Lanthanum(III) and praseodymium(III) complexes with isatin thiosemicarbazones.
Ten new lanthanum(III) and praseodymium(III) complexes of the general formula Na[La(L)2H2O] (Ln=La(III) or Pr(III); LH2=thiosemicarbazones) derived from the condensation of isatin with 4-phenyl thiosemicarbazide, 4-(4-chlorophenyl) thiosemicarbazide, 4-(2-nitrophenyl) thiosemicarbazide, 4-(2-bromophenyl) thiosemicarbazide and 4-(2-methylphenyl) thiosemicarbazide, have been synthesized in methanol in presence of sodium hydroxide. The XRD spectra of the complexes were monitored to verify complex formation. The complexes have also been characterized by elemental analysis, molar conductance, electronic absorption and fluorescence, infrared, far infrared, 1H and 13C NMR spectral studies. Thermal studies of these complexes have been carried out in the temperature range 25-800 degrees C using TG, DTG and DTA techniques. All these complexes decompose gradually with the formation of Ln2O3 as the end product. The Judd-ofelt intensity parameter, oscillator strength, transition probability, stimulated emission cross section for different transitions of Pr3+ for 4-phenyl thiosemicarbazones have been calculated.


[Inflammatory Biomarkers and Postpartum Depression: A Systematic Review of Literature].
Postpartum Depression (PPD) affects over 15% new mothers. Its etiology is multifactorial and still partly unknown. Some hypotheses suggest a link with inflammation. This review aims to explore the existence of inflammatory biomarkers associated with PPD. The possibility of potential adjunct treatments, linked with these biomarkers, will be discussed. The systematic review of literature was performed using in PubMed, PsycInfo and Embase, and 25 articles were included. Various biomarkers were identified. The most often studied are C-reactive protein (CRP), interleukins 6 and 10, tumor necrosis factor-alpha and interferon-gamma. Although few results appear as significant during the various testing times, the dosage of some inflammation biomarkers, including CRP, at the very end of pregnancy or immediately after delivery could predict PPD. Interactions between inflammation and the corticotropic axis could explain PPD onset. Epigenetic mechanisms could lead to pro-inflammatory state. Several therapeutics provide interest due to their anti-inflammatory property. Further studies are needed to assess these biomarkers value as predictive factors of PPD and to consider adjunct treatments to antidepressants. If this value is confirmed, the inflammatory marker dosage, in particular CRP, could help to provide early screening of women at risk of PPD, parallel of the clinical evaluation. A zinc supplementation could then be offered.


Using vehicular trajectory data to explore risky factors and unobserved heterogeneity during lane-changing.
This study aims to investigate contributing factors to potential collision risks during lane-changing processes from the perspective of vehicle groups and explore the unobserved heterogeneity of individual lane-changing maneuvers. Vehicular trajectory data, extracted from the Federal Highway Administration's Next Generation Simulation dataset, are utilized and 579 lane-changing vehicle groups are examined. Stopping distance indexes are developed to evaluate the potential collision risks of lane-changing vehicle groups. Three mixed binary logit models and three mixed logit models with heterogeneity in means and variances are established based on different perception reaction time. Model estimation results show that several variables significantly affect the risk status of lane-changing vehicle groups, including the mean values of clearance distance and speed differences between the leading vehicle in the current lane and the subject vehicle, standard deviations of clearance distance, and speed differences between these two vehicles, as well as standard deviations of the speed difference between the subject vehicle and the following vehicle in the target lane. Interestingly, the influences of the last three variables differ considerably across the observations and the mean of the random parameter for standard deviations of clearance distance between CLV and SV is associated with the mean speed difference between CLV and SV. Since one of the explanations is individual heterogeneity, personalized designs for advanced driver assistance system would be an effective measure to reduce the risk.


Transfer of specificity for human immunodeficiency virus type 1 into primary human T lymphocytes by introduction of T-cell receptor genes.
The introduction of genes encoding T-cell receptor (TCR) chains specific for human immunodeficiency virus into T cells of infected patients represents a means to quantitatively and qualitatively improve immunity to the virus. Our results demonstrate that the high level of TCR expression required for physiologic functioning can be reproducibly achieved with retroviral vectors encoding full-length unmodified TCR chains under the control of a strong internal constitutive phosphoglycerate kinase promoter.


Old women with a recent fall history show improved muscle strength and function sustained for six months after finishing training.
Restricted physical activity as a consequence of chronic disease or injury is a predictor of functional decline. The aim of this study was to test the hypothesis that a 6- month multidimensional training program would have sustained beneficial effects upon the physiological, functional and psychological condition of old women with a recent history of falls. Participants were 65 home-dwelling women (70-90 years) identified from hospital records as having had an accidental fall. After assessment of muscle strength, balance performance, walking speed, balance confidence, and physical activity level, the participants were randomly assigned to a control group (n=33) or a training group (n=32), who performed a multidimensional training program including moderate resistance exercise and balance exercise twice weekly for 6 months. Measurements were repeated after 6 and 12 months. Six months of multidimensional training resulted in significant improvements and between-group differences in isometric knee extension strength (p<0.05), trunk extension/ flexion strength (p<0.001), habitual/maximal walking speed (p<0.001) and balance performance (p<0.001). At follow-up, 6 months after intervention, these improvements were preserved in the training group and there was also a significant between- group difference with regard to balance confidence. No between-group differences were found concerning number of falls or physical activity level during the one-year study period. A multi-dimensional training program produced significant improvements in physiological and functional risk factors for falls and disability in women aged 70-90 years with a recent history of falls.


Mammary microbial dysbiosis leads to the zoonosis of bovine mastitis: a One-Health perspective.
Bovine mastitis is a prototypic emerging and reemerging bacterial disease that results in cut-by-cut torture to animals, public health and the global economy. Pathogenic microbes causing mastitis have overcome a series of hierarchical barriers resulting in the zoonotic transmission from bovines to humans either by proximity or remotely through milk and meat. The disease control is challenging and has been attributed to faulty surveillance systems to monitor their emergence at the human-animal interface. The complex interaction between the pathogens, the hidden pathobionts and commensals of the bovine mammary gland that create a menace during mastitis remains unexplored. Here, we review the zoonotic potential of these pathogens with a primary focus on understanding the interplay between the host immunity, mammary ecology and the shift from symbiosis to dysbiosis. We also address the pros and cons of the current management strategies and the extent of the success in implementing the One-Health approach to keep these pathogens at bay.


Amino acid transport in normal and Rous sarcoma virus-transformed chicken embryo fibroblasts.
A study was made of the transport of a variety of amino acids by uninfected and Rous sarcoma virus-infected chicken embryo fibroblasts. Following a period of amino acid starvation, transformed, but not normal cells, showed increased levels of transport for alpha-aminoisobutyric acid, proline and alanine, three amino acids which are transported primarily by the A transport system. There was no starvation-induced increase in the transport of leucine, phenylalanine, lysine, or cycloleucine. In the absence of starvation, normal and transformed cells exhibited comparable rates of amino acid transport. Cycloheximide was able to block the increase in uptake. The enhanced uptake was characterized by an increase in Vmax for transport and little change in Km. The data demonstrate that an alteration in the regulation of the A amino acid transport system is an early event in malignant transformation by Rous sarcoma virus. However, since this alteration in made manifest only following a period of starvation, our findings suggest that increased amino acid uptake does not play a role in generating the other manifestations of the transformed state seen in cell culture.


Micro-Raman spectroscopy shows how the coating process affects the characteristics of hydroxylapatite.
The diversity in the structural and chemical state of apatites allows implant manufacturers to fine-tune implant properties. This requires suitable manufacturing processes and characterization tools to adjust the amorphous phase and hydroxyl content from the source hydroxylapatite. Hydroxylapatite was processed by high-velocity oxy-fuel spraying, plasma spraying and flame spraying, and primarily analyzed by Raman spectroscopy. Investigation of rounded splats, the building blocks of thermal spray coatings, allowed correlation between the visual identity of the splat surface and the Raman spectra. Splats were heat-treated to crystallize any remaining amorphous phase. The ν1 PO4 stretching peak at 950-970 cm(-1) displayed the crystalline order, but the hydroxyl peak at 3572 cm(-1) followed the degree of dehydroxylation. Hydroxyl loss was greatest for flame-sprayed particles, which create the longest residence time for the melted particle. Higher-frequency hydroxyl peaks in flame- and plasma-sprayed splats indicated a lower structural order for the recrystallized hydroxylapatite within the splats. Crystallization at 700 °C has shown potential for revealing hydroxyl ions previously trapped in amorphous calcium phosphate. This work compares Fourier transform infrared and Raman spectroscopy to measure the hydroxyl content in rapidly solidified apatites and shows that Raman spectroscopy is more suitable.


Mitochondria-related miR-151a-5p reduces cellular ATP production by targeting CYTB in asthenozoospermia.
Mitochondria, acting as the energy metabolism factory, participate in many key biological processes, including the maintenance of sperm viability. Mitochondria-related microRNA (miRNA), encoded by nuclear genome or mitochondrial genome, may play an important regulatory role in the control of mitochondrial function. To investigate the potential role of mitochondria-related miRNAs in asthenozoospermia, we adopted a strategy consisting of initial screening by TaqMan Low Density Array (TLDA) and further validation with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Validation of the profiling results was conducted in two independent phases. Eventually, two seminal plasma miRNAs (sp-miRs) (miR-101-3p, let-7b-5p) were found to be significantly decreased, while sp-miR-151a-5p was significantly increased in severe asthenozoospermia cases compared with healthy controls. To further study their potential roles in asthenozoospermia, we then evaluated mitochondrial function of GC-2 cells transfected with these potentially functional miRNAs. Our results demonstrated that transfection with miR-151a-5p mimics decreased the mitochondrial respiratory activity. Besides, Adenosine Triphosphate (ATP) level was decreased when transfected with miR-151a-5p mimics. In addition, Cytochrome b (Cytb) mRNA and protein levels were also decreased when miR-151a-5p was overexpressed. These results indicate that miR-151a-5p may participate in the regulation of cellular respiration and ATP production through targeting Cytb.


Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis.
Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase-polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.


Impact of human factor design on the use of order sets in the treatment of congestive heart failure.
Although standardized physician order sets are often part of quality improvement projects, the specific design elements contributing to increased adoption and compliance with use often are not considered. To evaluate the impact of human factor design elements on congestive heart failure (CHF) order set utilization, and compliance with recommended CHF clinical practice guidelines (CPG). This was a descriptive retrospective medical record review of adult patients who were admitted from our emergency department with the primary diagnosis of CHF. We collected data on acuity and CPG parameters before and after the introduction of a new CHF order set. The new orders were succinct and visually well organized, with narrative information to encourage use of CPG. Eighty-seven patients were studied before, and 84 after, the introduction of new orders. There were no differences in the use of the order sets based on patient acuity before or after the intervention. Order set use significantly increased by the first postintervention interval (POST) and reached 72% (95% confidence interval [CI] = 52% to 86%) during the third POST, compared with a baseline utilization of 9% (95% CI = 5% to 17%; p < 0.001). Compliance with CPG for angiotensin-converting enzyme reached significance in the second POST and was maintained in the third at 83% (95% CI = 61% to 94%), compared with a baseline value of 25% (95% CI = 7% to 59%; p = 0.008). Intravenous nitroglycerin also increased significantly from the first POST and reached 78% (95% CI = 55% to 91%) in the third POST, compared with baseline of 12% (95% CI = 2% to 47%; p < 0.003). Furosemide dosing, systolic blood pressure reduction, and urine output did not significantly change. Introduction of an order set for CHF with attention to human factor design elements significantly improved utilization of the orders and compliance with CPG.


Hormonal predictors of sexual motivation in natural menstrual cycles.
Little is known regarding which hormonal signals may best predict within- and between-women variance in sexual motivation among naturally cycling women. To address this, we collected daily saliva samples across 1-2 menstrual cycles from a sample of young women; assayed samples for estradiol, progesterone, and testosterone; and also collected daily diary reports of women's sexual behavior and subjective sexual desire. With respect to within-cycle, day-to-day fluctuations in subjective desire, we found evidence for positive effects of estradiol and negative effects of progesterone. Desire exhibited a mid-cycle peak, similar to previous findings; measured progesterone concentrations statistically mediated the fall in desire from mid-cycle to the luteal phase, but no combination of hormone measures substantially mediated the follicular phase rise in desire, which suggests that other signals may be implicated in this effect. Hormonal predictors of within-cycle fluctuations in sexual behavior generally reached only trend levels of statistical significance, though the patterns again suggested positive effects of estradiol and negative effects of progesterone. Between-women and within-women, between-cycle effects of hormone concentrations were generally absent, although statistical power was more limited at these higher levels of analysis. There were no significant effects of testosterone concentrations when controlling for the effects of estradiol and progesterone, which raises questions regarding the importance of this hormone for the regulation of sexual motivation in natural cycles. Our study is among the first to identify hormonal predictors of within-cycle fluctuations in sexual motivation, and thus adds novel evidence regarding the endocrine correlates of human sexuality.


Effects of methylphenidate in ADHD adults on target evaluation processing reflected by event-related potentials.
Attention deficit/hyperactivity disorder (ADHD) is a widely examined disease in childhood. There is evidence that the disease responds well to medication with methylphenidate (MPH). The effect of MPH in adults with ADHD is a question that is often raised, because many adults request such therapy today. As yet, there is a lack of studies on event-related potentials (ERPs) and MPH in ADHD adults. In the present study we examined 10 adults diagnosed with ADHD, with and without MPH medication (30 mg daily), by means of ERP in a visual Go/NoGo experiment to gain information about target evaluation processing in these patients and about the effects on these attentional processes during medication with MPH. Visually, there seem to be differences in the frontal electrodes for the N2 and in the parietal electrodes for the P300. But these differences do not achieve statistical significance. There are also no statistically relevant differences for the N1 or the slow wave. MPH does not seem to have an effect on target evaluation processing, when comparing the ERPs of non-medicated and medicated ADHD adults. Especially the P3 does not appear to be modulated by medication with MPH in these ADHD adults, in contrast to findings in ADHD children.


Long-Term Outcomes After Pediatric Tracheostomy-Candidates for and Timing of Decannulation.
Although pediatric tracheostomy has been a widely performed, life-saving procedure, its long-term outcomes have remained unclear. This study aimed to review outcomes after tracheostomy at a Japanese tertiary hospital and clarify candidates for and timing of decannulation. Hospital records of critically ill children who underwent tracheostomy from 2001 to 2014 were retrospectively reviewed, subsequently analyzing outcomes according to demographics, complications, and decannulation. After excluding those who were lost to follow-up or had irreversible neuromuscular impairment, the remaining patients were divided into the decannulation (D group) and nondecannulation (ND group) groups and compared. In total, 184 patients who underwent tracheostomy were analyzed (median age at operation: 0.5 y). The major indication for tracheostomy was irreversible neuromuscular impairment (46%). Surgery-related and overall mortality rates were 1% and 25%, respectively, while the successful decannulation rate was 21%. No significant difference in surgical indications or comorbidities was observed between the D (n = 39) and ND (n = 50) groups, except for infection (7 in D group versus 0 in ND group; P = 0.002) and chromosome-gene disorder (15% versus 34%; P = 0.04). The ND group had a significantly higher mortality rate than the D group (46% versus 3%; P < 0.0001). The median time to decannulation was 3.6 years, while that for infection was 0.7 y. Patients who underwent tracheostomy at our institution due to temporary infections achieved more successful and earlier decannulation compared to other indications. Chromosome-gene disorder as a comorbidity can negatively affect decannulation.


Mucoepidermoid carcinoma of the trachea in a child.
Primary tracheal neoplasms in children, especially malignant lesions, are extremely rare. We report a unique case of low-grade mucoepidermoid carcinoma of the trachea in a 4-year old child, presenting as new-onset asthma. Using the ventilating resectoscope, endoscopic excision was accomplished without complications. The case is presented with documentation including airway films, endoscopic photographs, and histopathology. The diagnosis of tracheal masses depends upon maintaining a high index of suspicion, complemented by imaging and timely diagnostic endoscopy. A review of the literature is included.


Acoustic input to the lateral pontine nuclei.
Axon and terminal degeneration were studied in the cat dorsolateral pontine nucleus (DLPN) after lesion of the inferior colliculus. In separate experiments the acoustic responses of 111 units of the lateral pontine nuclei were studied in cats anesthetized with chloralose-urethane. Lesions of all three nuclei of the inferior colliculus (central, pericentral and external) lead to a very similar pattern of terminal degeneration in a discrete region of ipsilateral DLPN. This is suggestive of a highly convergent projection in which topography may be blurred. Most units responded to binaural stimulation, and the most common binaural response consisted of excitatory inputs from each ear which were facilitated at some binaural intensity levels and occluded at others. Discharge rates changed as a result of alterations in the number of spikes evoked at the onset of the stimulus, and sustained discharges were rarely encountered. Units were broadly and irregularly tuned; binaural inhibition was very uncommon. Unit response characteristics suggested that, while the projection from the inferior colliculus was highly convergent, only a subclass of inferior colliculus neurons may be involved. However, the acoustic properties of lateral pontine units were strikingly similar to those of the cerebellar vermis, a region to which DLPN is known to project.


[Metronomic Chemotherapy--A New Path to Treat Advanced Non-small Cell Lung Cancer].
Metronomic chemotherapy is an emerging strategy to fight cancer. Unlike traditional chemotherapy, metronomic chemotherapy is defined by the frequent, repetitive administration of chemotherapeutic drugs at relatively low doses, and without prolonged drug-free break. Initially thought to play a role inhibiting tumor angiogenesis by targeting activated endothelial cells in tumors, metronomic chemotherapy is a multi-targeted therapy,including activation of immunity, effect on tumour initiating cells, induction of tumor dormancy. It is from eradicateing tumor cells to improve effect, reduce the toxicity and improve quality of life for treatment of advanced non-small cell lung cancer (NSCLC). Metronomic chemotherapy which can avoid the toxicity of traditional chemotherapy and rebounding is explored in clinical studies of advanced NSCLC, as a promising treatment strategy.


Understanding water activity change in oil with temperature.
Our recent studies and several publications suggest that the low water activity (aw) of oil in thermal processing might be a major contributing factor towards the increased thermal resistance of bacteria in oils. In this study, we developed a reliable method to measure the water activity of oil by measuring the equilibrium relative humidity in a small headspace. Using this method, water activity of peanut oil was found to decrease exponentially with increasing temperature. A model derived from excess Gibbs free energy was fitted to the observations with an R2 = 99.6% and RMSE = 0.01 (aw). Our results suggest that the sharply reduced water activity of oil resulting from a rise in temperature could cause desiccation of bacteria. This is a possible explanation for the protective effect of oil in thermal processing.


Renin-angiotensin mediation of adrenal catecholamine secretion induced by haemorrhage.
The mechanism involved in catecholamine (CA) release from cat adrenal gland, in response to haemorrhage was studied. In intact cats, in cats with bilateral cervical vagotomy or following bilateral ureteral ligation, haemorrhage induced an increased catecholamine release from the adrenal (with increased percentage of noradrenaline). Acute bilateral nephrectomy, chronic sodium loading with repeated administration of desoxycorticosterone acetate (DOCA), or acute denervation of the adrenal gland, completely abolished the increased CA release from the adrenal gland following haemorrhage. Haemorrhage induced an increase of plasma renin concentration in intact cats and after ureteral ligation but there was no increase in plasma renin after haemorrhage in cats with bilateral nephrectomy or following pretreatment with DOCA and salt load. Following haemorrhage in intact cats, blood pressure showed an immediate fall followed by rapid recovery. The recovery of blood pressure after haemorrhage was abolished in cats with bilateral nephrectomy. It is concluded that the adreno-medullary response to haemorrhage in the cat, depends primarily on the intact renal renin angiotensin system. Angiotensin, generated peripherally, probably affects the CNS and activates the sympathetic nerves.


Radiologic manifestations of intraventricular and subarachnoid racemose neurocysticercosis.
Neurocysticercosis is a major cause of acquired epilepsy around the globe. The racemose form of this disease, which has a predilection for the subarachnoid space, is rare in the US. The patient described here had a combination of intraventricular and subarachnoid cysticercal cysts. In the following report, the CT and MR characteristics of this rare form of neurocysticercosis both before and after treatment are described, and the current issues surrounding management are briefly discussed.


Fixation of beneficial mutations in the presence of epistatic interactions.
We investigate the effect of deleterious mutations on the process of fixation of new advantageous mutants in an asexual population. In particular we wish to study the dependence of the process on the strength of the deleterious mutations. We suppose the existence of epistatic interaction between the genes. We study the model by means of branching process theory and also by numerical simulations. Our results show the occurrence of two distinct regimes of behavior for the probability of fixation of these variants. The occurrence of either regime depends on the ratio between the selective advantage of the beneficial mutation sb and on the selective parameter for deleterious mutations sd. In the former, which takes place for sb/sd< or =1, the probability of fixation increases with the epistasis parameter , whereas for sb/sd>>1 the probability of fixation is a complex function of and the mutation rate U. Surprisingly, we find that for the multiplicative landscape (alpha=1) the probability of fixation Pfix is given by Pfix= pib)e-U/sd where pi(sb) is the probability of fixation for the two-allele model in the absence of mutations as calculated by Haldane (1927, Proc. Camb. Phil. Soc., 26, 220-230) and Kimura (1962, Genetics, 47, 713-719).


Pharmacogenomics.
Pharmacogenetics is the intersection of the fields of pharmacology and genetics. Simply stated, pharmacogenetics is the study of how genetic variations affect the ways in which people respond to drugs. These variations can manifest themselves as differences in the drug targets or as differences in the enzymes that metabolize drugs. A difference in the target will usually lead to differences in how well the drug works, whereas differences in metabolizing enzymes can result in differences in either efficacy or toxicity. It's also possible that genes not directly involved in a particular pathway could end up being predictive of clinical outcomes. Although pharmacogenomics has the potential to radically change the way health care is provided, it is only in its infancy. In the future, pharmacogenomics could find uses along the entire drug discovery and development timeline, all the way from target discovery and validation to late-stage clinical trials. Beyond that, pharmacogenomics tests could find their way into the doctor's office as a means to get the right medicine to the right patient at the right time. While genetics and genomics are often used synonymously, pharmacogenetics is more focused in scope than and is viewed as a subset of pharmacogenomics, which encompasses factors beyond those that are inherited.


A new strategy of gene trapping in ES cells using 3'RACE.
"Gene trapping" in embryonic stem (ES) cells is a novel approach to identify a series of genes in mammals concomitant with the production of the corresponding mutant mice. However, this approach is currently unable to identify genes that are not expressed in ES cells. Here we describe a strategy to identify gene trapping clones which is not based on expression of a reporter gene. It uses the neor gene which lacks a polyadenylation signal and has a splice donor signal. Expression of the neor gene as fusion transcripts with the 3' end containing the polyadenylation signal of tagged genes allows the identification of these clones by 3' rapid amplification of the cDNA end in undifferentiated ES cells, even if the genes are not expressed in ES cells. Amplification was observed in about 25% of G418-resistant clones. Sequence analyses suggested the amplifications represent gene trapping events. The feasibility of this approach was further assessed by analysing one clone, PAT-12, in detail.


Economic consequences of rheumatic heart disease: A scoping review.
Rheumatic heart disease (RHD) remains endemic in less-resourced regions and countries and results in high medical and non-medical costs to households, health systems, and society. This scoping review maps out the available evidence on the economic impact of RHD and its antecedents and suggests future research priorities. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We identified articles through systematic electronic database search supplemented by expert knowledge of unpublished literature. Studies were included if they collected empirical RHD-related costing data as a primary or secondary objective and if the data were collected from 2000 onward. Main quantitative findings by intervention, costing perspective, and location were charted, and a standardized quality assessment tool was used to appraise included studies. The index search identified 2519 electronic records and two grey-literature graduate theses. Six full texts were included in the review. Primary prevention costs were modest, while secondary and especially tertiary prevention were more costly. Most estimates were of health sector costs and for tertiary interventions. Only two studies described RHD-related costs in non-high-income countries. Most studies were of adequate methodological quality. Research into the costs of RHD has mostly been done in wealthy countries. Costs from the household perspective, which are particularly important in countries with limited public healthcare finance, are lacking. To inform advocacy and guide implementation of the 2018 World Health Assembly resolution on RHD, high-quality, local cost estimates will be needed from a range of representative, RHD-endemic countries.


The osteogenesis effect of rhBMP2-loaded calcium phosphate cements in repairing dental extraction sockets.
After extracting impacted mandibular third molars (IMM3), the resulting bone loss at the distal surface of the distal root of mandibular second molars (MM2) is responsible for the poor stability of MM2. This study aimed to identify the clinical osteogenesis effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate cements (CPCs) and rhBMP-2 delivery systems (rhBMP-2/CPCs, named CPCII) on bone loss repair at the distal surface of the MM2 distal root after IMM3 extraction. Written informed consent was obtained from every participant whose IMM3 needed extraction. The impact of IMM3 on both sides was basically identical. From April 2014 to March 2016, extraction of IMM3 was performed in 9 patients (5 males/4 females, 26-42 years old). One side was randomly selected as the experimental group, and CPCII systems were implanted into the distal surface of the distal root in dental extraction sockets. The wounds on the other side were sutured and allowed to heal naturally (be treated as the control group). New bone formation in the alveolar fossa was detected 3 and 12 months after the operation by cone-beam computed tomography (CBCT) to measure the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CAR). The CAR-CEJ distance on the test side was less than that on the control side (P<0.5). The quantity of new bone formation in the experimental group was greater than that in the control group. CPCII systems have osteogenic potential in the healing process of tooth extraction sockets.


Comparative survival following permanent ventricular and dual-chamber pacing for patients with chronic symptomatic sinus node dysfunction with and without congestive heart failure.
To determine whether survival following permanent ventricular demand pacing differs from survival following permanent dual-chamber pacing in patients with symptomatic sinus node dysfunction (unexplained sinus bradycardia, subsidiary rhythms, sinus arrest, sinoatrial block, or the bradycardia/tachycardia syndrome), we followed 79 patients who received a VVI pacemaker (group 1) and 49 patients who received a DVI or DDD pacemaker (group 2) for 1 to 5 years. There was no significant difference in sex distribution, mean age, or the incidence of coronary heart disease, hypertension, valvular heart disease, diabetes mellitus, stroke, or renal failure between groups 1 and 2. Overall, the predicted cumulative survival rates at 1, 3, and 5 years were 89%, 82%, and 74%, respectively, for group 1 and 94%, 86%, and 78%, respectively, for group 2. In patients with preexistent congestive heart failure (CHF), predicted cumulative survival rates at 1, 3, and 5 years were 78%, 69%, and 57%, respectively, for group 1 (n = 23) and 90%, 83%, and 75%, respectively, for group 2 (n = 16). Five-year predicted cumulative survival was significantly lower in group 1 patients with CHF than in group 2 patients with CHF (p less than 0.03). There was no significant difference in 5-year cumulative survival rates between groups 1 and 2 in patients without CHF. The results suggest that permanent dual-chamber pacing enhances survival to a greater extent than permanent ventricular demand pacing in patients with chronic symptomatic sinus node dysfunction and CHF.


Evidence that Na+/H+ exchanger 1 is an ATP-binding protein.
Na(+)/H(+) exchanger (NHE) 1 is a member of the solute carrier superfamily, which regulates intracellular ionic homeostasis. NHE1 is known to require cellular ATP for its activity, despite there being no requirement for energy input from ATP hydrolysis. In this study, we investigated whether NHE1 is an ATP-binding protein. We designed a baculovirus vector carrying both epitope-tagged NHE1 and its cytosolic subunit CHP1, and expressed the functional NHE1-CHP1 complex on the surface of Sf9 insect cells. Using the purified complex protein consisting of NHE1 and CHP1 from Sf9 cells, we examined a photoaffinity labeling reaction with 8-azido-ATP-biotin. UV irradiation promoted the incorporation of 8-azido-ATP into NHE1, but not into CHP1, with an apparent Kd of 29.1 µM in the presence of Mg(2+). The nonlabeled nucleotides ATP, GTP, TTP and CTP all inhibited this crosslinking. However, ATP had the strongest inhibitory effect, with an apparent inhibition constant (IC50) for ATP of 2.2 mM, close to the ATP concentration giving the half-maximal activation of NHE1 activity. Importantly, crosslinking was more strongly inhibited by ATP than by ADP, suggesting that ATP is dissociated from NHE1 upon ATP hydrolysis. Limited proteolysis with thrombin and deletion mutant analysis revealed that the 8-azido-ATP-binding site is within the C-terminal cytoplasmic domain of NHE1. Equilibrium dialysis with NHE1-derived peptides provided evidence that ATP directly binds to the proximal cytoplasmic region (Gly542-Pro598), which is critical for ATP-dependent regulation of NHE1. These findings suggest that NHE1 is an ATP-binding transporter. Thus, ATP may serve as a direct activator of NHE1.


Signal correlations in ecological niches can shape the organization and evolution of bacterial gene regulatory networks.
Transcriptional regulation plays a significant role in the biological response of bacteria to changing environmental conditions. Therefore, mapping transcriptional regulatory networks is an important step not only in understanding how bacteria sense and interpret their environment but also to identify the functions involved in biological responses to specific conditions. Recent experimental and computational developments have facilitated the characterization of regulatory networks on a genome-wide scale in model organisms. In addition, the multiplication of complete genome sequences has encouraged comparative analyses to detect conserved regulatory elements and infer regulatory networks in other less well-studied organisms. However, transcription regulation appears to evolve rapidly, thus, creating challenges for the transfer of knowledge to nonmodel organisms. Nevertheless, the mechanisms and constraints driving the evolution of regulatory networks have been the subjects of numerous analyses, and several models have been proposed. Overall, the contributions of mutations, recombination, and horizontal gene transfer are complex. Finally, the rapid evolution of regulatory networks plays a significant role in the remarkable capacity of bacteria to adapt to new or changing environments. Conversely, the characteristics of environmental niches determine the selective pressures and can shape the structure of regulatory network accordingly.


Giant Cell Tumor After Distal Radius Open Reduction and Internal Fixation in a Pregnant Woman: A Case Report.
A 32-year-old pregnant woman presented with new wrist pain after a fall. She had undergone surgical repair to the same wrist 6 years previously for a distal radius fracture. At that time, there was no evidence of a bone lesion. Current radiographs revealed a radiolucent lesion in the metaepiphyseal region. Intraoperative frozen section confirmed a giant cell tumor (GCT). Definitive management consisted of intralesional curettage, burring, and cementation of the distal radius with reapplication of distal radius plate. Currently, there is no known link between GCT and fracture or pregnancy.


Burn Scar Management and Reconstructive Surgery.
This chapter highlights the importance of a comprehensive burn scar treatment plan in approaching a burn survivor. General concepts of burn scar physiology and a practical system to describe burn scars based on cause, biology, and symptoms are presented. Common scar management modalities including nonsurgical, surgical, and adjuvant therapies are further discussed.


The Teaching and Learning Cultural Competence in a Multicultural Environment (CCMEn) Model.
Within the European higher education context, students and lecturers are encouraged to engage in teaching and learning activities abroad. This frequently involves using a second language and being exposed to students and lecturers from culturally different backgrounds. To design a model for teaching and learning cultural competence in a multicultural environment (CCMEn). Theory development from empirical experience, research, and scholarly works. This model was developed based on our experience of teaching and learning cultural competence in a multicultural environment in a nursing education context; it rests on three pillars, namely, Coyle's Content and Language Integrated Learning educational approach, the concept of social and emotional learning, as defined by the Collaborative for Academic, Social and Emotional Learning, and the existing literature surrounding teaching and learning cultural competence in higher education. The CCMEn model is intended to guide the process of teaching and learning cultural competence in a multicultural environment through the use of a second language and has been adapted from existing educational approaches and theory. Teaching and learning in multilingual and multicultural contexts in Europe is becoming more common. Students who learn alongside students and teachers from different cultural backgrounds need to be supported from an academic, linguistic and socioemotional perspective. We believe that the CCMEn model can serve as a guide to enhancing student learning in this context.


Polymyositis with myoglobinuria in pregnancy: a report and review of the literature.
A pregnant patient developed fulminant polymyositis with myoglobinuria after terbutaline and magnesium sulfate tocolysis. Her response to prednisone was dramatic. Rapid relapse occurred after inadvertent postcesarean dose reduction. Our patient again responded to increased prednisone. She and her twin babies are well.


The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine.
The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.


Glycoproteins synthesized by cultured cardiac valve endothelial cells: unique absence of fibronectin production.
We have previously reported that cultured porcine cardiac valve endothelial cells released less fibronectin into the culture supernatant when compared to other porcine endothelial cells. In this report we compared the spectrum of glycoproteins synthesized by cardiac valve endothelial cells to glycoproteins synthesized by comparison endothelial cells derived from the ascending thoracic aorta. The cells were endogenously radiolabeled and extracted with detergent. Glycoproteins in the cell extracts were then isolated on wheat germ lectin-agarose and compared using autoradiography following polyacrylamide gel electrophoresis. Fibronectin was identified by immunoblotting with specific antibody. The results showed that the outstanding difference between the endothelial cell types was the virtual absence of fibronectin in the cardiac valve endothelial cell extract.


A new strategy for obtaining highly concentrated phosphorus recovery solution in biofilm phosphorus recovery process.
Recovery of phosphorus (P) from wastewater is of great significance for alleviating the shortage of P resources. At present, the P recovery process is faced with the problem of excessive organic carbon consumption when obtaining a P-concentrated recovery solution. This study proposed a new strategy to obtain a more highly concentrated P recovery solution with minimal carbon consumption by strengthening the P storage capacity of the biofilm. A biofilm sequencing batch reactor (BSBR) process was modified to treat synthetic wastewater. The effect of the dissolved oxygen (DO) concentration on the P storage capacity of the biofilm was investigated at DO concentrations of DO 3.5 mg/L (PL) and DO 6.5 mg/L (PH). The results showed a maximum P storage of 101.2 and 149.6 mg-P/g-mixed liquid suspended solids under the two conditions. Strengthening the P storage capacity of the biofilm resulted in a net increase in the P recovery rate, which was as high as 66.96% in a harvesting cycle, and total soluble P>220 mg/L in the P recovery solution was successfully achieved. Meanwhile, the carbon cost of P recovery in the BSBR was reduced to 41.57 g-chemical oxygen demand/g-P, and the carbon utilization efficiency was enhanced. To highlight the new strategy, the P recovery performance of the BSBR was given and the relationship between P content and anaerobic P release was discussed. In addition, the changes in the microbial communities under PL and PH conditions were analyzed.


Variation in the co-expression profile highlights a loss of miRNA-mRNA regulation in multiple cancer types.
Recent research provides insight into the ability of miRNA to regulate various pathways in several cancer types. Despite their involvement in the regulation of the mRNA via targeting the 3'UTR, there are relatively few studies examining the changes in these regulatory mechanisms specific to single cancer types or shared between different cancer types. We analyzed samples where both miRNA and mRNA expression had been measured and performed a thorough correlation analysis on 7494 experimentally validated human miRNA-mRNA target-gene pairs in both healthy and tumoral samples. We show how more than 90% of these miRNA-mRNA interactions show a loss of regulation in the tumoral samples compared with their healthy counterparts. As expected, we found shared miRNA-mRNA dysregulated pairs among different tumors of the same tissue. However, anatomically different cancers also share multiple dysregulated interactions, suggesting that some cancer-related mechanisms are not tumor-specific. 2865 unique miRNA-mRNA pairs were identified across 13 cancer types, ≈ 40% of these pairs showed a loss of correlation in the tumoral samples in at least 2 out of the 13 analyzed cancers. Specifically, miR-200 family, miR-155 and miR-1 were identified, based on the computational analysis described below, as the miRNAs that potentially lose the highest number of interactions across different samples (only literature-based interactions were used for this analysis). Moreover, the miR-34a/ALDH2 and miR-9/MTHFD2 pairs show a switch in their correlation between healthy and tumor kidney samples suggesting a possible change in the regulation exerted by the miRNAs. Interestingly, the expression of these mRNAs is also associated with the overall survival. The disruption of miRNA regulation on its target, therefore, suggests the possible involvement of these pairs in cell malignant functions. The analysis reported here shows how the regulation of miRNA-mRNA interactions strongly differs between healthy and tumoral cells, based on the strong correlation variation between miRNA and its target that we obtained by analyzing the expression data of healthy and tumor tissue in highly reliable miRNA-target pairs. Finally, a go term enrichment analysis shows that the critical pairs identified are involved in cellular adhesion, proliferation, and migration.


Surgery for oesophageal cancer at Galway University Hospital 1993-2008.
Surgical volume and outcome remain controversial in the management of oesophageal cancer. To assess the outcome of oesophagectomy for cancer at Galway University Hospital (GUH). Between 1994 and 2008, patients who underwent oesophagectomy were analysed. During the study period, 126 oesophagectomies were performed for cancer. The average surgeon volume was 9 cases per year. The 30-day and overall in-hospital mortality rates were 6.3 and 7.9%, respectively. Restructuring of our critical care services has led to a reduction in 30-day mortality from 8.2 to 5.1%. The use of neoadjuvant chemoradiotherapy has increased from 17 to 35% during the study period. In patients who underwent resection, the 3 and 5-year overall survival rates were 45 and 29%, respectively. Operative morbidity and mortality at GUH are comparable with worldwide outcomes. Improved resources and national restructuring of cancer services have significantly improved the quality of care and outcomes of patients.


Primary keratinocytes have an adhesion dependent S phase checkpoint that is absent in immortalized cell lines.
In order to understand the mechanism through which loss of anchorage inhibits growth, we have investigated the events that occur in murine keratinocytes upon substratum detachment utilizing both primary cells and established immortalized cell lines. Our data has revealed that while both primary and immortalized cells undergo growth arrest in suspension, the nature of this arrest is markedly different. Primary cells exhibit a growth arrest that is characterized by rapid cessation of DNA synthesis resulting in a static S phase population. In contrast, an immortalized non-tumorgenic cell line, Balb MK, exhibits growth arrest as measured by thymidine incorporation, but does not prevent cells that have entered S phase from continuing into G2/M, and accumulating as a 4N population. In contrast to both primary and MK cells, the tumorigenic SLC-1 cell line did not accumulate in a specific cell cycle interval and were able to undergo continuous growth in suspension. Examination of cyclin A protein and its associated activity revealed that cyclin A protein levels decreased in primary but not MK cells; suggesting the continued presence of cyclin A may allow continued DNA synthesis observed in MK cells. Furthermore, we demonstrate the accumulation of suspension cultured MK cells as a 4N population correlated with the loss of cyclin A/cdk2 kinase activity, which in turn occurred through the accumulation of p27kip1, whereas neither p27kip1 accumulation nor loss of cyclin A activity was observed in SLC-1 cells. Our results clearly reveal that the process of growth inhibition in suspension cultured cells may occur in several forms with distinct characteristics that are dependent on the status of cyclin/cdk complexes and CKI proteins. Tumor derived cells in suspension did not lose cyclin A dependent kinase activity and thus continued to grow and divide.


The influence of aetiology on inflammatory and neurohumoral activation in patients with severe heart failure: a prospective study comparing Chagas' heart disease and idiopathic dilated cardiomyopathy.
Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.


HIV risk environment for Ghanaian women: challenges to prevention.
Ghana is experiencing high rates of HIV transmission and women have been identified as a group with increased vulnerability to infection. Women's vulnerability may be influenced by factors such as gender, unequal power relationships and poverty. Research was undertaken in Ghana from January to May 1999 to examine the experiences of HIV sero-positive women. Thirty-one women were interviewed to explore the broad context of disease transmission and to identify factors that mediated women's ability to protect themselves from infection. The poverty experienced by many of the women during their childhood years, coupled with a societal belief that favored the education of males, restricted the participants' educational and vocational opportunities. With limited education and few vocational skills, many of the women took boyfriends to assist them with the purchase of food, clothing and shelter, as a strategy for survival. For most women, the use of condoms with sexual partners was restricted by the high value placed on fertility, the negative association of condoms with prostitution, and the women's limited ability to influence decision-making in this area. The women's narratives provide a compelling description of the context of HIV transmission in Ghana. Strategies to expand and intensify the response to HIV prevention are presented and critiqued.


Effects of 17 β-estradiol on lipopolysacharride-induced intracellular adhesion molecule-1 mRNA expression and Ca²+ homeostasis alteration in human endothelial cells.
Recent evidence showed that 17 β-estradiol (E₂) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca²+ concentration ([Ca²+](i)) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E₂ (1 μM, 24 h) on the expression of intracellular adhesion molecule-1 (ICAM-1) and [Ca²+](i) were investigated in a lipopolysaccharide (LPS) (100 ng/mL, 18 h)-stimulated human endothelial cell line, EA.hy926, using real-time PCR and spectrofluorometry, respectively. PCR analysis revealed a significant increase in ICAM-1 expression in calcium ionophore A23187 (1 nM)- or LPS-stimulated cells. Pretreatment of cells with E(2) significantly inhibited LPS-induced ICAM-1 mRNA expression. [Ca²+](i) was monitored in Fura-2AM-loaded cells in the presence and absence of extracellular Ca²+ with thapsigargin (TG, 1 μM), a sarco/endoplasmic reticulum ATPase inhibitor or ATP (100 μM). The extent of TG- or ATP-induced [Ca²+](i) increase was significantly higher in LPS-stimulated cells than in control cells. Pre-treatment of LPS-stimulated cells with E₂ limited the Ca²+ response to the same level as in control cells. Furthermore, ICI 182,780, an estrogen receptor antagonist, attenuated the inhibitory actions of E₂ on ICAM-1 mRNA expression and Ca²+ responses, suggesting that estrogen receptors mediate, at least in part, the effects of estrogen. These data suggest a potential underlying mechanism for the protective effect of E₂ against atherosclerosis.


Protein resonance assignment by BSH-CP-based 3D solid-state NMR experiments: A practical guide.
Solid-state NMR (ssNMR) spectroscopy has evolved into a powerful method to obtain structural information and to study the dynamics of proteins at atomic resolution and under physiological conditions. The method is especially well suited to investigate insoluble and noncrystalline proteins that cannot be investigated easily by X-ray crystallography or solution NMR. To allow for detailed analysis of ssNMR data, the assignment of resonances to the protein atoms is essential. For this purpose, a set of three-dimensional (3D) spectra needs to be acquired. Band-selective homo-nuclear cross-polarization (BSH-CP) is an effective method for magnetization transfer between carbonyl carbon (CO) and alpha carbon (CA) atoms, which is an important transfer step in multidimensional ssNMR experiments. This tutorial describes the detailed procedure for the chemical shift assignment of the backbone atoms of 13 C-15 N-labeled proteins by BSH-CP-based 13 C-detected ssNMR experiments. A set of six 3D experiments is used for unambiguous assignment of the protein backbone as well as certain side-chain resonances. The tutorial especially addresses scientists with little experience in the field of ssNMR and provides all the necessary information for protein assignment in an efficient, time-saving approach.


Comparative study of iron acquisition by biotype 1 and biotype 2 strains of Actinobacillus pleuropneumoniae.
Four strains of the swine pathogen, Actinobacillus pleuropneumoniae, namely, the type strain (ATCC 27088; biotype 1), the 'reference' strain of biotype 2 (Bertschinger 2008/76), and two additional biotype 1 strains, strain BC181, which is less virulent than the type strain, and strain K17, which was isolated from a lamb, were investigated with respect to iron acquisition. All strains produced iron-repressible outer membrane proteins. However, only the type and biotype 2 strains could acquire iron from porcine transferrin and no organism could utilize human, bovine or ovine transferrin, or ovine or porcine lactoferrin; haemoglobin supported good growth of all strains except strain K17. In all cases, iron acquisition from transferrin and haemoglobin required direct contact between the organisms and the proteins indicating the existence of specific receptors. An affinity isolation technique, using biotinylated porcine transferrin plus streptavidin-agarose, allowed the isolation of the following polypeptides from total membranes of organisms grown under iron-restricted conditions: 99 kDa and 64 kDa from ATCC 27088; 93 kDa from Bertschinger 2008/76; 95 kDa (trace amounts) and 60 kDa from BC181; none from K17. These results indicate that the 93-99 kDa polypeptides are involved in the acquisition of iron from porcine transferrin and that the inability of strain K17 to use transferrin as an iron source is due, probably, to the lack of, or a defect in, an analogous component.


[Isolated antenatal pyelic dilatation: postnatal follow-up and care for vesico-ureteral reflux].
To assess the risk of aneuploidia in case of isolated antenatal pyelic dilatation and to detail urological care for these children. Prenatal and postnatal follow-up was analyzed in 350 cases. The overall rate of chromosome anomalies was 1.3%. Trisomy 21 was found alone in one case (0.3%). The sex ratio was 26% girls and 74% boys. Vesico-ureteral reflux was similar in both sexes (13%). The question of proposing karyotyping in case of isolated pyelic dilatation remains unsolved because minimal subjective signs such as slightly excessive amniotic fluid can completely change the assessment of the risk of aneuploidia. The frequency of postnatal vesico-ureteral reflux associated with prenatal pyelic dilatation warrants complete prenatal ultrasound screening.


NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury.
Acute lung injury (ALI) is a pulmonary disorder that causes acute respiratory failure, thus leading to relative high mortality worldwide. However, the molecular mechanisms of ALI remain largely unknown. MicroRNA (miRNA)-dependent control of gene expression at a post-transcriptional level has been recently reported. Herein, we identify a candidate miRNA, miR-495, that affects the progression of ALI. Alveolar macrophages (NR8383) were treated with 1 μg/mL lipopolysaccharide (LPS) to establish a cell-injury model. Combined with the data from western blot, methylation-specific PCR, methylated DNA immunoprecipitation, and chromatin immunoprecipitation assays, NLRP3 inflammasome activation and methylation-dependent repression of miR-495 were found in LPS-exposed NR8383 cells. Dual-luciferase reporter gene assay and miR-495 gain-of-function experiments confirmed that NLRP3 was a target of miR-495. Next, the expression of miR-495 and NLRP3 was overexpressed or silenced to assess their effects on NLRP3 inflammasome activation, alveolar macrophage inflammation, and pyroptosis in vitro. As demonstrated, overexpressed miR-495 alleviated alveolar macrophage inflammation and pyroptosis and inhibited NLRP3 inflammasome activation by negatively regulating the NLRP3 gene. Consistently, elevated miR-495 alleviated lung injury and reduced the neutrophil infiltration and inflammation in rat models of LPS-induced ALI. Taken together, the data in our study demonstrated that methylation of the miR-495 promoter could downregulate miR-495, whose elevation could attenuate the activation of the NLRP3 inflammasome to protect against ALI, which provides novel therapeutic targets for ALI treatment.


The English Lexicon Project.
The English Lexicon Project is a multiuniversity effort to provide a standardized behavioral and descriptive data set for 40,481 words and 40,481 nonwords. It is available via the Internet at elexicon.wustl.edu. Data from 816 participants across six universities were collected in a lexical decision task (approximately 3400 responses per participant), and data from 444 participants were collected in a speeded naming task (approximately 2500 responses per participant). The present paper describes the motivation for this project, the methods used to collect the data, and the search engine that affords access to the behavioral measures and descriptive lexical statistics for these stimuli.


Risk factors for mortality-morbidity after emergency-urgent colorectal surgery.
The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. The median age of patients was 73 (range 17-98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm(3) (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63-6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score > or =3 (OR = 2.9, 95% CI 1.9-4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4-7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4-3.4, p = 0.0003). The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients' ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.


Characterization of Trypanosoma brucei s.l. subspecies by isoenzymes in domestic pigs from the Fontem sleeping sickness focus of Cameroon.
Though it has been established that domestic animals (especially the pig) are potential reservoir hosts for Trypanosoma brucei gambiense in West Africa, there is little data to this effect concerning Central Africa. Instead, some previous authors report the absence of Trypanozoon type trypanosomes in domestic animals in Cameroon. Thirty-two domestic pigs were sampled by KIVI (kit for in vitro isolation) of trypanosomes in the northern region (Bechati) of the Fontem sleeping sickness focus of Cameroon. Twenty-one of these were found positive, from 15 of which 17 isolates were successfully obtained. Isoenzyme characterization revealed that isolates from 4 of the 15 pigs belonged to zymodemes associated with T. brucei gambiense group 1. The prevalence of this disease in the local human population is, however, very low. It is evident from this study that the domestic pig may be a potential reservoir host for T. brucei gambiense in the Fontem focus. There is, however, need for an extensive study on domestic animals in Cameroon and other neighbouring countries for a better comprehension of the epidemiology of sleeping sickness within the Central African region.


Vitrified-warmed embryo transfer is associated with mean higher singleton birth weight compared to fresh embryo transfer.
To test for differences in birth weight between singletons born after IVF with fresh embryo transfer vs. vitrified-warmed 2PN embryo transfer (vitrification protocol). Retrospective analysis of 464 singleton live births after IVF or ICSI during a 12 year period. University hospital. Fresh embryo transfer, vitrified-warmed 2PN embryo transfer (vitrification protocol). Birth weight standardized as a z-score, adjusting for gestational week at delivery and fetal sex. As a reference, birth weight means from regular deliveries from the same hospital were used. Multivariate regression analysis was used to investigate the relationship between the dependent variable z-score (fetal birth weight) and the independent predictor variables maternal age, weight, height, body mass index, RDS prophylaxis, transfer protocol, number of embryos transferred, indication for IVF treatment and sperm quality. The mean z-score was significantly lower after fresh transfer (-0.11±92) as compared to vitrification transfer (0.72±83) (p<0.001). Multivariate regression analysis indicated that only maternal height and maternal body mass index, but not type of cryopreservation protocol, was a significant predictor of birth weight. In this analysis focusing on 2PN oocytes, vitrified-warmed embryo transfer is associated with mean higher birth weight compared to fresh embryo transfer. Maternal height and body mass index are significant confounders of fetal birth weight and need to be taken into account when studying birth weight differences between ART protocols.


Association of Obesity and Type 2 Diabetes with Non-Hodgkin Lymphoma: The Multiethnic Cohort.
Given the role of the immune system in non-Hodgkin lymphoma (NHL) etiology, obesity and type 2 diabetes (T2D) may impact NHL development. We examined the association of body mass index (BMI) and T2D with NHL in the multiethnic cohort (MEC). The MEC recruited >215,000 participants in Hawaii and Los Angeles from five racial/ethnic groups; NHL cases were identified through cancer registry linkages. T2D status, and BMI at age 21 and cohort entry were derived from repeated self-reports; for T2D, Medicare claims were also applied. HRs and 95% confidence intervals (CI) for BMI and T2D as predictors of NHL were determined using Cox regression adjusted for relevant covariates. Among 192,424 participants, 3,472 (1.8%) with NHL and 68,850 (36%) with T2D after 19.2 ± 6.6 years follow-up, no significant association between T2D and NHL (HR, 1.04; 95% CI, 0.96-1.13) was observed. Stratification by BMI at cohort entry showed a significant association of T2D with NHL among individuals with normal weight only (HR, 1.18; 95% CI, 1.03-1.37). In a model with both BMI values plus T2D, only overweight (HR, 1.13; 95% CI, 1.01-1.26) and obesity (HR, 1.25; 95% CI, 0.99-1.59) at age 21 were associated with NHL incidence. Stratification by sex, race/ethnicity, and NHL subtype indicated no differences. Our findings suggest an association between T2D and NHL incidence in several subgroups but not in the total population and an elevated risk related to early-life BMI. Excess body weight in early life, rather than T2D, may be a predictor of NHL incidence.


Impact of inverse unequal height strut structure on the functional performance of an additively manufactured cardiovascular stent.
Recently, additive manufacturing (AM) has been investigated as an innovative method to manufacture stents due to its capability in producing complex and customized structures. In this paper, the cardiovascular stents of M-type and N-type with inverse unequal height strut structure and N-type with equal height strut structure were designed and manufactured by Selective Laser Melting (SLM). Following surface polishing, balloon expansion, plane compression and three-point bending experiments were carried out to evaluate the mechanical performance of the stent. The stents designed with inverse unequal height strut structure showed higher radial support performance and lower radial recoil when compared to the stents with uniform design. This study proved the feasibility of SLM in rapid manufacturing of cardiovascular stents that can be used for performance evaluation in design stage.


Study on prevalence and associated risk factors of epizootic lymphangitis in equine in Nagele Arsi town, southeastern Ethiopia.
Epizootic lymphangitis is a contagious, chronic and overwhelming disease of equids, characterized by chronic discharging skin nodules. This study was aimed to investigate the prevalence and associated risk factors of epizootic lymphangitis in equines at Nagele Arsi town, southeastern Ethiopia. A cross-sectional study using a random sampling technique was employed from December 2021 to June 2022 via clinical and microscopic examinations of the lesions. The overall prevalence of epizootic lymphangitis was 4.37% with a prevalence of 6.69%, 0.72%, and 0% in horses, donkeys, and mules, respectively. The sex, species, harness type, season, and body condition scores of equids have shown statistically significant differences (p < 0.05) with the prevalence of epizootic lymphangitis. Macroscopically, the lesions revealed varying degrees of nodule to ulcer on the sternum, limbs, face, and cervical region of the equine. Upon giemsa stain, fungal hyphae with a halo (unstained capsule-like) structure were observed. Histologically, pyogranulomatous inflammation with fibroplasia was appreciated. In conclusion, epizootic lymphangitis was rampant in the study area. This requires a detailed investigation incorporating a large sample size using fungal culture and other molecular techniques including PCR.


High genome plasticity and frequent genetic exchange in Leishmania tropica isolates from Afghanistan, Iran and Syria.
The kinetoplastid protozoan Leishmania tropica mainly causes cutaneous leishmaniasis in humans in the Middle East, and relapse or treatment failure after treatment are common in this area. L. tropica's digenic life cycle includes distinct stages in the vector sandfly and the mammalian host. Sexual reproduction and genetic exchange appear to occur more frequently than in other Leishmania species. Understanding these processes is complicated by chromosome instability during cell division that yields aneuploidy, recombination and heterozygosity. This combination of rare recombination and aneuploid permits may reveal signs of hypothetical parasexual mating, where diploid cells fuse to form a transient tetraploid that undergoes chromosomal recombination and gradual chromosomal loss. The genome-wide SNP diversity from 22 L. tropica isolates showed chromosome-specific runs of patchy heterozygosity and extensive chromosome copy number variation. All these isolates were collected during 2007-2017 in Sweden from patients infected in the Middle East and included isolates from a patient possessing two genetically distinct leishmaniasis infections three years apart with no evidence of re-infection. We found differing ancestries on the same chromosome (chr36) across multiple samples: matching the reference genome with few derived alleles, followed by blocks of heterozygous SNPs, and then by clusters of homozygous SNPs with specific recombination breakpoints at an inferred origin of replication. Other chromosomes had similar marked changes in heterozygosity at strand-switch regions separating polycistronic transcriptional units. These large-scale intra- and inter-chromosomal changes in diversity driven by recombination and aneuploidy suggest multiple mechanisms of cell reproduction and diversification in L. tropica, including mitotic, meiotic and parasexual processes. It underpins the need for more genomic surveillance of Leishmania, to detect emerging hybrids that could spread more widely and to better understand the association between genetic variation and treatment outcome. Furthering our understanding of Leishmania genome evolution and ancestry will aid better diagnostics and treatment for cutaneous leishmaniasis caused by L.tropica in the Middle East.


Diabetes mellitus and intraocular lens implantation.
Prospective evaluation of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE-posterior chamber IOL) in 234 eyes of 20 diabetics, with and without nonproliferative retinopathy, and 209 nondiabetics demonstrated no statistically significant difference in operative or postoperative complications. A postoperative final visual acuity of 20/40 or better was achieved in 65% of diabetic surgical eyes and in 90% of nondiabetic surgical eyes, a difference that was statistically significant (P = 0.0049). When eyes with diabetic retinopathy or other pre-existing ophthalmic disease responsible for decreased vision were excluded, postoperative visual acuity of 20/40 or better was obtained in 93% of diabetic eyes and 96% of nondiabetic eyes, a difference that was not statistically significant (P = 0.5045). Therefore, the relatively less favorable outcome of ECCE-posterior chamber IOL surgery in diabetics, with or without nonproliferative retinopathy, is due to greater frequency of retinopathy or other ophthalmic disease responsible for decreased vision. Based on this study and all available information, guidelines regarding diabetes mellitus and intraocular lens implantation are presented.


[Role of conformational sub-states on the reaction capacity of protein molecules].
A review of the recent data on protein dynamics (mainly myoglobin) by X-ray technique, Mössbauer spectroscopy and Rayleigh scattering of Mössbauer radiation is given. The connection between dynamical and functional properties of biological systems are discussed.


Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice.
Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1⁻/⁻) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1⁻/⁻ hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1⁻/⁻ astrocytes also showed more intracellular Ca²⁺ signal oscillations mediated by functional connexin 43 hemichannels and P2Y₁ receptors. Therefore, Npc1⁻/⁻ astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.


Macrophages in Marseille.
Immunology has recently witnessed several new developments in understanding the biology of macrophages. These exciting developments were the focus of a conference in Marseille, France, in January 2013. This conference is summarized here.


Seasonal changes in the histoenzymatic distribution of acid and alkaline phosphatases activity in the B cells of the thoracic ganglion of fresh-water crab, Potamon magnum magnum (Pretzman).
The present study deals with acid and alkaline phosphatases activity determination in B cells of the thoracie ganglion of Potamon magnum magnum. Intense alkaline and acid phosphatases activity is seen in the neurosecretory granules as well as in the neural sheath. Acid phosphatase activity unlike alkaline phosphatase distribution, is seen in form of positive stained spherules showing different pattern of distribution. Alkaline phosphatase activity is linked with the metabolic process. The significance of these results is discussed.


Influence of plaque characteristics on fractional flow reserve for coronary lesions with intermediate to obstructive stenosis: insights from integrated-backscatter intravascular ultrasound analysis.
The aim of this study was to determine the correlation between the fractional flow reserve (FFR) values and volumetric intravascular ultrasound (IVUS) parameters derived from classic gray-scale IVUS and integrated backscatter (IB)-IVUS, taking into account known confounding factors. Patients with unstable angina pectoris with the frequent development of vulnerable plaques often showed the discrepancy between the FFR value and the quantitative coronary angiography findings. Our target population was 107 consecutive subjects with 114 isolated lesions who were scheduled for elective coronary angiography. The FFR was calculated as the mean distal coronary pressure divided by the mean aortic pressure during maximal hyperemia. Various volumetric parameters such as lipid plaque volume (LPV) and percentage of LPV (%LPV) were measured using IB-IVUS. Simple and multivariate linear regression analysis was employed to evaluate the correlation between FFR values and various classic gray-scale IVUS and IB-IVUS parameters. The Akaike information criterion (AIC) was used to compare the goodness of fit in an each model. Both the %LPV (r = -0.24; p = 0.01) and LPV (r = -0.40; p < 0.01) were significantly correlated with the FFR value. Only the LPV (AIC = -147.0; p = 0.006) and %LPV (AIC = -152.9; p = 0.005) proved to be independent predictors for the FFR value even after the adjustment of known confounding factors. The volumetric assessment by IB-IVUS could provide better information in terms of the relationship between plaque morphology and the FFR values as compared to the classic IVUS 2-dimensional gray-scale analysis.


Negative regulation of interleukin-1beta-activated neutral sphingomyelinase by protein kinase C in rat mesangial cells.
Endogenous ceramide is produced by the action of acidic or neutral sphingomyelinases (SMase) in response to stimuli such as proinflammatory cytokines or other inducers of stress. Interleukin-1beta (IL-1beta) is known to stimulate ceramide formation in rat renal mesangial cells; however, the respective subtype of SMase and its regulation have not been investigated. We found that IL-1beta induced an increase in endogenous ceramide levels via the action of a neutral SMase but not an acidic SMase in rat mesangial cells. Cytokine-induced activation of neutral SMase was inhibited by stimulation of protein kinase C (PKC) by the phorbol ester TPA which caused a reduction of ceramide back to control levels. This inhibitory effect of TPA was reversed by the specific PKC-inhibitor Ro-318220. Long-term incubation (24 h) of mesangial cells with TPA, which downregulates PKC-alpha, -delta, and -epsilon isoenzymes, resulted in a recovery of IL-1beta-stimulated neutral SMase activity as well as ceramide formation. These data implicate an important modulatory function of PKC in ceramide production in IL-1beta-activated mesangial cells.


Therapy of psoriasis with retinoid plus PUVA: clinical and histologic data.
In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology.


3D patient-derived tumor models to recapitulate pediatric brain tumors In Vitro.
Brain tumors are the leading cause of cancer-related deaths in children. Tailored therapies need preclinical brain tumor models representing a wide range of molecular subtypes. Here, we adapted a previously established brain tissue-model to fresh patient tumor cells with the goal of establishing3D in vitro culture conditions for each tumor type.Wereported our findings from 11 pediatric tumor cases, consisting of three medulloblastoma (MB) patients, three ependymoma (EPN) patients, one glioblastoma (GBM) patient, and four juvenile pilocytic astrocytoma (Ast) patients. Chemically defined media consisting of a mixture of pro-neural and pro-endothelial cell culture medium was found to support better growth than serum-containing medium for all the tumor cases we tested. 3D scaffold alone was found to support cell heterogeneity and tumor type-dependent spheroid-forming ability; both properties were lost in 2D or gel-only control cultures. Limited in vitro models showed that the number of differentially expressed genes between in vitro vs. primary tissues, are 104 (0.6%) of medulloblastoma, 3,392 (20.2%) of ependymoma, and 576 (3.4%) of astrocytoma, out of total 16,795 protein-coding genes and lincRNAs. Two models derived from a same medulloblastoma patient clustered together with the patient-matched primary tumor tissue; both models were 3D scaffold-only in Neurobasal and EGM 1:1 (v/v) mixture and differed by a 1-mo gap in culture (i.e., 6wk versus 10wk). The genes underlying the in vitrovs. in vivo tissue differences may provide mechanistic insights into the tumor microenvironment. This study is the first step towards establishing a pipeline from patient cells to models to personalized drug testing for brain cancer.


DNA amplification by the polymerase chain reaction to detect sub-clinical Pneumocystis carinii colonization in HIV-positive and HIV-negative male homosexuals with and without respiratory symptoms.
Pneumocystis carinii colonization was studied in 90 men using the polymerase chain reaction. These comprised ten heterosexual controls; ten HIV-seronegative homosexual controls; 20 HIV-seropositive homosexuals with blood CD4 count > 400 x 10(6) l-1; 20 HIV-seropositive homosexuals with CD4 < 400 x 10(6) l-1; ten HIV-seropositive homosexuals with CD4 < 60 x 10(6) l-1 receiving PCP chemoprophylaxis; and 20 HIV-seropositive homosexuals with respiratory symptoms but without PCP. Induced sputum was obtained from all but the last group, who had bronchoalveolar lavage, and all specimens were tested for P. carinii using the polymerase chain reaction. The first four groups received no pneumocystis chemoprophylaxis, and all but the last group were asymptomatic. P. carinii colonization did not occur in the two control groups. P. carinii colonization rates were significantly different in the CD4 > 400, CD4 < 400, and CD4 < 60 groups (10%, 20%, and 40% respectively) (P < 0.025). Two patients (one each from CD4 < 400 and CD4 < 60) developed PCP 4-6 weeks after sputum induction, both had previously had high levels of P. carinii on sputum induction. Two patients from the CD4 < 400 group had high levels of P. carinii but did not develop PCP. In the symptomatic group, two subjects had low levels of P. carinii, but did not develop PCP. We have demonstrated P. carinii colonization in HIV-seropositive homosexuals in association with a low peripheral CD4 count. The polymerase chain reaction may be a useful technique for determining the need and efficacy of anti-pneumocystis chemoprophylaxis.


Conservative management of the abnormal smear during pregnancy. A long-term follow-up.
One hundred and thirty-two pregnant women who had a smear suggestive of cervical intra-epithelial neoplasia (CIN) II or more during the 10th to 12th gestational week, were followed with repeated smears and colposcopy every month and, when indicated, a colposcopically guided biopsy. Post-partum follow-up included cytology, colposcopy, portio biopsies and endocervical curettage. Seventy-nine women with normal findings post partum were checked once a year in a long-term study. A close correlation (71% of CINIII) was found between cytological and histological diagnoses in cases of persistent (three or more) abnormal smears. However, in women with regression of the cytological diagnosis, high frequencies of histologically verified CIN were found. Thus, 37.5% (18/48) of normal or CINI smears were histologically still CINIII. Histologically verified CIN during pregnancy, on the other hand, showed a post partum progression of two degrees or more of CIN in only two cases. Cytology seemed to be inappropriate post partum, with 23.3% smears which were normal or suggestive of CINI, when histology showed CINIII. In a long-term follow-up, 24% of women with a normal post partum follow-up for at least one year had a subsequent recurrence of CIN. It is concluded that follow-up of abnormal smears during pregnancy with repeated smears is not a reliable method. Post-partum follow-up should include at least colposcopy and a biopsy when indicated by the colposcopical examination. Women with a normal post partum follow-up constitute a high risk group for future recurrence of CIN and should be carefully followed for at least 5 years.


BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype.
Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. Targeted sequencing was performed on 407 plasma samples from 375 men with mCRPC. Using the CLIA-certified PredicineCARE™ cell-free DNA (cfDNA) assay, pathogenic alterations in 152 key genes (including 27 DDR-related genes) were assessed, as was the presence and mechanisms of biallelic loss in BRCA2. At least one DDR alteration was present in 34.5% (129/375) of patients (including monoallelic alterations). The most frequently altered DDR genes were BRCA2 (19%), ATM (13%), FANCA (5%), CHEK2 (5%) and BRCA1 (3%). Patients with BRCA alterations, especially BRCA2, had significantly worse progression-free survival (PFS) (Hazard ratio (HR) 3.3 [95% CI 1.9-6.0]; Cox regression p < 0.001), overall survival (HR 2.2 [95% CI 1.1-4.5]; Cox regression p = 0.02) and PSA response rates to androgen receptor (AR) pathway inhibitors (32% vs 60%, chi-square p = 0.02). BRCA-deficient tumours were also enriched for alterations within multiple genes including in the AR and PI3K pathways. Zygosity of BRCA2 alterations had no discernible impact on clinical outcomes, with similarly poor PFS for monoallelic vs biallelic loss (median 3.9 months vs 3.4 months vs copy neutral 9.8 months). These data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected. Enrichment of actionable genomic alterations in cfDNA from BRCA-deficient mCRPC may support rational co-targeting strategies in future clinical trials. Several funding sources have supported this study. A full list is provided in the Acknowledgments. No funding was received from Predicine, Inc. during the conduct of the study.


Erlotinib in first-line therapy for non-small cell lung cancer: a prospective phase II study.
This phase II study evaluated efficacy of first-line erlotinib therapy for chemo-naïve patients with non-small cell lung cancer (NSCLC) by their clinicopathological and/or molecular characteristics. Eligible patients received erlotinib 150 mg daily until disease progression, followed by a gemcitabine/carboplatin doublet. By clinicopathological characteristics, the patients were categorized as squamous cell carcinoma (SQCC group), ever-smoker with adenocarcinoma (ever-smoking ADCC group), or never-smoker with adenocarcinoma (never-smoking ADCC group). Epidermal Growth Factor Receptor (EGFR) mutations were prospectively assessed by a direct sequencing method and confirmed retrospectively by the Scorpion amplified refractory mutation system (ARMS). Seventy-five patients participated in this study. The direct sequencing method detected 18 EGFR mutations while ARMS detected an additional 3 EGFR mutations and 1 second EGFR T790M mutation. The objective response rates (ORR) were 71.7% in never-smoking ADCC, 25.0% in ever-smoking ADCC, but no response in SQCC, while those of the patients with EGFR mutant and wild-type ere 85.7% and 10.0%, respectively. Even in never-smoking ADCC, the EGFR mutants responded better, with ORR of 88.9% and survived longer, with median survival time of 25.4 months, than those with wild-type EGFR with ORR of 25.0% and median survival time of 16.6 months (p<0.05). ORR for gemcitabine and carboplatin was 16.1%. The decision to administer first-line erlotinib should be decided by molecular characteristics, if known, but can be made by clinico-pathological characteristics as second best policy.


Clinical efficacy of novel combinations of older beta-lactam and beta-lactamase inhibitors: Where are the evidences?
India is well known for the rampant growth of ESBLs that jeopardized the clinical utility of standalone beta-lactam. Pharmaceutical organizations fancied to rescue these beta-lactams by combining them with generic beta-lactamase inhibitors despite such combinations were never investigated in non-clinical or clinical studies. Lack of stringency in regulatory review practices allowed the market entry of these combinations. CSE 1034 (ceftriaxone, sulbactam and EDTA) and cefoperazone sulbactam are the most irrational antibiotics in clinical use. The effectiveness of such combinations relies on multiple factors such as relative beta-lactamase stability of the standalone beta-lactam, the inhibitory potency of the beta-lactamase inhibitor and more importantly the adequacy of the dose incorporated in the formulation. Unfortunately, none of the unconventional BL-BLI inhibitor combinations marketed in India has been subjected to such evaluations. Therefore, their therapeutic utility is uncertain. Besides questionable therapeutic utility, sub-optimal exposures would lead to the selection of resistant clones.


Role of ultrasonography in the detection of small adrenal masses.
Computed tomography (CT) scanning is commonly used for evaluation of adrenal masses in adults. In this prospective study we evaluated whether adrenal gland masses of less or equal than 20 mm in diameter could be detected by modern abdominal ultrasonography (US). Between July 1999 and June 2000, 44 consecutive patients with 50 adrenal masses documented by contrast-enhanced CT (left adrenal gland, n = 31; right adrenal gland, n = 19; bilateral, n = 6; median size, 15 [5 +/- 80] mm) and, additionally, 50 patients without CT findings of an adrenal mass were prospectively evaluated by high-resolution US performed by physicians. Based upon CT measurement, 34 adrenal masses were </= 20 mm and 16 were > 20 mm in diameter. The overall sensitivity of US for the detection of adrenal masses was 96 % (48/50) (94 % [29/31] for left and 100 % [19/19] for right adrenal masses, respectively). The overall specificity of US for the detection of adrenal masses was 92 % (92/100) (90 % [45/50] for left and 94 % [47/50] for right adrenal masses, respectively). Thus, the diagnostic accuracy of US for the detection of adrenal masses is 93 % (140/150). Sensitivity and specificity of US for the detection of adrenal masses </= 20 mm (n = 34) did not differ significantly from those > 20 mm (n = 16). US is effective for detecting small adrenal masses. In rare cases small masses of the left adrenal gland might be missed and nodular adrenal hyperplasia or retroperitoneal lymph nodes might be misinterpreted as adrenal masses.


The efficiency of cypermethrin (NRDC 149) for the treatment and eradication of the sheep louse Damalinia ovis.
A synthetic pyrethroid, cypermethrin (NRDC 149), showed activity in killing lice (Damalinia ovis) in the fleece of sheep at concentrations as low as 1 ppm in a dip. In addition concentrations of 5 and 10 ppm showed a persistent effect and prevented reinfestation from contact challenge sheep for 7 and 19 weeks respectively.


Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor.
N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit models of ear edema and neutropenia.


Medical students' perceptions of racial diversity and gender equality.
To assess attitudes of medical students toward issues of racial diversity and gender equality and to ascertain changes in these attitudes during the pre-clinical curriculum. Attitudes toward multiculturalism and gender equality were assessed using a 43-item questionnaire. The survey was completed by incoming Year 1 students in 2000 and 2001, and was completed again in 2002 by the students who had entered in 2000. Mean scores were analysed at baseline by gender, ethnic group and political affiliation using analysis of variance. The paired scores of the first and follow-up surveys of the 2000 entering class were compared using paired t-tests. Upon entry into medical school, women, minority group students and Democrats scored significantly higher on the cultural sensitivity scale than their comparison groups. No significant changes were seen overall in the matched data. However, minority groups showed a significant increase in scores, while Republicans and white men experienced a non-significant decline. In addition, incoming students judged cultural competency education to be important. The perceived need to increase the numbers of minority group doctors varied by gender, ethnic group and political affiliation. Among incoming medical students, perceptions of racial diversity and gender equality vary along ethnic, gender and political lines. Additionally, pre-clinical education was associated with increased cultural sensitivity by minority group students, but not by others. These findings demonstrate the continuing need for diversity in medical school and for medical students to recognise and address their personal and group biases.


Spontaneous esophageal perforation related to a duodenal ulcer with pyloric stenosis: report of a case.
This report describes a case of spontaneous esophageal perforation that was considered to be etiologically related to a duodenal ulcer with pyloric stenosis. The patient was a 54-year-old Japanese man who presented following the sudden onset of severe abdominal pain and dyspnea after an episode of vomiting. He had a history of duodenal ulcer. Computed tomography revealed an extremely dilated stomach containing abundant food residue, intraabdominal effusion, bilateral pleural effusion, and mediastinal emphysema, findings that strongly suggested esophageal perforation. Esophagoscopy confirmed perforation of the lower esophagus. Laparotomy revealed marked contamination, including food residue in the abdominal cavity, and a severely dilated stomach attributed to pyloric stenosis caused by a duodenal ulcer. A 2-cm longitudinal perforation was found on the right side of the lower esophagus. Because the patient's general condition was too poor to tolerate a one-stage operation (primary closure of the perforation, gastrectomy, and reconstruction), we initially performed decompression gastrostomy and control of the esophageal leakage with T-tube placement. Following the T-tube was removed 1 month later, distal gastrectomy and reconstruction of the gastrojejunostomy (Billroth II method) could be safely performed.