evolutionary foundations of depression and somatisation, but also links them to escalating physical non-communicable disease through archived socioeconomic adversity (allostatic load). Social alienation (in the absence of trauma) may prime and activate this ancient repertoire in which sensitised responses lay the foundation for persistent maladaptive states of aversive sensory misinterpretation, behavioural avoidance, anhedonia, and neuroinflammation presenting as widespread non-nociceptive pain, non-pain somatisation, and severe depression. The ecological perspective illuminates perverse clinical presentations, shows how some approaches to care may facilitate self-reinforcement in maladaptive syndromes, and offers pointers for inclusive rehabilitative clinical and social care.


Preventive rather than therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute and chronic DSS-induced colitis in mice.
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.


Coping with mental illness: a family's struggle for peace.
Families struggle with the day-to-day worrying about behaviors of acting out at school and work, and the loss of normalcy that they used to have in their everyday lives. Families with a loved one with mental illness live in an almost constant state of uncertainty due to the unpredictability of the illness. This article addresses the challenges inherent to the acute psychiatric admission process of a patient and family.


Septal Q wave in exercise testing: evaluation by single-photon emission computed tomography.
Changes of septal Q waves in lead V5 by exercise were evaluated with single-photon emission computed tomography. Coronary artery disease was present in 66 patients, 48 of whom had left anterior descending coronary artery (LAD) involvement. Forty-one subjects had normal coronary arteries. All patients under investigation were classified into 3 groups: group A (18 patients)--regression of Q amplitude during exercise; group B (48 patients)--progression or no change of Q wave or a new Q wave during exercise; and group C (41 patients)--no Q waves at rest and during exercise. Perfusion defects of the septum were calculated 3-dimensionally and expressed as a percent of the total septum. Seventeen patients (94%) in group A showed septal perfusion defects by exercise and all of them had LAD stenosis. Forty-three patients (90%) in group B showed no septal perfusion defects, but the others with perfusion defects had LAD stenosis. In group C, 23 of 41 patients (56%) had an LAD lesion, of whom 91% showed septal perfusion defects; none of the remaining 18 patients without LAD stenosis showed perfusion defects. The area of septal perfusion defects during exercise was larger in group A (62 +/- 19%) and in group C (52 +/- 19%) than in group B (23 +/- 9%) (groups A vs B, p less than 0.001; groups C vs B, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


The ultrastructure of an IOL "cocoon membrane".
A white cocoon membrane emanating from an inferotemporal focus in the iris stroma totally ensheathed a Binkhorst four-loop iris plane lens 18 months after implantation. The membrane was removed and studied by scanning (SEM) and transmission (TEM) electron microscopy. By SEM the external surface of the membrane was characterized by a fibrillar meshwork, with only an occasional scattered spindle-shaped or rounded inflammatory cell occupying the surface. One-micron plastic sections revealed both spindle and polyhedral heavily pigmented cells in the outer aspect of the membrane, and compressed elongated nonpigmented spindle cells scattered throughout the central portions. By TEM cells clinging to the outermost aspects were bipolar iris stromal melanocytes with small melanosomes, inactive fibroblasts, or histiocytes with cytoplasmic ruffles. The larger rounded pigmented cells in the superficial region were viable or degenerated iris pigment epithelial cells or macrophages. Most of the substance of the membrane was composed of collagen fibrils 100-500 A in diameter with and without 640 A periodicity; these fibrils were generally oriented parallel to the spindle cells but did not display distinct bundling or a lamellar architecture. The spindle cells in the center of the lesion were active fibroblasts with abundant rough-surfaced endoplasmic reticulum and scattered actin myofilaments; they contained rare small and large melanin granules indicative of phagocytosis. It has been concluded that the membrane was produced predominantly by iris stromal fibroblasts probably activated by the haptics of the IOL or McCanell suture.


Accuracy of a novel accelerometer-based navigation (Naviswiss) for total hip arthroplasty in the supine position.
This study aimed to determine the accuracy of acetabular cup insertion using a novel accelerometer-based navigation system in total hip arthroplasty (THA). A single-surgeon study was conducted in which 62 prospective patients with navigation and 42 retrospective patients without navigation in a supine position were compared. Absolute values for errors of radiographic inclination and anteversion were calculated. Navigation error was also calculated. Factors that affected absolute value of navigation error in cup alignment were determined. In the navigation group, mean absolute errors for radiographic inclination and anteversion were 4.1° and 4.3°, respectively. In the control group, mean absolute errors were 6.6° in inclination (p < 0.01) and 5.9° in anteversion (p = 0.04). Mean absolute values of navigation error were 2.8° in inclination and 2.8°in anteversion. Factors affecting navigation errors were not found. This novel accelerometer-based navigation system significantly increased the accuracy of cup placement during THA in the supine position.


Elderly donors for HCV(+) versus non-HCV recipients: patient survival following liver transplantation.
Chronic liver failure due to hepatitis C virus (HCV)-related cirrhosis is the leading indication for liver transplantation. Inferior long-term results have been reported for liver transplantation in HCV(+) patients, especially when marginal donor livers are utilized. The aim of this study was to analyze retrospectively the outcome of liver transplantation patients from elderly donors in the case of HCV(+) versus non-HCV recipients. Among 330 liver transplantations performed from January 1994 to December 2006, we selected 244 excluding acute hepatic failure, children, and retransplants. Among these patients we analyzed 232 subjects who underwent the piggyback technique. Donor risk index (DRI) as described by Feng et al was applied using 1.7 as a cutoff value. We used Kaplan-Meier survival and Cox hazard regression analyses. We studied 14 donor variables using descriptive statistical tests. There were 148 (63.8%) HCV(+) recipients and 84 (36.2%) non-HCV liver transplant recipients. Among HCV(+) recipients, 130/148 (87.8%) patients received livers, from donors less than 50 years old, and 18/148 (12.2%), over 50 years. The descriptive statistics of patient categorical variables are shown in Table 1, and continuous variables in Table 2. The cumulative proportional survival curves are shown in Figs 1 and 2. Mortality predictive factors in HCV(+) liver transplant recipients with donor age > 50 years old as determined by Cox hazard regression showed that death risk was increased with hazard ratios for warm ischemia = 1.01 (P = .001); for red blood cell intraoperative requirements = 2.63 (P = .003); for Child-Turcotte-Pugh classification points = 2.25 (P = .04), and for DRI > 1.7 = 2.19 (P = .03). In conclusion, advancing donor age, as well as the use of nonideal donors, intraoperative bleeding, and prolonged warm ischemia, had an adverse influence on patient survival for HCV(+) recipients.


Response pattern features of mitral cells in the goldfish olfactory bulb.
Temporal discharge characteristics of goldfish olfactory bulb mitral cells are investigated. In contrast to earlier findings, it has been shown that every response is determined by only two features, namely, the mean activities of the early and the late response (dynamic and static response component). As both activities can be lower than, indistinguishable from, or higher than prestimulus activity, the two response features correspond to 9 possible response pattern types.


Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients.
The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318-3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204-2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177-2.402, P = 0.004). Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared.


Localized benign mesothelioma of the pleura associated with a hypoglycemic episode.
A patient had severe, episodic hypoglycemia with a mass occupying almost the entire left hemithorax. This mass was initially thought to be an inoperable intrathoracic malignant neoplasm. The findings during operation and the histologic appearance, however, were of a unique, localized benign mesothelioma.


Long-Term Outcome of the GORE EXCLUDER AAA Endoprosthesis for Treatment of Infrarenal Aortic Aneurysms.
To evaluate long-term outcome of GORE EXCLUDER AAA Endoprosthesis (W.L. Gore & Associates, Inc, Flagstaff, Arizona) for elective treatment of infrarenal aortic aneurysms and to evaluate performance of different generations of the device. A retrospective analysis was performed of 248 patients undergoing elective endovascular aneurysm repair with the GORE EXCLUDER between January 2000 and December 2015 in 2 hospitals. Primary endpoint was reintervention-free survival. Secondary endpoints were technical success, overall survival, rupture-free survival, endoleaks, sac diameter change (> 5 mm), limb occlusion, and migration (> 5 mm). Median follow-up time was 26 months (range, 1-190 months). Assisted primary technical success was 96.8%. Reintervention-free survival for 5 and 10 years was 85.2% and 75.6%, respectively. Independent risk factors for reintervention were technical success (P < .001), type I endoleak (P < .001), and type II endoleak (P = .003). Late adverse events requiring reintervention included rupture (0.4%), limb occlusion (0.4%), and stent migration (0.4%). Type Ia (4.8%), Ib (2.8%), II (35.9%), and V (6.5%) endoleaks were reported throughout follow-up. Sac growth was more prevalent with the original GORE EXCLUDER compared with the low permeability GORE EXCLUDER (P = .001) and in the presence of type I, II, and V endoleaks (P < .05). Three conversions (1.2%) were performed. Overall survival at 5 and 10 years was 68.4% and 49.0%, with no reported aneurysm-related deaths. Treatment with the GORE EXCLUDER is effective with acceptable reintervention rates in the long-term and few device-related adverse events or ruptures up to 10 years. Observed late adverse events and new-onset endoleaks emphasize the need for long-term surveillance.


Susceptibility of MDR Pseudomonas aeruginosa to ceftolozane/tazobactam and comparison of different susceptibility testing methods.
Infections caused by MDR Pseudomonas aeruginosa are on the rise, particularly in critically ill patients. Therefore, there is a need to evaluate new antimicrobial regimens. The objectives of this study were to investigate the ceftolozane/tazobactam resistance rates of MDR and XDR P. aeruginosa, the underlying resistance genes, the clonal structure and different antimicrobial susceptibility testing (AST) methods regarding their accuracy for ceftolozane/tazobactam testing. In total, 112 MDR and XDR P. aeruginosa (from infection and colonization) from one German tertiary care hospital were included (2013-16). AST was done using broth microdilution (BMD), gradient diffusion test strips and disc diffusion. Resistance genes were screened by PCR. A randomly selected subset of 77 isolates was subjected to WGS to assess the clonal structure. In total, 38 isolates (33.9%) were resistant to ceftolozane/tazobactam according to the BMD reference method. Resistance was significantly lower in MDR P. aeruginosa (4.8%) compared with XDR P. aeruginosa (50%, P < 0.0001). The underlying mechanism in carbapenemase-positive ceftolozane/tazobactam-resistant isolates (n = 38) was blaIMP (n = 25), blaVIM (n = 4) and blaGES (n = 1). The resistance mechanism of the remaining eight ceftolozane/tazobactam-resistant isolates remained unclear. Although our strain collection was diverse, resistance to ceftolozane/tazobactam was almost exclusively associated with MLST ST235. The disc diffusion method was accurate for ceftolozane/tazobactam AST (no false-susceptible results, categorical agreement = 92.9%). Ceftolozane/tazobactam resistance was low in MDR P. aeruginosa, but higher in XDR P. aeruginosa. The disc diffusion method showed an acceptable accuracy for ceftolozane/tazobactam AST.


Dynamic synchronisation of central oscillators in essential tremor.
Coherence analysis of electromyography (EMG) signals in essential tremor (ET) suggests that tremor in the right and left arm is induced by independent central oscillators. The sensorimotor cortex seems to be part of the tremor-generating neuronal network in ET. Here, we investigated using electroencephalography (EEG) whether the independence of central oscillators in ET is supported by the analysis of cortical activity. In 8 patients with ET, bilateral hand tremor was activated by wrist extension. EMGs from the wrist flexors and extensors were recorded simultaneously with an EEG. EEG-EMG coherence was estimated for 74 epochs of 60 s duration. In 42.6% of the cases, EEG-EMG coherence at the tremor frequency existed only with the contralateral sensorimotor cortex. However, 21.6% of the tremor-EMGs were coherent with EEG activity over both the contralateral and ipsilateral sensorimotor cortex. Bilateral and exclusively contralateral EEG-EMG coherence could alternate within the same recording. Bilateral EEG-EMG coherence was associated with increased right-left EEG-EEG coherence, increased right-left EMG-EMG coherence as well as with increased tremor strength. In ET, central oscillators in the right and left brain are not entirely independent of each other. They may dynamically synchronise, presumably by interhemispheric coupling via the corpus callosum.


The debate in the diagnosis of coeliac disease - time to go 'no-biopsy'?
Duodenal biopsies have been central to making a diagnosis of coeliac disease for the last 70 years. Recent paediatric guidelines have reduced the emphasis on duodenal biopsies with the incorporation of a 'no-biopsy' arm to the diagnostic pathway. This review discusses the no-biopsy approach in adults and highlights advances in alternative (non-biopsy) diagnostic modalities in coeliac disease. Evidence suggests that a no-biopsy approach for the diagnosis of adult coeliac disease is accurate. However, a number of factors still favour duodenal biopsy sampling in specific patient groups. Moreover, several factors need to be considered if this pathway is implemented into local gastroenterology services. Duodenal biopsies remain an important step in the diagnosis of adult coeliac disease. However, an alternative approach that removes the necessity for biopsies may be an option in selected adults. If further guidelines incorporate this pathway, then efforts should focus on supporting a dialogue between primary and secondary care to facilitate the appropriate implementation of this approach.


Spinal epidural abscess: a rapidly progressive disease.
We report a case of spinal epidural abscess in a 42-year-old diabetic. The patient first presented with four days of low back pain with radicular symptoms following exertion. When he returned five days later with overt symptoms and signs of spinal cord compression, an epidural mass was diagnosed by myelogram and computed tomography scan. Following drainage of a large posterior epidural abscess, the patient was left with residual weakness requiring ongoing physical therapy.


A new technique in avian semen evaluation.
Modification of a technique used in human fertility is presented and shown to be a simple, inexpensive and quantitative method for estimating the subsequent fertility of a semen sample.


Sequestering of the 3' splice site in a theophylline-responsive riboswitch allows ligand-dependent control of alternative splicing.
Despite the important role of alternative splicing in various aspects of biological processes, our ability to regulate this process at will remains a challenge. In this report, we asked whether a theophylline-responsive riboswitch could be adapted to manipulate alternative splicing. We constructed a pre-mRNA containing a single upstream 5' splice site and two 3' splice sites, of which the proximal 3' splice site is embedded in theophylline-responsive riboswitch. We show that this pre-mRNA spliced with preferential utilization of proximal 3' splice site in vitro. However, addition of theophylline to the splicing reaction promoted splicing at distal 3' splice site thereby changing the ratio of distal-to-proximal 3' splice site usage by more than twofold. Our data suggest that theophylline influenced 3' splice site choice without affecting the kinetics of the splicing reaction. We conclude that an in vitro selected riboswitch can be adapted to control alternative splicing, which may find many applications in basic, biotechnological, and biomedical research.