Clopidogrel trial in patients with elective percutaneous coronary intervention for stable angina and old myocardial infarction (CLEAN).
Clopidogrel in combination with aspirin has been widely used in patients who have undergone coronary stent implantation. However, the benefit to Japanese patients with stable angina (SA) or old myocardial infarction (OMI) undergoing percutaneous coronary intervention (PCI) still remains unclear.The aim of this multicenter, randomized, double-blind, clinical study was to evaluate the safety of a clopidogrel 300 mg loading dose followed by a 75 mg maintenance dose compared to ticlopidine 100 mg twice daily in patients with SA or OMI undergoing PCI who were on aspirin (81 to 100 mg once daily). The primary endpoint was the composite of safety events comprising clinically significant bleeding, blood disorders, elevated liver function values, and study drug discontinuation up to week 12. The key secondary endpoints were major adverse cardiac events (MACE), major adverse cardiac and cerebrovascular events (MACCE), and bleeding events. A total of 1003 patients were randomly allocated to receive either clopidogrel or ticlopidine and 931 patients underwent PCI. The cumulative incidence of the composite safety endpoint in the clopidogrel group was statistically lower than that of ticlopidine (P < 0.0001, hazard ratio; 0.259; 95%CI; 0.187 to 0.359). There were no statistically significant differences between treatments with respect to MACE at week 12 (P = 0.7899) nor to the bleeding events (P = 0.5292, stratified log-rank test).Clopidogrel was found to have a better benefit/risk profile than ticlopidine in Japanese patients with SA or OMI undergoing PCI.


Ontogeny of caudal fourth ventricular tanycytes in the rabbit brain: a Golgi study.
A Golgi study of the floor of the caudal fourth ventricle in the developing and adult rabbit brain stem revealed the presence of several clusters of tanycytes. These tanycytes possessed ciliated apical surfaces and basal shafts extending into the substance of the medulla and pons where they intermingled with specific neuronal fields. These shafts ended in the serotonergic nuclei raphe obscurus and pallidus, and the noradrenergic locus coeruleus and nucleus intercalatus (group A2). The tanycyte shafts extended into the medullary midline early in ontogeny (day 18 of gestation), following which the neurons of the raphe began to sprout neurites. These shafts then formed the underlying structure for a large medullary dendrite bundle. These shafts developed extensive spines during early neonatal ontogeny, which then diminished in number through adulthood. the tanycyte shafts extending into locus coeruleus and nucleus intercalatus developed later in ontogeny than the midline shafts, just before birth. These shafts also persisted into adulthood in close relationship with the monoamine neurons. We suggest that the tanycytes on the floor of the fourth ventricle may take up substances from the CSF and transport them to the region of the monoamine nuclei where the shafts terminate, in a manner similar to median eminence tanycytes. The early development of shafts from fourth ventricular tanycytes suggests a possible regulatory role for these cells over the neuritic sprouting and maturation of the monoaminergic nuclei.


Intelligence, reaction time, and inspection time.
Forty-eight subjects with IQ scores ranging from 57 to 138 discriminated between two lines of markedly different length, exposed for varying periods of time. Estimates of inspection time, lambda, a measure assumed to reflect the rate at which sensory input is processed, were obtained from the pattern of errors made by each subject and, therefore, independently from the reaction time (RT) required to respond. lambda correlated negatively with IQ scores. RTs of nonretarded subjects increased as stimulus-exposure duration decreased, whereas for retarded subjects RTs remained constant. This is interpreted as indicating differences between the groups in response strategy under conditions of difficult discrimination. The rate of information processing was also estimated in a different choice RT situation, using as an index the reciprocal of the slope of the function relating RT to degree of stimulus choice. Retarded subjects had slower rates and longer RTs than nonretarded subjects. A second experiment controlling for response-selection factors confirmed that this slowness could not be attributed to gross-movement difficulties and that a slower rate of information transmission seemed to be involved.


Role of ischaemia in the initiation of peptic ulcer.
Study of intramural vascular pathways to the human gastroduodenal mucosa shows that some persons have patches of mucosa supplied by end arteries. These patches occur only in the ulcer-bearing areas. It is suggested how this may contribute to the initiation of peptic ulceration and explain some of its features.


The innate immune response in tauopathies.
Tauopathies, which include frontotemporal dementia, Alzheimer's disease, and chronic traumatic encephalopathy, are a class of neurological disorders resulting from pathogenic tau aggregates. These aggregates disrupt neuronal health and function leading to the cognitive and physical decline of tauopathy patients. Genome-wide association studies and clinical evidence have brought to light the large role of the immune system in inducing and driving tau-mediated pathology. More specifically, innate immune genes are found to harbor tauopathy risk alleles, and innate immune pathways are upregulated throughout the course of disease. Experimental evidence has expanded on these findings by describing pivotal roles for the innate immune system in the regulation of tau kinases and tau aggregates. In this review, we summarize the literature implicating innate immune pathways as drivers of tauopathy.


Injury and Mortality Among Children Identified as at High Risk of Maltreatment.
To determine if children identified by a predictive risk model as at "high risk" of maltreatment are also at elevated risk of injury and mortality in early childhood. We built a model that predicted a child's risk of a substantiated finding of maltreatment by child protective services for children born in New Zealand in 2010. We assigned risk scores to the 2011 birth cohort, and flagged children as "very high risk" if they were in the top 10% of the score distribution for maltreatment. We also set a less conservative threshold for defining "high risk" and examined children in the top 20%. We then compared the incidence of injury and mortality rates between very high-risk and high-risk children and the remainder of the birth cohort. Children flagged at both 10% and 20% risk thresholds had much higher postneonatal mortality rates than other children (4.8 times and 4.2 times greater, respectively), as well as a greater relative risk of hospitalization (2 times higher and 1.8 times higher, respectively). Models that predict risk of maltreatment as defined by child protective services substantiation also identify children who are at heightened risk of injury and mortality outcomes. If deployed at birth, these models could help medical providers identify children in families who would benefit from more intensive supports.


Phase resetting of the rhythmic activity of embryonic heart cell aggregates. Experiment and theory.
Injection of a current pulse of brief duration into an aggregate of spontaneously beating chick embryonic heart cells resets the phase of the activity by either advancing or delaying the time of occurrence of the spontaneous beat subsequent to current injection. This effect depends upon the polarity, amplitude, and duration of the current pulse, as well as on the time of injection of the pulse. The transition from prolongation to shortening of the interbeat interval appears experimentally to be discontinuous for some stimulus conditions. These observations are analyzed by numerical investigation of a model of the ionic currents that underlie spontaneous activity in these preparations. The model consists of: Ix, which underlies the repolarization phase of the action potential, IK2, a time-dependent potassium ion pacemaker current, Ibg, a background or time-independent current, and INa, an inward sodium ion current that underlies the upstroke of the action potential. The steady state amplitude of the sum of these currents is an N-shaped function of potential. Slight shifts in the position of this current-voltage relation along the current axis can produce either one, two, or three intersections with the voltage axis. The number of these equilibrium points and the voltage dependence of INa contribute to apparent discontinuities of phase resetting. A current-voltage relation with three equilibrium points has a saddle point in the pacemaker voltage range. Certain combinations of current-pulse parameters and timing of injection can shift the state point near this saddle point and lead to an interbeat interval that is unbounded . Activation of INa is steeply voltage dependent. This results in apparently discontinuous phase resetting behavior for sufficiently large pulse amplitudes regardless of the number of equilibrium points. However, phase resetting is fundamentally a continuous function of the time of pulse injection for these conditions. These results demonstrate the ionic basis of phase resetting and provide a framework for topological analysis of this phenomenon in chick embryonic heart cell aggregates.


The effect of recombinant human lactoferrin from the milk of transgenic cows on Salmonella enterica serovar typhimurium infection in mice.
Lactoferrin (LF) is a multifunctional protein with antibacterial and immunomodulatory activities. Given this beneficial effect, transgenic approaches have been used to produce lactoferrin. The aim of the current study was to investigate the in vivo effect of recombinant human lactoferrin (rhLF) from the milk of transgenic cows on Salmonella enterica serovar typhimurium (ST) infection in mice. Two hours before the infection with 0.3 ml at 2 × 10(5) CFU ml(-1) of ST, each animal in the ST + rhLF group received 0.3 ml of rhLF with 20 mg ml(-1) concentration while the ST group received PBS as placebos with the same volume through oral gavage. The mice were infected with ST once only on the first day. After the infection, the mice received 0.3 ml of rhLF with 20 mg ml(-1) (6 mg d(-1)) concentration or PBS, respectively, for 7 days. Mortality and weight were monitored daily. Bacterial enumeration in the blood, liver, and spleen and histopathological analysis of the liver, spleen, kidney and intestine were conducted. The results showed that rhLF decreased the bacterial load in the liver and spleen of mice, reduced the degree of mice hepatomegaly and splenomegaly, and attenuated infectious inflammation with less histopathological abnormalities in the liver, spleen and kidney of mice in the ST infection. This study showed that rhLF with 6 mg per day had antibacterial activity of alleviating the infection caused by ST bacteria, which indicated that rhLF could be used as a supplement in special products.


Augmentation of human K-cell activity with interferon.
Our laboratory recently reported that interferon (IF) could augment human antibody-dependent cellular cytotoxicity (ADCC) and cytotoxicity by natural killer (NK) cells. Although there is general agreement that IF can boost the activity of human NK cells, two laboratories have reported a failure to boost ADCC. We have therefore examined in more detail the effects of IF on human ADCC. We have found, by several lines of evidence, that IF can indeed appreciably augment the activity of K cells, the subpopulation of lymphocytes that mediate ADCC: (1) human leucocyte IF, purified to homogeneity, boosted ADCC: (2) IF augmented ADCC against target cells that were completely resistant to NK activity; and (3) the ADCC activity of leukaemic cells from a patient with chronic lymphocytic leukaemia (CLL) which lacked any detectable NK activity was boosted by IF. These results are consistent with the hypothesis that human NK and K cells are the same subpopulation of lymphocytes and that the mechanisms regulating their activity are similar. However, the absence of NK activity in the CLL patient strongly supports the idea that not all FcR-positive cells are NK and that ADCC effectors devoid of NK may exist. However, further evidence is required to analyse this point.


Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy.
Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury. Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates. Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3μg/mmol versus 533.6μg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups. Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.


Cobalt-chromium as a framework material in implant-supported fixed prostheses: a preliminary report.
Sixty-six consecutive patients treated at the Prosthodontic Clinic in Uppsala, Sweden, received implant-supported fixed prostheses of the Brånemark type. The prosthesis frameworks were made of cobalt-chromium alloys. Different techniques for attaching the gold cylinders to the frameworks were used. Mechanical attachment with self-curing polymethyl methacrylate (PMMA), partial soldering combined with PMMA attachment, and soldering only were used. No abnormal tissue reactions were seen. Radiographic examination of the fixtures was performed at the time of prosthesis placement and at the 1- and 3-year follow-ups. A few cases of minor bone loss were detected but not related to the materials used in the superstructures.


Hypovirus infection induces proliferation and perturbs functions of mitochondria in the chestnut blight fungus.
The chestnut blight fungus, Cryphonectria parasitica, and hypovirus have been used as a model to probe the mechanism of virulence and regulation of traits important to the host fungus. Previous studies have indicated that mitochondria could be the primary target of the hypovirus. In this study, we report a comprehensive and comparative study comprising mitochondrion quantification, reactive oxygen species (ROS) and respiratory efficiency, and quantitative mitochondrial proteomics of the wild-type and virus-infected strains of the chestnut blight fungus. Our data show that hypovirus infection increases the total number of mitochondria, lowers the general ROS level, and increases mitochondrial respiratory efficiency. Quantification of mitochondrial proteomes revealed that a set of proteins functioning in energy metabolism and mitochondrial morphogenesis, as well as virulence, were regulated by the virus. In addition, two viral proteins, p29 and p48, were found to co-fractionate with the mitochondrial membrane and matrix. These results suggest that hypovirus perturbs the host mitochondrial functions to result in hypovirulence.


The influence of uterine artery embolisation on ovarian reserve, fertility, and pregnancy outcomes - a review of literature.
Uterine fibroids are considered to be the most frequent female benign tumours. Fibroids affect mainly women of reproductive age. The most frequently reported signs and symptoms of fibroids include disturbances of the menstrual cycle such as heavy bleeding and painful menstruation, pelvic masses associated with pelvic pain, urinary problems or constipation, as well as infertility and recurrent pregnancy loss. The mainstay of fibroid treatment is still surgery. However, many patients seek alternative treatment options for fibroids, to preserve their uterus and fertility. One of the most important alternative treatment options for fibroids is uterine artery embolisation (UAE). However, there are some concerns that UAE may negatively influence ovarian function and even result in premature menopause. Moreover, the use of UAE in patients with future reproductive plans is still controversial, due to the possible pregnancy complications. The purpose of this review is to summarise the current knowledge regarding the possible influence of UAE on fertility, pregnancy outcome, and ovarian reserve.


Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds.
Conjugated polymers have been proposed as promising materials for scaffolds in tissue engineering applications. The restricted processability and biodegradability of conjugated polymers limit their use for biomedical applications however. Here we synthesised a block-co-polymer of aniline tetramer and PCL (AT-PCL), and processed it into fibrous non-woven scaffolds by electrospinning. We showed that fibronectin (Fn) adhesion was dependant on the AT-PCL oxidative state, with a reduced Fn unfolding length on doped membranes. Furthermore, we demonstrated the cytocompatibility and potential of these membranes to support the growth and osteogenic differentiation of MC3T3-E1 over 21 days.


Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients.
Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.


Orthodontists' instructions for oral hygiene in patients with removable and fixed orthodontic appliances.
The aim of this questionnaire-based survey was to evaluate information on frequencies, instructions and products relating to oral hygiene (OH) in orthodontic practices. Using a computer-generated randomization list, 1000 orthodontists were selected and sent a questionnaire. The size and number of inhabitants of the federal states of Germany were considered. The federal states with the highest return rate (Baden-Wuerttemberg [BW], Bavaria [B], Hesse [H], Lower Saxony [LS], Nordrhein-Westphalia [NRW]) were considered and differences between the 16 federal states were divided into North, South, East and Central Germany. The response rate of the questionnaires was 52.4%. The majority (53.8%) worked in one practice alone. Most (59.1%) have been orthodontists for 5-25 years. For vestibular multibracket appliances (MBA) in BW, B, H and LS over 90% recommended interdental brushes (IDB). In NRW 91.4% recommend fluoride gel. In B and H more than 80% chose electric toothbrush (ETB), in BW, LS and NRW more than 80% manual toothbrush (MTB). For lingual MBA (LMBA) in BW, H, LS and NRW with approximately 50% each fluoride gel, IDB and MTB were chosen. In B fluoride gel, IDB and ETB. For removable apparatus (RA), five federal states recommended MTB (>80%) and ETB (BW, B, H > 80%; NRW > 70%; LS > 60%). Electric toothbrushes are recommended for the use with all appliances, only with removable appliances manual toothbrushes are favoured. For vestibular MBA it is strongly advised to use IDB additionally.


Physical, antioxidant and structural characterization of blend films based on hsian-tsao gum (HG) and casein (CAS).
The effects of hsian-tsao gum (HG) addition on the physical properties, antioxidant activities and structure of casein (CAS) film have been investigated. It has been observed that HG addition provided CAS film with better mechanical properties and resistant to moisture, stronger barrier properties against light and higher antioxidant activities than pure CAS film. Fourier transformation infrared (FTIR) data indicated that hydrogen bonding interactions and Maillard reactions occurred between CAS and HG, giving rise to a more compact structure than CAS film. The results of X-ray diffraction and differential scanning calorimetry (DSC) indicated that CAS and HG were compatible, and addition of HG destroyed the original crystalline domains of CAS film, and the blend films exhibited higher glass transition temperatures than CAS film. Moreover, nuclear magnetic resonance (NMR) analysis showed that HG addition significantly changed the mobility of water molecule in CAS film. Especially, ratio of the high mobility water of CAS/HG films significantly decreased as compared to CAS film.


Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic actions of parathyroid hormone and parathyroid hormone-related protein on the skeleton.
So what have we learned from the Takeuchi case? It has been 80 years since malignancy-associated hypercalcemia was described. It has been 45 years since HHM was first described. It has been 15 years since PTHrP was identified, and 12 years since PTHrP immunoassays became available for clinical research. We now know almost everything about HHM in pathophysiological terms, and we can reproduce the cardinal features of the syndrome in laboratory animals and humans. The Takeuchi case reminds us that we still have a few things to learn about HHM. Specifically, "Why is the regulation of 1,25(OH)2D different in patients with HHM and HPT?" and "Why is normal osteoblast-osteoclast coupling dysregulated in HHM?" or more fundamentally, "What regulates osteoblast-osteoclast coupling, and why is it deranged in HHM?" Given the rate of accumulation of new information about HHM, about the anabolic effects of PTH and PTHrP, and about osteoblast-osteoclast coupling over the past 10 years, there is reason to be optimistic that the answers to these questions will soon become clear.


Robust room temperature emissions of trion in darkish WSe2 monolayers: effects of dark neutral and charged excitonic states.
Owing to nonzero charge and spin degrees of freedom, trions offer unprecedented tunability and open new paths for applications in devices based on 2D semiconductors. However, in monolayer WSe2, the trion photoluminescence is commonly detected only at low temperatures and vanishes at room temperature, which undermines practical applications. To unveil how to overcome this obstacle, we have developed a comprehensive theory to probe the impact of different excitonic channels on the trion emission in WSe2 monolayers, which combines ab initio tight-binding formalism, Bethe-Salpeter equation and a set of coupled rate equations to describe valley dynamics of excitonic particles. Through a systematic study in which new scattering channels are progressively included, we found that, besides the low electron density, strong many-body correlations between bright and dark excitonic states quenches the trion emission in WSe2. Therefore, the reduction of scatterings from bright to dark states is required to achieve trion emission at room temperature for experimentally accessible carrier concentrations.


Yeast cell cycle analysis: combining DNA staining with cell and nuclear morphology.
In studies of eukaryotic cell cycle regulation, the budding yeast Saccharoymyces cerevisiae offers many advantages as a model system. Due to its simple growth requirements and genetic tractability, this organism is a powerful tool for investigating the molecular regulation of cell cycle control. One earlier disadvantage to performing cell cycle analyses in yeast was that existing methods were restricted to either visual analysis or flow cytometry, both of which present limitations in the scope and accuracy of the data obtained. This unit demonstrates the combined use of DNA content measurements and bright-field image analysis using multispectral imaging flow cytometry (MIFC) to provide a more precise quantitation of yeast cell cycle distribution. The advantage of this method is the ability to analyze large numbers of cells using multiple cell cycle indicators in a relatively short amount of time.


The Rodent Forced Swim Test Measures Stress-Coping Strategy, Not Depression-like Behavior.
The forced swim test (FST) measures coping strategy to an acute inescapable stress and thus provides unique insight into the neural limb of the stress response. Stress, particularly chronic stress, is a contributing factor to depression in humans and depression is associated with altered response to stress. In addition, drugs that are effective antidepressants in humans typically promote active coping strategy in the FST. As a consequence, passive coping in the FST has become loosely equated with depression and is often referred to as "depression-like" behavior. This terminology oversimplifies complex biology and misrepresents both the utility and limitations of the FST. The FST provides little construct- or face-validity to support an interpretation as "depression-like" behavior. While stress coping and the FST are arguably relevant to depression, there are likely many factors that can influence stress coping strategy. Importantly, there are other neuropsychiatric disorders characterized by altered responses to stress and difficulty in adapting to change. One of these is autism spectrum disorder (ASD), and several mouse genetic models of ASD exhibit altered stress-coping strategies in the FST. Here we review evidence that argues a more thoughtful consideration of the FST, and more precise terminology, would benefit the study of stress and disorders characterized by altered response to stress, which include but are not limited to depression.


Asymmetric periflexural exanthem of childhood and influenza virus infection.
Asymmetric periflexural exanthem of childhood (APEC) is a self-limited disease characterized by unilateral exanthem. The etiology is unknown, but a viral agent is suspected. Most often there is no formal proof of an associated viral etiology, but several associations between APEC and some viruses have been described. We report a 2-year-old girl with APEC associated with influenza A. This case allows us to provide an additional argument on a probable viral etiology of APEC and a possible etiologic role of influenza A.


Endo-restorative Management of a Type II Dens Invaginatus in Mandibular Premolar Associated with a Large Cyst.
We present the management of a case of Type II dens invaginatus in a mandibular premolar with a large invagination in the coronal third of the root on mesial aspect of the crown in proximity of cementoenamel junction significantly compromising the strength of the crown structure. We describe in detail the various measures taken to assess the internal tooth structure destruction and enhance the fracture resistance of the involved premolar. The case has a long-term follow-up of 36 months showing clinical and radiographic signs of healing. We highlight use of a simple "foil coated fiber postblocker technique" for root reinforcement in the first premolar. Successful management of teeth with dens invaginatus can be effectively done using with careful treatment planning and selection of reinforcing adhesive restorative materials.


Carrageenan based hydrogels for drug delivery, tissue engineering and wound healing.
Carrageenan is a class of naturally occurring sulphated polysaccharides, which is currently a promising candidate in tissue engineering and regenerative medicine as it resemblances native glycosaminoglycans. From pharmaceutical drug formulations to tissue engineered scaffolds, carrageenan has broad range of applications. Here we provide an overview of developing various forms of carrageenan based hydrogels. We focus on how these fabrication processes has an effect on physiochemical properties of the hydrogel. We outline the application of these hydrogels not only pertaining to sustained drug release but also their application in bone and cartilage tissue engineering as well as in wound healing and antimicrobial formulations. Administration of these hydrogels through various routes for drug delivery applications has been critically reviewed. Finally, we conclude by summarizing the current and future outlook that promotes the seaweed-derived polysaccharide as versatile, promising biomaterial for a variety of bioengineering applications.


Persistence of Chlamydia psittaci in Various Temperatures and Times.
Chlamydia psittaci, an obligate intracellular gram-negative bacteria, causes an important zoonotic disease in humans, namely, psittacosis. The objective of this study was to determine the persistent viability of C. psittaci at various temperature conditions. The cloacal swab samples were collected from feral and racing pigeons to find a C. psittaci field strain. The bacterial isolation showed that 1.3% of feral pigeons were PCR positive, while all samples of racing pigeons were PCR negative. Also, bacterial characterization suggested that it belonged to genotype B, which had bacterial titers 3.2 and 3.89 log 50% lethal dose/ml, respectively. A bacterial persistence test was performed, and the results showed that C. psittaci could survive at 56 C for up to 72 hr. In conclusion, C. psittaci could be found in feral pigeons in central Thailand. The bacteria can survive in equatorial temperature areas. This study was the first to report that C. psittaci could survive and has infectivity at 56 C for 72 hr. Therefore, awareness of C. psittaci infection in humans is necessary and should be a public health concern.


[Holter monitoring data in children with gastroesophageal reflux disease].
The aim of research is to estimate the functional state of the cardiovascular system in children with gastroesophageal reflux disease (GERD) with the help of Holter monitoring. 117 children of school age were examined: 69 children with GERD and 48 children with chronic gastroduodenitis. All children passed esophagogastroduodenoscopy, 24-hour pH-monitoring, electrocardiography and Holter monitoring. According to Holter monitoring data it was revealed that children with GERD had increased low-frequency components of frequency domain analyses, increased number of nocturnal PVCs and increased time of enhanced dispertion periods. Holter monitoring in patients with GERD can be used to detect preclinical ectopic rhythm, to evaluate autonomic dysfunction by frequency domain analyses, to predict nocturnal symptoms.


The partitioning of water uptake between growth forms in a Neotropical savanna: do herbs exploit a third water source niche?
In addition to trees and grasses, the savannas of central Brazil are characterised by a diverse herbaceous dicot flora. Here we tested whether the coexistence of a highly diversified assemblage of species resulted in stratification or strong overlap in the use of soil water resources. We measured oxygen and hydrogen isotope ratios of stem water from herbs, grasses and trees growing side by side, as well as the isotopic composition of water in soil profile, groundwater and rainfall, and predawn (Ψ(pd)) and midday (Ψ(md)) leaf water potentials. We used a stable isotope mixing model to estimate vertical partitioning of soil water by the three growth forms. Grasses relied on shallow soil water (5-50 cm) and were strongly anisohydric. Ψ(pd) and Ψ(md) decreased significantly from the wet to the dry season. Trees extracted water from deeper regions of the soil profile (60-120 cm) and were isohydric. Ψ(pd) and Ψ(md) did not change from the wet to the dry season. Herbs overlapped with grasses in patterns of water extraction in the dry season (between 10 and 40 cm), but they took up water at soil depths intermediate (70-100 cm) to those of trees and grasses during the wet season. They showed seasonal changes in Ψ(pd) but not in Ψ(md). We conclude that vertical partitioning of soil water may have contributed to coexistence of these three growth forms and resulted in a more complex pattern of soil water extraction than the two-compartment model of soil water uptake currently used to explain the structure and function of tropical savanna ecosystems.


Comparison of spiramycin with erythromycin for lower respiratory tract infections.
The efficacy and safety of 2 g oral spiramycin daily were compared with those of 2 g of oral erythromycin daily in a multicentre open prospective trial, involving 198 patients, with a mean age of 61.75 years, with a clinical and radiological diagnosis of acute lower respiratory tract infection. The diagnoses were: acute bronchitis (96), acute superinfection of chronic bronchitis (60) and pneumonia (42). The patients were assessed before therapy and after three and ten days of therapy. Seventy-four (76.3%) of the patients were cured in the spiramycin group and 64 (63.4%) were cured in the erythromycin group (P less than 0.05). Significantly more patients complained of side effects in the erythromycin group (41.4%) than in the spiramycin group (11.8%) P less than 0.001.


Comparison between Fluorescence Imaging and Elemental Analysis to Determine Biodistribution of Inorganic Nanoparticles with Strong Light Absorption.
Black porous silicon nanoparticles (BPSi NPs) are known as highly efficient infrared light absorbers that are well-suitable for photothermal therapy (PTT) and photoacoustic imaging (PAI). PTT and PAI require a sufficient number of effectively light-absorbing NPs to be accumulated in tumor after intravenous administration. Herein, biodistribution of PEGylated BPSi NPs with different sizes (i.e., 140, 200, and 300 nm in diameter) is investigated after intravenous administration in mice. BPSi NPs were conjugated with fluorescent dyes Cy5.5 and Cy7.5 to track them in vitro and in vivo, respectively. Optical imaging with an in vivo imaging system (IVIS) was found to be an inadequate technique to assess the biodistribution of the dye-labeled BPSi NPs in vivo because the intrinsic strong absorbance of the BPSi NPs interfered fluorescence detection. This challenge was resolved via the use of inductively coupled plasma optical emission spectrometry to analyze ex vivo the silicon content in different tissues and tumors. The results indicated that most of the polyethylene glycol-coated BPSi NPs were found to accumulate in the liver and spleen after intravenous injection. The smallest 140 nm particles accumulated the most in tumors at an amount of 9.5 ± 3.4% of the injected dose (concentration of 0.18 ± 0.08 mg/mL), the amount known to produce sufficient heat for cancer PTT. Furthermore, the findings from the present study also suggest that techniques other than optical imaging should be considered to study the organ biodistribution of NPs with strong light absorbance properties.


Cyclic Ca2+ changes in intracellular stores of gonadotropes during gonadotropin-releasing hormone-stimulated Ca2+ oscillations.
Gonadotropin-releasing hormone induces oscillatory release of Ca2+ from inositol trisphosphate-sensitive stores of gonadotropes. Simultaneously with electrophysiological measures of cytoplasmic [Ca2+], corresponding changes in [Ca2+] within intracellular stores were monitored with a fluorescent dye, mag-indo-1. Each cycle of oscillation released only 10% of the detectable stored Ca2+. Some Ca2+ was recovered by the stores using a mechanism sensitive to inhibitors of intracellular Ca2+ ATPases, and much of the remainder was temporarily and rapidly pumped into other intracellular compartments or out of the cell. The dynamics of Ca2+ oscillations are thus more complex than a repeated emptying and refilling of a single compartment. The free concentrations measured show that intracellular Ca2+ store compartments contain strong Ca2+ buffers.


Establishment of magnetic beads-based enzyme immunoassay for detection of chloramphenicol in milk.
In this research, magnetic beads-based enzyme immunoassays were investigated for rapid analysis of chloramphenicol (CAP) in milk. To improve sensitivity of CAP determination, two kinds of immunomagnetic separation methods were designed and compared. Magnetic polystyrene microspheres were conjugated with anti-CAP antibody (Method I) or goat-anti-mouse IgG (Method II). The whole determination could be finished in 1.25 h. Both methods showed high sensitivity to CAP in buffer, and obtained an IC(50) value of 0.05 ng mL(-1) for Method I and 0.4 ng mL(-1) for Method II. The methods showed high specificity, only showing a little cross-reaction towards CAP succinate. The two methods were applied to detect CAP in milk. The recovery rates were 80-106% and the coefficients of variation (CVs) were 4.7-15%. The immunomagnetic assay showed promising potential in rapid screening field for CAP analysis. Between the two methods, Method I is more sensitive, and Method II is more suitable for producing a general assay by changing a primary antibody for another analyte.


Enhancer element potentially involved in human survivin gene promoter regulation in lung cancer cell lines.
We have revealed evolutionarily conserved regions in a 4500-bp DNA sequence 5'-adjacent to the survivin (BIRC5) gene. In the transcribed region of the BIRC5 gene we have detected and characterized in detail a 3'-fragment of the CpG island that stimulated in enhancer-like way the gene promoter activity in normal cells and in a number of cancer, in particular lung cancer, cell lines. When added to the initial 1498-bp survivin promoter region, a transcribed DNA fragment of a CpG island approximately twofold enhanced the promoter activity in cancer cells and in normal lung fibroblasts. The observed effect did not depend upon the orientation of the fragment and distances between the fragment and the transcription initiation site. In the case of a heterologous SV40 virus promoter, the effect was less pronounced. In addition to earlier reports, the results provide new information on the BIRC5 gene expression regulation and also demonstrate that this gene exon sequences can play a significant role in BIRC5 gene expression regulation. The data provide another possibility to increase survivin promoter activity without changing its cancer specificity for application in cancer (in particular, lung cancer) gene therapy.


Electrosurgical transurethral resection of the prostate and transurethral incision of the prostate (monopolar techniques).
We summarize the current guidelines, techniques, efficacy and complications associated with monopolar transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP) for benign prostatic hyperplasia (BPH). Patients who elect to have endoscopic surgical bladder outlet reduction are faced with an abundance of evolving treatment options. As new technology comes and goes, TURP and TUIP remain the gold standard for which new treatments are compared. A review of past and contemporary data including American and European guidelines was performed. Techniques, efficacy, durability, short term and long term complications of TURP and TUIP are summarized. Small prostate sizes < 30 mL without a median lobe can be effectively treated with TUIP with decreased perioperative complications and sexual side effects compared to TURP. Monopolar TURP demonstrates significant improvements in IPSS, peak flow rate (Qmax), and quality of life (QoL) with durable (8 year-22 year) outcomes. Secondary intervention increases by 1%-2% annually. Thirty-day mortality rate is low (0.1%) as well as incidence of TUR syndrome (< 1.1%). Short term and long term complications include bleeding requiring transfusion, clot retention, acute urinary retention (AUR), and urinary tract infections as well as incontinence, bladder neck contracture, urethral stricture, and sexual dysfunction. Monopolar TURP and TUIP are effective endoscopic treatments for BPH with durable long term results. While the short term and long term complication rates are acceptable, new technologies aim to increase tolerability of bladder outlet reduction by decreasing treatment related morbidity.


Intra- and submembrane particle densities during CO2 stimulation of H+ secretion in turtle bladder.
The apical cell membranes of the H+ secreting, alpha-intercalated cells of turtle urinary bladder (TB) are characterized by studs (cytoplasmic domains of V-adenosinetriphosphatase) on thin-section transmission electron microscopy and by intramembrane particles (spherical units, SPUs) occurring as rod-shaped particles on freeze-fracture electron microscopy. To examine the relationship between studs and SPUs, morphometric studies were carried out on bladders maintained in 5% CO2 and in the absence of exogenous CO2. The stud density per square micrometer of apical membrane was 3,909 +/- 352 (+/-SE) in four TBs (29 alpha-cells) at 5% CO2 and 3,667 +/- 448 (+/-SE) in the paired halves of the same bladders without CO2 (25 alpha-cells). Corresponding densities of SPUs counted on apical membranes of the same bladders (n = 4) were 3,941 +/- 545 in 5% CO2 and 3,599 +/- 511 without CO2. The similarity of the densities of studs and SPUs under both conditions indicates that each SPU within the membrane is matched by one stud projecting into the cytoplasm. The one-for-one relationship between studs and SPUs was preserved over a wide range of transport rates. Addition of CO2 caused only inconsistent increments in the densities of studs and SPUs despite substantial increases in H+ transport rate. Slight variations in spacing of studs were consistent with patterns of distribution of SPUs on fracture surfaces.


Hypotonia during amikacin administration in a patient treated with continuous ambulatory peritoneal dialysis.
In this report we present the history of a patient treated with continuous ambulatory peritoneal dialysis (CAPD) in whom episodes of hypotonia can be related to the administration of amikacin, an antibiotic from the aminoglycosides group. The 68-year-old female patient was admitted for initiation of renal replacement therapy with CAPD. Her renal failure was probably attributable to hypertension. Three days after catheter implantation, the patient reported dysuric symptoms, and a urine culture showed significant growth of Escherichia coli. Amikacin 250 mg and cefazolin 1.0 g were administered intravenously once daily in accordance with the antibiogram. On the third day of antibiotic administration, the patient fainted, showing an arterial blood pressure of 90/60 mmHg. On the subsequent 2 days, decreases of postural arterial blood pressure to between 90/60 mmHg and 80/50 mmHg were reported two or three times daily. The patient was treated with antibiotics for the next 6 days and felt very bad the entire time, with an arterial blood pressure of 80/50 mmHg. The patient's condition improved 2 days after discontinuation of treatment with antibiotics, and episodes of hypotonia stopped. The decrease in the arterial blood pressure observed in our patient during intravenous administration of amikacin can, with a high probability, be related to the calcimimetic activity of this aminoglycoside and the resulting inhibition of parathyroid secretion.


Factors Associated With Psychological Adjustment in Adults With Cleft Lip and/or Palate: Findings From a National Survey in the United Kingdom.
Research has identified adults born with cleft lip and/or palate (CL/P) to be at risk of poorer psychological outcomes compared to the general population. This study investigated factors that may contribute to positive and negative adjustment in adults born with CL/P. A survey was designed and distributed by the Cleft Lip and Palate Association in collaboration with the Centre for Appearance Research CAR at the University of the West of England (UWE). There were 207 eligible responses (95% completed online) received between July and October 2018. Dependent variables included the Body Esteem Scale for Adolescents and Adults, Harter's Self Perception Profile for Adults (Global Self-Worth, Social Competence, and Intimacy subscales), the Fear of Negative Appearance Evaluation Scale, and the Revised Adult Attachment Scale. Independent variables were the Revised Life Orientation Test, biodemographic data, and self-reported single-item questions. Factors associated with positive adjustment included reports of a happy childhood, talking about CL/P with family, close friendships, comfort in public spaces, satisfaction with appearance, and a positive life orientation. Psychological distress was associated with a desire for further surgery to improve appearance and/or function. Several factors were identified that may influence psychological adjustment in adults with CL/P. Throughout childhood, family-centered practice to support family cohesion and an open dialogue about CL/P is indicated, as is support for young people to develop social confidence. For adults returning to the cleft service, treatment options for appearance and/or functional concerns should be explored, with access to psychological support when indicated. Interventions to increase optimism, resilience, and self-acceptance may also be warranted throughout the life span.


Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root Ganglia and Spinal Cord Dorsal Horn to Nerve Injury-induced Nociceptive Hypersensitivity.
Peripheral nerve injury-induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury-induced nociceptive hypersensitivity is unknown. Quantitative real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, or immunohistochemistry were carried out to examine the expression of SUV39H1 mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG μ-opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1 siRNA on fifth lumbar spinal nerve ligation (SNL)-induced DRG MOR down-regulation and nociceptive hypersensitivity were examined. SUV39H1 was detected in neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1 siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group). The findings of this study suggest that SUV39H1 contributes to nerve injury-induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury-induced nociceptive hypersensitivity.


A cryptic species of Aphis gossypii (Hemiptera: Aphididae) complex revealed by genetic divergence and different host plant association.
Three cryptic species, Aphis gossypii, Aphis glycines, and Aphis rhamnicola sp. nov., are recognized as sharing buckthorn plant, Rhamnus spp. as primary hosts. These aphid species have morphological similarities; however, there are significant genetic differences between the three cryptic species. Based on the high level of genetic divergence and the different secondary host association, we described a new species, Aphis rhamnicola sp. nov., for apterous and alate vivipara, fundatrix, ovipara, and gynopara, including diagnostic key for the host sharing species in the genus Aphis.


Temporal trends and demographic risk factors for hospital admissions due to carbon monoxide poisoning in England.
Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning is a preventable cause of morbidity and mortality. Epidemiological data on UNFR CO poisoning can help monitor changes in the magnitude of this burden, particularly through comparisons of multiple countries, and to identify vulnerable sub-groups of the population which may be more at risk. Here, we collected data on age- and sex- specific number of hospital admissions with a primary diagnosis of UNFR CO poisoning in England (2002-2016), aggregated to small areas, alongside area-level characteristics (i.e. deprivation, rurality and ethnicity). We analysed temporal trends using piecewise log-linear models and compared them to analogous data obtained for Canada, France, Spain and the US. We estimated age-standardized rates per 100,000 inhabitants by area-level characteristics using the WHO standard population (2000-2025). We then fitted the Besag York Mollie (BYM) model, a Bayesian hierarchical spatial model, to assess the independent effect of each area-level characteristic on the standardized risk of hospitalization. Temporal trends showed significant decreases after 2010. Decreasing trends were also observed across all countries studied, yet France had a 5-fold higher risk. Based on 3399 UNFR CO poisoning hospitalizations, we found an increased risk in areas classified as rural (0.69, 95% CrI: 0.67; 0.80), highly deprived (1.77, 95% CrI: 1.66; 2.10) or with the largest proportion of Asian (1.15, 95% CrI: 1.03; 1.49) or Black population (1.35, 95% CrI: 1.20; 1.80). Our multivariate approach provides strong evidence for the identification of vulnerable populations which can inform prevention policies and targeted interventions.


Antigen-induced histamine release from guinea pig basophils.
Guinea pig blood was found to contain an average of 106 +/- 21 ng/ml of histamine. Of this total, approximately 85-90% was of platelet origin and the rest from basophils. Basophils contain about 0.72 pg of histamine/cell. Concanavalin A (1-5 microgram/ml) induced the release of approximately 65% of the basophilic histamine. When basophils were isolated from animals sensitized to ovalbumin or keyhole limpet hemocyanin, addition of the appropriate antigen induced histamine release at concentrations of 0.01 microgram/ml or lower. Individual animals were studied over time by repetitive bleeding. The circulating basophils remained sensitized for at least 17 weeks postsensitization. However, release did not occur if animals had been sensitized less than 7 days earlier. This assay facilitates the investigation of basophil sensitization since animals can be studied on several occasions following immunization. The mechanisms, timing and role of basophil sensitization in various types of immune and hypersensitivity reactions can now be evaluated.


Heterogeneity of the human corticotropin-releasing factor-binding protein.
Human corticotropin-releasing factor (hCRF), secreted by the placenta, principally in the third trimester, is specifically bound in the peripheral circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from the circulation. We postulate that the protein may be returned to the blood in a form that is immunologically altered and not well recognized by the reported RIAs. We report that a stable isoform can result from temporary denaturation of recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein, which can bind CRF, has been found to bind to an antibody raised against a synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not to a second similar N-terminal antibody, although it was closely matched in titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF-BP. It is proposed that as a result of in vivo post-ligand binding events, isoforms may be susceptible to cleavage. After affinity purification, which involves denaturation, recombinant CRF-BP was often found to be cleaved after storage in the presence of protease inhibitors. Here we present evidence for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.


Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions.
In the last years there has been a considerable advance in the knowledge on the regulation of astrocytes by sex steroids under physiological and pathological conditions. By the activation of a variety of nuclear and membrane receptors, sex steroid hormones regulate the functions of astrocytes and their communication with other cell types in the central nervous system. Under physiological conditions astrocytes participate in the neuroendocrine and behavioral actions of gonadal steroids, as well as in the hormonal control of brain tissue homeostasis. Under pathological conditions astrocytes mediate, at least partially, the neuroprotective effects of gonadal steroid hormones; given that sex steroids modulate reactive astrogliosis and reduce the release of pro-inflammatory molecules by these cells. Given the side effects that sex steroids may have when administered systemically, a number of synthetic agonists of the receptors for gonadal steroid hormones in the nervous system have been developed, and may be considered for clinical use after brain injury as potential enhancers of the neuroprotective astrocytic functions.


Fracture resistance of endodontically treated teeth restored with a bulkfill flowable material and a resin composite.
To determine and compare the fracture resistance of endodontically treated teeth restored with a bulk fill flowable material (SDR) and a traditional resin composite. Thirty maxillary and 30 mandibular first molars were selected based on similar dimensions. After cleaning, shaping and filling of the root canals and adhesive procedures, specimens were assigned to 3 subgroups for each tooth type (n=10): Group A: control group, including intact teeth; Group B: access cavities were restored with a traditional resin composite (EsthetX; Dentsply-Italy, Rome, Italy); Group C: access cavities were restored with a bulk fill flowable composite (SDR; Dentsply-Italy), except 1.5 mm layer of the occlusal surface that was restored with the same resin composite as Group B. The specimens were subjected to compressive force in a material static-testing machine until fracture occurred, the maximum fracture load of the specimens was measured (N) and the type of fracture was recorded as favorable or unfavorable. Data were statistically analyzed with one-way analysis of variance (ANOVA) and Bonferroni tests (P<0.05). No statistically significant differences were found among groups (P<0.05). Fracture resistance of endodontically treated teeth restored with a traditional resin composite and with a bulk fill flowable composite (SDR) was similar in both maxillary and mandibular molars and showed no significant decrease in fracture resistance compared to intact specimens. No significant difference was observed in the mechanical fracture resistance of endodontically treated molars restored with traditional resin composite restorations compared to bulk fill flowable composite restorations.


Assessment of the impact of different fecal storage protocols on the microbiota diversity and composition: a pilot study.
Fecal samples are currently the most commonly studied proxy for gut microbiota. The gold standard of sample handling and storage for microbiota analysis is maintaining the cold chain during sample transfer and immediate storage at - 80 °C. Gut microbiota studies in large-scale, population-based cohorts require a feasible sample collection protocol. We compared the effect of three different storage methods and mock shipment: immediate freezing at - 80 °C, in 95% ethanol stored at room temperature (RT) for 48 h, and on blood collection card stored at RT for 48 h, on the measured composition of fecal microbiota of eight healthy, female volunteers by sequencing the V4 region of the 16S rRNA gene on an Illumina MiSeq. Shared operational taxonomic units (OTUs) between different methods were 68 and 3% for OTUs > 0.01 and < 0.01% mean relative abundance within each group, respectively. α and β-diversity measures were not significantly impacted by different storage methods. With the exception of Actinobacteria, fecal microbiota profiles at the phylum level were not significantly affected by the storage method. Actinobacteria was significantly higher in samples collected on card compared to immediate freezing (1.6 ± 1.1% vs. 0.4 ± 0.2%, p = 0.005) mainly driven by expansion of Actinobacteria relative abundance in fecal samples stored on card in two individuals. There was no statistically significant difference at lower taxonomic levels tested. Consistent results of the microbiota composition and structure for different storage methods were observed. Fecal collection on card could be a suitable alternative to immediate freezing for fecal microbiota analysis using 16S rRNA gene amplicon sequencing.


Optical non-orthogonal multiple access based on amino acids and extended zigzag.
We propose a novel security-enhanced power division multiplexing (SPDM) optical non-orthogonal multiple access scheme in conjunction with seven-core optical fiber in this paper. This scheme could improve the security of data transmission at the physical layer and the split ratio of the access network, ensuring more users can be served at the same time. Additionally, multiple signals can be superimposed in the digital domain, leading to a significant improvement in spectral efficiency. We have further experimentally demonstrated the transmission of 47.25 Gb/s SPDM orthogonal frequency division multiplexing (OFDM) signals in a 2 km seven-core fiber system. The experimental results confirm that our scheme can increase the number of access users by 14 times without influencing the privacy of different users. It is worth mentioning the signal encryption method based on amino acids combine with extended zigzag is proposed for the first time as we know. Meanwhile, the key space reaches 10182, indicating that the data transmission process can be effectively protected from the attack of stealers. The proposed security-enhanced power division multiplexing space division multiplexing passive optical network (SPDM-SDM-PON) support multi-threading and multi-functions, showing a great potential to be applied in the future telecommunication systems.


Endocavitary radiation therapy for rectal adenocarcinoma: 10-year results.
Local control, survival, and toxicity in patients treated with endocavitary radiation therapy for rectal cancer were evaluated. Thirty-five patients received a total of 20 to 155 Gy in 1 to 5 fractions with 50 kV x-rays through a treatment proctoscope. Twenty-nine of the 35 patients were treated with curative intent. Median follow-up was 102 months. Local control was achieved in 23 of the 29 patients treated curatively and in 3 of the 6 treated palliatively. Local control for patients treated curatively was 76% at 10 years. No local failures occurred after 21 months. For patients treated curatively, survival was 65% at 5 years and 42% at 10 years. Toxicity within 90 days after treatment was observed in 77% of the patients. Toxicity occurring more than 90 days after treatment was observed in 80%, but only 1 patient needed a colostomy, which was for a perforation after the biopsy of a benign ulcer. In conclusion, radiation therapy resulted in a local control rate of 76% at 10 years in curatively treated patients. Although most patients experience toxicity from this treatment, loss of sphincter function is rare.


Carcinoid tumor of lung with Cushing's syndrome.
Carcinoid tumor of lung with Cushing's syndrome is a rare condition. We report a 38-year-old man, with a 28-month history of Cushing's syndrome presented with hypertension, diabetes mellitus, decreased libido, muscle weakness and fatigability, moon facies, buffalo hump, truncal obesity, cutaneous striae, and easy bruisability. Diagnosis was made by measurements of ACTH (149 pg/mL) and cortisol levels (36 microg/dL) and computerized tomography of the chest.


Characteristics and Outcomes of Glaucoma Associated With Congenital Ectropion Uvea.
To determine the visual outcomes and effectiveness of glaucoma surgeries in congenital ectropion uvea. Retrospective interventional case series. Surgeries and examination findings were collected on 11 eyes of 8 patients with congenital ectropion uvea at 2 academic sites from 2001 to 2021. Visual outcomes, surgical success (intraocular pressure [IOP]: 5-20 mm Hg, no additional IOP-lowering surgery, no visually devastating complications), and survival rates of glaucoma surgeries were assessed. Glaucoma in bilateral congenital ectropion uvea was diagnosed at an earlier age (0.02 ± 0.01 years) than unilateral disease (8.9 ± 5.3 years, P = .002). All eyes required glaucoma surgery with 91% requiring multiple surgeries (3.5 ± 2.1, median 3 surgeries per eye). Trabeculotomy (8 eyes) showed 13% success rate. Although none of the 4 eyes that underwent trabeculectomy with mitomycin C needed repeat trabeculectomy, glaucoma drainage device placement, or cycloablation, 75% required bleb revision surgery. Glaucoma drainage devices (7 eyes) had a 57% success rate with 3 eyes requiring subsequent cycloablation (2) or trabeculectomy (1). At the final follow-up (8.5 ± 6.6 years, median: 7.9 years), all eyes achieved IOP control, and IOP was lower compared with presentation (13.2 ± 2.6 mm Hg vs 32.9 ± 9.9 mm Hg, P = .002). Best-corrected logarithm of the minimum angle of resolution visual acuity at the final follow-up was 0.2 ± 0.2. Bilateral congenital ectropion uvea presents with glaucoma earlier than unilateral cases. The majority of eyes required multiple glaucoma surgeries. Angle surgery was less effective than trabeculectomy or glaucoma drainage devices. IOP control was obtained in all eyes and affected individuals had good visual outcomes.


[Effects of bamboo charcoal on the growth of Trifolium repens and soil bacterial community structure].
The effects of addition rates (0, 3% and 9%) and particle sizes (0.05, 0.05-1.0 and 1.0-2.0 mm) of bamboo charcoal on the growth of Trifolium repens and soil microbial community structure were investigated. The results showed that bamboo charcoal addition greatly promoted the early growth of T. repens, with the 9% charcoal addition rate being slightly better than the 3% charcoal addition rate. The effects of different particle sizes of bamboo charcoal on the growth of T. repens were not different significantly. Growth promotion declined with time during 120 days after sowing, and disappeared completely after 5 months. DGGE analysis of the bacterial 16S rDNA V3 fragment indicated that bamboo charcoal altered the soil bacterial community structure. The amount and Shannon diversity index of bacteria in the bamboo charcoal addition treatments increased compared with CK. The quantitative analysis showed that the amount of bacteria in the treatment with bamboo charcoal of fine particle (D < 0.05 mm) at the 9% addition rate was significantly higher than in the other treatments. The fine bamboo charcoal had a great effect on soil bacteria amount compared with the charcoal of other sizes at the same addition rate.


Immunoblot evaluation of the specificity of the 29-kDa antigen from young adult female worms Angiostrongylus cantonensis for immunodiagnosis of human angiostrongyliasis.
The antigenic components of Angiostrongylus cantonensis young adult female worm somatic extract (FSE) were revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The sera tested were from patients with proven angiostrongyliasis, other parasitic diseases, and healthy adults. Both the sera and cerebrospinal fluid (CSF) were tested from patients with clinical angiostrongyliasis. The CSF from patients with other neurological diseases were also included. Using SDS-PAGE, we found that the FSE comprised more than 30 polypeptides. Immunoblot analysis revealed at least 12 or 13 antigenic bands in patients with proven or clinical angiostrongyliasis, respectively. The patterns of reactivity recognized by the serum and CSF antibodies against FSE were similar. These antigenic components had molecular masses ranging from less than 14.4 to more than 94 kDa. The prominent antigenic band of 29-kDa might serve as a reliable marker for the diagnosis of angiostrongyliasis. The sensitivity, specificity, positive and negative predictive values of immunoblot analysis in this antigenic band were 55.6%, 99.4%, 83.3% and 97.4%, respectively.


Human Alveolar and Splenic Macrophage Populations Display a Distinct Transcriptomic Response to Infection With Mycobacterium tuberculosis.
Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb.


Visualization of membrane protein domains by cryo-electron microscopy of dengue virus.
Improved technology for reconstructing cryo-electron microscopy (cryo-EM) images has now made it possible to determine secondary structural features of membrane proteins in enveloped viruses. The structure of mature dengue virus particles was determined to a resolution of 9.5 A by cryo-EM and image reconstruction techniques, establishing the secondary structural disposition of the 180 envelope (E) and 180 membrane (M) proteins in the lipid envelope. The alpha-helical 'stem' regions of the E molecules, as well as part of the N-terminal section of the M proteins, are buried in the outer leaflet of the viral membrane. The 'anchor' regions of E and the M proteins each form antiparallel E-E and M-M transmembrane alpha-helices, leaving their C termini on the exterior of the viral membrane, consistent with the predicted topology of the unprocessed polyprotein. This is one of only a few determinations of the disposition of transmembrane proteins in situ and shows that the nucleocapsid core and envelope proteins do not have a direct interaction in the mature virus.


The effects of simple graphical and mental visualization of lung sounds in teaching lung auscultation during clinical clerkship: A preliminary study.
The study aimed to evaluate visualization-based training's effects on lung auscultation during clinical clerkship (CC) in the Department of Respiratory Medicine on student skills and confidence. The study period was December 2020-November 2021. Overall, 65 students attended a lecture on lung auscultation featuring a simulator (Mr. Lung™). Among them, 35 (visualization group) received additional training wherein they were asked to mentally visualize lung sounds using a graphical visualized lung sounds diagram as an example. All students answered questions on their self-efficacy regarding lung auscultation before and after four weeks of CC. They also took a lung auscultation test with the simulator at the beginning of CC (pre-test) and on the last day of the third week (post-test) (maximum score: 25). We compared the answers in the questionnaire and the test scores between the visualization group and students who only attended the lecture (control group, n = 30). The Wilcoxon signed-rank test and analysis of covariance were used to compare the answers to the questionnaire about confidence in lung auscultation and the scores of the lung auscultation tests before and after the training. Confidence in auscultation of lung sounds significantly increased in both groups (five-point Likert scale, visualization group: pre-questionnaire median 1 [Interquartile range 1] to post-questionnaire 3 [1], p<0.001; control group: 2 [1] to 3 [1], p<0.001) and was significantly higher in the visualization than in the control group. Test scores increased in both groups (visualization group: pre-test 11 [2] to post-test 15 [4], p<0.001; control group: 11 [5] to 14 [4], p<0.001). However, there were no differences between both groups' pre and post-tests scores (p = 0.623). Visualizing lung sounds may increase medical students' confidence in their lung auscultation skills; this may reduce their resistance to lung auscultation and encourage the repeated auscultation necessary to further improve their long-term auscultation abilities.


The influence of DNA and nucleosome structure on integration events directed by HIV integrase.
DNA copies of the human immunodeficiency virus (HIV) genome integrate nonrandomly into the chromosomal DNA of the host cell. In this report, we investigate the molecular basis of this selectivity using the virus-encoded HIV integrase to direct integration of a synthetic HIV long terminal repeat substrate into either DNA molecules of known structure or previously defined nucleosomal complexes. We find that the structure of the target greatly influences the site of integration, and, moreover, DNA curvature, flexibility, and rigidity in solution all influence the frequency of integration. Importantly, for DNA with all of these properties, the distortion of the double helix directed by association with the histone proteins promotes the integration reaction and alters the distribution of sites that are selected for integration. We suggest that both intrinsic DNA structure and the folding of DNA into chromosomal structures will exert a major influence on target site selection for integration of the viral genome.


Facile aqueous synthesis and electromagnetic properties of novel 3D urchin-like glass/Ni-Ni(3)P/Co(2)P(2)O(7) core/shell/shell composite hollow structures.
Novel 3D urchin-like glass/Ni-Ni(3)P/Co(2)P(2)O(7) core/shell/shell composite hollow structures are fabricated for the first time by controlled stepwise assembly of granular Ni-Ni(3)P alloy and ribbon-like Co(2)P(2)O(7) nanocrystals on hollow glass spheres in aqueous solutions at mild conditions. It is found that the shell structure and the overall morphology of the products can be tailored by properly tuning the annealing temperature. The as-obtained composite core/shell/shell products possess low density (ca. 1.18 g cm(-3)) and shape-dependent magnetic and microwave absorbing properties, and thus may have some promising applications in the fields of low-density magnetic materials, microwave absorbers, etc. Based on a series of contrast experiments, the probable formation mechanism of the core/shell/shell hierarchical structures is proposed. This work provides an additional strategy to prepare core/shell composite spheres with tailored shell morphology and electromagnetic properties.


Fatalistic Cancer Beliefs and Information Seeking in Formerly Incarcerated African-American and Hispanic Men: Implications for Cancer Health Communication and Research.
African-American and Hispanic men are disproportionately affected by cancer experiencing higher rates of cancer-related morbidity and mortality for many cancers (but not all). These challenges may be magnified for a subpopulation of African-American and Hispanic men who have been incarcerated. A survey assessing demographics, incarceration experience, psychosocial, behavioral, and cancer health information seeking was administered to 230 previously incarcerated men aged 35 years and older. Data analysis was performed to assess the association between fatalism, perceived susceptibility, and health information seeking in this population. This study revealed the following: the majority of the participants (68.7%) held the fatalistic belief: "When I think of cancer, I automatically think of death." Second, the fatalistic belief, "There's not much you can do to lower your chances of getting cancer," is more prevalent among those who perceived a higher risk of developing cancer. Third, older participants (those between 55 and 70 years old) and widowed are less likely to think of death when they think of cancer. In addition, those who use the Internet to look for health or medical information (i.e., engaging in health information seeking) are less likely to agree with the fatalistic belief: "It seems like everything causes cancer." Given the high incidence of certain cancers among African-American and Hispanic men and the vulnerability of those involved in the criminal justice system, our findings highlight the importance of understanding perceived susceptibility to cancer, fatalistic beliefs about cancer, and information seeking in formerly incarcerated men.


A case of unilocular hydatid disease imported from Saudi Arabia.
A 39-year-old Korean man with general malaise was found to have two hepatic cysts by computed tomography. He had the history of close contact with domesticated wild dog in Saudi Arabia in 1976. Two cysts, 15cm and 10cm in diameter which contained clear fluid, were excised from both lobes of the liver. He was pathologically diagnosed as unilocular hydatid disease. This case is regarded as an imported case from Saudi Arabia.


Body Dysmorphic Disorder: Neurobiological Features and an Updated Model.
Body Dysmorphic Disorder (BDD) affects approximately 2% of the population and involves misperceived defects of appearance along with obsessive preoccupation and compulsive behaviors. There is evidence of neurobiological abnormalities associated with symptoms in BDD, although research to date is still limited. This review covers the latest neuropsychological, genetic, neurochemical, psychophysical, and neuroimaging studies and synthesizes these findings into an updated (yet still preliminary) neurobiological model of the pathophysiology of BDD. We propose a model in which visual perceptual abnormalities, along with frontostriatal and limbic system dysfunction, may combine to contribute to the symptoms of impaired insight and obsessive thoughts and compulsive behaviors expressed in BDD. Further research is necessary to gain a greater understanding of the etiological formation of BDD symptoms and their evolution over time.


Significance analysis of PAX8 expression in endometrial carcinoma.
To analyze the expression and prognostic value of paired-box 8 (PAX8) expression in uterine corpus endometrial carcinoma (UCEC) by bioinformatics. The expression of PAX8 gene in UCEC was analyzed by R language and immunohistochemistry. The correlation between PAX8 expression and clinicopathological features was analyzed by R language. The prognostic factors was analyzed by univariate/multivariate regression. The survival curve of patients was analyzed by Kaplan-Meier Plotter (K-M Plotter). The diagnostic value of PAX8 in UCEC was analyzed by receiver operating characteristic curve, and the relationship between PAX8 expression and methylation was analyzed by Ualcan. The relationship between methylation and prognosis was analyzed by MethSurv database. The expression of PAX8 in cancer tissues was significantly higher than that in normal tissues. The expression of PAX8 was related to clinical stage, age, histological type, histologic grade, tumor invasion and disease-specific survival event. Univariate/multivariate regression analysis showed that clinical stage, tumor invasion, and PAX8 expression were the influence factors of overall survival (OS), while histologic grade and PAX8 expression were the influence factors of disease-specific survival, and patients with low expression had a longer OS. The area under the curve of receiver operating characteristic curve was 0.81 for PAX8 diagnosis of UCEC. PAX8 was hypomethylated in cancer tissue, and patients with hypermethylated PAX8 had a longer OS. The high expression of PAX8 induced by hypomethylation may play an important role in the occurrence and prognosis of UCEC.


Ear health and quality of life in pet rabbits of differing ear conformations: A UK survey of owner-reported signalment risk factors and effects on rabbit welfare and behaviour.
The impacts of ear disease on animal welfare and behaviour are little documented. Ear disease may be common in rabbits, but difficult to recognise, and lop-ears have previously been indicated as a risk factor for ear disease. We aimed to better understand the range of ear conditions in pet rabbits, signalment risk factors, and impacts on welfare and behaviour. Through an online questionnaire, we investigated owner-reported signalment, veterinary diagnosis of ear conditions, impaired hearing, and ear pain for UK pet rabbits. Relationships between ear condition measures and ear conformation, quality of life, and behaviour were analysed using logistic regression. Of 551 valid responses, 28.5% of rabbits reportedly had experienced ear conditions; 21.2% diagnosed or mentioned by vets, with otitis and excess cerumen most common. Approximately 25% of lop-eared rabbits had ear conditions indicated by a vet versus 10% of erect-eared rabbits. Lop-eared, half-lop, and older rabbits were most at risk (P<0.050). Rabbits reported as showing ear pain responses had reduced owner-reported quality of life compared with other rabbits (P<0.050). Rabbits with ear problems were less likely to be responsive to relevant sounds, and performed binky behaviour (joy jumps) less frequently, than rabbits without such issues. Understanding prevalence and risk factors for ear conditions is critical to improving welfare standards across this widely owned pet species. The findings suggest that improved recognition and treatment of ear conditions, and avoiding breeding from rabbits with early signs, or a family history, of ear disease are necessary to help combat this animal welfare issue.


Alteration of Spontaneous Brain Activity After Hypoxia-Reoxygenation: A Resting-State fMRI Study.
Zhang, Jiaxing, Ji Chen, Cunxiu Fan, Jinqiang Li, Jianzhong Lin, Tianhe Yang, and Ming Fan. Alteration of spontaneous brain activity after hypoxia-reoxygenation: A resting-state fMRI study. High Alt Med Biol. 18:20-26, 2017.-The present study was designed to investigate the effect of hypoxia-reoxygenation on the spontaneous neuronal activity in brain. Sixteen sea-level (SL) soldiers (20.5 ± 0.7 years), who garrisoned the frontiers in high altitude (HA) (2300-4400 m) for two years and subsequently descended to sea level for one to seven days, were recruited. Control group consisted of 16 matched SL natives. The amplitude of low-frequency fluctuations (ALFF) of regional brain functional magnetic resonance imaging signal in resting state and functional connectivity (FC) between brain regions was analyzed. HA subjects showed significant increases of ALFF at several sites within the bilateral occipital cortices and significant decreases of ALFF in the right anterior insula and extending to the caudate, putamen, inferior frontal orbital cortex, temporal pole, and superior temporal gyrus; lower ALFF values in the right insula were positively correlated with low respiratory measurements. The right insula in HA subjects had increases of FC with the right superior temporal gyrus, postcentral gyrus, rolandic operculum, supramarginal gyrus, and inferior frontal triangular area. We thus demonstrated that hypoxia-reoxygenation had influence on the spontaneous neuronal activity in brain. The decrease of insular neuronal activity may be related to the reduction of ventilatory drive, while the increase of FC with insula may indicate a central compensation.


The environmental pollutant endosulfan disrupts cerebral cortical function at low doses.
Endosulfan can induce convulsions that could lead to brain damage. The variability and lack of specificity of neurological signs and symptoms in the pre-convulsive stages makes early diagnosis difficult. We sought to determine if electrophysiological exploration of the cerebral cortex could yield objective signs of endosulfan intoxication at levels that do not elicit convulsions. Endosulfan was administered intravenously to Sprague-Dawley adult rats under urethane anesthesia at doses from 0.5 to 4mg/kg. EEG power and the evoked potentials (EP) to forepaw electrical stimulation were studied over the contralateral (S1CL) and homolateral (S1HL) cortical somatosensory areas and the contralateral visual area (V1CL). At each area, five EP waves were measured. Arterial blood pressure, heart rate and body temperature were also recorded. Endosulfan induced a dose-related increase in EPs at all sites. At S1CL, EP peak amplitude was greater than baseline at 1, 2 and 4mg/kg for the first negative, second positive and third negative waves, and at 2 and 4mg/kg for the first and third positive waves. Similar but less marked trends were observed at S1HL and V1CL. A shift of EEG power to higher frequencies (alpha and beta EEG bands) was only present at 4mg/kg. In conclusion, endosulfan induced a large increase of cortical evoked potentials amplitudes at doses that did not elicit convulsions. These responses could be used as a non-invasive diagnostic tool to detect low-level endosulfan intoxication in humans and to help establish the NOAEL and LOAEL levels of this pollutant.


The role of statins as therapeutic agents in cancer.
Statins are the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This enzyme catalyzes conversion of HMG-CoA to mevalonate, which are the intermediates in cholesterol biosynthetic pathway. Statins also play an important role in carcinogenesis, because they are able to affect the cancer cell metabolism. Their effect has been observed in several cellular processes, such as angiogenesis, metastasis, apoptosis and cell proliferation. However, these effects are highly dependent on type of cancer and individual statins vary in their antitumor potential. This review summarizes the recent epidemiological evidence and preclinical studies that showed effects of all clinically used statins in vitro and in vivo. We also consider the results of different observational and retrospective studies focused on association among statins and cancer risk which are still under open discussion.


Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery.
Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.SIGNIFICANCE STATEMENT Although disease-associated microglia (DAM) have been the subject of strong research interest during recent years (Keren-Shaul, 2017; Jordão, 2019), their cellular origin and their role in "normal" acute injury processes is not well understood. Our work directly addresses the origin and the role of DAM in traumatic injury response. Further, we use a microglia depletion model to prove that DAM in spinal cord injury (SCI) are indeed derived from homeostatic microglia, and that they strongly enhance recovery. Thus, in this work we significantly expand the knowledge of immune response to traumatic injury, demonstrate the applicability to human injury via our unique access to injured human spinal cord tissue, and provide the community with a comprehensive dataset for further exploration.


Management of multiple myeloma: the impact of ixazomib's approval in Canada.
Donna E Reece speaks to Laura Dormer, Commissioning Editor: Dr Donna E Reece is a Professor of Medicine and Director of the Program for Multiple Myeloma and Related Diseases in the Department of Medical Oncology and Hematology at Princess Margaret Hospital/University of Toronto. She earned a Bachelor of Arts degree at the University of Texas, Austin, and graduated as valedictorian with a medical degree from Baylor College of Medicine, Houston, Texas. She completed an internship in Internal Medicine at the University of Colorado Affiliated Hospitals, a residency and Chief Residency in Internal Medicine at Jewish Hospital, St Louis, and a Fellowship in Hematology/Oncology at Barnes Hospital, Washington University, St Louis, Missouri. She was a fellow and later a leukemia/stem cell transplant staff physician at Vancouver General Hospital/University of British Columbia for over 10 years. She then served as Director of the Outpatient Leukemia/Stem Cell Transplant Program, and later interim director, of the Blood and Marrow Transplant Program of the Markey Cancer Center at the University of Kentucky, Lexington, Kentucky until her appointment to Princess Margaret Hospital in Toronto in 2001. Dr Reece received the David and Molly Bloom Chair in Myeloma Research in 2009. She is currently the co-chair of the Multiple Myeloma Clinical Trials Group of the National Cancer Institute of Canada, member of the Scientific Advisory Board of the International Myeloma Foundation, and member of the Project Review Committee of the MMRC (Multiple Myeloma Research Consortium). She is also the Chief Medical Officer of the Myeloma Canada Research Network and serves on the board of directors of Myeloma Canada. Her career focus has been in the areas of hematopoietic stem cell transplantation, lymphoid malignancies and plasma cell dyscrasias. She has published numerous articles in these areas.


The usefulness of dynamic O-(2-18F-fluoroethyl)-L-tyrosine PET in the clinical evaluation of brain tumors in children and adolescents.
Experience regarding O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET in children and adolescents with brain tumors is limited. Sixty-nine (18)F-FET PET scans of 48 children and adolescents (median age, 13 y; range, 1-18 y) were analyzed retrospectively. Twenty-six scans to assess newly diagnosed cerebral lesions, 24 scans for diagnosing tumor progression or recurrence, 8 scans for monitoring of chemotherapy effects, and 11 scans for the detection of residual tumor after resection were obtained. Maximum and mean tumor-to-brain ratios (TBRs) were determined at 20-40 min after injection, and time-activity curves of (18)F-FET uptake were assigned to 3 different patterns: constant increase; peak at greater than 20-40 min after injection, followed by a plateau; and early peak (≤ 20 min), followed by a constant descent. The diagnostic accuracy of (18)F-FET PET was assessed by receiver-operating-characteristic curve analyses using histology or clinical course as a reference. In patients with newly diagnosed cerebral lesions, the highest accuracy (77%) to detect neoplastic tissue (19/26 patients) was obtained when the maximum TBR was 1.7 or greater (area under the curve, 0.80 ± 0.09; sensitivity, 79%; specificity, 71%; positive predictive value, 88%; P = 0.02). For diagnosing tumor progression or recurrence, the highest accuracy (82%) was obtained when curve patterns 2 or 3 were present (area under the curve, 0.80 ± 0.11; sensitivity, 75%; specificity, 90%; positive predictive value, 90%; P = 0.02). During chemotherapy, a decrease of TBRs was associated with a stable clinical course, and in 2 patients PET detected residual tumor after presumably complete tumor resection. Our findings suggest that (18)F-FET PET can add valuable information for clinical decision making in pediatric brain tumor patients.


Enhancing the sexual function of women living with chronic pain: a cognitive-behavioural treatment group.
Chronic pain significantly impacts women's quality of life in the domain of sexual function. Treatment aimed at improving the sexual function of women living with chronic pain is minimal or absent within an interdisciplinary rehabilitation pain program. To evaluate a cognitive-behavioural treatment group designed to improve the sexual function of women with chronic pelvic pain, daily headache pain and neuromusculoskeletal pain within an interdisciplinary rehabilitation pain program. Participants were 47 women who attended the treatment group. A physical therapist and a psychologist facilitated the group. The participants completed a modified version of the Sexual Activity Questionnaire pregroup and at one month postgroup, and a Treatment Helpfulness Questionnaire at the final group session. All 47 women found the treatment group helpful. Sexual function improved as evidenced by significant differences (Wilcoxon signed-rank test, P<0.05) from pregroup to postgroup on measures of enjoyment, lubrication, satisfaction after sexual activity and satisfaction with frequency. Improvements occurred despite no change in pain level during penetration or fatigue level from pregroup to postgroup. Treatment helpfulness results showed that women valued the knowledge and skills gained in the group. Qualitative findings suggest that a cognitive shift, and communication and partner involvement may be mechanisms of change for improved sexual function. The sexual function of women with chronic pain can be significantly enhanced by a cognitive-behavioural treatment group delivered within an interdisciplinary rehabilitation pain program.


Multilingual validation of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF).
Pain is the leading cause of animal suffering, hence the importance of validated tools to ensure its appropriate evaluation and treatment. We aimed to test the psychometric properties of the short form of the Unesp-Botucatu Feline Pain Scale (UFEPS-SF) in eight languages. The original scale was condensed from ten to four items. The content validation was performed by five specialists in veterinary anesthesia and analgesia. The English version of the scale was translated and back-translated into Chinese, French, German, Italian, Japanese, Portuguese and Spanish by fluent English and native speaker translators. Videos of the perioperative period of 30 cats submitted to ovariohysterectomy (preoperative, after surgery, after rescue analgesia and 24 h after surgery) were randomly evaluated twice (one-month interval) by one evaluator for each language unaware of the pain condition. After watching each video, the evaluators scored the unidimensional, UFEPS-SF and Glasgow composite multidimensional feline pain scales. Statistical analyses were carried out using R software for intra and interobserver reliability, principal component analysis, criteria concurrent and predictive validities, construct validity, item-total correlation, internal consistency, specificity, sensitivity, the definition of the intervention score for rescue analgesia and diagnostic uncertainty zone, according to the receiver operating characteristic (ROC) curve. UFEPS-SF intra- and inter-observer reliability were ≥0.92 and 0.84, respectively, for all observers. According to the principal component analysis, UFEPS-SF is a unidimensional scale. Concurrent criterion validity was confirmed by the high correlation between UFEPS-SF and all other scales (≥0.9). The total score and all items of UFEPS-SF increased after surgery (pain), decreased to baseline after analgesia and were intermediate at 24 h after surgery (moderate pain), confirming responsiveness and construct validity. Item total correlation of each item (0.68-0.83) confirmed that the items contributed homogeneously to the total score. Internal consistency was excellent (≥0.9) for all items. Both specificity (baseline) and sensitivity (after surgery) based on the Youden index was 99% (97-100%). The suggestive cut-off score for the administration of analgesia according to the ROC curve was ≥4 out of 12. The diagnostic uncertainty zone ranged from 3 to 4. The area under the curve of 0.99 indicated excellent discriminatory capacity of UFEPS-SF. The UFEPS-SF and its items, assessed by experienced evaluators, demonstrated very good repeatability and reproducibility, content, criterion and construct validities, item-total correlation, internal consistency, excellent sensitivity and specificity and a cut-off point indicating the need for rescue analgesia in Chinese, French, English, German, Italian, Japanese, Portuguese and Spanish.


Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds.
Compounds containing two alkyne groups in close vicinity at the rigid skeleton of camphorsulfonamide show unique reactivities when treated with electrophiles or catalytic amounts of platinum(II). The formed product structures depend not only on the reagents used but also on the substituents attached to the triple bonds. Cycloisomerisations with perfect atom economy lead to polycyclic heterocycles that resemble to some extent the AB ring system of paclitaxel. Herein, we present practical synthetic methods for the selective synthesis of precursor dialkynes bearing different substituents (alkyl, aryl) at the triple bonds, based on ketals or an imine as protecting groups. We show for isomeric dialkynes that the reaction cascade induced by Pt(II) includes ring annulation, sulphur reduction, and ring enlargement. One isomeric dialkyne additionally allows for the isolation of a pentacyclic compound lacking the ring enlargement step, which we have proposed as a potential intermediate in the catalytic cycle.


Regulation of expression of 1,25D3-MARRS/ERp57/PDIA3 in rat IEC-6 cells by TGF beta and 1,25(OH)2D3.
We examined the transcriptional regulation of expression of the redox-sensitive Membrane-Associated-Rapid Response, Steroid-binding (1,25D(3)-MARRS) protein specific for 1,25(OH)(2)D(3) in a rat small intestinal cell line, IEC-6, that demonstrates rapid responses to 1,25(OH)(2)D(3). 1,25D(3)-MARRS binds and is activated by 1,25(OH)(2)D(3), but is not itself up-regulated by treatment with 1,25(OH)(2)D(3), nor is there a Vitamin D response element (VDRE) in its proximal promoter. We previously reported that transforming growth factor beta (TGFbeta) increased steady state levels of 1,25D(3)-MARRS transcript and protein approximately two-fold [Rohe B, Safford SE, Nemere I, Farach-Carson, MC. Identification and characterization of 1,25D(3)-membrane-associated rapid response, steroid (1,25D(3)-MARRS)-binding protein in rat IEC-6 cells. Steroids 2005;70:458-63]. To determine if this up-regulation could be attributed to the function of a highly conserved consensus smad 3 binding element present in the proximal promoter of the 1,25D(3)-MARRS gene, we created a promoter-reporter [SEAP] construct that was responsive to TGFbeta (200 pM). Deletion or mutation of the smad 3 element greatly reduced the response of the 1,25D(3)-MARRS promoter to TGFbeta. Subsequent studies found that the smad 3 response element is bound by a protein found in the IEC-6 nuclear extract, most likely smad 3. Interestingly, although 1,25(OH)(2)D(3) alone did not increase expression of the 1,25D(3)-MARRS promoter-reporter, co-treatment of transfected IEC-6 cells with 1,25(OH)(2)D(3) and TGFbeta shifted the dose-response curve to a lower effective concentration (100 pM peptide). We conclude that TGFbeta is a transcriptional regulator of 1,25D(3)-MARRS expression via a functional smad 3 element and that cross-talk with non-classical 1,25(OH)(2)D(3)-stimulated pathways occurs. The findings have broad implications for redox-sensitive signaling phenomena including those that regulate phosphate transport in the intestine.