Sirtuin6 and Lipoxin A4 levels are decreased in severe periodontitis.
Sirtuin6 plays an important role in the regulation of inflammation, homeostasis, and apoptosis, and it has anti-inflammatory effects on several diseases. Lipoxin A4 is a pro-resolving lipid mediator of inflammation and inhibits hypoxia-induced apoptosis and oxidative stress. Considering that Lipoxin A4 and Sirtuin6 have protective effects on inflammatory diseases, the aim of this study is to determine the possible roles of these molecules on periodontitis inflammation in saliva and serum and to reveal the relationship of these data with clinical periodontal parameters. A total of 20 stage III/grade B periodontitis and 20 periodontally healthy subjects were included in this cross-sectional study (all never smokers and systemically healthy). Clinical periodontal parameters (plaque index, probing pocket depth, bleeding on probing, clinical attachment loss) were recorded. Saliva and serum levels of Sirtuin6 and Lipoxin A4 were analyzed by enzyme-linked immunosorbent assay. Serum Sirtuin6 and saliva Lipoxin A4 levels were significantly lower in the periodontitis group than the control group (respectively, p = 0.0098, p = 0.0008). There were negative correlations between all periodontal clinical parameters and saliva Lipoxin A4 level (p < 0.05) and between probing pocket depth, clinical attachment loss, and serum and saliva Sirtuin6 levels (respectively, r = - 0.465 and r = - 0.473, p < 0.05). Decreased levels of serum Sirtuin6 and saliva Lipoxin A4 in periodontitis patients and their correlation with clinical periodontal parameters suggest that serum Sirtuin6 and saliva Lipoxin A4 may be related with periodontal inflammation. Scientific rationale for the study: Sirtuin6 is one of seven members of the family of NAD + dependent protein that played an important role in the regulation of inflammation, energy metabolism, homeostasis, and apoptosis. Sirtuin6 is associated with the pathogenesis of several diseases. Lipoxin A4 is a lipid mediator that inhibits hypoxia-induced apoptosis and oxidative stress, and it has an active role in the resolution of periodontal inflammation. No studies that investigated the potential role Sirtuin6 and its relationship with inflammation resolution and apoptosis mechanisms in severe periodontitis patients. the serum Sirtuin6 and saliva Lipoxin A4 levels were significantly lower and negatively correlated with clinical periodontal parameters in the patients with periodontitis than the healthy controls. this study shows that serum Sirtuin6 and saliva Lipoxin A4 may be candidate biomarkers related with periodontal inflammation and estimating to periodontal status. NCT05417061.


A novel, high performance enzyme for starch liquefaction. Discovery and optimization of a low pH, thermostable alpha-amylase.
High throughput screening of microbial DNA libraries was used to identify alpha-amylases with phenotypic characteristics compatible with large scale corn wet milling process conditions. Single and multiorganism DNA libraries originating from various environments were targeted for activity and sequence-based screening approaches. After initial screening, 15 clones were designated as primary hits based upon activity at pH 4.5 or 95 degrees C without addition of endogenous Ca(2+). After further characterization, three enzyme candidates were chosen each with an exceptional expression of one or more aspects of the necessary phenotype: temperature stability, pH optimum, lowered reliance on Ca(2+) and/or enzyme rate. To combine the best aspects of the three phenotypes to optimize process compatibility, the natural gene homologues were used as a parental sequence set for gene reassembly. Approximately 21,000 chimeric daughter sequences were generated and subsets screened using a process-specific, high throughput activity assay. Gene reassembly resulted in numerous improved mutants with combined optimal phenotypes of expression, temperature stability, and pH optimum. After biochemical and process-specific characterization of these gene products, one alpha-amylase with exceptional process compatibility and economics was identified. This paper describes the synergistic approach of combining environmental discovery and laboratory evolution for identification and optimization of industrially important biocatalysts.


The role of apoptosis in response to photodynamic therapy: what, where, why, and how.
Photodynamic therapy (PDT), a treatment for cancer and for certain benign conditions, utilizes a photosensitizer and light to produce reactive oxygen in cells. PDT is primarily employed to kill tumor and other abnormal cells, so it is important to ask how this occurs. Many of the photosensitizers currently in clinical or pre-clinical studies of PDT localize in or have a major influence on mitochondria, and PDT is a strong inducer of apoptosis in many situations. The purpose of this review is to critically evaluate all of the recently published research on PDT-induced apoptosis, with a focus on studies providing mechanistic insights. Components of the mechanism whereby PDT causes cells to undergo apoptosis are becoming understood, as are the influences of several signal transduction pathways on the response. Future research should be directed to elucidating the role(s) of the multiple steps in apoptosis in directing damaged cells to an apoptotic vs. necrotic pathway and for producing tumor ablation in conjunction with tissue-level mechanisms operating in vivo.


Lessons from India in organizational innovation: a tale of two heart hospitals.
Recent discussions in health reform circles have pinned great hopes on the prospect of innovation as the solution to the high-cost, inadequate-quality U.S. health system. But U.S. health care institutions-insurers, providers, and specialists-have ceded leadership in innovation to Indian hospitals such as Care Hospital in Hyderabad and the Fortis Hospitals around New Delhi, which have U.S.-trained doctors and can perform open heart surgery for $6,000 (compared to $100,000 in the United States). The Indian success is a window into America's stalemate with inflating costs and stagnant innovation.


The concept of spiritual care in mental health nursing.
In this paper we aim to clarify the issue of spiritual care in the context of mental health nursing. The concept of spirituality in nursing has received a great deal of attention in recent years. However, despite many articles addressed to the issue, spiritual care remains poorly understood amongst nursing professionals and, as a result, spiritual needs are often neglected within the context of health care. A series of focus groups was conducted to obtain the views of service users, carers and mental health nursing professionals about the concept of spirituality and the provision of spiritual care in mental health nursing. According to the views expressed in our focus groups, spiritual care relates to the acknowledgement of a person's sense of meaning and purpose to life which may, or may not, be expressed through formal religious beliefs and practices. The concept of spiritual care was also associated with the quality of interpersonal care in terms of the expression of love and compassion towards patients. Concerns were expressed that the ethos of mental health nursing and the atmosphere of care provision were becoming less personal, with increasing emphasis on the 'mechanics of nursing'. The perceived failure of service providers to attend adequately to this component of care may be symptomatic of a medical culture in which the more readily observable and measurable elements in care practice have assumed a prominence over the more subjective, deeply personal components. In order for staff to acknowledge these issues it is argued that a more holistic approach to care should be adopted, which would entail multidisciplinary education in spiritual care.


Effect of naproxen on cancellous bone in ovariectomized rats.
Nonsteroidal anti-inflammatory drugs (NSAIDs) affect bone metabolism in vitro and in vivo. They delay but do not alter the outcome of healing processes in bone. In some bone loss models, they block bone resorption and slow the rate of loss. We studied the effect of naproxen, a potent NSAID, on cancellous bone of the proximal tibial metaphysis of 6-month-old adult female ovariectomized rats. Animals were ovariectomized, divided into groups, and fed standard diets differing only in naproxen content for 42 days. The rats of the groups ate 2.0, 5.5, 12.7, and 32 mg naproxen per kg body weight per day, respectively. Serum levels of naproxen were determined. Bone volume, mineralizing surface, osteoblast activity, osteoclast surface, and bone resorption rate were determined by bone histomorphometric techniques. The rats' dose-related serum naproxen levels ranged from 4 to 28 micrograms/ml. Naproxen inhibited up to 70% of the bone loss occurring after ovariectomy at a serum level of 4 micrograms/ml. We deduced that naproxen blocked bone resorption in ovariectomized rats by slowing osteoclast activity at all doses. In contrast, naproxen slowed bone formation only at serum levels greater than 20 micrograms/ml in ovariectomized rats. These findings may have clinical relevance in helping to prevent postmenopausal bone loss in women.


[Laboratory experimental studies on quantitative blood flow measurement with the c.w. ultrasound Doppler procedure: II. Flow measurements].
The reliability of Doppler blood flow measurement was examined by testing a cw Doppler flowmeter on a flow-rig. Comparing the Doppler measurements with those simultaneously obtained by means of EFM, the correlation coefficient was found to be 0.989 for continuous, and 0.985 for pulsatile streaming. With velocities up to 40 cm/sec there was a systemic overestimation of flow velocity which was attributed to the effects of the high pass filter used. Unequal distribution of intensity within the sound field is discussed. Systemic underestimation of velocities over 45 cm/sec is due to the interaction of the low pass filter. Identification of the 90 degrees reference angle using the cw Doppler technique seems to be appropriate. Within zones of turbulence caused by eccentric stenoses no reliable flow values could be determined.


Listeria rhomboencephalitis in a patient on a tumor necrosis factor α inhibitor (etanercept).
We describe a case of an 87-year-old woman with rheumatoid arthritis on etanercept who developed subacute encephalopathy. Magnetic resonance imaging and blood cultures led to the diagnosis of Listeria monocytogenes rhomboencephalitis, which proved to be fatal. Postmortem examination of the brain revealed abscesses with extensive necrosis. Gram stain showed small gram-positive rods in the necrotic tissue and the wall lining the abscesses. While rhomboencephalitis is a rare entity, and clinical recognition may be hampered by immunosuppression such as in this case, early blood cultures, lumbar puncture, and empiric treatment with ampicillin should be initiated in all patients with suspected rhomboencephalitis if suggested by imaging and by a clinical concern for infection.


Magnetic resonance imaging in psoriatic arthritis: a review of the literature.
Psoriatic arthritis is a diverse condition that may be characterized by peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis. Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular and entheseal lesions, and provides a unique picture of the disease process that cannot be gained using other imaging modalities. This review focuses on the literature on MRI in psoriatic arthritis published from 1996 to July 2005. The MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema, bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical arthropathy. Comparisons have been drawn with the more extensive literature describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.


Analytical strategies in the structural characterization of elcatonin.
Elcatonin is a synthetic peptide of 32 amino acid residues, that differs from natural peptide hormone (eel calcitonin) in that the 1 and 7 cystine residues are replaced with alpha-amino suberic acid (Asu). Elcatonin is pharmacologically important, since it inhibits osteoclastic bone reserption and induces calcium uptake from body fluids. It is also used for the treatment of Page's disease and hypercalcemic conditions. Until now the structural characterization of elcatonin has been obtained by proteolytic digestion followed by high performance liquid chromatographic (HPLC) analysis of the peptide fragments. Capillary electrophoresis and fast-atom bombardment have also been employed. This work describes the results obtained when a liquid chromatograph, coupled to mass spectrometer using electrospray ionization (LC/ESI-MS) was applied to elcatonin analysis. After digestion with trypsin, the resulting peptides were separated by HPLC with 'on-line' UV detection, and directly injected into the ESI source. The molecular weights of all the fragments were detected, and the sequences of two of them were determined by collisionally induced dissociation in the ESI source. To confirm these 'on-line' results, the 'off-line' approach was also applied. In this case, the fragments from tryptic digestion were isolated by preparative HPLC, concentrated and analyzed by direct infusion into the ESI-MS system. Then, different elcatonin digests obtained using other proteases, e.g. protease V8 and clostripain, were analyzed by direct infusion, and these results combined with those achieved by the 'on-line' analysis allowed us to obtain the entire mapping of elcatonin.


Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery.
To describe the change in ventilatory practice in a tertiary paediatric intensive care unit (PICU) in the 5-year period after the introduction of high-flow nasal prong (HFNP) therapy in infants <24 months of age. Additionally, to identify the patient subgroups on HFNP requiring escalation of therapy to either other non-invasive or invasive ventilation, and to identify any adverse events associated with HFNP therapy. The study was a retrospective chart review of infants <24 months of age admitted to our PICU for HFNP therapy. Data was also extracted from both the local database and the Australian New Zealand paediatric intensive care (ANZPIC) registry for all infants admitted with bronchiolitis. Between January 2005 and December 2009, a total of 298 infants <24 months of age received HFNP therapy. Overall, 36 infants (12%) required escalation to invasive ventilation. In the subgroup with a primary diagnosis of viral bronchiolitis (n = 167, 56%), only 6 (4%) required escalation to invasive ventilation. The rate of intubation in infants with viral bronchiolitis reduced from 37% to 7% over the observation period corresponding with an increase in the use of HFNP therapy. No adverse events were identified with the use of HFNP therapy. HFNP therapy has dramatically changed ventilatory practice in infants <24 months of age in our institution, and appears to reduce the need for intubation in infants with viral bronchiolitis.


Rapid prototyping of cell culture microdevices using parylene-coated 3D prints.
Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers (e.g. polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily cast from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community.


In patients with early inflammatory polyarthritis, ACPA positivity, younger age and inefficacy of the first non-biological DMARD are predictors for receiving biological therapy: results from the Norfolk Arthritis Register.
To identify baseline disease-related predictors in patients with early inflammatory polyarthritis (IP) for starting subsequent biological therapy and to determine if patients who failed their first non-biological disease-modifying antirheumatic drug (DMARD) within 6 months were more likely to need biological therapy. Patients with early IP recruited between 1990 and 1994 (cohort 1) and between 2000 and 2004 (cohort 2) in the Norfolk Arthritis Register were included in this study. The association between possible predictors with the start of biological therapy was assessed using Cox proportional hazards regression models. 32/407 (7.9%) patients in cohort 1 and 45/416 (10.8%) patients in cohort 2 received biological therapy during follow-up. In both cohorts, anti-citrullinated protein antibody (ACPA) positivity (cohort 1, HR 7.62, 95% CI 2.46 to 23.58; cohort 2, HR 4.68, 95% CI 2.23 to 9.78) was the strongest predictor for starting biological therapy. In cohort 2, younger patients (HR 0.97, 95% CI 0.95 to 0.99) and patients who failed their first non-biological DMARD within 6 months due to inefficacy were also more likely to receive biological therapy (HR 2.35, 95% CI 1.05 to 5.27). Patients with early IP who are ACPA positive, are younger or who fail their first non-biological DMARD due to inefficacy within 6 months are more likely to need biological therapy.


Decreasing early hypoglycemia frequency in at-risk newborns after implementing a new hypoglycemia screening algorithm.
Neonatal hypoglycemia may affect long-term neurodevelopment. Quality improvement (QI) initiative for Mother-Baby-Unit (MBU) admissions (birthweight ≥ 2100 g; ≥35 weeks' gestation) over two epochs from 2016-2019 to reduce the frequency of early (≤3 h) neonatal hypoglycemia in small and large newborns. New algorithm using Olsen's growth curves, hypoglycemia thresholds of <2.22 mmol/L [40 mg/dL] (0-3 h) and <2.61 mmol/L [47 mg/dL] (>3 to 24 h), feeding optimization and 24-hour glucose checks for small for gestational age and preterm newborns. Among 39,460 newborns, using subsets with identical screening criteria, early hypoglycemia decreased significantly after QI implementation among large for gestational age newborns with birthweight >3850 g (66%) and small for gestational age newborns with birthweight <2500 g (70%). Among all MBU admissions, the adjusted odds of any hypoglycemia in 24 h decreased (P < 0.001). Feeding optimization may decrease early hypoglycemia frequency in large and small newborns.


Pathologic findings in patients with ureteropelvic junction obstruction and crossing vessels.
To define the role of crossing vessels in the pathophysiology of ureteropelvic junction (UPJ) obstruction, we analyzed the relationship between the presence of crossing vessels and UPJ pathologic findings in patients undergoing laparoscopic pyeloplasty. The significance of crossing renal vessels in patients with UPJ obstruction is unclear. We performed a retrospective analysis of 155 consecutive patients undergoing laparoscopic pyeloplasty. Pathologic specimens from the UPJ were evaluated in 95 patients. The presence or absence of crossing vessels was documented intraoperatively. The histopathologic findings allowed for categorization into 5 groups: group 1, normal ureteral tissue; group 2, chronic inflammation; group 3, smooth muscle hypertrophy, group 4, fibrosis; and group 5, smooth muscle atrophy. The pathologic findings between patients with and without crossing vessels were compared. Overall, crossing vessels were identified in 98 patients (63.2%). Of the 95 cases with specimens retrieved for histologic analysis, 65 had crossing vessels and 30 did not. The most common UPJ histologic finding in patients with crossing vessels was no intrinsic abnormality (43%). In contrast, this was seen in only 10% of patients without a crossing vessel. In the group without crossing vessels, chronic inflammation (40%) was the predominant histologic findings. Patients with a crossing vessel were less likely to have intrinsic histologic pathologic findings (P < .0003). Patients with crossing vessels and UPJ obstruction had no histologic abnormalities identified in 43% of cases. This finding implicates crossing vessels in the pathogenesis of select cases of UPJ obstruction and direct mechanical compression as the etiology of obstruction in these individuals.


A rapid method for determination of endoproteinase substrate specificity: specificity of the 3C proteinase from hepatitis A virus.
The preferred amino acid residues at the P'1 and P'2 positions of peptide substrates of the 3C proteinase from hepatitis A virus (HAV-3C) have been determined by a rapid screening method. The enzyme was presented with two separate mixtures of N-terminal acetylated peptides, which were identical in sequence except for the amino acids at the P'1 or P'2 positions, where a set of 15 or 16 amino acids was introduced. Enzyme-catalyzed hydrolysis of the peptide mixtures generated free amino termini, which allowed direct sequence analysis by Edman degradation. The relative yield of each amino acid product in the appropriate sequencing cycle gave the amount of each substrate mixture component hydrolyzed. This allowed the simultaneous evaluation of the relative kcat/Km values for each component in the mixture. The peptide substrates preferred by the HAV-3C proteinase in the P'1 mixture were glycine, alanine, and serine. The enzyme has little specificity at P'2; only arginine and proline peptides were excluded as substrates. This method provides a rapid determination of the preferred residues for a peptide substrate and should be applicable to other endoproteinases.


Prostate cancer progression and surrounding microenvironment.
Bidirectional cellular interactions between prostate cancer and prostate or bone stroma are needed for local tumor growth and distant metastasis. The genetics of cancer cells is affected by the host microenvironment and, reciprocally, permanent gene expression changes occur in the stroma surrounding epithelial cancer cells. The immune-mediated micromilieu also affects the progression of prostate cancer; the role of the immune system in controlling the growth of prostate cancer cells is complex, with immune escape mechanisms prevailing over effective antitumor response. Moreover, tumor stem cell models to explain the origin and progression of prostate cancer require appropriate environmental conditions. On the basis of a review of the literature, this article aims to outline the recent advances in the elucidation of the molecular mechanisms underlying the interactions between prostate cancer and its microenvironment.


Molecular variations related to the regional differences in periosteal growth at the mandibular ramus.
Periosteal growth at human mandibular ramus is characterized by bone apposition at the posterior border and resorption at the anterior border. Molecular control of this regional variation is unclear. This study examined the expression of several molecules involved in bone apposition/resorption at these regions in vivo and in vitro. By using growing pigs as a model, the periosteal growth was assessed at the mandibular ramus by vital staining and histological observations. In parallel, periosteal tissues were harvested and pulverized for RNA and protein extraction. Periosteal cells were also isolated, expanded in osteogenic media, and subjected to a single dose of dynamic tensile strain (0, 5, or 10% magnitude at 0.5 Hz) to examine their responses to mechanical loading. Real-time RT-PCR and Western blot analyses were used to examine mRNA and protein expression from periosteal tissues and cultured cells. Histological observation confirmed an anterior-resorption/posterior-apposition pattern in the pig mandibular ramus. Both in vivo tissue and in vitro cells demonstrated greater mRNA expression of receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and bone morphogenetic protein 2 (BMP2) at the anterior region, while OPG expression at the anterior region was lower than the posterior region. In response to the application of a single dose of dynamic tensile strain, cultured periosteal cells appeared to change the expression profile of osteogenic markers but not that of RANKL/OPG and BMP2. These findings suggest that the unique regional variation of periosteal activity at the mandibular ramus is regulated by a differential expression of RANKL/OPG ratio (likely through differential induction of OPG) and BMP2.


700 MW peak power of a 380 fs regenerative amplifier with Tm:YAP.
We report on a high power ultrashort pulse regenerative amplifier system, entirely based on thulium-doped laser materials operating around 1.94 μm. At a repetition rate of 1 kHz the Tm:YAP regenerative amplifier emits pulse energies > 700 μJ, only limited by the damage threshold of the Tm:YAP crystal. The pulses can be compressed to 380 fs at an efficiency of 50 %. Purging of the regenerative amplifier cavity with nitrogen is necessary due to atmospheric absorptions causing long ps pedestals in the autocorrelation.


Molecular Effects of Silver Nanoparticles on Monogenean Parasites: Lessons from Caenorhabditis elegans.
The mechanisms of action of silver nanoparticles (AgNPs) in monogenean parasites of the genus Cichlidogyrus were investigated through a microarray hybridization approach using genomic information from the nematode Caenorhabditis elegans. The effects of two concentrations of AgNPs were explored, low (6 µg/L Ag) and high (36 µg/L Ag). Microarray analysis revealed that both concentrations of AgNPs activated similar biological processes, although by different mechanisms. Expression profiles included genes involved in detoxification, neurotoxicity, modulation of cell signaling, reproduction, embryonic development, and tegument organization as the main biological processes dysregulated by AgNPs. Two important processes (DNA damage and cell death) were mostly activated in parasites exposed to the lower concentration of AgNPs. To our knowledge, this is the first study providing information on the sub-cellular and molecular effects of exposure to AgNPs in metazoan parasites of fish.


Happier than thou? A self-enhancement bias in emotion attribution.
People tend to judge themselves as exhibiting above average levels of desirable traits-including competence, kindness, and life satisfaction-but does this self-enhancement extend to emotional responses? Here, we explore this question by having people attribute emotions to themselves and others following simple gambles. We demonstrate that people display an emotional self-enhancement bias that varies with the context of the emotion-eliciting situation. People judge themselves as experiencing more positive emotional reactions on average, and they also believed that others' emotions are more sensitive to gamble outcomes, such that people judge others to experience stronger negative affect in response to negative outcomes (Study 1). This self-enhancement bias further tracks social distance, such that people attribute less positive and more negative emotion to more dissimilar, as compared with more similar others (Study 2). People also predict less favorable emotional states for themselves and others experiencing events in the future, as compared with the present (Study 3), suggesting that this attribution bias extends across multiple dimensions of psychological distance. Broadly, these data suggest that people exhibit self-enhancement in emotion attribution, but do so in subtle ways that depend on situational and social factors. (PsycINFO Database Record


Estrogen-dependent growth of a rat pituitary tumor involves, but does not require, a high level of vascular endothelial growth factor.
Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogen-dependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain. However, VEGF is not increased by estrogen treatment in an F(1) hybrid of F344 and BN, even though F(1) hybrid rats do form pituitary tumors in response to estrogen. Quantitative trait locus (QLT) mapping reveals that control of estrogen-dependent VEGF expression is linked to the Edpm5 QTL, which was previously identified as a QTL for estrogen-dependent pituitary tumor growth. In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogen-dependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level. Taken together, our results support the association of VEGF expression with growth of the estrogen-induced rat pituitary tumor, as has been reported by others, but they also indicate that there is significant pathways of growth regulation that are independent of high-level VEGF expression.


[Choice of the method of minimally invasive treatment of high venovenous blood reflux in patients with varicose disease of the lower extremity veins].
An analysis of complex examination and the following treatment of 337 patients with varicose disease was made. According to the results of the examination three groups of patients were established: the first group--of low intensive, the second group--of mean intensive, the third group--of highly intensive blood reflux. The patients of the first group were treated by the method of injection-sclerosing therapy. In the second group the sclero-surgical technology was used: after crossectomy into the lumen of the varicosity altered part of the great subcutaneous vein the sclerosing substance was administered through a catheter. In the third group ablation of the great subcutaneous vein of the femur was performed and obturation of the varicosity altered veins of the crus with the autovein ablated from the femur. In the first group recurrent diseases were noted in 9.1%, in the second group--in 9.4%, in the third--in 3% of the patients.


Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats.
The basolateral amygdala (BLA) is intimately involved in the development of conditional fear. Converging lines of evidence support a role for this region in the storage of fear memory but do not rule out a time-limited role in the memory consolidation. To examine this issue, we assessed the stability of BLA contribution to fear memories acquired across the adult lifetime of rats. Fear conditioning consisted of 10 tone-shock pairings in one context (remote memory), followed 16 months later by 10 additional tone-shock pairings with a novel tone in a novel context (recent memory). Twenty-four hours after recent training, rats were given NMDA or sham lesions of the BLA. Contextual and tone freezing were independently assessed in individual test sessions. Sham-lesioned rats showed high and comparable levels of freezing across all context and tone tests. In contrast, BLA-lesioned rats displayed robust freezing deficits across both recent and remote tests. Subsequent open-field testing revealed no effects of BLA lesions on activity patterns in a dark open field or during bright light exposure. Lesioned rats were able to reacquire normal levels of context-specific freezing after an overtraining procedure (76 unsignaled shocks). Together, these findings indicate that BLA lesions do not disrupt freezing behavior by producing hyperactivity, an inability to suppress behavior, or an inability to freeze. Rather, the consistent pattern of freezing deficits at both training-to-lesion intervals supports a role for the BLA in the permanent storage of fear memory.


C8-Guanine modifications: effect on Z-DNA formation and its role in cancer.
Base modifications are known to affect the structure and function of DNA. C8-guanine adducts from various carcinogenic compounds have been shown to be potent Z-DNA inducers. Hence, it has been hypothesized that Z-DNA plays a role in cancer and other genetic diseases. In this comprehensive review, Z-DNA and the effect of prevalent C8-guanine adducts on the B-Z transition are addressed. The discoveries of Z-DNA binding proteins including ADAR1, E3L, DLM1, and PKZ have suggested the relevance of Z-DNA in living systems. In addition, increasing evidence on the Z-DNA connection to gene transcription and inhibition reveals potential biological functions of the left-handed DNA. Finally, C8-guanine adducts that promote Z-DNA formation can be used as a tool to explore the Z-DNA function and its role in carcinogenesis.


Using precursor ion scan of 184 with liquid chromatography-electrospray ionization-tandem mass spectrometry for concentration normalization in cellular lipidomic studies.
Cellular lipidomic studies have been favored approaches in many biomedical research areas. To provide fair comparisons of the studied cells, it is essential to perform normalization of the determined concentration before lipidomic analysis. This study proposed a cellular lipidomic normalization method by measuring the phosphatidylcholine (PC) and sphingomyelin (SM) contents in cell extracts. To provide efficient analysis of PC and SM in cell extracts, flow injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS) with a precursor ion scan (PIS) of m/z 184 was used, and the parameters affecting the performance of the method were optimized. Good linearity could be observed between the cell extract dilution factor and the reciprocal of the total ion chromatogram (TIC) area in the PIS of m/z 184 within the dilution range of 1- to 16-fold (R2 = 0.998). The calibration curve could be used for concentration adjustment of the unknown concentration of a cell extract. The intraday and intermediate precisions were below 10%. The accuracy ranged from 93.0% to 105.6%. The performance of the new normalization method was evaluated using different numbers of HCT-116 cells. Sphingosine, ceramide (d18:1/18:0), SM (d18:1/18:0) and PC (16:1/18:0) were selected as the representative test lipid species, and the results showed that the peak areas of each lipid species obtained from different cell numbers were within a 20% variation after normalization. Finally, the PIS of 184 normalization method was applied to study ischemia-induced neuron injury using oxygen and glucose deprivation (OGD) on primary neuronal cultured cells. Our results showed that the PIS of 184 normalization method is an efficient and effective approach for concentration normalization in cellular lipidomic studies.


Excellent school performance at age 16 and risk of adult bipolar disorder: national cohort study.
Anecdotal and biographical reports suggest that bipolar disorder may be associated with high IQ or creativity, but evidence for any such connection is weak. To investigate possible associations between scholastic achievement and later bipolar disorder, using prospective data, in a whole-population cohort study. Using individual school grades from all individuals finishing compulsory schooling in Sweden between 1988 and 1997, we tested associations between scholastic achievement at age 15-16 and hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. Individuals with excellent school performance had a nearly fourfold increased risk of later bipolar disorder compared with those with average grades (hazard ratio HR = 3.79, 95% CI 2.11-6.82). This association appeared to be confined to males. Students with the poorest grades were also at moderately increased risk of bipolar disorder (HR = 1.86, 95% CI 1.06-3.28). These findings provide support for the hypothesis that exceptional intellectual ability is associated with bipolar disorder.


Attitudes among healthcare professionals to the reporting of adverse drug reactions in Nepal.
Healthcare professional's knowledge and attitudes to adverse drug reaction (ADR) and ADR reporting play vital role to report any cases of ADR. Positive attitudes may favour ADR reporting by healthcare professionals. This study was aimed to investigate the attitudes towards and ways to improve adverse drug reaction (ADR) reporting among healthcare professionals working at four Regional Pharmacovigilance Centres (RPCs) of Nepal. A cross sectional study was done by survey using a self-administered structured questionnaire. The questionnaire was distributed to 450 healthcare professionals working at four RPCs. The overall response rate was 74.0%. There were 74.8% of healthcare professionals who had seen patient experiencing an ADR; however, only 20.1% had reported. Reporting form not available (48.1%) and other colleagues not reporting ADR cases (46.9%) would significantly discourage the ADR reporting among healthcare professionals working at four RPCs. Healthcare professionals perceived that seriousness of the reaction (75.6%); unusual reaction (64.6%); reaction to new product (71.2%); new reaction to existing product (70.2%); and confidence in diagnosis of ADR (60.8%) were important factors on the decision to report ADR. Awareness among healthcare professionals (85.9%), training (76.0%), collaboration (67.0%), and involve pharmacist for ADR reporting (63.1%) were mostly recognized ways to improve reporting. Regular newsletter on current awareness in drug safety (71.2%), information on new ADR (65.8%), and international drug safety information (64.0%) were the identified feedbacks they would like to receive from the Nepal pharmacovigilance programme. Healthcare professionals working at four RPCs of Nepal have positive attitudes towards ADR reporting. Awareness among healthcare professionals, training and collaboration would likely improve reporting provided they would receive appropriate feedback from the national pharamcovigilance programme.


Support for rejection and reception policies toward asylum seekers in Italy: The role of conservative ideologies and legitimizing myths.
Based on Social Dominance Theory (SDT), this study investigates the relationships between ideologically conservative attitudes (social dominance orientation, SDO; right-wing authoritarianism, RWA), legitimizing myths (false belief in asylum seekers as bogus; perception of in-group threats), and citizens' support for restricted reception and rejection of asylum policies. A sample of 539 people living in Italy filled in an anonymous questionnaire administered using a cross-sectional design. The results support the expectations, showing that people high in SDO and RWA were more likely to hold the belief that asylum seekers are making false claims and to perceive that the latter pose a threat to the in-group, which in turn increased support for both of restrictive policies. Findings suggest that conservative ideologies can positively affect citizens' support for restrictive asylum seeker policies based on both rejection and restricted reception by supplying ideological justification for not accommodating them in the host society.


Working conditions and mental health in teachers: a preliminary study.
Unfavourable working conditions are associated with poor mental health and many studies show that teachers are at risk of this. To investigate if and to what extent specific dimensions of working conditions are associated with symptoms of depression and anxiety in teachers in state schools in Italy. A cross-sectional questionnaire survey of Italian state schoolteachers using the Karasek Job Content Questionnaire, the Self-Rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D). We tested the hypotheses that high job demand, low decision latitude and low support are associated with anxiety and depression in teachers using a correlation matrix and hierarchical multiple regression models. 113/180 (63%) of schoolteachers invited to participate completed the survey. 49% scored above the cut-off on CES-D and 11% on SAS. CES-D was positively correlated with job demand (r = 0.517, P < 0.01) and negatively with social support (r = -0.226, P < 0.05). SAS was positively correlated with job demand (r = 0.408, P < 0.01). Hierarchical multiple regression analysis showed that job demand was significantly associated with CES-D and SAS scores, explaining 28 and 25% of variance respectively. About half of the teachers in this study scored above the threshold for depression and ~1 in 10 for anxiety on self-rating questionnaires. Poor mental health in teachers is significantly associated with high job demand and low social support. These results should be confirmed in larger, more representative samples.


Microbial metabolism of the pyridine ring. Formation of pyridinediols (dihydroxypyridines) as intermediates in the degradation of pyridine compounds by micro-organisms.
1. Several species of micro-organisms that were capable of utilizing pyridine compounds as carbon and energy source were isolated from soil and sewage. Compounds degraded included pyridine and the three isomeric hydroxypyridines. 2. Suitable modifications of the cultural conditions led to the accumulation of pyridinediols (dihydroxypyridines), which were isolated and characterized. 3. Three species of Achromobacter produced pyridine-2,5-diol from 2- or 3-hydroxypyridine whereas an uncommon Agrobacterium sp. (N.C.I.B. 10413) produced pyridine-3,4-diol from 4-hydroxypyridine. 4. On the basis of chemical isolation, induction of the necessary enzymes in washed suspensions and the substrate specificity exhibited by the isolated bacteria, the initial transformations proposed are: 2-hydroxypyridine --> pyridine-2,5-diol; 3-hydroxypyridine --> pyridine-2,5-diol and 4-hydroxypyridine --> pyridine-3,4-diol. 5. A selected pyridine-utilizer, Nocardia Z1, did not produce any detectable hydroxy derivative from pyridine, but carried out a slow oxidation of 3-hydroxypyridine to pyridine-2,3-diol and pyridine-3,4-diol. These diols were not further metabolized. 6. Addition of the isomeric hydroxypyridines to a model hydroxylating system resulted in the formation of those diols predicted by theory.


Covalent Labeling/Mass Spectrometry of Monoclonal Antibodies with Diethylpyrocarbonate: Reaction Kinetics for Ensuring Protein Structural Integrity.
Diethylpyrocarbonate (DEPC)-based covalent labeling together with mass spectrometry is a promising tool for the higher-order structural analysis of antibody therapeutics. Reliable information about antibody higher-order structure can be obtained, though, only when the protein's structural integrity is preserved during labeling. In this work, we have evaluated the applicability of DEPC reaction kinetics for ensuring the structural integrity of monoclonal antibodies (mAbs) during labeling. By monitoring the modification extent of selected proteolytic fragments as a function of DEPC concentration, we find that a common DEPC concentration can be used for different monoclonal antibodies in formulated samples without perturbing their higher-order structure. Under these labeling conditions, we find that the antibodies can accommodate up to four DEPC modifications without being structurally perturbed, indicating that multidomain proteins can withstand more than one label, which contrasts to previously studied single-domain proteins. This more extensive labeling provides a more sensitive measure of structure, making DEPC-based covalent labeling-mass spectrometry suitable for the higher-order structural analyses of mAbs.


Neither gonadotropin nor cumulus cell expansion is needed for the maturation of competent porcine oocytes in vitro†.
In-vitro maturation (IVM) of oocytes from immature females is widely used in assisted reproductive technologies. Here we illustrate that cumulus cell (CC) expansion, once considered a key indicator of oocyte quality, is not needed for oocytes to mature to the metaphase II (MII) stage and to gain nuclear and cytoplasmic competence to produce offspring. Juvenile pig oocytes were matured in four different media: (1) Basal (-gonadotropins (GN) - FLI); (2) -GN + FLI (supplement of FGF2, LIF, and IGF1); (3) +GN - FLI; and (4) +GN + FLI. There was no difference in maturation to MII or progression to the blastocyst stage after fertilization of oocytes that had been matured in -GN + FLI medium and oocytes matured in +GN + FLI medium. Only slight CC expansion occurred in the two media lacking GN compared with the two where GN was present. The cumulus-oocytes-complexes (COC) matured in +GN + FLI exhibited the greatest expansion. We conclude that FLI has a dual role. It is directly responsible for oocyte competence, a process where GN are not required, and, when GN are present, it has a downstream role in enhancing CC expansion. Our study also shows that elevated phosphorylated MAPK may not be a necessary correlate of oocyte maturation and that the greater utilization of glucose by COC observed in +GN + FLI medium probably plays a more significant role to meet the biosynthetic needs of the CC to expand than to attain oocyte developmental competence. Gene expression analyses have not been informative in providing a mechanism to explain how FLI medium enhances oocyte competence without promoting CC expansion.


The Effect of a Comprehensive, Interdisciplinary Medication Review on Quality of Life and Medication Use in Community Dwelling Older People with Polypharmacy.
Background: We conducted a comprehensive medication review at the patients' home, using data from electronic patient records, and with input from relevant specialists, general practitioners and pharmacists formulated and implemented recommendations to optimize medication use in patients aged 60+ years with polypharmacy. We evaluated the effect of this medication review on quality of life (QoL) and medication use. Methods: Cluster randomized controlled trial (stepped wedge), randomly assigning general practices to one of three consecutive steps. Patients received usual care until the intervention was implemented. Primary outcome was QoL (SF-36 and EQ-5D); secondary outcomes were medication changes, medication adherence and (instrumental) activities of daily living (ADL, iADL) which were measured at baseline, and around 6- and 12-months post intervention. Results: Twenty-four general practices included 360 women and 410 men with an average age of 75 years (SD 7.5). A positive effect on SF-36 mental health (estimated mean was stable in the intervention, but decreased in the control condition with -6.1, p = 0.009,) was found with a reduced number of medications at follow-up compared to the control condition. No significant effects were found on other QoL subscales, ADL, iADL or medication adherence. Conclusion: The medication review prevented decrease of mental health (SF36), with no significant effects on other outcome measures, apart from a reduction in the number of prescribed medications.


Phototherapeutic keratectomy in Salzmann's nodular degeneration.
To describe the outcome in vision and refraction of phototherapeutic keratectomy (PTK) in Salzmann's nodular degeneration (SND). Five eyes of four patients underwent PTK with the objective of restoring an acceptable refractive status and improving visual acuity. This surgical technique aims to make the nodules level with the corneal surface using an excimer laser. Best corrected visual acuity (BCVA) improved in all five eyes. Astigmatism was reduced in four eyes and increased somewhat in one. During the observation period one eye suffered a late recurrence that required a penetrating graft. Salzmann's nodular degeneration is a rare disease that is sometimes difficult to diagnose as it has some resemblance to other diseases. The aetiology of the disease is unknown. Phototherapeutic keratectomy is a safe and effective mode of treatment. Recurrences occur with time.


Prevalence of leprosy among slum dwellers.
Distribution of leprosy among slum dwellers in two areas of Bangalore City were studied. Out of a random sample of 483 it was found that 150 were suffering from leprosy while 74 tuberculoid and 25 lepromatous cases were detected, the remaining showed up as borderline and polyneuritic types. The important socio economic features and the consequences of this chronic disease have been discussed.


A prognostic model for one-year mortality in patients requiring prolonged mechanical ventilation.
A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognoses to patients or surrogate decision makers. Our objective was to develop and validate a prognostic model for 1-yr mortality in patients ventilated for 21 days or more. The authors conducted a prospective cohort study. The study took place at a university-based tertiary care hospital. Three hundred consecutive medical, surgical, and trauma patients requiring mechanical ventilation for at least 21 days were prospectively enrolled. Predictive variables were measured on day 21 of ventilation for the first 200 patients and entered into logistic regression models with 1-yr and 3-mo mortality as outcomes. Final models were validated using data from 100 subsequent patients. One-year mortality was 51% in the development set and 58% in the validation set. Independent predictors of mortality included requirement for vasopressors, hemodialysis, platelet count < or = 150 x 10(9)/L, and age > or = 50 yrs. Areas under the receiver operating characteristic curve for the development model and validation model were .82 (SE .03) and .82 (SE .05), respectively. The model had sensitivity of .42 (SE .12) and specificity of .99 (SE .01) for identifying patients who had > or = 90% risk of death at 1 yr. Observed mortality was highly consistent with both 3- and 12-mo predicted mortality. These four predictive variables can be used in a simple prognostic score that clearly identifies low-risk patients (no risk factors, 15% mortality) and high-risk patients (three or four risk factors, 97% mortality). Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged ventilation.


A methodology for quantitative performance evaluation of detection algorithms.
We present a methodology for the quantitative performance evaluation of detection algorithms in computer vision. A common method is to generate a variety of input images by varying the image parameters and evaluate the performance of the algorithm, as algorithm parameters vary. Operating curves that relate the probability of misdetection and false alarm are generated for each parameter setting. Such an analysis does not integrate the performance of the numerous operating curves. We outline a methodology for summarizing many operating curves into a few performance curves. This methodology is adapted from the human psychophysics literature and is general to any detection algorithm. The central concept is to measure the effect of variables in terms of the equivalent effect of a critical signal variable, which in turn facilitates the determination of the breakdown point of the algorithm. We demonstrate the methodology by comparing the performance of two-line detection algorithms.


Phase Separation by Entanglement of Active Polymerlike Worms.
We investigate the aggregation and phase separation of thin, living T. tubifex worms that behave as active polymers. Randomly dispersed active worms spontaneously aggregate to form compact, highly entangled blobs, a process similar to polymer phase separation, and for which we observe power-law growth kinetics. We find that the phase separation of active polymerlike worms does not occur through Ostwald ripening, but through active motion and coalescence of the phase domains. Interestingly, the growth mechanism differs from conventional growth by droplet coalescence: the diffusion constant characterizing the random motion of a worm blob is independent of its size, a phenomenon that can be explained from the fact that the active random motion arises from the worms at the surface of the blob. This leads to a fundamentally different phase-separation mechanism that may be unique to active polymers.


[Neurochemistry of lipids in the nervous system, fatty acids in particular. Neurotoxicologic prospects].
Each membrane in the brain is constituted of peculiar fatty acids which are related to its biological function. The nervous system is a highly lipid-rich tissue, essentially represented by fatty acids. The brain is able to synthetize both saturated and mono-unsaturated fatty acids independently of the chain length. The nature, the localization, the biochemical mechanisms and the regulation process of synthesis have been studied at the cellular and subcellular level. The fate of fatty acids, particularly their function of precursor in the synthesis of lipids, has been analysed. However the fact all the fatty acids are not synthetized in situ, strongly suggests that they have a seric origin. The seric fatty acids are eventually synthetized in the liver or can originate from diet. Malnutrition (pre- or post-natal) causes serious abnormalities in the brain fatty acids composition. The alimentary origin of poly-unsaturated fatty acids being absolute, the relative quantities of fatty acids of the w3 and w6 series must be precisely determined. The poly-unsaturated fatty acids control the membrane fluidity, and therefore their metabolic activities.


Gabapentin-induced rhabdomyolysis in a patient with diabetic neuropathy.
Gabapentin (GBP) is a drug which is frequently used in diabetic neuropathy. Common adverse effects of GBP include drowsiness, dizziness, ataxia, somnolence, and fatigue. Rhabdomyolysis is an extremely rare side effect of GBP. In this report we describe a case of GBP-induced rhabdomyolysis in a 63-year-old diabetic woman. She presented with severe muscle pain in her extremities, fatigue, decreased urine output and urine discoloration within 3 weeks after starting treatment with GBP (900 mg/day) for diabetic neuropathy. Laboratory tests revealed extreme elevations of muscle enzymes, increased creatinine and potassium levels. She required hemodialysis as a result of anuria. Investigation confirmed the diagnosis of rhabdomyolysis, and discontinuation of GBP resulted in resolution of clinical and biochemical features of rhabdomyolysis.


RANK receptor oligomerisation in the regulation of NFκB signalling.
The interaction of receptor activator of NFκB (RANK), a member of the tumour necrosis factor receptor superfamily, with RANK ligand is crucial for the formation, function and survival of osteoclasts. The role of the cytoplasmic oligomerisation domain (pre-ligand assembly domain; PLAD or 'IVVY' motif) in the ligand-dependent activation of downstream NFκB signalling has not been studied previously. The discovery of truncating mutations of TNFRSF11A (W434X and G280X that lack the PLAD) as the cause of rare cases of osteoclast-poor osteopetrosis offered the opportunity for functional study of this region. Recapitulating the W434X mutation by transcription activator-like effector nuclease (TALEN)-mediated targeted disruption of Tnfrsf11a within the region homologous to W434X in the mouse macrophage-like cell line RAW264.7 impaired formation of osteoclast-like cells. Using overexpression studies, we demonstrated that, in contrast to WT-RANK, the absence of the PLAD in G280X-RANK and W434X-RANK prevented ligand-independent but not ligand-dependent oligomerisation. Cells expressing W434X-RANK, in which only two of the three TRAF6-binding motifs are present, continued to exhibit ligand-dependent NFκB signalling. Hence, the absence of the PLAD did not prevent ligand-induced trimerisation and subsequent NFκB activation of RANK, demonstrating that therapeutic targeting of the PLAD in the prevention of osteoporosis may not be as effective as proposed previously.


The prophylactic effect of a dry-cow antibiotic against Streptococcus uberis.
The prophylactic use of a dry-cow antibiotic for reducing the incidence of mastitis due to Streptococcus uberis was studied in four seasonally calving dairy herds involving 378 cows. The treatment was a long-acting dry-cow antibiotic preparation administered immediately after the last milking of lactation. New intramammary infections were identified by comparing the bacteriological status of quarters at drying off with that after calving, or through manual udder palpation during the dry period. The administration of dry-cow antibiotic to uninfected quarters at drying off reduced the overall incidence of new infections with Streptococcus uberis from 12.3% for untreated quarters to 1.2% of quarters (p<0.01). The reduction was significant (p<0.01) for both dry-period and post-calving infections. The susceptibility of uninfected quarters to new infection by Streptococcus uberis appeared to be unrelated to the infection status of a cow at drying off. Clinical infections during the dry period were most prevalent (97%) in quarters identified as having open teat canals. Fewer open teat canals (p<0.05) were observed among antibiotic treated quarters over the first 4 weeks of the dry period. Treated quarters had a lower (p<0.05) incidence of new clinical infection during the ensuing lactation and lower somatic cell counts. This did not affect production levels of milk, milk fat or protein. The results clearly indicated a prophylactic benefit for the dry cow antibiotic treatment against new Streptococcus uberis infections during the dry period.


Predictors and level of sustainability of community prevention coalitions.
After many years in which evaluations had generally not found the coalition approach to be effective, the community-coalition approach has recently been shown to produce a public health impact if best practices are utilized. The next challenge is to foster sustainability among coalitions in order to achieve long-term public health outcomes. This study examined the level of and predictors of sustainability among Communities That Care (CTC) sites in Pennsylvania. Board functioning and the funding of 110 CTC sites were assessed through the reports of board members, staff, and technical-assistance providers from 2003 through 2006; data were analyzed in 2007. Ninety percent of CTC coalitions continued after the 3-year initial funding period, with 3%-8% of sites terminating each year thereafter. Approximately two thirds of CTC sites continued to operate 4 years after the termination of the original 3-year implementation grant. Many of the sites attracted funding at a level equivalent to or greater than the initial grant. Overall coalition functioning, as reported by either board members or technical-assistance providers, along with planning for sustainability, predicted both survival and post-launch funding. Evidence suggests that board functioning predicts survival, at least in part independently of its influence on funding; and that planning for sustainability predicts sustainability, at least in part independently of overall coalition functioning.


Heterozygosity, heteromorphy, and phylogenetic trees in asexual eukaryotes.
Little attention has been paid to the consequences of long-term asexual reproduction for sequence evolution in diploid or polyploid eukaryotic organisms. Some elementary theory shows that the amount of neutral sequence divergence between two alleles of a protein-coding gene in an asexual individual will be greater than that in a sexual species by a factor of 2tu, where t is the number of generations since sexual reproduction was lost and u is the mutation rate per generation in the asexual lineage. Phylogenetic trees based on only one allele from each of two or more species will show incorrect divergence times and, more often than not, incorrect topologies. This allele sequence divergence can be stopped temporarily by mitotic gene conversion, mitotic crossing-over, or ploidy reduction. If these convergence events are rare, ancient asexual lineages can be recognized by their high allele sequence divergence. At intermediate frequencies of convergence events, it will be impossible to reconstruct the correct phylogeny of an asexual clade from the sequences of protein coding genes. Convergence may be limited by allele sequence divergence and heterozygous chromosomal rearrangements which reduce the homology needed for recombination and result in aneuploidy after crossing-over or ploidy cycles.


Tuning Caco-2 Permeability by Cocrystallization: Insights from Molecular Dynamics Simulation.
Emerging evidence suggests that intestinal permeability can be potentially enhanced through cocrystallization. However, a mechanism for this effect remains to be established. In this study, we first demonstrate the enhancement in intestinal permeability, evaluated by the Caco-2 cell permeability assay, of acetazolamide (ACZ) in the presence of a conformer, p-aminobenzoic acid (PABA), delivered in the form of a 1:1 cocrystal. The binding strength of ACZ and PABA with the Pgp efflux transporter, either alone or as a mixture, was calculated using molecular dynamics simulation. Results show that PABA weakens the binding of ACZ with Pgp, which leads to a lower efflux ratio and elevated permeability of ACZ. This work provides molecular-level insights into a potentially effective strategy to improve the intestinal permeability of drugs. If the same cocrystal also exhibits higher solubility, oral bioavailability of BCS IV drugs can likely be improved by forming a cocrystal with a Pgp inhibitor.


Effective healthcare system response to consecutive Florida hurricanes.
In September 2004, two consecutive hurricanes (Hurricane Frances and Hurricane Jeanne) made landfall in Stuart, FL, and created healthcare needs that overtaxed the capacity of the local healthcare system. To determine the character and structure of the response to these hurricanes, researchers from the University of New Mexico, Center for Disaster Medicine conducted both a structured written survey of employees and a guided group interview with healthcare system management. The written survey queried staff on topics related to their ability and willingness to get to work and stay at work during the storms. The roundtable interview with leadership resulted in analysis of the preexisting Emergency Operations Plan and its use during the storms, including preparation and execution of plans for staffing, facility operation, communication, community resource utilization, and recovery. In addition, the interaction with federally deployed Disaster Medical Assistance Teams was documented and reviewed. In general, prior planning on the part of the healthcare system in Stuart, FL, resulted in a successful response to both hurricanes. Employees were willing and able to provide the necessary care for patients during the hurricanes, overcoming many physical and emotional barriers that arose during the month-long response. These barriers included concern for the safety of family and pets, inoperable or insufficient communication methods, and damage to employees' personal property and homes. Recommendations for healthcare system preparedness and response were formulated by the researchers based on this healthcare system's successful response to back-to-back hurricanes, including recommendations for interacting with disaster medical resources.


Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence.
Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature-aging syndrome caused by a dominant mutation in the gene encoding lamin A, which leads to an aberrantly spliced and processed protein termed progerin. Previous studies have shown that progerin induces early senescence associated with increased DNA-damage signaling and that telomerase extends HGPS cellular lifespan. We demonstrate that telomerase extends HGPS cellular lifespan by decreasing progerin-induced DNA-damage signaling and activation of p53 and Rb pathways that otherwise mediate the onset of premature senescence. We show further that progerin-induced DNA-damage signaling is localized to telomeres and is associated with telomere aggregates and chromosomal aberrations. Telomerase amelioration of DNA-damage signaling is relatively rapid, requires both its catalytic and DNA-binding functions, and correlates in time with the acquisition by HGPS cells of the ability to proliferate. All of these findings establish that HGPS premature cellular senescence results from progerin-induced telomere dysfunction.


Calibration of the Welding Advanced REACH Tool (weldART).
This paper reports a study to develop and calibrate a deterministic model of welding fume exposure based on a four-compartment mass-balance model - The Welding Advanced REACH Tool (weldART). To achieve this aim, measurements of welding fume exposure were collected along with data on exposure determinants needed in the modelling. The welding fume exposure data was obtained from workers in a structural steel fabrication plant. Welders were engaged in three processes: flux-cored arc welding (FCAW), shielded metal arc welding (SMAW) and gas tungsten arc welding (GTAW). Aerosol concentration was measured using 13 mm diameter Swinnex sampling heads and MicroPEM direct-reading aerosol monitors. The model was initially developed with three spatial compartments (near-field (NF), far-field (FF), and welding plume (WP)). However, in the welding scenario investigated the FF had a very large volume and it was necessary to subdivide the room volume into an intermediate zone representing the FF along with the remaining room zone (RM). We fitted linear equations forced through the origin to the gravimetric concentrations measured inside the welders' visor and the weldART model estimates. The flowrates between the model compartments were adjusted by trial and error to obtain proportionate concentrations in each compartment. The FCAW process generated higher welding fume particulate concentrations than SMAW and GTAW. The MicroPEM monitors considerably underestimated and were poorly correlated with the corresponding data from the Swinnex samplers. It was concluded that the MicroPEM data were unreliable. The model calibration showed a strong association between the personal exposure measurement and the weldART model values (R2 = 0.94), with the average estimated value 1.3 times the measurements. The NF and the FF model estimates were poorly correlated with the corresponding compartment measurements (R2 = 0.37 and 0.35, respectively), although on average the model estimates were close to the measurement data (ratio of modelled to measured 0.9, and 1.0, respectively). The calibration shows that the weldART model is able to predict the exposure of welding fume particulate.


Listeria monocytogenes sclerokeratitis: a case report and literature review.
To report a case of Listeria monocytogenes sclerokeratitis and to review the literature. Case report. A 25-year-old non-contact lens-wearing male rugby player was referred with progressive infective sclerokeratitis unresponsive to topical antivirals and antibiotics. On examination, visual acuity was perception of light, and a large corneal abscess with overlying epithelial defect and hypopyon was present. The corneal lesion was cheesy white and raised with nasal scleritis. This raised the suspicion of a fungal keratitis. Empirical treatment with intensive topical antifungals was unsuccessful. A previous corneal scrape had been negative for bacteria and fungi. A corneal biopsy was performed, and Listeria monocytogenes was eventually isolated from enrichment culture. Antibiotic sensitivities showed it to be resistant to cefuroxime, methicillin, and ceftazidime but sensitive to all other antibiotics tested including ofloxacin. The treatment course was complicated by a corneal perforation that needed an emergency therapeutic penetrating keratoplasty. Five months later, best-corrected visual acuity was 6/9 + 4, with a clear functioning graft. Listeria monocytogenes is a rare cause of corneal/scleral infection in humans. It often runs an aggressive course and responds poorly to initial intensive antibiotic treatment despite favorable in vitro sensitivities. It can be difficult to culture, and we suggest a corneal biopsy with extended incubation to improve diagnostic yield.


A natural variant of the cysteine protease virulence factor of group A Streptococcus with an arginine-glycine-aspartic acid (RGD) motif preferentially binds human integrins alphavbeta3 and alphaIIbbeta3.
The human pathogenic bacterium group A Streptococcus produces an extracellular cysteine protease [streptococcal pyrogenic exotoxin B (SpeB)] that is a critical virulence factor for invasive disease episodes. Sequence analysis of the speB gene from 200 group A Streptococcus isolates collected worldwide identified three main mature SpeB (mSpeB) variants. One of these variants (mSpeB2) contains an Arg-Gly-Asp (RGD) sequence, a tripeptide motif that is commonly recognized by integrin receptors. mSpeB2 is made by all isolates of the unusually virulent serotype M1 and several other geographically widespread clones that frequently cause invasive infections. Only the mSpeB2 variant bound to transfected cells expressing integrin alphavbeta3 (also known as the vitronectin receptor) or alphaIIbbeta3 (platelet glycoprotein IIb-IIIa), and binding was blocked by a mAb that recognizes the streptococcal protease RGD motif region. In addition, mSpeB2 bound purified platelet integrin alphaIIbbeta3. Defined beta3 mutants that are altered for fibrinogen binding were defective for SpeB binding. Synthetic peptides with the mSpeB2 RGD motif, but not the RSD sequence present in other mSpeB variants, blocked binding of mSpeB2 to transfected cells expressing alphavbeta3 and caused detachment of cultured human umbilical vein endothelial cells. The results (i) identify a Gram-positive virulence factor that directly binds integrins, (ii) identify naturally occurring variants of a documented Gram-positive virulence factor with biomedically relevant differences in their interactions with host cells, and (iii) add to the theme that subtle natural variation in microbial virulence factor structure alters the character of host-pathogen interactions.


[Epidemiologic and preventive studies of the precursors of atherosclerosis in children and adults].
A total of 1920 schoolchildren of both sexes were examined at 12 to 13 years of age, with a follow-up of 242 children showing elevated BP and a random normotensive sample of 230. A set of features was identified that showed the greatest predictive value with respect to mean BP at five years' follow-up: baseline BP, the Katle index, the magnitude of the S wave and heart rate. A study of possible approaches to the prevention of atherosclerotic precursors in eleven-year-olds has been launched, with the action on certain risk factors, such as limited physical activity, elevated BP, smoking, excessive body weight lipid disorders (in boys only).


Virtual-screening workflow tutorials and prospective results from the Teach-Discover-Treat competition 2014 against malaria.
The first challenge in the 2014 competition launched by the Teach-Discover-Treat (TDT) initiative asked for the development of a tutorial for ligand-based virtual screening, based on data from a primary phenotypic high-throughput screen (HTS) against malaria. The resulting Workflows were applied to select compounds from a commercial database, and a subset of those were purchased and tested experimentally for anti-malaria activity. Here, we present the two most successful Workflows, both using machine-learning approaches, and report the results for the 114 compounds tested in the follow-up screen. Excluding the two known anti-malarials quinidine and amodiaquine and 31 compounds already present in the primary HTS, a high hit rate of 57% was found.


Early diagnosis of monomicrobial Clostridioides difficile bacteremia in a patient without colitis.
Bacteremia is a rare finding among Clostridioides difficile infections. We describe a case of a 67-year-old man with resected colorectal cancer with colostomy who presented with small bowel obstruction and was admitted for lysis of adhesions. On day 8 of admission, he developed leukocytosis and raised inflammatory markers with isolation of Gram-positive bacilli in several blood cultures, which was presumptively identified through blood culture pelleting and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) as C. difficile. The diagnosis was confirmed with conventional culture and reference lab identification and the patient demonstrated clinical response with parenteral then oral vancomycin that briefly worsened when therapy was switched to parenteral metronidazole and then improved once oral vancomycin was resumed. Our case was notable in that the combination of pelleting and MALDI-TOF offered early diagnosis in this patient whose positive blood cultures were suspicious for contamination and in whom there was an absence of diarrheal illness or features of colitis on abdominal imaging. Early diagnosis is critical for the timely initiation of therapy, implementation of infection prevention and control measures and in selection of appropriate therapy for antimicrobial stewardship.


Lactulose and combination therapy of hepatic encephalopathy: the role of the intestinal microflora.
Lactulose is the most frequently utilized agent in the treatment of hepatic encephalopathy because of its efficacy and the fact that it has few serious side effects. How this nonabsorbable disaccharide works has been a matter of controversy, but evidence suggests that metabolism by the enteric flora is necessary for its mechanism of action. When the intestinal flora metabolized lactulose, bacterial incorporation of nitrogen increases as does the bacterial mass. The presence of a carbohydrate and the acidic environment caused by the production of organic acids also act to reduce the breakdown of other nitrogen-containing compounds to ammonia and other potential cerebral toxins. The administration of lactulose to humans causes an increase in fecal nitrogen, but very little increase in ammonia nitrogen. Most of the nitrogen is contained in the fecal bacterial and the soluble fractions of stool. The administration of lactulose causes a reduction in the urea production rate consistent with a reduced entry of ammonia into portal blood, but it does not appear to directly inhibit urea degradation. Other nonabsorbable saccharides, particularly those contained in dietary fiber, appear to have effects similar to those of lactulose. There is some evidence that neomycin can be given with lactulose to cause an additive effect in the treatment of hepatic encephalopathy. This effect is most prominent in patients who have not responded adequately to lactulose alone. At this point, the other antibiotics studied do not appear to have additive effects with lactulose.


Multidisciplinary Real-World Experience With Bilastine, a Second Generation Antihistamine
Introduction: Allergic conditions frequently require treatment with antihistamines. First-generation antihistamines can potentially interfere with restful sleep, cause "morning after" effects, impair learning and memory, and reduce work efficiency. Second-generation antihistamines, such as bilastine, have been demonstrated to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events. Method: A real-world case project was developed to help optimize patient care by recognizing the role bilastine can play for allergic conditions where antihistamine treatment is needed. The presented real-world patient cases conducted by the panel members are supported with evidence from the literature, where available. Any discussion concerning off-label use should be considered an expert opinion only. Results: The real-world cases presented here used bilastine in conditions such as perennial and seasonal allergic rhinitis, chronic urticaria, as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions. The treated patients were between 9 and 76-years old providing information on a full spectrum of patients that require treatment with antihistamines. Conclusions: The presented real-world cases using the second-generation antihistamine, bilastine, demonstrated favorable outcomes for the treated patients. While effectively relieving symptoms, the antihistamine was reported to be safe and well-tolerated. J Drugs Dermatol. 2020;19(2)145-154. doi:10.36849/JDD.2020.4835


Effect of amide hydrogen bonding on spontaneously formed gel-emulsions by two pyridyl carboxylic acid based amphiphiles, sodium salt of 2-dodecylpyridine-5-carboxylic acid and sodium salt of [2-dodecylpyridine-5-carboxylic]glycine: entrapment and release of vitamin B12.
The present study offers the demonstration and rational design of two synthesized single chain pyridyl carboxylic acid (nicotinic acid) based amphiphilic gelators named the sodium salt of 2-dodecylpyridine-5-carboxylic acid (SDDPC) and the sodium salt of [2-dodecylpyridine-5-carboxylic]glycine (SDDPCG). The gelation abilities were tested in a series of organic solvents, by a number of physical methods including X-ray diffraction, FTIR spectroscopy, rheology, DSC, optical and electron microscopy. The minimum gelation concentration and gelation number of the gelators in different solvents were determined. No gelation was observed when pure solvents were employed. The gelation properties of these two compounds found that the gelation depends on H-bonding of the amide linkage. X-ray diffraction study indicates the presence of two recognizable morphologies for SDDPC in a gel-emulsion, whereas for SDDPCG a single type of aggregate is predominant. FTIR spectra suggest that the presence of intermolecular hydrogen bonding facilitates the gelation process. Rheological measurements demonstrated that the gel-emulsions are mechanically stable and exhibit typical viscoelastic properties. Optical microscopy images show a network structure in the gel phase and a fibril structure in the xerogel. SEM images confirmed the presence of network as well as a flex-like thick fibrous network for both the amphiphiles, forming three dimensional (3-D) networks. Both the gelators showed a remarkable response toward external pH. The gel-emulsions were used in the controlled and/or pH triggered release of entrapped (within the gel-emulsions) vitamin B12 at different pHs.


Spaying and urinary incontinence in bitches under UK primary veterinary care: a case-control study.
To evaluate associations between spaying and urinary incontinence in bitches under primary veterinary care in the UK. A case-control study was nested within the study population of 333,910 bitches, which included all bitches within the VetCompass database with an electronic patient record in 2016 or in both 2015 and 2017. The electronic records were searched automatically for urinary incontinence cases, which were manually reviewed for inclusion. All non-cases were included as controls. Additional demographic and clinical information was extracted on cases and controls. The study included 427 incident cases and 1708 controls that were presented between November 1, 2014 and October 31, 2017. Prior spaying was associated with increased odds of urinary incontinence (odds ratio: 3.01; 95% CIs: 2.23 to 4.05). Increased odds of urinary incontinence were additionally associated with increasing age and increasing bodyweight. Age at spay was not associated with urinary incontinence. The findings support spaying as a major risk factor associated with urinary incontinence, but age at spay appears to be of less clinical importance. These results will help assist clinicians in making evidence-based recommendations on spaying while taking other considerations for urinary incontinence into account.


The transcriptional response to tumorigenic polarity loss in Drosophila.
Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA profiling of Scrib mutant tumors reveals multiple signatures of neoplasia, including altered metabolism and dedifferentiation. Prominent among these is upregulation of cytokine-like Unpaired (Upd) ligands, which drive tumor overgrowth. We identified a polarity-responsive enhancer in upd3, which is activated in a coincident manner by both JNK-dependent Fos and aPKC-mediated Yki transcription. This enhancer, and Scrib mutant overgrowth in general, are also sensitive to activity of the Polycomb Group (PcG), suggesting that PcG attenuation upon polarity loss potentiates select targets for activation by JNK and Yki. Our results link epithelial organization to signaling and epigenetic regulators that control tissue repair programs, and provide insight into why epithelial polarity is tumor-suppressive.


Survival of indicator organisms during enrichment on tetrachloroethene.
A laboratory study was performed as the basis for a full-scale bioaugmentation project at a site contaminated with chlorinated ethenes. The objectives of this study were to 1) develop a protocol to enrich for a tetrachloroethene (PCE)-dechlorinating culture from waste activated sludge and anaerobic digester biosolids and 2) monitor the survival of fecal coliform bacteria and bacteriophage, which model enteric viruses, during the enrichment process. A culture was enriched in 8 days with the ability to degrade 6-microM PCE to cis-dichloroethene. Using the enrichment protocol in two identical experiments, significant inactivation of fecal coliform bacteria (2 log) and somatic coliphage (0.33 log) was observed in one of the experiments; no inactivation occurred in the second experiment. The number of F-specific coliphage decreased in both experiments (0.87 and 1.26 log inactivation). Despite the decrease in some of the coliform and bacteriophage numbers, the quantity of organisms and phage particles present after enrichment was still high (approximately 7.5 x 10(5) most probable number/L, 6.9 x 10(6) plaque-forming units (PFU)/L, and 3.3 x 10(5) PFU/L, for fecal coliform bacteria, somatic coliphage, and F-specific coliphage, respectively). This may be cause for concern, depending on the current and future groundwater use at or near a site undergoing bioaugmentation with cultures derived from waste activated sludge and anaerobic digester biosolids.


Protective effect of resveratrol against pressure overload-induced heart failure.
Transverse aortic constriction (TAC)-induced pressure overload (PO) causes adverse cardiac remodeling and dysfunction that progresses to heart failure (HF). The purpose of this study was to determine whether the potent antioxidant, resveratrol, significantly attenuates PO-induced HF in wild-type mice. Male C57BL6 mice were subjected to either sham or TAC surgery. One group of TAC mice was given daily resveratrol treatment. Echocardiographic, biometric, and immunohistological analyses were performed on the three groups of mice. All echocardiographic parameters demonstrated significantly greater adverse cardiac remodeling and dysfunction in the TAC compared to the sham mice. Increases in the ratios of heart weight (HW)/body weight (BW) and lung weight (LW)/BW and a sharp decline in the percentage of ejection fraction and fractional shortening were found in TAC relative to sham mice. Likewise, the TAC protocol increased markers of oxidative stress, cardiac hypertrophy, inflammation, fibrosis, hypoxia, and apoptosis. These pathological changes were significantly attenuated by resveratrol treatment. Resveratrol treatment significantly attenuates the adverse cardiac remodeling and dysfunction produced by the TAC protocol in C57/BL6 mice and this activity is mediated, at least in part, by the inhibition of oxidative stress and inflammation indicating a therapeutic potential of resveratrol in HF.


Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study.
Survival rates after severe injury are improving, but complication rates and outcomes are variable. This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery. We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15). We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models. We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis. The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation.


The utilization of yeast in heavy wastewater treatment.
Wastewater discharged from vermicelli factories has high concentration of COD and BOD, it is considered to be heavy wastewater. Strach degrading yeast was isolated and applied to treat the vermicelli wastewater. A semicontinuous yeast dominant activated sludge method and an immobilized yeast cells system were used in treating the clarified vermicelli wastewater. When the solid retention time and hydraulic retention time were kept at 7.14 days, using a semicontinuous culture, the solid loading was 0.48 g COD/g MLSS.day, volumetric loading was 1.03 kg COD/m3.day, and the COD removal was about 92%. When the yeast cells were immobilized with 1% Na-alginate solution, in the batch culture system, the COD removal of the immobilized cells was about 73% in 12 hours; with the air bubble system, the immobilized cells had the ability to remove COD of 90%. It indicated that the immobilized cells can treat heavy wastewater directly, and the hydraulic retention time could be reduced from 7.14 days to 24 hours.


[Accomodation tonus in myopia and its potential prognostic value].
60 patients with different degree of myopia were examined to study habitual accomodation tonus (HAT) and accomodation rest tonus (ART). HAT was calculated as a difference between standard autorefratometer measurements before and after cycloplegia; HAT in open field (HAT-OF) was estimated using open-field autorefractometer before and after cycloplegia with a patient looking at the distant object; ART was considered as a difference between refraction in dark conditions (dark focus) and cycloplegic refraction using open-field autorefractometer Grand Seiko WR-5100K (Japan). In examined patients ART was maximal (-0,87 +/- 0,08 dpt) and HAT-OF-minimal (-0,15 +/- 0,04 dpt). The high values of accomodation tonus (both HAT and ART) were associated with higher rates of myopia progressing. For the first time dynamic refraction measured using open-field autorefractometer confirmed the phenomenon of "negative" accomodation.


Imaging Methodology for Hip Preservation: Techniques, Parameters, and Thresholds.
The concept of hip impingement and hip-preserving surgery has been appreciated in more detail since 2001 when a new surgical approach was reported and a hypothesis linking femoroacetabular impingement (FAI) with osteoarthritis was presented. Paralleling the introduction of hip arthroscopy, these events led to an increasing interest in the hip, and the number of publications has risen rapidly over the past 15 years, despite limited evidence levels and inconsistent methodology. Accordingly, etiology, diagnosis, prognosis, and the effects of treatment for FAI are still elusive due to a number of uncertainties and a lack of clear diagnostic criteria.Future research must focus on developing high-quality scientific studies, so thorough and reproducible methodology is needed. This review provides researchers, radiologists, and clinicians with a comprehensive approach to hip imaging with a focus on strategies to help guide the clinical diagnosis. Using evidence from current literature and knowledge from experienced clinicians, some of the imaging methodology challenges are deciphered.


Use of molecularly-cloned haematopoietic growth factors in persons exposed to acute high-dose, high-dose rate whole-body ionizing radiations.
Exposure to acute, high-dose, high dose-rate whole-body ionizing radiations damages the bone marrow resulting in rapid decreases in concentrations of blood cells, especially lymphocytes, granulocytes and platelets with associated risks of infection and bleeding. In several experimental models including non-human primate radiation exposure models giving molecularly cloned haematopoietic growth factor including granulocyte/macrophage colony-stimulating factor (G/M-CSF; sargramostim) and granulocyte colony-stimulating factor (G-CSF; filgrastim and pegylated G-CSF [peg-filgrastim]) accelerates bone marrow recovery and increases survival. Based on these data these molecules are US FDA approved for treating victims of radiation and nuclear incidents, accident and events such as nuclear terrorism and are included in the US National Strategic Stockpile. We discuss the immediate medical response to these events including how to estimate radiation dose and uniformity and which interventions are appropriate in different radiation exposures settings. We also discuss similarities and differences between molecularly cloned haematopoietic growth factors.


Pilot Results for ECoLoGiC-Tx: A New Conversation-Level Intervention Improving Language in People With Moderate to Severe Aphasia.
This study reports pilot data for a novel intervention, ECoLoGiC-Tx, delivered to four people with moderate to severe aphasia. ECoLoGiC-Tx addresses language and communication in unstructured, participant-led conversation. The speech-language pathologist (SLP) uses a framework to choose turns that facilitate a social interaction. When communication breakdown occurs, the SLP implements a least-to-most hierarchy to maximize the people with aphasia's (PWA's) independence in self-repair. ECoLoGiC-Tx draws its theoretical underpinnings from conversation analysis and theories of rehabilitation, including principles of complexity, neuroplasticity, and learning. Four PWA attended 60-min sessions twice weekly for 10 weeks. Assessment occurred at pretreatment, posttreatment, and 6-week maintenance. Outcomes included established discourse measures for conversation and monologue, tests of language and functional communication, and patient-/family-reported outcome measures (P/FROMs). Discourse samples were collected three times per assessment. Interrater reliability and fidelity for assessment and treatment procedures are reported. Participants presented with Broca's aphasia (one moderate, one severe) or conduction aphasia (one moderate, one severe). Each demonstrated improvements in discourse, test batteries, and P/FROMs. They all demonstrated reduced aphasia severity measured by the Western Aphasia Battery-Revised at posttreatment or maintenance. Change in conversation and monologue was robust for three participants, but was mixed for one person (P1: moderate Broca's aphasia). P/FROMs indicated improvement at posttreatment and maintenance for all participants. Most treatment gains were maintained at 6-week follow-up. This study provides promising results for ECoLoGiC-Tx to improve language function of people with chronic moderate to severe aphasia. Generalization occurred to tests, functional communication, spontaneous conversation, and structured monologue tasks.


Application of machine learning methodology for PET-based definition of lung cancer.
We applied a learning methodology framework to assist in the threshold-based segmentation of non-small-cell lung cancer (NSCLC) tumours in positron-emission tomography-computed tomography (PET-CT) imaging for use in radiotherapy planning. Gated and standard free-breathing studies of two patients were independently analysed (four studies in total). Each study had a pet-ct and a treatment-planning ct image. The reference gross tumour volume (GTV) was identified by two experienced radiation oncologists who also determined reference standardized uptake value (SUV) thresholds that most closely approximated the GTV contour on each slice. A set of uptake distribution-related attributes was calculated for each PET slice. A machine learning algorithm was trained on a subset of the PET slices to cope with slice-to-slice variation in the optimal suv threshold: that is, to predict the most appropriate suv threshold from the calculated attributes for each slice. The algorithm's performance was evaluated using the remainder of the pet slices. A high degree of geometric similarity was achieved between the areas outlined by the predicted and the reference SUV thresholds (Jaccard index exceeding 0.82). No significant difference was found between the gated and the free-breathing results in the same patient. In this preliminary work, we demonstrated the potential applicability of a machine learning methodology as an auxiliary tool for radiation treatment planning in NSCLC.


[Validity of airway predictors in outpatient medicine].
Isolation of the airway sometimes determines the survival or death of the patient. To anticipate the presence of a difficult airway (DA) there are a number of indicators that are validated for hospitals: Mallampati, sternum and thyromental distance, interdental distance and Cormack grade. The aim of this study is to evaluate the use of these indicators in the ambulatory setting and to know the incidence of DA. This data was collected from 324 intubations. Most patients were males (65.2%). The average age of the population was 63 years and no significant difference in age between DA and DA was found. A DA presence of 20.7% was objectified and an alternative device utilization of 21.4%. The thyromental distance was abnormal in 59% of patients and sternomentonal distance in 56.4% but neither showed an association with the presence of DA (p = 0.681 and p = 0.415 respectively). Interdental distance was less than 3 cm if presence is associated with DA (p = 0.005). The sensitivity and specificity of all measures are low. According to our series the sternum and thyromental distance are not useful in the ambulatory setting, but interdental distance is useful for predicting a DA.


Attention deficit and impulsivity: selecting, shifting, and stopping.
The present selective review addresses attention, inhibition, and their underlying brain mechanisms, especially in relation to attention deficit/hyperactivity disorders (AD/HD), and the effects of methylphenidate. In particular, event-related potential (ERP) studies suggest a deficit in the early-filtering aspect of selective attention in children with AD/HD. Results from stop tasks are consistent with impairments in stopping performance in AD/HD, but in children (as opposed to adults) these effects cannot be easily dissociated from more general impairments in attention to the task, and therefore an interpretation in terms of inhibitory control is not straightforward. On the other hand, the beneficial effects of methylphenidate are more specific to stopping, and there are no clearcut effects of methylphenidate on measures of selective attention. Even when group differences pertain specifically to stopping performance (as with adults with AD/HD), ERP evidence suggests at least a partial contribution of differences in switching attention to the stop signal, as revealed in measures of sensory cortex activation. ERP evidence from cued go/nogo tasks underlines the importance of taking into account the contribution of higher order control processes involved in anticipation of and preparation for task stimuli. It suggests that in certain conditions, expectancy, rather than response bias, contributes to increased behavioral response tendencies, and that a presumed index of response inhibition, the nogo N2, may rather reflect conflict monitoring. In sum, direct reflections of brain activity suggest that mechanisms of expectation and attention, rather than of response bias or inhibitory control, govern behavioral manifestations of impulsivity.