The use of a 4-step algorithm in the electrocardiographic diagnosis of ST-segment elevation myocardial infarction by novice interpreters.
The electrocardiographic (ECG) diagnosis of ST-segment elevation myocardial infarction (STEMI) represents a challenge to all health care providers, particularly so for the novice ECG interpreter. We have developed--and present in this article--a 4-step algorithm that will detect STEMI in most instances in the prehospital and other nonemergency department (ED) settings. The algorithm should be used in adult patients with chest pain or equivalent presentation who are suspected of STEMI. It inquires as to the presence of ST-segment elevation as well as the presence of STEMI confounding/mimicking patterns; the algorithm also makes use of reciprocal ST-segment depression as an adjunct in the ECG diagnosis of STEMI. If STEMI is detected by this algorithm, then management decisions can be made based upon this ECG diagnosis. If STEMI is not detected using this algorithm, then we can only note that STEMI is not "ruled in"; importantly, STEMI is not "ruled out." In fact, more expert interpretation of the ECG will be possible once the patient (and/or the ECG) arrive in the ED where ECG review can be made with the more complex interpretation used by expert physician interpreters.


Regulation of CD28 expression on umbilical cord blood and adult peripheral blood CD8+ T cells by interleukin(IL)-15/IL-21.
Interleukin (IL)-15 and IL-21, both belonging to common γ-chain-signaling cytokine family, have an important role to maintain homeostatic proliferation of CD8(+) T cells. CD28, an essential co-stimulatory molecule on T cells, may be a marker of replicative senescence. We investigated the effect of IL-15 and IL-21, alone or in combination, on activation, apoptosis, cytokine production and cytotoxic function of magnetic bead purified umbilical cord blood (UCB) and adult peripheral blood (APB) CD8(+) T cells with regards to their CD28 expression. We established that (1) IL-15-induced CD8(+) T cell proliferation was associated with a preferential expansion of CD28(-) population in UCB, which could be partially counteracted by IL-21; (2) UCB CD8(+) T cells were more readily responsive to IL-15 compared to their adult counterparts in terms of CD69 expression, with the majority of CD69-bearing CD8(+) T cells were CD28(-); (3) IL-21 further promoted interferon-gamma, but not tumor necrosis factor-alpha production from IL-15 treated CD8(+) T cells; (4) IL-21 also synergized with IL-15 to enhance perforin and granzyme B expression of CD8(+) T cells, especially in APB CD8(+)CD28(-) subsets; (5) IL-21 resulted in CD8(+) T cells apoptosis both in APB and UCB cells, mainly in CD8(+)CD28(-) subsets. Taken together, we demonstrate differential IL-15/IL-21 response in UCB CD8(+) T cells with regards to CD28 expression. Our results suggest that combining IL-21 and IL-15 immunotherapy may be better than IL-15 alone to ameliorate graft-versus-host disease while preserving antitumor effect in the post-UCB transplantation period.


Laparoscopic resection of benign hepatic cysts: a new standard.
We sought to evaluate the feasibility and outcomes of laparoscopic resection of symptomatic hepatic cysts. Fifty-one patients underwent laparoscopic resections for symptomatic hepatic cysts. Resection was accomplished laparoscopically with an Endo-GIA vascular stapler. Data were collected in a prospective database. Median patient age was 60 years, with a median lesion diameter of 13 cm. Indication for surgical treatment was pain in 92% of patients. Laparoscopic resection was successful in 100% of patients. A pure laparoscopic approach was used in 58% of patients, the remaining used a hand port. Median operating time was 178 minutes. Preoperative diagnosis was polycystic liver in 88% and simple cyst in 12% diagnosed by preoperative imaging. Histologic examination showed 90% to be simple cysts and 10% cystadenomas. There were nine minor perioperative complications. Median hospital stay was 2 days. Relief of symptoms was achieved in all patients operated on for pain, with a median followup of 13 months. Two patients required reoperation for recurrence of the same cyst. CT or MRI was used for yearly followup. Laparoscopic resection of symptomatic liver cysts is a feasible and effective method to relieve symptoms with minimal surgical trauma. This series represents the largest report of laparoscopic management for benign hepatic cysts and provides evidence for a routine laparoscopic approach to benign symptomatic cysts. Traditional surgical methods should be reserved for when a malignancy is expected, laparoscopy is contraindicated, or for recurrence after an initial laparoscopic approach.


Activated Fc alpha T cells in Crohn's disease are involved in regulation of IgA.
Activated peripheral T cells (APT) of patients with Crohn's disease (CD) have been analysed for the expression of IgA-Fc receptors and for competence of IgA regulation. It was found that within the subset of APT an increased number of cells express binding sites for IgA (IgA-Fc), that was not found in other diseases with elevated numbers of APT. Moreover the number of IgA-Fc receptor expressing T cells was found to be increased in the inflamed mucosa too. Cocultures with autologous B cells revealed that isolated IgA-Fc receptor bearing T cells of patients with CD suppress IgA secretion. These data support the hypothesis that APT are involved in the immunopathogenesis of CD.


Aortic impedance and hydraulic power in the chick embryo from stages 18 to 29.
Little is known about the hemodynamic properties of the rapidly expanding arterial bed during embryonic development. Using a servo-null pressure system and 20-MHz pulsed Doppler velocity meter, we recorded simultaneous dorsal aortic pressure and velocity waveforms. The waveforms were digitized at 3-msec intervals and subjected to Fourier analysis. We calculated hydraulic energy and the impedance spectrum to 10 Hz. From stages 18 to 29, heart rate (148 +/- 3 to 193 +/- 9 beats/min), systolic pressure (1.14 +/- 0.12 to 3.04 +/- 0.10 mm Hg), and mean dorsal aortic blood flow (21 +/- 2 to 214 +/- 19 mm3/min) increased. Peripheral vascular resistance (Z0: 30.4 +/- 4.8 to 6.4 +/- 0.7 dyne x sec/mm5), and the impedance moduli (Z1: 6.5 +/- 1.0 to 1.7 +/- 0.2 dyne x sec/mm5; Z2: 6.1 +/- 1.2 to 1.7 +/- 0.1 dyne x sec/mm5; Z3: 7.3 +/- 1.1 to 1.7 +/- 0.2 dyne x sec/mm5) decreased. Total hydraulic power increased from 48 +/- 7 to 2,606 +/- 96 nW, while the proportion of oscillatory energy increased from 29 +/- 2% to 65 +/- 4%. With development hydraulic load decreases, total external work increases and the dorsal aorta and embryonic vascular bed becomes more compliant. A greater proportion of total energy is expanded in pulsatile blood flow, suggesting that ventricular-arterial coupling is less efficient later in development.


Repair of potentially lethal damage in yeast induced by fast neutrons.
Survival curves of 3 diploid (D7) yeast strains: one wild-type, one deficient in excision of pyrimidine dimers (UV-sensitive) and one blocked in DNA double-strand-break repair (X-ray-sensitive), were compared after irradiation with cyclotron-produced fast neutrons. It was observed that both the UV-sensitive (rad3/rad3) and the X-ray-sensitive (rad52/rad52) mutants were more sensitive to neutrons than the wild-type. The role of DNA double-strand-breaks in neutron-induced cell death was further studied by comparing the relative sensitivity of the rad52/rad52 mutant to gamma-rays and fast neutrons. A comparison of the dose modification factors revealed that the deficiency in DNA double-strand-break repair did not make the yeast cells more sensitive to neutrons than to photons, which suggests that lesions of a different type may also be produced by neutrons. Survival curves obtained upon immediate plating and after delayed plating of neutron-irradiated cells showed that all 3 yeast strains were efficient in liquid holding recovery. The role of different repair pathways in cellular recovery from neutron-induced lethal damage is discussed.


High medium-term incidence of major cardiovascular events in discharged patients with unstable angina.
The introduction of high-sensitivity troponin (hsTn) assays has reduced the diagnosis of unstable angina (UA) in favor of non-ST elevation myocardial infarction (NSTEMI) in the context of non-ST elevation acute coronary syndrome (NSTEACS). It is unclear whether the detection of these hsTn levels affects the prognosis and therefore whether a different therapeutic approach is warranted. This study aims to determine whether using hsTn results in medium-term prognostic differences in patients with UA and NSTEMI. This multicenter, prospective registry study included consecutive patients who underwent hsTn assays and were discharged with a diagnosis of NSTEACS. Patients were followed for two years. Outcomes were the occurrence of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke), major bleeding, and all-cause mortality. Patients with UA and NSTEMI did not show differences in terms of the invasive interventions received, the coronary artery disease diagnosed, the type of revascularization performed, or the proportion presenting MACE (UA 18.1% vs. NSTEMI 18.9%; p = 0.79). However, patients with NSTEMI had higher cardiovascular mortality at two years (UA 4% vs. NSTEMI 9.2%; p = 0.012), as well as, all-cause mortality (UA vs. 7.9% vs. NSTEMI 16.4%; p = 0.002). Medium-term incidence of MACE was similar in patients with UA and NSTEMI, but cardiovascular and all-cause mortality in NSTEMI patients was over twice that of patients with UA.


The smallest superatom Au4(PPh3)4I2 with two free electrons: synthesis, structure analysis, and electrocatalytic conversion of CO2 to CO.
Atomically precise metal nanoclusters (NCs) have emerged as a new class of ultrasmall nanoparticles with both free valence electrons and precise structures (from the metal core to the organic ligand shell) and provide great opportunities to understand the relationship between their structures and properties, such as electrocatalytic CO2 reduction reaction (eCO2RR) performance, at the atomic level. Herein, we report the synthesis and the overall structure of the phosphine and iodine co-protected Au4(PPh3)4I2 (Au4) NC, which is the smallest multinuclear Au superatom with two free e- reported so far. Single-crystal X-ray diffraction reveals a tetrahedral Au4 core stabilized by four phosphines and two iodides. Interestingly, the Au4 NC exhibits much higher catalytic selectivity for CO (FECO: > 60%) at more positive potentials (from -0.6 to -0.7 V vs. RHE) than Au11(PPh3)7I3 (FECO: < 60%), a larger 8 e- superatom, and Au(i)PPh3Cl complex; whereas the hydrogen evolution reaction (HER) dominates the electrocatalysis when the potential becomes more negative (FEH2 of Au4 = 85.8% at -1.2 V vs. RHE). Structural and electronic analyses reveal that the Au4 tetrahedron becomes unstable at more negative reduction potentials, resulting in decomposition and aggregation, and consequently the decay in catalytic performance of Au based catalysts towards the eCO2RR.


EBCOG position statement inequalities in antenatal care provision in Europe: In the wake of an EBCOG survey.
Health inequalities adversely affect the health outcomes generally but more so for those who are socially deprived, immigrants of unknown status and low socioeconomic status. The inequitable access to care during pregnancy can lead to long term adverse inter-generational effects. Current economic crisis within Europe will have deepening effect on the health of the vulnerable families. The European Board and College of Obstetrics and Gynaecology calls for action by the European Union.


Metabolism-based category formation for the prioritisation of genotoxicity hazard assessment for plant protection product residues (part 3): Strobilurins.
In dietary risk assessment of plant protection products, residues of active ingredients and their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. To characterise similarity, in terms of metabolism, a metabolic similarity profiling scheme has been developed from an analysis of 46 chemicals of strobilurin fungicides and their metabolites for which either Ames, chromosomal aberration or micronucleus test results are publicly available. This profiling scheme consists of a set of ten sub-structures, each linked to a key metabolic transformation present in the strobilurin metabolic space. This metabolic similarity profiling scheme was combined with covalent chemistry profiling and physico-chemistry properties to develop chemical categories suitable for chemical prioritisation via read-across. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing. The key challenge in the approach was identified as being the need for metabolism data and individual groups of plant protection products as the basis for the development of such profiling schemes.


A novel pathogenic variant of the LDLR gene in the Asian population and its clinical correlation with familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties. We present here a novel non-synonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity discovered during an in-house genetic test. We postulate that their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia.


Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides.
To determine whether ventilator-associated pneumonia caused by oxacillin-resistant Staphylococcus aureus (VAP-ORSA) treated with glycopeptides is associated with an increased mortality rate. Retrospective matched cohort study. Four intensive care units in teaching hospitals. Seventy-five patients were matched to 75 controls. None. All adult intensive care unit patients with microbiologically documented VAP-ORSA were matched to intubated controls who did not develop VAP-ORSA, based on disease severity (Acute Physiology and Chronic Health Evaluation II score) at admission (+/-3 points), diagnostic category, and length of stay before pneumonia onset. Population characteristics and intensive care unit mortality rates of patients with VAP-ORSA and their controls without pneumonia were compared. Attributable mortality was determined by subtracting the crude mortality rate of controls from the crude mortality rate of VAP-ORSA patients. Thirty-six of the 75 matched VAP-ORSA patients died, representing a crude mortality rate of 48%, whereas 19 of the 75 controls died, a crude mortality rate of 25.3% (p < .01). Excess mortality was estimated to be 22.7% (95% confidence interval, 2.4-42.9%). Median length of intensive care unit stay in the surviving pairs was 33 days (interquartile range, 25-75%: 25-45 days) for VAP-ORSA patients and 21 days (interquartile range, 25-75%: 15-34.75 days) days for controls (p = .054). Despite appropriate glycopeptide therapy, there is an increased attributable mortality for pneumonia by ORSA, after careful adjustment for disease severity and diagnostic category.


Mutagenesis of both prophenoloxidases in the fall armyworm induces major defects in metamorphosis.
Upon infection, the phenoloxidase system in arthropods is rapidly mobilized and constitutes a major defense system against invaders. The activation of the key enzymes prophenoloxidase (PPO) and their action in immunity through melanization and encapsulation of foreign bodies in hemolymph has been described in many insects. On the other hand, little is known about PPOs involvement in other essential functions related to insect development. In this paper, we investigated the function of the two PPOs of the crop pest, Spodoptera frugiperda (PPO1 and PPO2). We show that PPOs are mainly expressed in hemocytes with the PPO2 expressed at higher levels than the PPO1. In addition, these two genes are expressed in the same tissue and at the same stages of insect development. Through the generation of loss-of-function mutants by CRISPR/Cas9 method, we show that the presence of PPOs is essential for the normal development of the pupa and the survival of the insect.


High Salt Intake Worsens Aortic Dissection in Mice: Involvement of IL (Interleukin)-17A-Dependent ECM (Extracellular Matrix) Metabolism.
Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding clinical signs or symptoms. Although high salt intake is a proposed risk factor for cardiovascular diseases, the relationship between AD and high salt intake has not been clarified. We examined the effect of high-salt challenge on a mouse AD model. Approach and Results: AD was induced in male mice by continuous infusion of β-aminopropionitrile and Ang II (angiotensin II). High-salt challenge exacerbated aortic wall destruction in AD. Deletion of Il17a (IL-17KO [IL (interleukin)-17A knockout]) did not affect the AD phenotype at baseline, but it abolished the high salt-induced worsening of the aortic destruction. Unexpectedly, aortas of IL-17KO mice exhibited global changes in ECM (extracellular matrix)-related genes without alteration of proinflammatory genes, altered architecture of collagen fibers, and reduced stiffness before AD induction. The aortas of IL-17KO mice were less sensitive to AD-inducing stimuli, as shown by the induction of phenotypic modulation markers SMemb and vimentin, suggesting a reduced stress response. The aortas of IL-17KO mice had a higher population of smooth muscle cells with nuclear-localized phosphorylated Smad2, indicative of TGFβ (transforming growth factor-beta) signal activation. Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFβ1. These findings indicate that high salt intake has a worsening effect on AD in the context of high aortic wall stiffness, which is under the control of IL-17A through ECM metabolism. Therefore, salt restriction may represent a low-cost and practical way to reduce AD risk.


Resolving mechanisms of toxicity while pursuing ecotoxicological relevance?
In this age of modern biology, aquatic toxicological research has pursued mechanisms of action of toxicants. This has provided potential tools for ecotoxicologic investigations. However, problems of biocomplexity and issues at higher levels of biological organization remain a challenge. In the 1980s and 1990s and continuing to a lesser extent today, organisms residing in highly contaminated field sites or exposed in the laboratory to calibrated concentrations of individual compounds were carefully analyzed for their responses to priority pollutants. Correlation of biochemical and structural analyses in cultured cells and tissues, as well as the in vivo exposures led to the production and application of biomarkers of exposure and effect and to our awareness of genotoxicity and its chronic manifestations, such as neoplasms, in wild fishes. To gain acceptance of these findings in the greater environmental toxicology community, "validation of the model" versus other, better-established often rodent models, was necessary and became a major focus. Resultant biomarkers were applied to heavily contaminated and reference field sites as part of effects assessment and with investigations following large-scale disasters such as oil spills or industrial accidents. Over the past 15 years, in the laboratory, small aquarium fish models such as medaka (Oryzias latipes), zebrafish (Danio rerio), platyfish (Xiphophorus species), fathead minnow (Pimephales promelas), and sheepshead minnow (Cyprinodon variegatus) were increasingly used establishing mechanisms of toxicants. Today, the same organisms provide reliable information at higher levels of biological organization relevant to ecotoxicology. We review studies resolving mechanisms of toxicity and discuss ways to address biocomplexity, mixtures of contaminants, and the need to relate individual level responses to populations and communities.


Effect of clofibrate treatment on glutathione content and the activity of the enzymes related to peroxide metabolism in rat liver and heart.
Clofibrate treatment was shown to increase the content of reduced glutathione in rat liver and kidney, but did not alter the glutathione level in heart, brain, spleen and small intestine. Clofibrate did not affect the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in rat liver and heart. The drug decreased the activity of glutathione-S-transferase in the cytosolic fraction of liver homogenate. Glutathione-S-transferase activity in small intestine was also reduced. The administration of clofibrate decreased the content of polypeptides with mol. wt of 22,000 and 24,000 (possible monomers of glutathione-S-transferase) in the cytosolic fraction of liver cells.


Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.
Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.


Health and the social power of women.
The relationship between women's social status and the survival chances of their children is explained and illustrated with examples. When women (and girls) have low status, relatively little social investment is made in them, and this is reflected in girls' and boys' differential mortality rates. Several health-related social investment indicators are given, and matched against children's mortality patterns by ecological regions of Africa and Asia. The cultural propensity to invest in girls (nutrition, education, etc.) and their resultant survival chances, are explained by ecology which in past centuries has largely determined agricultural economies that either had a high demand for female labour or did not. In the former, women are more likely to control the wealth they produce and use it for transactions that put others in their social debt, thus growing in social power. Policy implications of planning and implementing primary health care in these different types of societies are explored.


Total synthesis and semi-synthetic approaches to analogues of antibacterial natural product althiomycin.
Numerous analogues of the naturally occurring antibiotic althiomycin have been synthesised exploiting both total- and semi-synthetic methodologies. The antibacterial activity of these derivatives has been determined in whole cell assays and indicates the natural product exhibits a restricted SAR.


An epidemiological study of tics.
We devised a questionnaire for estimation of each tic, and used a two-step investigation procedure, first by a parent questionnaire with 1,218 responses and second by a confirmatory telephone interview for 197 positive responses. The average estimated values were 11.3% for boys and 5.2% for girls. The prevalences were--blinking: 4.2%, head-jerking: 1.6%, shrugging: 1.2%, mouth-twitching: 0.6%, face-distortion: 0.5%, mouth-opening: 0%, throat-clearing: 2.7%, sniffing: 0.6%, and vocalization: 0.2%. According to the criteria in DSM-III-R, 5.1% of 1,218 had TTD, 2.2% had CMVTD, and 0.5% had Tourette disorder.


Extracorporeal membrane oxygenation: evolving epidemiology and mortality.
The evolution of the epidemiology and mortality of extracorporeal membrane oxygenation (ECMO) remains unclear. The present study investigates the evolving epidemiology and mortality of various ECMO techniques in Germany over time, used for both severe respiratory and cardiac failure. Data on all patients receiving venovenous (vv-ECMO) and venoarterial (va-ECMO) ECMO as well as pumpless extracorporeal lung assist/interventional lung assist (PECLA/ILA) outside the operating room in Germany from 1 January 2007 through 31 December 2014 were obtained from the Federal Statistical Office of Germany and analyzed. The incidence of vv-ECMO and va-ECMO in the population increased threefold from 1.0:100,000 inhabitants/year in 2007 to a maximum of 3.0:100,000 in 2012, and from 0.1:100,000 in 2007 to 0.7:100,000 in 2012 and to a maximum of 3.5:100,000 in 2014, respectively. The incidence of arteriovenous PECLA/ILA also increased from 0.4:100,000 to a maximum of 0.6:100,000 in 2011, but decreased thereafter to 0.3:100,000 in 2014. The relative proportion of older patients receiving ECMO is steadily increasing. In-hospital mortality decreased over time and reached 58 and 66 % for vv-ECMO and va-ECMO in 2014, respectively. In addition, mortality steadily increased with age and was especially high in the first 48 h of ECMO use. In a high-income country like Germany, the use of ECMO has been rapidly increasing since 2007 for both respiratory and cardiac support, with a recent plateau in vv-ECMO use. In-hospital mortality decreased with increasing ECMO utilization, but remains high, especially in older patients and in the first 48 h of use.


Prospective Association of Obesity Patterns with Subclinical Carotid Plaque Development in Early Postmenopausal Chinese Women.
This study aimed to examine the prospective associations of general and abdominal obesity patterns with carotid plaque development among early postmenopausal Chinese women. A total of 518 postmenopausal women aged 50 to 64 years were recruited between 2002 and 2004 and were followed up at 3 years and 5 years. Carotid plaque was measured using B-mode ultrasonography, whereas general and abdominal obesity were defined as BMI ≥ 25 kg/m2 and waist-hip ratio ≥ 0.85, respectively. Sociodemographic, lifestyle, mental health, disease history, and clinical measurements were also assessed for confounding control. Multivariable binary logistic regression analyses on plaque development at 5 years were performed among 322 women with no carotid plaque at baseline. Over the 5-year follow-up period, 70 women (21.7%) developed carotid plaque. Baseline abdominal obesity independently predicted plaque development (adjusted odds ratio = 2.30; 95% CI: 1.15-4.60), but general obesity did not. Women with normal-weight abdominal obesity were more than twice as likely to develop carotid plaque (adjusted odds ratio = 2.43; 95% CI: 1.02-5.75) compared with women with no obesity, with their risk comparable to women with both general and abdominal obesity. Abdominal obesity was a critical predictor of subclinical carotid plaque development among early postmenopausal Chinese women. Policy makers should recognize the need to identify high-risk midlife women with normal-weight abdominal obesity in public health and clinical practice.


Effect of naloxone on the bladder activity of rabbits with acute spinal injury.
Naloxone enhances bladder activity in patients with chronic spinal cord injury. However, there are few reports on naloxone for bladder morbidity in acute spinal cord injury. We performed a prospective, controlled study of the effects of naloxone on bladder function in rabbits with and without surgical transection of the spinal cord at the 10th thoracic vertebra. Acute and chronic stages of injury were defined according to bladder function. Naloxone was given intravenously at both stages, and intrathecally at the acute stage. Bladder activity was monitored by cystometry. Blood concentrations of methionine-enkephalin were measured by radioimmunoassay. Spinal cord injuries were acute 1 or 2 days after surgery, and chronic after 1 or 2 weeks. Bladder capacity significantly decreased after 0.01 mg of intravenous naloxone in uninjured control rabbits, and after 0.03 mg of intravenous naloxone in rabbits with chronic-phase injuries. During the acute-injury phase, 0.3 mg of intravenous naloxone, or 0.02 mg of intrathecal naloxone, was necessary to evoke the micturition reflex. No significant changes in blood enkephalin levels were seen before or after spinal cord injury. In rabbits with acute spinal cord injury, intrathecal naloxone evoked the micturition reflex at a much lower dose than did intravenous naloxone. Intrathecal naloxone promises to become a new therapy for the acute stage of spinal cord injury for active recovery of bladder function, and could replace current therapy.


Clinical value of LHPP-associated microRNAs combined with protein induced by vitamin K deficiency or antagonist-II in the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma.
Alpha-fetoprotein (AFP) has received extensive attention in the differential diagnosis of hepatocellular carcinoma (HCC), especially for AFP-negative HCC (AFP-NHCC). The current study aimed to explore the value of targeted regulation of LHPP expression-related microRNAs (miRs) and protein induced by vitamin K deficiency or antagonist-II (PIVKA-II) in the differential diagnosis of AFP-NHCC. A retrospective study was conducted on a testing set-including 214 AFP-NHCC patients, 200 cirrhosis, and 210 controls, and a validation set-including 140 AFP-NHCC patients, 134 cirrhosis, and 128 controls recruited from The First Affiliated Hospital of Hunan Normal University. Serum miRs were examined using quantitative real-time PCR method. Serum PIVKA-II was measured by enzyme-linked immunosorbent assay. Compared with adjacent tissues, LHPP protein levels in cancer tissues were significantly decreased (P < .05). Predictive software and dual-luciferase reporter assays showed that miR-363-5p and miR-765 can target LHPP expression. Serum miR-363-5p, miR-765, and PIVKA-II levels were significantly higher in AFP-HCC patients than in cirrhosis and controls. A logistic regression model combining miR-363-5p, miR-765, and PIVKA-II was performed. This model presented a high discriminating value (AUC: 0.930, sensitivity/specificity: 79.4%/95.4%) than any single indicator. In the validation set, this model still showed a high discriminating value (AUC: 0.936, sensitivity/specificity: 83.6%/94.7%). Current model combining serum miR-363-5p, miR-765, and PIVKA-II has potential significance for diagnosis of AFP-NHCC.


A Streamlined Surgical Approach to Laparoscopic Sacrocolpopexy for Post-Hysterectomy Vault Prolapse.
To describe a streamlined laparoscopic sacrocolpopexy (LSCP) surgical technique in women with post-hysterectomy vault prolapse and to evaluate the functional outcomes, complication rates, and surgical morbidity within our centre. We retrospectively reviewed the charts of 180 patients scheduled for LSCP between November 2002 and May 2013 in a tertiary care centre. Patients were followed-up at six weeks, six months, and yearly after surgery. We reviewed patient demographics, preoperative and postoperative symptoms, and perioperative variables. Objective success of the surgery was defined as having a less than stage 2 vault prolapse, and subjective success was defined as the absence of bulge or prolapse symptoms. Success and complication rates were calculated. Of the 180 patients who underwent surgery, 144 patients underwent the procedure as planned and had at least six months of follow-up. At the last follow-up visit, 133 of these 144 patients (92.4%) were free of prolapse symptoms. Several bladder and bowel symptoms showed significant improvement. Anatomical success of vault support was achieved in 140 of 144 patients (97.2%), and 119 patients (82.6%) had no prolapse beyond the hymen. Early complications (within the first 6 weeks) occurred in 8.3% of 162 patients with limited outcome data, and late complications (after 6 weeks) occurred in 11.5% of the 144 patients with long-term data. There were no cystotomies or mesh exposures. At an average of 32 months, this cohort of patients had low prolapse recurrence rates and no reports of cystotomy or mesh erosion. The abridged LSCP technique, as practised in our institution, is safe and effective in the surgical management of post-hysterectomy vault prolapse.


Joseph Gensoul's operation for sarcoma of the maxillary antrum, one century before Moore.
Joseph Gensoul is considered an important figure of the 19th century Lyonnais Medical School. His contribution to maxillofacial surgery and his legendary abilities secured him a place in the history of Medicine.


Midfoot and forefoot issues cavovarus foot: assessment and treatment issues.
This chapter addresses the etiology and diagnosis of forefoot and midfoot cavovarus deformities, the relevant anatomy and biomechanics, and specific procedures for correction of the forefoot and midfoot. Associated hindfoot and ankle procedures will be referenced; however, their specifics will be reserved for other chapters.


Technology evaluation roundtable discusses role of private sector.
Working from the premise that health care technology should be studied from a multiperspective approach rather than a unidirectional approach, a group of health care opinion leaders gathered to discuss how private or public-private sector efforts could lead to this broad-based approach and to more effective and efficient utilization of health technology.


Developmental changes in the left ventricular diastolic wall strain on M-mode echocardiography.
The diastolic wall strain (DWS) of the left ventricle has been proposed as an indicator of left ventricular (LV) wall stiffness. The DWS is calculated as follows using M-mode echocardiography:[Formula: see text]Although this index is simple and clinically useful, normal values for children, including neonates, have not been reported. The DWS was measured in 235 healthy people, ranging from neonates to adults. They were classified into 8 subgroups according to their age. The DWS was compared with conventional echocardiographic parameters for left ventricle function, including shortening fraction of the left ventricle, the Tei index, E/A of mitral flow, mitral annular tissue Doppler velocity during systole (s') and during early diastole (e'), and the E/e' ratio. The DWS in the just after birth group was 0.28 ± 0.11, which was significantly lower than that of the remaining groups (p < 0.05), except for the neonate group at 5-10 days after birth. The DWS was highest in the 1-9 years of age group, and then gradually decreased with age. Stepwise regression of various echocardiographic parameters showed that e' was the most relevant parameter for the DWS (β = 0.64). Normal values for the DWS of the left ventricle change with age. The data reported in this study can be used as normal values for the DWS of the left ventricle determined by M-mode echocardiography.


Renewed growth of identified brainstem axons into fetal cortical transplants in adult rat.
Transplantation of fetal neocortex into the site of trigeminal brainstem injury induces regeneration of trigeminal primary afferent axons in adult rats. Renewed growth of injured primary afferent fibers into donor cortex can be extensive, though the innervation pattern does not resemble that normally seen in either brainstem or somatosensory cortex. Examination of the structural and functional characteristics of individual regenerate axon collaterals suggests that their morphology is determined by both intrinsic and postsynaptic target factors. Marked topographic alterations, however, question the utility of fetal cortical transplantation procedures in effecting functional recovery from brainstem injury.


Chronic intracerebroventricular infusion of angiotensin II increases brain AT1 receptor expression in young rats.
The aim of the present study was to determine the effect of chronic intracerebroventricular infusion of angiotensin II (ANG II) on the expression of brain AT1 receptors in young (3-4 weeks) rats. One week of icv ANG II infusion produced a significant increase in brain AT1 receptor protein (Western blot) and mRNA (relative RT-PCR) expression. These data raise the possibility that ANG II may play a role in postnatal expression of brain AT1 receptors.


Assessment of composition and anisotropic elastic properties of secondary osteon lamellae.
Measurement of the elastic properties of single osteon lamellae is still one of the most demanding tasks in bone mechanics to be solved. By means of site-matched Raman microspectroscopy, acoustic microscopy and nanoindentation the structure, chemical composition and anisotropic elasticity of individual lamellae in secondary osteons were investigated. Acoustic impedance images (911-MHz) and two-dimensional Raman spectra were acquired in sections of human femoral bone. The samples were prepared with orientations at various observation angles theta relative to the femoral long axis. Nanoindentations provided local estimations of the elastic modulus and landmarks necessary for spatial fusion of the acoustic and spectral Raman images. Phosphate nu(1) (961 cm(-1)) and amide I (1665 cm(-1)) band images representing spatial distributions of mineral and collagen were fused with the acoustic images. Acoustic impedance was correlated with the indentation elastic modulus E(IT) (R(2)=0.61). Both parameters are sensitive to elastic tissue anisotropy. The lowest values were obtained in the direction perpendicular to the femoral long axis. Acoustic images exhibit a characteristic bimodal lamellar pattern of alternating high and low impedance values. Since this undulation was not associated with a variation of the phosphate nu(1)-band intensity in the Raman images, it was attributed to variations of the lamellar orientation. After threshold segmentation and conversion to elastic modulus the orientation and transverse isotropic elastic constants were derived for individual ensembles of apparent thin and thick lamellae. Our results suggest that this model represents the effective anisotropic properties of an asymmetric twisted plywood structure made of transverse isotropic fibrils. This is the first report that proves experimentally the ability of acoustic microscopy to map tissue elasticity in two dimensions with micrometer resolution. The combination with Raman microspectroscopy provides a unique way to study bone and mineral metabolism and the relation with mechanical function at the ultrastructural tissue level.


Traumatic brain injury.
In childhood, traumatic brain injury (TBI) poses the unique challenges of an injury to a developing brain and the dynamic pattern of recovery over time, inflicted TBI and its medicolegal ramifications. The mechanisms of injury vary with age, as do the mechanisms that lead to the primary brain injury. As it is common, and is the leading cause of death and disability in the USA and Canada, prevention is the key, and we may need increased legislation to facilitate this. Despite its prevalence, there is an almost urgent need for research to help guide the optimal management and improve outcomes. Indeed, contrary to common belief, children with severe TBI have a worse outcome and many of the consequences present in teenage years or later. The treatment needs, therefore, to be multifaceted and starts at the scene of the injury and extends into the home and school. In order to do this, the care needs to be multidisciplinary from specialists with a specific interest in TBI and to involve the family, and will often span many decades.


pH-modulation of chloride channels from the sarcoplasmic reticulum of skeletal muscle.
The understanding of the role of cytoplasmic pH in modulating sarcoplasmic reticulum (SR) ion channels involved in Ca2+ regulation is important for the understanding of the function of normal and adversely affected muscles. The dependency of the SR small chloride (SCl) channel from rabbit skeletal muscle on cytoplasmic pH (pHcis) and luminal pH (pHtrans) was investigated using the lipid bilayer-vesicle fusion technique. Low pHcis 6.75-4.28 modifies the operational mode of this multiconductance channel (conductance levels between 5 and 75 pS). At pHcis 7.26-7.37 the channel mode is dominated by the conductance and kinetics of the main conductance state (65-75 pS) whereas at low pHcis 6.75-4.28 the channel mode is dominated by the conductance and kinetics of subconductance states (5-40 pS). Similarly, low pHtrans 4.07, but not pHtrans 6.28, modified the activity of SCl channels. The effects of low pHcis are pronounced at 10(-3) and 10(-4) M [Ca2+]cis but are not apparent at 10(-5) M [Ca2+]cis, where the subconductances of the channel are already prominent. Low pHcis-induced mode shift in the SCl channel activity is due to modification of the channel proteins that cause the uncoupling of the subconductance states. The results in this study suggest that low pHcis can modify the functional properties of the skeletal SR ion channels and hence contribute, at least partly, to the malfunction in the contraction-relaxation mechanism in skeletal muscle under low cytoplasmic pH levels.


Eligibility Criteria and Genetic Testing Results from a High-Risk Cohort for Hereditary Breast and Ovarian Cancer Syndrome in Southeastern Ontario.
Germline mutations in breast and ovarian cancer are rare, with approximately 5% to 10% and 13% being hereditary in origin, respectively. In 2001, the Ontario Ministry of Health and Long Term Care, in an effort to contain costs, defined criteria to determine an individual's eligibility for BRCA genetic screening. We studied a cohort of individuals that have undergone genetic testing at Kingston General Hospital between 2001 and late 2013. We focused on determining whether the 13 risk criteria, defined by an expert working group for the Ontario Ministry of Health and Long Term Care, have performed according to expectations in this cohort. Our findings show that all of the criteria perform well by identifying carriers at the expected 10% rate defined by the guidelines. We demonstrate that loose application of the risk criteria does not further enrich for BRCA variant carriers. Our assessment of the established risk criteria that have been in use in Ontario for more than a decade, provide evidence for their effectiveness, and offer insights into how they may be expanded or improved.


Baclofen antagonism by 4-amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid in the cat spinal cord.
When administered microelectrophoretically, 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (MBFG) reversibly reduced the presynaptic depression by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in muscle low-threshold afferent fibres of the cat as well as the postsynaptic depression by (-)-baclofen of the firing of these neurones. MBFG, as an antagonist of (-)-baclofen, may be useful in investigating the structure-activity relationships of central and peripheral baclofen receptors.


Inhibition of lexical representations after violated semantic predictions.
There is a consensus that humans predict upcoming words during sentence processing. Prediction makes language comprehension fast and efficient if this anticipatory processing is accurate. However, often times, predictions are not correct. There is a lack of research investigating the cognitive operations at play when predictions are violated. According to several proposals, such violations lead to an inhibition of the predicted word to facilitate the integration of the unexpected word. Across four experiments, we have tested whether predicted words are indeed inhibited when listeners encounter unexpected stimuli, and whether the linguistic status (word or sound) and semantic congruency of a word (plausible or implausible) influences this purported inhibitory process. Using a Cross-Modal Lexical Priming paradigm, we showed that when predictions are violated, the activation of the predicted word is inhibited, resulting in increased reaction times. These inhibitory effects appear to be language specific, in that they are only observed after unexpected words, as opposed to non-linguistic sounds (tones). However, contrary to a long-held assumption in the field of sentence processing, inhibitory effects are not modulated by the semantic congruency of the unexpected word (i.e., whether the unexpected word is plausible within the sentence context). Indeed, in the current study, any linguistic information that violated listeners' semantic prediction resulted in the inhibition of the predicted word. Thus, the current findings are more compatible with a view in which unexpected linguistic events that are meaningful engage inhibitory processes with the specific purpose of inhibiting the predicted, though out-of-date, word.


Aggregation-Enhanced Two-Photon Absorption of Anionic Conjugated Polyelectrolytes.
The two-photon absorption properties of anionic poly(phenylene ethynylene)-type conjugated oligo- and polyelectrolytes are studied in molecularly dissolved and aggregated forms in aqueous solution. Several different polyvalent cations are used to induce aggregation. It is found that both materials in the aggregated form exhibit enhanced two-photon excited fluorescence (2PEF) and two-photon cross section (σ2) compared with the molecularly dissolved structures. The 2PEF and σ2 are unaffected by the nature of the polyvalent cation that is used to induce aggregation. The two-photon absorption cross section enhancement arises because of the increase in the difference dipole moment (Δμ) in the aggregates of the conjugated materials, an effect that is attributed to the introduction of charge transfer character into the aggregate excited state.


Stabilization of chitosan based electrospun nanofibers through a simple and safe method.
A simple and safe method was used to stabilize nanofibrous structure of chitosan (CS) based mats obtained from acidic solution. The electrospun CS based nanofibrous mats were fabricated using CS/poly ethylene oxide in acetic acid aqueous solution. Exposure to water vapor at 40-70 °C for 30-120 min was implemented in order to stabilizing the CS mats. Scanning electron microscopy of the treated mats revealed preservation of nanofibrous structure after immersion in phosphate buffered saline (pH = 7.4). This result along with infrared spectroscopy and thermogravimetric analysis confirmed removal of acetic acid residues and neutralization of CS mats after treatment with water vapor. Stabilization with water vapor also led to augmentation in tensile strength and elastic moduli of CS mats comparing to as-spun mats while the elongation was decreased. Furthermore, the crystallinity and thermal stability of mats were slightly increased after neutralization. In comparison with glutaraldehyde cross-linked mats, water vapor treated mats showed higher swelling ratio and enhanced cell compatibility.


Consistencies and contradictions: Revisiting the relationship between women's education and infant mortality from a distributional perspective.
The connection between women's education and infant mortality is one of the most consistent and powerful relationships established in public health. A large body of cross-national research highlights the benefits of women's access to education, especially for improving population health in developing countries. However, most of this literature assumes the relationship is uniform across cases. In this study, we revisit the education-health link using a distributional approach. To do so, we conduct a series of unconditional quantile regression analyses that estimate the impact of female secondary school enrollment on infant mortality rates across 153 countries from 1970 to 2016. This technique allows for the possibility that the relationship between education and health may vary across the distribution of mortality. Indeed, results show that the education advantage is distribution-specific. We find that the expected benefits of women's education are limited to the middle of the distribution where infant mortality rates range from about 11 to 55 deaths per 1000 live births. However, we find no significant effect where mortality is comparatively low or high. Both consistent with and contradictory to prior research, these findings provide a more nuanced picture of how women's access to education relates to global health inequalities.


A study to evaluate the efficacy of toluidine blue and cytology in detecting oral cancer and dysplastic lesions.
Recent advances in techniques for detecting oral premalignant lesions and oral squamous cell carcinoma have improved the chances of early diagnosis. Adjuncts for detection of lesions include toluidine blue staining and cytologic examination. The primary objective of this study was to assess the efficacy of 1% toluidine blue (modified Mashberg technique) and cytology in detection of oral premalignant lesions and oral squamous cell carcinoma. The study included 86 participants suspected of having oral premalignant lesions or oral squamous cell carcinoma. One percent toluidine blue was applied to the lesions, followed by cytology. A biopsy was then performed on the tissue. Histopathologically proven oral premalignant lesions/oral squamous cell carcinoma lesions were analyzed for sensitivity, specificity, postive predictive value, and negative predictive value of both screening techniques. The association of screening techniques and histopathologic diagnosis among the oral premalignant lesions, oral squamous cell carcinoma, and benign groups were analyzed using the Fisher exact test. P < .05 was considered significant. The specificity and sensitivity for oral squamous cell carcinoma and oral premalignant lesions detection of 1% toluidine blue was 81.35% and 66.67%, respectively, while cytology attained 77.97% and 70.37%, respectively. Negative predictive value and positive predictive value were 84.21% and 62.06% for 1% toluidine blue and 85.18% and 59.37% for cytologic examination, respectively. Comparison of 1% toluidine blue and cytology with histopathologic diagnosis shows a significant difference between carcinoma/epithelial dysplasia and no dysplasia and carcinoma/epithelial dysplasia and benign lesions (all, P < .05). The results of this study suggest that 1% toluidine blue and cytology have high sensitivity, specificity, and accuracy in detecting oral premalignant lesions and oral squamous cell carcinoma and can be used as an adjunct for early detection of such lesions.


Multifocal early gastric cancer of mixed type.
A report of three selected gastric resection specimens presents the problems of histological classification of individual early gastric cancer, illustrated in discrepancies between macroscopic or endoscopic, and histologic identification. Multifocal origin and different types of gastric cancer are demonstrated in all three cases. Problems related to exact histologic classification of this mixed type are discussed together with the prognosis and surgical consequences.


Preliminary study of prehospital use of smart glasses.
A smart glasses system is a computerized communicator with a transparent screen and video camera that can be worn as a pair of glasses. There have been no reports on the use of smart glasses in the prehospital setting. To conduct a preliminary investigation on whether smart glasses were smoothly used bidirectionally between the prehospital setting and the receiving hospital. From March 1, 2022, to March 31, 2022, one smart glasses unit was installed in an ambulance at one branch of the fire department near our hospital. The physician on the computer, who received video and voice transmission from the smart glasses when the ambulance was dispatched, evaluated the transmission status with regard to video reception, voice reception, and voice transmission. In addition, the activity time was compared between cases in which the smart glasses system was used (patient) and not used (control). During the investigating period, 12 cases were analyzed as patients. The rate of good video reception was 75%, the rate of good voice reception was 50%, and the rate of good voice transmission was 25%. There was no significant change in the activity time between the patient and control groups. We performed a preliminary investigation on the usability of smart glasses in the prehospital setting. Using smart glasses, patient information was shared by video and voice before arrival at the hospital, and did not affect the activity time. However, the instability of the communication status should be recognized.


An application of Mokken's model for stochastic, cumulative scaling in psychiatric research.
Rating scales used in psychiatric research are often based on factor analysis. In practice, the resulting factors or dimensions will generally be empirically derived rather than based on theoretical considerations. In addition, it often proves difficult to determine their validity. It is argued that the use of an hierarchical scale may be a partial answer to these problems. This is illustrated by the analysis of data from two interview schedules, using Mokken's model for stochastic, cumulative scaling. Data were derived from a follow-up study of patients with a first life-time episode of non-affective, functional psychosis. Two scales for the assessment of psychopathology and social dysfunctioning were constructed. Scale statistics proved to be satisfactory, while the order of items in the scales corresponded to a priori theoretical expectations.


Single Portal Segmental Labral Reconstruction of the Hip.
Many techniques have been described for reconstruction of the acetabular labrum, but the procedure is known to be technically rigorous leading to lengthy procedure times and traction times. Increasing efficiency of the procedure with respect to graft preparation and delivery remain areas for potential improvement. We describe a simplified procedure for arthroscopic segmental labral reconstruction using peroneus longus allograft and a single working portal to shuttle the graft into the joint via suture anchors placed at the terminal extents of the graft defect. This method allows for efficient preparation, placement and fixation of the graft that can be completed in under 15 minutes.


Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke.
Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans.


Close Encounters of the Tertiary Kind.
Elucidating the function of tumor-infiltrating regulatory T (Treg) cells has been difficult. In this issue of Immunity, Joshi et al. (2015) demonstrate that Treg cells associated with murine lung cancers are found within tertiary lymphoid structures and actively restrain effector T cells at the tumor site.


[Urinary enzymes in research and in clinical medicine. Report on a symposium of the Humboldt-Universität Berlin and the Bezirkskrankenhaus Frankfurt/Oder in Frankfurt/Oder, 22-25 April 1987].
The symposium was dedicated exclusively to the subject of urine enzymes. Thirty nine lectures were given, in which 58 participants from 10 countries presented and discussed our present state of knowledge in the field of urine enzyme diagnosis, covering all aspects from fundamental research to its clinical application. This report summarizes the essential points of interest that arose from the lectures and discussions.


Obsessionality, obsessive-compulsive disorder, and temporal lobe epilepsy.
We evaluated the prevalence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE) and we investigated the hypothesis that obsessionality may represent a trait in TLE. Eighty-two consecutive patients with epilepsy, 62 with TLE and 20 with idiopathic generalized epilepsy (IGE), and 82 matched healthy controls were evaluated using the SCID-IP, Y-BOCS, MMPI-2 (specifically the Psychasthenia and Obsessiveness scales), BDI, and STAI Y1 and Y2. Nine of the TLE patients, none of the IGE patients, and one of the controls had a diagnosis of OCD. Psychasthenia and Obsessiveness scores were significantly higher in the TLE than in the IGE and control groups. Patients with TLE and OCD differed significantly with respect to history of depression when compared with patients with TLE without OCD, whereas there were no differences in age at onset and duration of epilepsy, seizure pattern and frequency, MRI features, laterality of the EEG focus, antiepileptic drug therapy and combinations, and BDI scores.


Microdosimetry: Principles and applications.
to present the most important aspects of Microdosimetry, a research field in radiation biophysics. microdosimetry is the branch of radiation biophysics that systematically studies the spatial, temporal and spectral aspects of the stochastic nature of the energy deposition processes in microscopic structures. we briefly review its history, the people, the formalism and the theories and devices that allowed researchers to begin to understand the true nature of radiation action on living matter. we outline some of its applications, especially to Boron Neutron Capture Therapy, attempting to explain the biological effectiveness of the boron thermal neutron capture reaction.


Interhospital transport of the patient on extracorporeal cardiopulmonary support.
Portable extracorporeal cardiopulmonary support systems have enhanced the resuscitation and support of moribund patients outside of the operating room environment. The literature documents the successful application of emergency cardiopulmonary support within the hospital setting. Clinicians have reported the use of helicopter and ground ambulance to transport patients requiring intraaortic balloon counterpulsation and fixed-wing transport of neonates requiring extracorporeal membrane oxygenation. As medical transport capabilities extend the sphere of tertiary care to outlying medical facilities, there is a role for extracorporeal cardiopulmonary support in the initial stabilization and safe transport of critically ill patients, via air or ground ambulance. Potentially, the early application of life-sustaining technology can lower mortality and morbidity in patients with a survivable pathology. This is a report on the experience with the resuscitation and interhospital transport of patients on extracorporeal cardiopulmonary support.


The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - Survival analysis of 3892 patients.
The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification and treatment allocation for hepatocellular carcinoma (HCC). We conducted this retrospective study to assess the efficacy of different treatment options for patients with initial HCC diagnosis. Survival rate and median survival times associated with different treatment options in each stage of BCLC classification were compared using the Kaplan-Meier method and log-rank test. A total of 3892 patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at 5 years. The median survival times decreased from 57.7 months in very early stage to 1.6 months in terminal stage. Surgical resection offered the best survival benefit for patients in very early, early and even intermediate stages. Transarterial embolisation and conformal radiotherapy offered survival benefits for selected patients in advanced and terminal stages. In conclusion, following the treatment schedules allocated by BCLC staging had survival benefits for HCC patients.


Does insulin-like growth factor 1 contribute in red blood cell transfusions to the pathogenesis of retinopathy of prematurity during retinal neovascularization?
Red blood cell (RBC) transfusions are associated with the development of retinopathy of prematurity (ROP). During the period of retinal neovascularization a rise of insulin-like growth factor 1 (IGF-1) may trigger rapid growth of new blood vessels. To study endocrine factors in RBC transfusions that might be of importance for ROP. IGF-1, IGF-2 and their binding proteins 1-3 (IGFBP-1-3) were determined by radioimmunoassays in 7 very-low-birthweight (VLBW) infants with ROP >or= stage 2 receiving a RBC transfusion, in 10 controls (VLBW infants with ROP <or= stage 1, no transfusion), in supernatants of 7 RBCs and of 5 washed RBCs (WRBC). IGF-1 (mean +/- SD) in infants with ROP was 20.0 +/- 4.2 microg/l, in controls 35.9 +/- 15.2 microg/l (Mann-Whitney U test, p = 0.030). IGF-1 in RBC was 12.88 +/- 5.03 microg/l and in WRBC 0.45 +/- 0.74 microg/l (average of the three-course washing procedure). IGF-2 in infants with ROP was 485.67 +/- 158.73 microg/l, in controls 389.9 +/- 102.8 microg/l (not significant), in RBC 109.50 +/- 117.89 microg/l, in WRBC 61.07 +/- 30.0 microg/l. Except for IGFBP-3 other IGFBPs were barely or not detectable in RBC or WRBC. Considering lower IGF-1 concentrations in preterm infants than in adults (factor 20), the IGF-1 in RBC transfusions is equivalent to a single dose of 1 microg/kg IGF-1 (5-10% of the adult dose with proved metabolic responses). Endocrinological relationships between the donor's load and the acceptor's individual features are a new aspect of potential side effects of RBC transfusions. Further research is necessary to clarify the share of the described IGF administration on the development of ROP.


The pan-immune system of bacteria: antiviral defence as a community resource.
Viruses and their hosts are engaged in a constant arms race leading to the evolution of antiviral defence mechanisms. Recent studies have revealed that the immune arsenal of bacteria against bacteriophages is much more diverse than previously envisioned. These discoveries have led to seemingly contradictory observations: on one hand, individual microorganisms often encode multiple distinct defence systems, some of which are acquired by horizontal gene transfer, alluding to their fitness benefit. On the other hand, defence systems are frequently lost from prokaryotic genomes on short evolutionary time scales, suggesting that they impose a fitness cost. In this Perspective article, we present the 'pan-immune system' model in which we suggest that, although a single strain cannot carry all possible defence systems owing to their burden on fitness, it can employ horizontal gene transfer to access immune defence mechanisms encoded by closely related strains. Thus, the 'effective' immune system is not the one encoded by the genome of a single microorganism but rather by its pan-genome, comprising the sum of all immune systems available for a microorganism to horizontally acquire and use.


Genome-Wide Meta-Analysis of Cerebrospinal Fluid Biomarkers in Alzheimer's Disease and Parkinson's Disease Cohorts.
Amyloid-β, phosphorylated tau (p-tau), and total tau (t-tau) in cerebrospinal fluid are established biomarkers for Alzheimer's disease (AD). In other neurodegenerative diseases, such as Parkinson's disease (PD), these biomarkers have also been found to be altered, and the molecular mechanisms responsible for these alterations are still under investigation. Moreover, the interplay between these mechanisms and the diverse underlying disease states remains to be elucidated. To investigate genetic contributions to the AD biomarkers and assess the commonality and heterogeneity of the associations per underlying disease status. We conducted genome-wide association studies (GWASs) for the AD biomarkers on subjects from the Parkinson's Progression Markers Initiative, the Fox Investigation for New Discovery of Biomarkers, and the Alzheimer's Disease Neuroimaging Initiative, and meta-analyzed with the largest AD GWAS. We tested heterogeneity of associations of interest between different disease statuses (AD, PD, and control). We observed three GWAS signals: the APOE locus for amyloid-β, the 3q28 locus between GEMC1 and OSTN for p-tau and t-tau, and the 7p22 locus (top hit: rs60871478, an intronic variant for DNAAF5, also known as HEATR2) for p-tau. The 7p22 locus is novel and colocalized with the brain DNAAF5 expression. Although no heterogeneity from underlying disease status was observed for the earlier GWAS signals, some disease risk loci suggested disease-specific associations with these biomarkers. Our study identified a novel association at the intronic region of DNAAF5 associated with increased levels of p-tau across all diseases. We also observed some disease-specific genetic associations with these biomarkers. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.


Nicotine control: E-cigarettes, smoking and addiction.
Over the past year or so, electronic cigarettes, more commonly known as 'e-cigarettes', have achieved widespread visibility and growing popularity. These products, which deliver nicotine via an inhaled mist, have caused no small amount of controversy in public health circles, and their rise has been accompanied by energetic debate about their potential harms and benefits. Interspersed with an analysis of current media coverage on e-cigarettes and the response of mainstream tobacco control and public health to these devices, this article examines the emergence of nicotine as both as an 'addiction' and a treatment for addiction. We argue that by delivering nicotine in way that resembles the visual spectacle and bodily pleasures of smoking, but without the harms of combustible tobacco, e-cigarettes highlight the complex status of nicotine as both a poison and remedy in contemporary public health and tobacco control. In consequence, e-cigarettes jeopardize the carefully drawn distinctions between 'good' and 'bad' forms of nicotine.


Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.
The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1μg, 3μg, or 10μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN.


Why Delay? Early Enteral Nutrition in Pediatric Burn Patients Improves Outcomes.
Children who sustain moderate to large surface area burns present in a hypermetabolic state with increased caloric and protein requirements. A policy was implemented at our institution in 2017 to initiate enteral nutrition (EN) in pediatric burn patients within 4 hours of admission. The authors hypothesize that early EN (initiated within 4 hours of admission) is more beneficial than late EN (initiated ≥ 4 hours from admission) for pediatric burn patients and is associated with decreased rates of pneumonia, increased calorie and protein intake, fewer feeding complications, a shorter Intensive Care Unit (ICU) length of stay (LOS), and a reduced hospital LOS. Children who sustained a total body surface area (TBSA) burn injury ≥ 10% between 2011 and 2018 were identified in a prospectively maintained burn registry at Children's Hospital Colorado. Patients were stratified into two groups for comparison: early EN and late EN. The authors identified 132 pediatric burn patients who met inclusion criteria, and most (60%) were male. Approximately half (48%) of the study patients were in the early EN group. The early EN group had lower rates of underfeeding during the first week (P = .014) and shorter ICU LOS (P = .025). Achieving and sustaining adequate nutrition in pediatric burn patients with moderate to large surface area burn injuries are critical to recovery. Early EN in pediatric burn patients is associated with decreased underfeeding and reduced ICU LOS. The authors recommend protocols to institute feeding for patients with burns ≥ 10% TBSA within 4 hours of admission at all pediatric burn centers.


Hormesis in aging.
Hormesis in aging is represented by mild stress-induced stimulation of protective mechanisms in cells and organisms resulting in biologically beneficial effects. Single or multiple exposure to low doses of otherwise harmful agents, such as irradiation, food limitation, heat stress, hypergravity, reactive oxygen species and other free radicals have a variety of anti-aging and longevity-extending hormetic effects. Detailed molecular mechanisms that bring about the hormetic effects are being increasingly understood, and comprise a cascade of stress response and other pathways of maintenance and repair. Although the extent of immediate hormetic effects after exposure to a particular stress may only be moderate, the chain of events following initial hormesis leads to biologically amplified effects that are much larger, synergistic and pleiotropic. A consequence of hormetic amplification is an increase in the homeodynamic space of a living system in terms of increased defence capacity and reduced load of damaged macromolecules. Hormetic strengthening of the homeodynamic space provides wider margins for metabolic fluctuation, stress tolerance, adaptation and survival. Hormesis thus counter-balances the progressive shrinkage of the homeodynamic space, which is the ultimate cause of aging, diseases and death. Healthy aging may be achieved by hormesis through mild and periodic, but not severe or chronic, physical and mental challenges, and by the use of nutritional hormesis incorporating mild stress-inducing molecules called hormetins. The established scientific foundations of hormesis are ready to pave the way for new and effective approaches in aging research and intervention.


New aspects in deriving health-based guidance values for bromate in swimming pool water.
Bromate, classified as a EU CLP 1B carcinogen, is a typical by-product of the disinfection of drinking and swimming pool water. The aim of this study was (a) to provide data on the occurrence of bromate in pool water, (b) to re-evaluate the carcinogenic MOA of bromate in the light of existing data, (c) to assess the possible exposure to bromate via swimming pool water and (d) to inform the derivation of cancer risk-related bromate concentrations in swimming pool water. Measurements from monitoring analysis of 229 samples showed bromate concentrations in seawater pools up to 34 mg/L. A comprehensive non-systematic literature search was done and the quality of the studies on genotoxicity and carcinogenicity was assessed by Klimisch criteria (Klimisch et al., Regul Toxicol Pharmacol 25:1-5, 1997) and SciRAP tool (Beronius et al., J Appl Toxicol, 38:1460-1470, 2018) respectively. Benchmark dose (BMD) modeling was performed using the modeling average mode in BMDS 3.1 and PROAST 66.40, 67 and 69 (human cancer BMDL10; EFSA 2017). For exposure assessment, data from a wide range of sources were evaluated for their reliability. Different target groups (infants/toddlers, children and adults) and exposure scenarios (recreational, sport-active swimmers, top athletes) were considered for oral, inhalation and dermal exposure. Exposure was calculated according to the frequency of swimming events and duration in water. For illustration, cancer risk-related bromate concentrations in pool water were calculated for different target groups, taking into account their exposure using the hBMDL10 and a cancer risk of 1 in 100,000. Convincing evidence was obtained from a multitude of studies that bromate induces oxidative DNA damage and acts as a clastogen in vitro and in vivo. Since statistical modeling of the available genotoxicity data is compatible with both linear as well as non-linear dose-response relationships, bromate should be conservatively considered to be a non-threshold carcinogen. BMD modeling with model averaging for renal cancer studies (Kurokawa et al., J Natl. Cancer Inst, 1983 and 1986a; DeAngelo et al., Toxicol Pathol 26:587-594, 1998) resulted in a median hBMDL10 of 0.65 mg bromate/kg body weight (bw) per day. Evaluation of different age and activity groups revealed that top athletes had the highest exposure, followed by sport-active children, sport-active adults, infants and toddlers, children and adults. The predominant route of exposure was oral (73-98%) by swallowing water, followed by the dermal route (2-27%), while the inhalation route was insignificant (< 0.5%). Accepting the same risk level for all population groups resulted in different guidance values due to the large variation in exposure. For example, for an additional risk of 1 in 100,000, the bromate concentrations would range between 0.011 for top athletes, 0.015 for sport-active children and 2.1 mg/L for adults. In conclusion, the present study shows that health risks due to bromate exposure by swimming pool water cannot be excluded and that large differences in risk exist depending on the individual swimming habits and water concentrations.


Duchenne muscular dystrophy in a 4-year-old girl due to heterozygous frame shift deletion of the dystrophin gene and skewed X-inactivation.
X-linked recessive diseases affect males, whereas female carriers are generally asymptomatic.We report on a 4-year-old girl who presented with a classical phenotype of Duchenne Muscular Dystrophy (DMD), a severe X-linked recessive type of muscular dystrophy affecting boys in early childhood.A thorough diagnostic work-up revealed that this resulted from a heterozygous out-of frame deletion in the DMD-gene in combination with an X-inactivation ratio of <10:90 in blood leukocytes and muscle.The case exemplifies that a skewed X-inactivation pattern has to be taken into account as mechanism causing clinical symptoms in female carriers of X-linked recessive disorders.


Genetics of absence epilepsy in rats.
All rats of the WAG inbred strain show electrophysiological and behavioral phenomena reminiscent of human absence epilepsy. To study the genetic architecture of this kind of epilepsy, WAG rats were cross bred with inbred ACI rats which show no signs of epilepsy. Number and duration of spike-wave discharges per hour were determined from 24-h recordings of cortical EEG in parental strains and reciprocal F1 hybrids. All hybrids showed spike-wave discharges, indicating complete dominance for occurrence, but different genetic backgrounds were suggested for number and duration of the phenomena. These results imply that more than one gene is involved in absence epilepsy. Some genes determine the occurrence, while others may manipulate the actual number and duration of the epileptic phenomena.


Generation of platelet activating factor (PAF) by a human lung epithelial cell line.
A human lung epithelial cell line (ATC-CCL-185) was cultured in nutrient Ham-F12 medium. Cells in monolayers were stimulated with either ionophore A23187 (1 microM) or phorbol myristate acetate (PMA, 0.2 microM) for various periods of time. Samples were analysed by HPLC and the presence of platelet activating factor (PAF) was detected by bioassay of the release of [3H]serotonin from rabbit platelets undergoing aggregation. The ATC-CCL 185 cells were found to synthesize PAF following activation with either PMA or ionophore. Ionophore at 1 microM was found to be more potent than PMA at 0.2 microM in the induction of PAF synthesis (congruent to 80 ng/mg protein). The synthesis of PAF through ionophore stimulation reached a maximum at 5 min, whereas PMA stimulation peaked at 15-20 min. PMA induced approximately one third the level of PAF synthesis by the ionophore. The PAF synthesized by these CCL185 cells was found to be mainly associated with the cell membrane with less than 10% released into the medium. Release of PAF into cell supernatant was dependent on the presence of bovine serum albumin (BSA). In the absence of BSA, a large portion (approximately 90%) of PAF was found to be cell associated, and only 60% when BSA concentration reached greater than or equal to 0.2%. These results demonstrate the ability of this lung epithelial cell line to synthesis PAF thus, suggesting that epithelial cells might participate in the process of inflammatory lung diseases, through the generation of this important mediator.


Determinants of quality of life in Paget's disease of bone.
To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status. The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.


Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea.
Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).


The Resurgence of the Highly Ylidic N-Heterocyclic Olefins as a New Class of Organocatalysts.
In recent decades, N-heterocyclic carbenes have become established as a prevalent family of organocatalysts. N-Heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes, have recently also emerged as efficient promoters for CO2 fixation and polymerization reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry.


Assessment of nanoparticle immersion depth at liquid interfaces from chemically equivalent macroscopic surfaces.
We test whether the wettability of nanoparticles (NPs) straddling at an air/water surface or oil/water interface can be extrapolated from sessile drop-derived macroscopic contact angles (mCAs) on planar substrates, assuming that both the nanoparticles and the macroscopic substrates are chemically equivalent and feature the same electrokinetic potential. Pure silica (SiO2) and amino-terminated silica (APTES-SiO2) NPs are compared to macroscopic surfaces with extremely low roughness (root mean square [RMS] roughness ≤ 2 nm) or a roughness determined by a close-packed layer of NPs (RMS roughness ∼ 35 nm). Equivalence of the surface chemistry is assessed by comparing the electrokinetic potentials of the NPs via electrophoretic light scattering and of the macroscopic substrates via streaming current analysis. The wettability of the macroscopic substrates is obtained from advancing (ACAs) and receding contact angles (RCAs) and in situ synchrotron X-ray reflectivity (XRR) provided by the NP wettability at the liquid interfaces. Generally, the RCA on smooth surfaces provides a good estimate of NP wetting properties. However, mCAs alone cannot predict adsorption barriers that prevent NP segregation to the interface, as is the case with the pure SiO2 nanoparticles. This strategy greatly facilitates assessing the wetting properties of NPs for applications such as emulsion formulation, flotation, or water remediation.


Curcuma aeruginosa Roxb. exhibits cytotoxicity in A-549 and HeLa cells by inducing apoptosis through caspase-dependent pathways.
The aim of the current study was to examine the efficacy of the leaf, stem and rhizome of Curcuma aeruginosa Roxb. for their phytochemical content, antioxidant and anti-cancer activities. The different parts of C. aeruginosa were subjected to sequential extraction to give three fractions viz., hexane, ethyl acetate and methanol extract. The cytotoxic effect and the mode of action against A-549 human lung adenocarcinoma and HeLa cell lines were examined. C. aeruginosa presented no significant toxic effect in normal human lung cells (L-132). The methanol extracts were found to be the most cytotoxic and further investigation was carried out to understand the effects. The methanol extracts induced DNA damage after 24 h with significant increase in tail DNA and tail moment when compared to untreated control. Up-regulation in the expression of the caspase - 8 and - 3 activity was observed after 48 h of treatment. The mechanism of cell death and apoptosis induced by the methanol extracts on A549 and HeLa cells were studied using fluorescent staining. Bioactive compounds detected from the HPLC revealed phenol and flavonoid compounds: Gallic acid, quercetin, caffeic acid, kaempferol, rutin, coumaric acid and naringenin. GC-MS results identified the presence of sesquiterpenoids: α-curcumene, curzerene curcumenol, curzerenone epicurzerenone, caryophyllene oxide and diterpenoid, andrographolide. These compounds are known for inducing apoptosis in human cancer cells through caspase - dependent pathways. Therefore, C. aeruginosa and its potential to induce apoptosis in cancer cells suggest that they have potential in medical applications.


Ictal central apneas in temporal lobe epilepsies.
The objective of the study was to examine the frequency and characteristics of ictal central apnea (ICA) in a selective cohort of patients with mesial or neocortical temporal lobe epilepsy (TLE) undergoing surface video-electroencephalography (EEG) and multimodal recording of cardiorespiratory parameters. We retrospectively screened 453 patients who underwent EEG in a single center including nasal airflow measurements, respiratory inductance plethysmography of thoracoabdominal excursions, peripheral capillary oxygen saturation, and electrocardiography. Patients with confirmed TLE subtype, either by magnetic resonance imaging (MRI) lesions limited to the temporal neocortex or mesial structures and concordant neurophysiologic data, or patients who underwent invasive explorations were included. Ictal central apnea frequency and characteristics were analyzed in 41 patients with 164 seizures that had multimodal respiratory monitoring. The total occurrence of ICA in all seizures in this cohort was 79.9%. No significant difference was seen between mesial and neocortical temporal lobe seizures (79.8% and 80.0%, respectively). Ictal central apnea preceded EEG onset by 13 ± 11 s in 33.3% of seizures and was the first clinical sign by 18 ± 14 s in 48.7%. Longer ICA duration trended towards a more severe degree of hypoxemia. In a selective cohort of TLE defined by MRI lesion and/or intracranial recordings, the frequency of ICA was higher than previously reported in the literature. Multimodal respiratory monitoring has localizing value and is generally well tolerated. Ictal central apnea preceded both EEG on scalp recordings as well as clinical seizure onset in a substantial number of patients. Respiratory monitoring and ICA detection is even more paramount during invasive monitoring to confirm that the recorded seizure onset is seen before the first clinical sign.


Figurate purpuric eruptions on the trunk: acetaminophen-induced rashes.
A 23-year-old man had recurrent erythematous purpuric patches in a transverse-linear arrangement on his back and arms. One week prior to a recent episode, he took acetaminophen for 3 days. Four months earlier, he developed the same purpuric lesions at/around the same anatomical site when he took acetaminophen for pain-relief. A biopsy specimen showed capillaritis and extravasation of erythrocytes in the papillary dermis. A provocation test with acetaminophen confirmed these lesions as drug-induced rashes. The uncommon topographic and morphologic features of the purpuric lesion in this patient might be considered as an unusual expression of pigmented purpuric dermatosis caused by acetaminophen.


Rhino-orbital mucormycosis due to Apophysomyces ossiformis in a patient with diabetes mellitus: a case report.
The most common aetiological agents of mucormycosis are Rhizopus, Mucor, Apophysomyces and Lichtheimia. Apophysomyces is comparatively rare, as it has been reported in less than 3% of mucormycosis cases. The genus Apophysomyces includes six species, and only A. elegans, A. mexicanus, A. variabilis and A. ossiformis have been reported to cause infections in both immunocompetent and immunocompromised patients. We present a case of a 46-year-old male patient with bilateral blepharoedema, corneal opacity in the left eye and poorly controlled diabetes mellitus. The patient was subjected to total maxillectomy, exenteration of the left orbit and treatment with liposomal amphotericin B. Direct mycological analysis with KOH 10% revealed hyaline, coenocytic, long and wide hyphae. Apophysomyces ossiformis was identified from maxillary biopsy using 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient requested to be transferred to another hospital to continue treatment, where he died on the ninth day after admittance. To the best of our knowledge, this is the first case of rhino-orbital mucormycosis due to A. ossiformis with a fatal outcome. This case reveals the need to identify the fungus causing mucormycosis with molecular methods to identify adequate treatment therapies for patients with this infection.


RARβ Promoter Methylation as an Epigenetic Mechanism of Gene Silencing in Non-small Cell Lung Cancer.
The retinoid acid receptor-p (RARβ) gene is one of the tumor suppressor genes (TSGs), which is frequently deleted or epigenetically silenced at an early stage of tumor progression. In this study we investigated the promoter methylation and expression status of the RARβ gene in 60 surgically resected non-small cell lung cancer (NSCLC) tissue samples and 60 corresponding unchanged lung tissue samples, using methylation-specific PCR and real-time-polymerase chain reaction (qPCR) techniques. We correlated the results with the pathological features of tumors and clinical characteristics of patients. qPCR analysis detected a significantly lower RARβ expression in the patients with adenocarcinoma (AC) and large cell carcinoma (LCC) than in those with squamous cell carcinoma (SCC) (AC vs. SCC, p = 0.032; AC and LCC vs. SCC, p = 0.0 13). Additionally, significantly lower expression of the RARβ gene was revealed in the patients with non-squamous cell cancer with a history of smoking assessed as pack-years (PY < 40 vs. PY ≥ 40, p = 0.045). Regarding RARβ promoter methylation, we found significant differences in the methylation index in the SCC group when considering pTNM staging; with higher index values in T1a + T1b compared with T2a + T2b and T3 + T4 groups (p = 0.024). There was no correlation between the methylation status and expression level of the RARβ gene, which suggests that other molecular mechanisms influence the RARβ expression in NSCLC patients. In conclusion, different expression of the RARβ gene in SCC and NSCC makes the RARβ gene a valuable diagnostic marker for differentiating the NSCLC subtypes.


Blindness and scalp haematoma in a child following a snakebite.
Snake envenomation is a major public health problem of the Savannah regions of West Africa. Ocular manifestations of snakebites are rare with few reports documenting blindness as a complication. To highlight an unusual manifestation of snake bites and its attendant problems. A report of scalp haematoma and blindness in a 10 year old child presenting 2 weeks after a snake bite (presumably carpet viper) is a rare manifestation. Local swelling, epistaxis, bilateral proptosis, exposure keratopathy and use of traditional eye medications were associated findings. Anti-venom though administered late saved the child's life but blindness could not be reversed. Ocular ultrasonography revealed layered retrobulbar collection in the left eye, presumably due to hemorrhage. The skull x-ray showed a soft tissue swelling and aspirate from scalp swelling was bloody. Cranial Computed Tomography (CT) scan done late detected no abnormalities. Snakebite is associated with lifelong morbidity. Ocular manifestations must be treated as emergency. This case highlights the effect of ignorance and poverty in a setting of a common medical emergency leading to blindness and reduced quality of life.


Dipyridamole technetium 99m sestamibi myocardial tomography as an independent predictor of cardiac event-free survival after acute ischemic events.
A total of 137 consecutive patients with recent uncomplicated myocardial infarction (n = 31) or unstable angina (n = 106) were studied to determine the relative prognostic value of predischarge clinical risk stratification and intravenous dipyridamole stress sestamibi (MIBI) myocardial tomography in patients unable to exercise maximally after an acute ischemic coronary event. Patients were followed up after the index study for 10 +/- 5 months (range 1 to 23 months) to ascertain cardiac events that occurred in 20 patients (15%): nonfatal myocardial infarction (n = 5) or cardiac death (n = 15). Cardiac event rates were 35% in patients with a recent myocardial infarction and 8% in the group with unstable angina (p < 0.001). Patients with these cardiac events had more frequent abnormal MIBI study results, fixed defects, and reversible plus fixed (combined) defects (all p < 0.05). The univariate relative risk of death or myocardial infarction associated with an abnormal MIBI study was 6.0 (95% confidence limits 0.8 to 44.7). Multivariate stepwise logistic regression models identified an abnormal MIBI study and either fixed or reversible MIBI defects as being predictive of death or myocardial infarction (all p < 0.05). The Mantel-Haentzel 1-year cardiac event-free survival rate was excellent in 27 patients with a normal MIBI single-photon computed emission tomographic scan (100%) but significantly reduced in the 110 patients with an abnormal MIBI study (80%; p < 0.05 vs normal subjects). The presence of combined MIBI defects was associated with the poorest event-free survival rate (66%; difference not significant vs fixed or reversible defects only). We conclude that predischarge dipyridamole MIBI tomography provided independent prognostic information in this population of patients who were unable to exercise after a recent acute ischemic coronary event.


Hemostatic disturbances associated with implantation of an artificial heart.
Coagulation and platelet parameters have been assessed following implantation of a Jarvik 7 artificial heart. Initially an ongoing intravascular coagulation could not be overcome with heparin and coumarin. The in vivo formation of thromboxane A2 (as monitored by measurement of the major urinary metabolite) was increased 3-4 fold. Administration of aspirin every second to third day reduced the thromboxane formation dramatically. In parallel to this, the intravascular coagulation subsided, the demand for heparin decreased considerably and the clinical condition of the patient improved. These events provide evidence for a direct link between thromboxane formation and the coagulation cascade. The thromboxane formation was insufficiently suppressed around the 110th postoperative day. Two weeks later the patient suffered a cerebral embolus, followed by a bleeding in the embolized area. This case illustrates the applicability of antiplatelet treatment when the need for efficient antithrombotic treatment is especially pronounced. Aspirin, however, is not the ideal drug for this purpose.