Preterm birth with antenatal corticosteroid administration has injurious and persistent effects on the structure and composition of the aorta and pulmonary artery.
Preterm birth affects 8-12% of live births and is associated with the development of elevated arterial blood pressure and aortic narrowing in later life; this suggests that preterm birth may alter the development of arteries. Our objective was to determine the effects of preterm birth, accompanied by antenatal corticosteroid administration, on the structure of the aorta and pulmonary artery, which experience different alterations in pressure flow at birth. At 11 wk, preterm lambs had significantly thicker aortic walls and a smaller lumen, whereas the morphometry of the pulmonary artery was unaffected. Elastin deposition was markedly increased in the aorta and pulmonary artery and smooth muscle content was reduced in the aorta only. In preterm lambs we found injury in the aorta only; controls were unaffected. We conclude that moderate preterm birth after antenatal betamethasone can cause injury and persistent alterations in the structure and composition of the aorta, with lesser effects in the pulmonary artery. Our findings suggest that preterm birth may increase the risk of atherosclerosis and aortic aneurysms in later life. Using an established ovine model of preterm birth, lambs were born at 0.9 of gestation and underwent necropsy at 11 wk after birth; controls were born at term.


Unions call for better health support of pupils at school.
Urgent action is needed to protect the health needs of children and young people in schools, it is claimed.


Comparing measures of acute bowel toxicity in patients with prostate cancer treated with external beam radiation therapy.
This study strives to compare early measures of bowel toxicity in patients with prostate cancer receiving definitive or adjuvant 3D conformal external beam radiation therapy and concurrent daily endorectal application of amifostine. Eighteen patients were enrolled in the clinical study with a median follow-up of 12 months. Prescription doses ranged from 66 Gy to 76 Gy with a daily fractionation of 2 Gy. Acute bowel toxicity was measured at baseline, at Weeks 5 and 7 of radiotherapy, and at 1 and 3 months after the completion of therapy. Measures of acute bowel toxicity included the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, Expanded Prostate Cancer Index Composite (EPIC) self-assessment questionnaires, and proctoscopic examinations. The mean EPIC bowel scores changed significantly through the course of therapy and follow-up (p < 0.0001), with a progressive decrease in scores at Weeks 5 and 7 of treatment, a partial recovery at 3 months, and a correlation to the gold standard RTOG grade (p = 0.004). Proctoscopic toxicity scores were low, did not vary over time, and did not correlate with either EPIC or RTOG scores. The EPIC questionnaire measurements are most sensitive to changes in acute bowel toxicity through a course of radiotherapy and correlate with RTOG acute toxicity scores. Endoscopic examination of the rectal mucosa at the end and immediate follow-up of a course of therapy does not seem to be informative or reproducible between observers in the acute setting.


Importance of blood viscoelasticity in arteriosclerosis.
Corpuscular and biochemical components of blood create the viscoelastic nature of blood flow, which varies because of changes in flow velocity. The flow properties of blood are of special interest in arteriosclerotic diseases for vasoregulatory mechanisms are often disturbed in these states. The authors compared the rheologic properties of blood in patients with arteriosclerotic lesions (coronary heart disease: n = 56; cerebrovascular disease: n = 37; peripheral arterial occlusive disease: n = 29 and healthy controls: n = 42). With a new oscillating capillary rheometer imitating the physiologic pulsations of blood flow in an unbranched artery, the viscosity (eta') and elasticity (eta") of whole blood and plasma were measured (diameter of the capillary: 0.9928 mm; pulse rate: 2/s; shear rate: gamma = 0.03-200/s; temperature: 37 degrees C). In arteriosclerotic patients a statistically significant elevation of the viscoelasticity of whole blood and plasma was found. In addition, plasma fibrinogen levels were augmented in the patients' groups. Clotting parameters (Quick, partial thromboplastin time, platelet count) and total serum protein levels were in the normal range in all patients investigated. In conclusion the question arises whether the increase of blood viscoelasticity is an additional risk factor for patients with arteriosclerotic disease or if it is just a consequence of the underlying disease. The authors' observations concerning blood viscoelasticity support the clinical importance of improving blood rheology by appropriate therapeutic measures.


[Composition and excitability of afferent fibers of the pelvic nerve in cats].
The afferent fibers excitable by pelvic nerve stimulation were as follows: A (81 m/sec), A (59.6 m/sec), A (45.3 m/sec), A (17.9 m/sec), A (31.6 m/sec), B (11.3 m/sec). We failed to find C fibers. Analysis of the distribution of fibers showed that the majority of them entered the S2 dorsal root (DRS2). The fast-conducting fibers (Abeta1 and Abeta2) were found at DRL7--DRS2. The number of slow-conducting fibers increased in caudal direction. The most abundant in the pelvic nerve are Abeta3 fibers, and somewhat fewer in number are Abeta and Agamma fibers.


Musculo-tendinous stiffness of head-neck segment in the sagittal plane: an optimization approach for modeling the cervical spine as a single-joint system.
Despite the multi-linked architecture of the cervical spine, all previous studies that have made estimations of mechanical properties of the neck have considered the head-neck segment as a rigid link, with a fixed center of rotation at C7. The aim of this study was to consider the head-neck segment as a changeable geometry system for locating the resultant center of rotation and for calculating the musculo-tendinous stiffness by the quick-release method. Head kinematics during quick-releases was analyzed by recording the trajectory of surface markers. With an optimization procedure, the position of the resultant center of rotation of the head-neck segment was estimated. Thereafter, the angular displacement and acceleration of the head, together with the isometric torque developed by the cervical muscles were used to calculate the segment's stiffness. The results showed a consistent center of rotation and a significant increase of the musculo-tendinous stiffness with increasing torque.


A temporal study of gene expression in rat lung following fixed-volume hemorrhage.
Previous studies have indicated that hemorrhage may predispose the lung to respiratory distress syndrome. Gene expression profiling with oligonucleotide microarrays was used to evaluate the genetic responses of the lung to hemorrhage. Conscious rats, chronically instrumented with a catheter and telemetry device to record blood pressure, heart rate, and temperature, had 40% of their estimated blood volume removed at a rate of 1 ml/min over 7-10 min. Groups of three or more rats were euthanized at 1, 3, 6, 16, 24, 48, or 72 h following hemorrhage. Two additional groups were unmanipulated controls and instrumented animals with sham hemorrhage. Total RNA was isolated from lung, reverse-transcribed to cDNA, fluorescently labeled, and hybridized to oligonucleotide microarrays probing 5,671 rat genes. After hemorrhage, statistically detectable alteration of expression was seen in approximately 0.8% of the genes at some time during the 72-h test period (vs. sham hemorrhage) as determined by false discovery rate statistics in the statistical analysis of microarrays program. A subset was confirmed by RT-PCR analysis. Hemorrhage influenced genes that regulate intracellular signaling and structure, growth factors, and hormonal receptors. There also appeared to be increased expression of genes that may mediate sequestration of neutrophils and mononuclear cells from the circulation. This hemorrhage model, although producing severe hemodynamic alterations, avoided mortality and histological evidence of lung damage, a feature intended to help ensure reliable evaluation of gene expression. These results indicate that gene expression profiling with microarrays provides a new tool for exploring the response of a tissue to systemic blood loss.


Serial quantitative determination of hepatitis C virus RNA levels after liver transplantation. A useful test for diagnosis of hepatitis C virus reinfection.
After liver transplantation for hepatitis C virus (HCV)-related cirrhosis, recurrent viral infection is almost constant, resulting in acute graft dysfunction in 30-75% of cases. Acute graft dysfunction in the post-transplant period may also be the result of various causes (such as rejection, CMV infection, sepsis, or technical problems). Therefore, the role of HCV reinfection is often difficult to document. The aim of this study was to assess the diagnostic value of serial HCV RNA quantitation in this setting. Fourteen patients transplanted with follow-up greater than 6 months were studied. HCV RNA was quantitated before and serially after transplantation, using branched DNA technology. In cases of acute graft dysfunction, usual investigations and additional HCV RNA quantitation were conducted. There were 15 episodes of acute graft dysfunction in 12 patients. Six episodes had a hepatitic biochemical pattern, and 5 of them were associated with a concomitant HCV RNA peak. Nine episodes had a mixed, hepatitic, and cholestatic biochemical pattern, and 5 of them were associated with a concomitant peak of HCV RNA. Overall, 10 of 15 (66%) episodes of acute graft dysfunction were associated with HCV RNA peak, which strongly suggests that HCV was the etiologic factor. In 9 of these 10 episodes, no other cause of dysfunction was found, and one had associated CMV disease. In 5 cases, no peak of HCV RNA was observed and the causes of dysfunction were CMV (in 2 cases) and rejection, granulomatosis, and unknown (in 1 case each). Serial quantitations of HCV RNA levels after liver transplantation for cirrhosis C provide a useful tool in the diagnosis of HCV reinfection of the graft.


Left ventricular endocardial pacing and multisite pacing to improve CRT response.
Cardiac resynchronization therapy (CRT) is an established treatment for patients with moderate-to-severe heart failure and a wide QRS complex. However, the amount of reverse remodeling and clinical improvement is highly variable and poorly predictable. The left ventricular pacing site is of critical importance for the CRT response but is often imposed by the coronary sinus anatomical constraints and may result in suboptimal resynchronization. Alternative pacing sites, such as endocardial LV pacing or multisite pacing, have been proposed to improve CRT response rates and may be considered in nonresponders to standard resynchronization. However, adequately powered randomized studies are required to determine whether these pacing strategies result in improved outcome.


Twelve-hour and twenty four-hour preservation of small bowel allografts by simple hypothermia. Survival utilizing cyclosporine.
Canine small bowel was harvested and stored by simple hypothermic technique. After 12- and 24-hr storage, respectively, the small bowel graft was allotransplanted into recipients. All animals receiving 12-hr stored grafts (n = 9) survived beyond 5 days. In the 24-hr storage group, 67% of the animals (n = 9) survived beyond 5 days. Successful storage for such extended periods by simple hypothermia has not been achieved previously. Donor pretreatment with antibiotics as well as extensive intraluminal irrigation of the harvested small bowel are considered to be important technical features in this successful preservation.


Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory.
Questions remain about the contributions of transmural versus apicobasal repolarization gradients to the configuration of the T wave in control settings and after the induction of short-term cardiac memory. Short-term cardiac memory is seen as T-wave changes induced by altered ventricular activation that persists after restoration of sinus rhythm. We studied cardiac memory in anesthetized, open-chest dogs paced from the ventricle for 2 hours. Unipolar electrograms were recorded from as many as 98 epicardial and 144 intramural sites, and activation times and activation-recovery intervals (ARIs) were measured. In separate experiments, epicardial monophasic action potentials were recorded. We found no appreciable left ventricular intramural gradients in repolarization times (activation time+ARI) in either control conditions or after the induction of memory. In controls, there was a left ventricular apicobasal gradient, with the shortest repolarization times in anterobasal regions and longest repolarization times posteroapically. After induction of memory, repolarization times shortened uniformly throughout the ventricular wall. Monophasic action potential duration at 90% repolarization decreased by approximately 10 ms after induction of memory. In the intact canine left ventricle at physiological rates, there is no transmural gradient in repolarization. Apicobasal gradients in repolarization time, with shortest repolarization times in anterobasal areas and longest repolarization times in posteroapical regions, are important in the genesis of the T wave. Repolarization times and monophasic action potentials at the 90% repolarization level shorten after the induction of memory. The deeper T wave in the ECG after induction of memory may be explained by the more rapid phase 3 of the action potential.


The pharmacological potential of Phyllanthus niruri.
Phyllanthus niruri is a traditional shrub of the genus Phyllanthaceae with long-standing Ayurvedic, Chinese and Malay ethnomedical records. Preliminary studies from cell and animal model have provided valuable scientific evidence for its use. This review aims to summarize selected scientific evidence on the pharmacological properties of P. niruri over the past 35 years while identifying potential areas of further development of this herb as an economical adjunct. The review covers literature pertaining to the evidence base therapeutic potential of P. niruri spanning from 1980 to 2015 available on PubMed. Evidence suggests that the extracts of P. niruri possess hepatoprotective, antiviral, antibacterial, hypolipidaemic, hypoglycaemic, analgesic, anti-inflammatory, cardioprotective, anti-urolithiatic and antihyperuricaemic properties due its novel bioactive compounds. Scientific evidence suggests that there is strong pharmacological potential in developing P. niruri as a drug to be used in liver disorders and in antiviral therapy. Despites this, large-scale heterogeneity in study protocol and unstandardized reporting standards limit the ability for valuable comparison and may mask the ability to replicate these studies. Thus interpretation of findings should be performed with caution and further studies should be performed in line with best practices. More cheminformatics, toxicological and mechanistic studies would aid the progress to clinical trial studies.


CTAB-functionalized δ-FeOOH for the simultaneous removal of arsenate and phenylarsonic acid in phenylarsenic chemical warfare.
This study prepared a cetyltrimethylammonium bromide (CTAB) functionalized δ-FeOOH using the coprecipitation method to remove arsenate and phenylarsonic acid in water polluted by phenylarsonic chemical warfare agents. Under neutral conditions, the adsorption capacity for arsenate and phenylarsonic acid was 45.7 and 85.3 mg g-1, respectively. The adsorption process conformed to the pseudo-second-order kinetics and Freundlich isothermal adsorption model, and the adsorption was spontaneous and endothermic. The CTAB-functionalized δ-FeOOH could effectively resist the interference of coexisting anions except for CO32-, SiO32- and PO43-. Furthermore, the adsorption mechanism was proposed by combining the adsorption experimental results, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and density functional theory analyses. The results showed that the adsorption of arsenate by the CTAB-functionalized δ-FeOOH was mainly through the formation of bidentate-dinuclear inner-sphere complexes and electrostatic interactions. While for phenylarsonic acid, the formation of monodentate-mononuclear inner-sphere complexes on (100) and (110) crystal facets, and the formation of bidentate-dinuclear inner-sphere complexes on the (002) crystal facet, as well as hydrogen bonding, electrostatic interaction, and π-hydrophobic interaction between organic compounds were the primary mechanism. Moreover, the CTAB-functionalized δ-FeOOH could maintain about 60% of the adsorption capacity for the two pollutants after five cycles. Overall, CTAB-functionalized δ-FeOOH has good potential for the remediation of inorganic and organic arsenic-contaminated water bodies.


Histochemical demonstration of GABA-like immunoreactivity in cobalt labeled neuron individuals in the insect olfactory pathway.
Individual olfactory neurons in the antennal lobes of Periplaneta americana were investigated for their morphological and neurochemical properties by means of intracellular cobalt injection and indirect peroxidase-antiperoxidase immunohistochemistry. GABA-like immunoreactivity was demonstrated in many local interneurons but not in uniglomerular projection neurons.


Comparison of Periodontal Status According to the Additives of Coffee: Evidence from Korean National Health and Nutrition Examination Survey (2013-2015).
It is well known that periodontal disease is highly related to dietary habits. As coffee is a typical beverage consumed worldwide, the relationship between coffee and periodontal disease was analyzed in this study using the data from the Korean National Health and Nutrition Survey (KNHANES) 2013-2015. Complex-samples chi square tests were performed for the comparison of the demographic characteristics of the 6528 study subjects and coffee components. Poisson linear regression analysis was performed for the analysis of the periodontal condition and coffee component effects, while complex-samples logistic regression analysis was performed to determine the demographic characteristics and coffee component effects. Over the years, the proportion of people drinking coffee with syrup or drinking a coffee mix containing both syrup and cream has decreased significantly. The results of the analysis, conducted by integrating the study subjects' demographic characteristics and the coffee components, showed that the prevalence of periodontal disease was 0.83-times lower when drinking coffee with cream than when drinking black coffee. Coffee is the world's second largest trade commodity following oil, and about 70%-80% of the world's population drinks coffee. Drinking coffee with milk or cream can have a beneficial impact on periodontal disease.


Impact of platelets on major thrombosis in patients with a normal white blood cell count in essential thrombocythemia.
Cell counts have a significant impact on the complex mechanism of thrombosis in patients with essential thrombocythemia (ET). We recently demonstrated a considerable impact of white blood cell (WBC) counts on thrombotic risk in patients with optimized platelet counts by analysing a large anagrelide registry. In contrast, the current analysis of the registry aimed to estimate the influence of platelet counts on thrombotic risk in patients with optimized WBC counts. Cox regression analysis and Kaplan-Meier plot were applied on all patients in the registry with optimized WBC counts. By using the calculated cut-off of 593 G/L for platelets, Cox regression analysis revealed a clear influence of elevated platelet counts on the occurrence of a major thrombotic event (P < .001). A Kaplan-Meier plot revealed a markedly shorter time to a major thrombotic event for patients with platelet counts above the cut-off (P < .001). The data show clear impact of platelet lowering on the thrombotic risk in ET patients with normal WBC counts. Therefore, selective platelet lowering with anagrelide appears sufficient for thrombotic risk reduction in WHO-diagnosed ET patients lacking leukocytosis.


Dorsal and ventral respiratory groups of neurons in the medulla of the rat.
The aim of the present work was to identify and localize in rat the medullary neurons involved in respiration. Neural activity was recorded in ketamine-anesthetized, paralyzed and artificially ventilated rats. Active sites were marked by electrocoagulation. Neurons firing in relation to phrenic nerve activity were located between 0.5 and 2 mm lateral to the midline, extending from 0.5 mm caudal to 2 mm rostral to the posterior end of the area postrema. Two groups of respiratory neurons were found: a dorsal group located ventrolateral to the tractus solitarius and a ventral group located in the ventrolateral reticular formation close to the nucleus ambiguus. Neurons were classified as bulbospinal or laryngeal if stimulation of the spinal cord or the vagus nerve, respectively, elicited antidromic action potentials, or as propriobulbar if they were not activated. Neurons firing synchronously with lung inflation were termed pump (P) cells. The dorsal respiratory group includes inspiratory (I) bulbospinal and propriobulbar neurons, P cells, but few expiratory (E) propriobulbar neurons. The ventral respiratory group includes bulbospinal, laryngeal and propriobulbar I and E neurons. Laryngeal motoneurons project ipsilaterally whereas bulbospinal neurons project contralaterally. Cross-correlations between inspiratory bulbospinal neuronal activity and phrenic discharge suggest that bulbospinal I neurons of dorsal and ventral groups project monosynaptically to contralateral phrenic motoneurons. These results indicate a similarity of the medullary respiratory centers of rats and cats, suggesting that rats may profitably be used in studies of respiratory rhythmogenesis.


[Effect of the novel aminoadamantane derivative A-7 on Parkinsonian syndrome induced by systemic administration of neurotoxin MPTP].
A new antiparkinsonian drug, N-(2-adamantyl)hexamethyleneimine hydrochloride (A-7), was studied on the model of parkinsonism syndrome (PS) induced by MPTP neurotoxin. A-7 (5-20 mg/kg) attenuated the MPTP induced akinesia and rigidity manifestations in C57B1/6 mice, the effect being more pronounced than that of cyclodol and levodopa and comparable to that of midantane (amantadine). A-7 also decreased the PS manifestations in rats: removed tremor, rigidity, and oligokinesia, normalized the MPTP-violated bioelectrical activity of nucleus caudatus, sensomotor cortex, and dorsal hippocamp, and eliminated pathologic slow activity, paroxysmal discharges, and high-frequency activity discharges. The activity of A-7 exceeded that of levodopa (enhancing tremor) and cyclodol (not eliminating the pathologic slow activity).


Long-term effects of increasing acidity on low-pH sulfate-reducing bioprocess and bacterial community.
An ethanol-fed, sulfate-reducing anaerobic baffled reactor was operated over a period of 260 days to assess the effects of sequentially more acidic conditions (pH 4.5-2.5) on sulfate reduction and bacterial community. Results showed that the reactor could reduce sulfate and generate alkalinity at progressively lower pH values of 4.5, 3.5, and 2.5 in a synthetic wastewater containing 2500 mg/L sulfate. About 93.9% of the influent sulfate was removed at a rate of 4691 mg/L/day, and the effluent pH was increased to 6.8 even when challenged with influent pH as low as 2.5. Illumina MiSeq sequencing revealed that a step decrease in influent pH from 4.5 to 2.5 resulted in noticeable decrease in the biodiversity inside the sulfidogenic reactor. Additionally, complete and incomplete organic oxidizers Desulfobacter and Desulfovibrio were observed to be the most dominant sulfate reducers at pH 2.5, sustaining the low-pH, high-rate sulfate removal and alkalinity generation.


Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.
Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.


Activation of adipose tissue lipoprotein lipase by lipoprotein fractions from normals and patients with type v hyperlipoproteinemia.
The effects of the main lipoprotein density classes on the human adipose tissue lipoprotein lipase activity were studied. A dose-dependent stimulation of lipoprotein lipase activity was obtained for HDL and, to a lesser extent, for VLDL on a constant weight basis. LDL exerted virtually no effect. At higher concentrations, HDL as well as VLDL inhibited the stimulated lipolytic activity. In type V hyperlipoproteinemia, the stimulating effect of VLDL and of HDL was significantly lower, whereas the inhibiting action of HDL was markedly increased.


miR-142-3p simultaneously targets HMGA1, HMGA2, HMGB1, and HMGB3 and inhibits tumorigenic properties and in-vivo metastatic potential of human cervical cancer cells.
High-mobility group (HMG) proteins are oncogenic in different cancers, including cervical cancer; silencing their individual expression using sh-RNAs, siRNAs, and miRNAs has had anti-tumorigenic effects, but the consequences of their collective downregulation are not known. Since multiple gene targeting is generally very effective in cancer therapy, the present study highlighted the consequences of silencing the expression of HMGA1, A2, B1, and B3 using sh-RNAs or miR-142-3p (that can potentially target HMGA1, A2, B1, and B3) in cervical cancer cell lines. 3' UTR luciferase reporter assays were performed to validate HMGA1, A2, B1, and B3 as targets of miR-142-3p in human cervical cancer cells. Annexin V/PI dual staining and flow cytometry analyses were used to detect apoptotic cells. miR-142-3p-mediated regulation of cell death, colony formation, migration, and invasion was investigated in human cervical cancer cells together with in vivo metastasis in zebrafish. Concurrent knockdown of HMGA1, A2, B1, and B3 through their corresponding sh-RNAs inhibited cell viability and colony formation but induced apoptosis, and these effects were relatively reduced upon their individual knockdown. miR-142-3p targeted HMGA1, A2, B1, and B3 by binding to their 3'UTRs and induced apoptosis but inhibited proliferation, migration, and invasion of human cervical cancer cells. In addition, miR-142-3p expression decreased phospho-p65 and EMT-related proteins in cervical cancer cells and their in vivo metastatic potential upon implantation in zebrafish. These findings suggest that miR-142-3p acts as a tumor-suppressive miRNA by targeting HMGA1, A2, B1, and B3 and may serve as a potential therapeutic agent in human cervical cancer.


Double-blind, randomized controlled pilot study of bilateral cerebellar stimulation for treatment of intractable motor seizures.
The efficacy and safety of cerebellar stimulation (CS) was reevaluated in a double-blind, randomized controlled pilot study on five patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures. Bilateral modified four-contact plate electrodes were placed on the cerebellar superomedial surface through two suboccipital burr holes. The implanted programmable, battery-operated stimulator was adjusted to 2.0 microC/cm(2)/phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in preimplant basal phase (BL) of 3 months with the postimplant phases from 10 months to 4 years (average, eight epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into two groups: three with the stimulator ON and two with the stimulator OFF. After a 4-month postimplantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured. Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, two patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the three patients with the stimulation initially ON had a reduction of seizures to 33% (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All five patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the five patients had a mean seizure rate of 41% (14-75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of one per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, three patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11-38%). Tonic seizures: four patients had these seizures, which at 24 months were reduced to 43% (10-76%). Follow-up surgery was necessary in four patients because of infection in one patient and lead/electrode displacement needing repositioning in three patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05). The superomedial cerebellar cortex appears to be a significantly effective and safe target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1-2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the study period of 2 years and beyond.


Phenotype Algorithms to Identify Hidradenitis Suppurativa Using Real-World Data: Development and Validation Study.
Hidradenitis suppurativa (HS) is a potentially debilitating, chronic, recurring inflammatory disease. Observational databases provide opportunities to study the epidemiology of HS. This study's objective was to develop phenotype algorithms for HS suitable for epidemiological studies based on a network of observational databases. A data-driven approach was used to develop 4 HS algorithms. A literature search identified prior HS algorithms. Standardized databases from the Observational Medical Outcomes Partnership (n=9) were used to develop 2 incident and 2 prevalent HS phenotype algorithms. Two open-source diagnostic tools, CohortDiagnostics and PheValuator, were used to evaluate and generate phenotype performance metric estimates, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value. We developed 2 prevalent and 2 incident HS algorithms. Validation showed that PPV estimates were highest (mean 86%) for the prevalent HS algorithm requiring at least two HS diagnosis codes. Sensitivity estimates were highest (mean 58%) for the prevalent HS algorithm requiring at least one HS code. This study illustrates the evaluation process and provides performance metrics for 2 incident and 2 prevalent HS algorithms across 9 observational databases. The use of a rigorous data-driven approach applied to a large number of databases provides confidence that the HS algorithms can correctly identify HS subjects.


[The diagnostic nurse consultation in head and neck oncology].
The diagnosis announcement nurse consultation is carried out with the patient and/or their family. It is a time of exchange, listening and sharing of information. The diagnosis announcement nurse is available to answer questions from the patient and their family about the disease, the treatments and the follow-up care.


Chemical solutions for restoring scaling-induced injectivity impairment in offshore produced water re-injection.
Produced water re-injection (PWRI) is a promising and sustainable strategy to manage substantial quantities of produced water for subsurface energy production systems. This approach offers an alternative to the environmentally harmful practice of marine disposal. Nonetheless, produced water re-injection may lead to considerable reductions in the injectivity. The injectivity loss can be attributed to several factors, including inorganic scaling, which can obstruct the flow pathway through porous media near the wellbore as well as subsurface facilities (e.g., tubing). Scaling can also contribute to the formation of mixed organic-inorganic schmoo-like complexes. Iron-containing (FexSy, FexOy-FexOyHz), carbonate-, and sulfate-based scales (e.g., BaSO4, SrSO4, and CaCO3) are the primary precipitates that have disruptive effects during PWRI scheme, especially in reservoirs suffering from microbial souring activities. In this work, we first screened the mineral scales that may form under the relevant re-injection conditions using the composition of produced water and seawater samples from the Danish North Sea. Subsequently, we assessed the efficiency of a commercial scale inhibitor against the scaling of targeted mineral phases through a series of batch experiments, followed by the development of a model to simulate its inhibitory performance. To reduce the precipitation or deposition of different minerals in water injection applications, we evaluated the combined effect of adding other chemicals (i.e., an acid, an oxidizer, and a chelating agent) to the injection water along with the scale inhibitor. To do this, we described the relevant mineral-aqueous interactions (dissolution, precipitation, and solution complexation) in PHREEQC. This predictive model represents an alternative to time- and resource-intensive experiments and may aid in achieving optimized chemical recipes required to mitigate mineral scaling in water injection systems under various physiochemical conditions. This work can contribute to the development of more sustainable and efficient strategies for managing produced water, ultimately helping to reduce the environmental impacts of hydrocarbon production.


Antioxidant and Antibacterial Profiling of Pomegranate-pericarp Extract Functionalized-zinc Oxide Nanocomposite.
With the advancement in green nanotechnology, considerable attention is being given to the synthesis of different kinds of nanomaterials for biological applications. In this study, zinc oxide nanocomposites (ZnO NPs) were synthesized using Punica granatum L. (Pomegranate) pericarp ethanolic extract (PE) by the chemical precipitation method. The prepared ZnO NPs showed a characteristic peak at 270 nm in the UV-Vis spectrophotometer and chemical bond stretching in the Fourier transforms infrared spectroscopy (FT-IR) spectra, indicated the formation of PE-functionalized zinc oxide nanocomposite (PE-ZnO NPs). The SEM results showed agglomerated PE-ZnO NPs of a spherical shape with an average size of 80-100 nm. Moreover, biological assessment of the PE-ZnO NPs revealed significant scavenging activity in DPPH (116.5%) and ABTS+ (95.2%) radical assay methods, and substantial antibacterial activity against Bacillus cereus, Bacillus licheniformis, and Escherichia coli. Furthermore, PE-ZnO NPs showed about 96.3% of cell viability for human HaCaT cells at the maximum concentration (100 µg/mL), marked as a reliable bioactive agent. Therefore, the developed PE-ZnO NPs were elucidated with substantial ROS scavenger and non-antibiotic antibacterial agent and hence, can be applied in respective biological applications.


Mapping the psychoanalytic literature on bipolar disorder: a scoping review of journal articles.
To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder. A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021. Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was "object relations." Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with bipolar disorder - taking into account their analyzability and practical arrangements for conducting therapy - and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases. Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with bipolar disorder. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.


Synthesis, dispersion, and cytocompatibility of graphene oxide and reduced graphene oxide.
The synthesis, characterization, and toxicity of graphene oxide and reduced graphene oxide are reported. Prior to the cytocompatibility tests the stability of the suspensions in a wide range of concentrations (3.125-100 μg/mL) of three different dispersants is studied. Polyethylene glycol (PEG), polyethylene glycol-polypropylene glycol-polyethylene glycol (Pluronic P123), and sodium deoxycholate (DOC) are investigated as the dispersants. The toxicity depends on the type of dispersant and concentration of the nanomaterials in the suspensions. Detailed analysis suggests that graphene oxide functionalized with PEG in the concentration range between 3125 μg/mL and 25 μg/mL exhibits the best biocompatibility with mice fibroblast cells (line L929).


A high melting (105 degrees C) form of chromatin characterizes the potential of cells for mitosis.
The nuclei from different types of dividing cultured cells melted as four thermal transitions: I (60 degrees C), II (76 degrees C), III (88 degrees C), and IV (105 degrees C). The fourth transition was the predominant endotherm in all types of cells examined. In the melting profile of nuclei obtained from nondividing density-inhibited fibroblasts, transition IV remained the major endotherm; however, it was lost in nuclei from differentiated myoblasts and nutrient-depleted cells. In these cells, the loss in transition IV was compensated by a concomitant increase in transition III. In the nutrient-deprived cells the decrease in transition IV was followed by a gradual lowering in its melting temperature. The complete loss of transition IV was correlated with loss of cellular capacity to divide.


Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.
Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the 'fed' condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology.


Androgenetic Alopecia: Therapy Update.
Androgenetic alopecia (AGA), also known as male pattern hair loss (MPHL) or female pattern hair loss (FPHL), is the most common form of alopecia worldwide, and arises from an excessive response to androgens. AGA presents itself in a characteristic distribution unique to both sexes. Despite its prevalence, AGA can be quite challenging to treat. The condition is chronic in nature and stems from an interplay of genetic and environmental factors. There are only two US Food and Drug Administration (FDA)-approved drugs for the condition: topical minoxidil and oral finasteride. However, numerous non-FDA-approved treatments have been shown to be effective in treating AGA in various studies. Some of these treatments are relatively new and still to be explored, thus emphasizing the need for an updated review of the literature. In this comprehensive review, we discuss the evaluation of AGA and the mechanisms of action, costs, efficacies, and safety profiles of existing, alternative, and upcoming therapeutics for this widespread condition.


In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy.
Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy. Here, we have applied this technique to the in vivo diagnosis of Barrett's epithelium and associated neoplasia. Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus. Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed. In vivo histology was compared with the histologic specimens. All digitally stored images were re-assessed by a blinded investigator by the confocal Barrett classification system to predict histology. Intraobserver and interobserver variations of the involved endoscopists were evaluated by using kappa statistics. Endomicroscopy allowed distinguishing between different types of epithelial cells and detected cellular and vascular changes in Barrett's epithelium at high resolution during ongoing endoscopy in 63 patients. Barrett's esophagus and associated neoplasia could be predicted with a sensitivity of 98.1% and 92.9% and a specificity of 94.1% and 98.4%, respectively (accuracy, 96.8% and 97.4%). The mean kappa value for interobserver agreement for the prediction of histopathological diagnosis was .843, whereas the intraobserver agreement showed a mean kappa value of .892. Fluorescence-aided endomicroscopy of Barrett's esophagus allows in vivo histology of the mucosal layer during ongoing endoscopy. Gastric and Barrett's epithelium and Barrett's-associated neoplastic changes can be diagnosed with high accuracy. Thus, endomicroscopy may be helpful in the management of patients with Barrett's esophagus.


Comparison of immediate effects of myofascial release and fascial distortion model on the range of motion, pain pressure threshold, and balance in healthy adults.
Many fascial therapies have been demonstrated to positively affect the range of motion, pain sensitivity, balance, daily functioning, and participation in social activities. Among these therapies, myofascial release has been extensively studied and widely used in clinical trials. The fascial distortion model was recently introduced, and it has received much attention due to its rapid onset of action and ease of application. This study aims to compare the effects of myofascial release and the fascial distortion model on range of motion, pain sensitivity, and balance, with the goal of helping therapists select the most appropriate treatment. Sixteen healthy adults were included in a prospective, randomized, single-blind study. The subjects were randomly assigned to either the myofascial release or fascial distortion model groups. The outcome measures were functional reach test, pain pressure threshold, straight leg-raising test angle, and finger floor distance. The myofascial release and fascial distortion model groups showed significantly increased straight leg-raising angle and finger floor distance, but no between-group differences were observed (p > .05). The fascial distortion model group demonstrated significantly better pain control (p < .05), which was also better than in the myofascial release group (p < .05). The myofascial release group showed significantly improved balance control (p < .05); however, there was no difference between the two groups (p > .05). Either myofascial release or fascial distortion model can be chosen to improve the range of motion. However, if pain sensitivity is the goal, it is expected that the fascial distortion model will be more effective.


Prenatal diagnosis of dextrotransposition of the great arteries.
Dextrotransposition of the great arteries (DTGA) is a common cardiac cause of cyanosis in newborn infants that can cause acidosis and death within a short period of time unless there is a large atrial-level shunt or a patent ductus arteriosus. Here, we report a case of prenatal diagnosis of DTGA at 24+1 gestational weeks. In a tilted 4-chamber view, the pulmonary trunk branched to the left and the right pulmonary, with its root connected to the left ventricle outflow tract. In the short-axis view, the pulmonary trunk was shown to be parallel with the ascending aortic root. Cesarean section was performed due to the nonreassuring fetal status at 38+5 gestational weeks. The male neonate appeared to have mild cyanotic symptoms and weighed 3,108 g. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Neonatal echocardiography was performed immediately after birth and the findings confirmed DTGA associated with atrial septal defect secundum. Postnatally, angiography confirmed the echocardiographic diagnosis of DTGA with a large atrial septal defect secundum and a large patent ductus arteriosus. Jatene arterial switch operation and atrial septal defect closure with Gore-Tex patch were performed. The neonate withstood the operation well and was discharged 27 days after birth weighing 2,950 g and in a stable condition. Prenatal diagnosis of DTGA can greatly aid to prepare the patient's family and the surgeon and significantly improve the outcome of complex heart disease in the neonatal period.


Bacterial genome sequencing and drug discovery.
The availability of bacterial genome sequence information has opened up many new strategies for antibacterial drug hunting. There are obvious benefits for the identification and evaluation of new drug targets, but genomic-based technology is also beginning to provide new tools for the downstream, preclinical, optimisation of compounds. The greatest benefit from these new approaches lies in the ability to examine the entire genome (or several genomes) simultaneously and in total. In this way, one potential target can be evaluated against another, and either the total effects of functional impairment can be established or the effects of a compound can be compared across species.


Employee engagement, boredom and frontline construction workers feeling safe in their workplace.
Systems thinking is a philosophy currently prevalent within construction safety literature that is applied to understand and improve safety in sociotechnical systems. Among systems, the site-project organizational system is of particular interest to this paper. Using focus group and survey feedback research to learn about how safety incidents effect levels of construction workers engagement this paper reveals how a safety incident provides an opportunity to create a potential quality (productivity) upgrade within an organization. The research approach involved a qualitative study involving 27 frontline supervisors and a follow-up survey completed by 207 frontline workers in the Australian Asphalt and Pavement Industry. The focus group interviews supported the articulation of the concepts of tacit safety, explicit safety, situational awareness, foresight ability, practical intelligence and crew synergy. Our findings indicate that having regular shift changes and other job site workers being fatigued are influential on perceptions of tacit safety. An individual's foresight ability was found to be the most potent predictor of worker perceptions of work engagement. The paper explains that relatively small improvements in worker perceptions of safety can bring about significant improvements in employee engagement and productivity.


N-[6-(Di-methyl-amino)-9-phenyl-3H-telluro-xan-then-3-yl-idene]-N-methyl-methanaminium hexa-fluoro-phosphate monoclinic polymorph.
The title compound C23H23N2Te+·PF6 -, is a monoclinic polymorph of the previously reported triclinic structure [Calitree et al. (2007 ▸). Organometallics, 26, 6248-6257]. In the crystal, parallel offset π-π stacking [shortest centroid-centroid separation = 3.9620 (9) Å] and ionic inter-actions help to establish the packing.


Meta-analysis of genome-wide expression patterns associated with behavioral maturation in honey bees.
The information from multiple microarray experiments can be integrated in an objective manner via meta-analysis. However, multiple meta-analysis approaches are available and their relative strengths have not been directly compared using experimental data in the context of different gene expression scenarios and studies with different degrees of relationship. This study investigates the complementary advantages of meta-analysis approaches to integrate information across studies, and further mine the transcriptome for genes that are associated with complex processes such as behavioral maturation in honey bees. Behavioral maturation and division of labor in honey bees are related to changes in the expression of hundreds of genes in the brain. The information from various microarray studies comparing the expression of genes at different maturation stages in honey bee brains was integrated using complementary meta-analysis approaches. Comparison of lists of genes with significant differential expression across studies failed to identify genes with consistent patterns of expression that were below the selected significance threshold, or identified genes with significant yet inconsistent patterns. The meta-analytical framework supported the identification of genes with consistent overall expression patterns and eliminated genes that exhibited contradictory expression patterns across studies. Sample-level meta-analysis of normalized gene-expression can detect more differentially expressed genes than the study-level meta-analysis of estimates for genes that were well described by similar model parameter estimates across studies and had small variation across studies. Furthermore, study-level meta-analysis was well suited for genes that exhibit consistent patterns across studies, genes that had substantial variation across studies, and genes that did not conform to the assumptions of the sample-level meta-analysis. Meta-analyses confirmed previously reported genes and helped identify genes (e.g. Tomosyn, Chitinase 5, Adar, Innexin 2, Transferrin 1, Sick, Oatp26F) and Gene Ontology categories (e.g. purine nucleotide binding) not previously associated with maturation in honey bees. This study demonstrated that a combination of meta-analytical approaches best addresses the highly dimensional nature of genome-wide microarray studies. As expected, the integration of gene expression information from microarray studies using meta-analysis enhanced the characterization of the transcriptome of complex biological processes.


A national survey of hospital-based transfusion services on their approaches to platelet bacterial risk mitigation in response to the FDA final guidance for industry.
Bacterial contamination of platelets is the leading infectious risk to the United States (US) blood supply. On 30 September 2019, the US Food and Drug Administration (FDA) published a Final Guidance for Industry to reduce the risk of transfusing platelets contaminated by bacteria. A national survey was undertaken to assess readiness, attitudes, and the potential impact on hospital-based transfusion services. A survey was distributed to transfusion services in all 50 US states. Summary statistics were performed along with review and categorization of email feedback and free text comments. Eighty-three transfusion services from 48 states participated in this survey study. Currently, the most common approach is primary culture performed at manufacturing (n = 49/83, 59%). Of the bacterial risk mitigation strategies provided by the FDA, the most frequently preferred are (a) pathogen reduced platelets (PRP) for up to 5-day storage (n = 36/77, 47%), (b) large volume delayed sampling (LVDS) ≥48 hours for up to 7-day storage (n = 16/77, 21%), and (c) primary culture ≥24 hours + secondary rapid testing for up to 7-day storage (n = 7/77, 9%). The main motivating factors for the survey participants' selected strategies to comply with FDA final guidance were product availability from supplier, reducing the risk of septic transfusion reactions (STR), and complexity of implementing and performing a new or additional test. While having platelets to transfuse and preventing STR are of the utmost importance, nationwide, the majority of transfusion services do not want to take on performing new or additional testing in their laboratories.


Ethanol-glucocorticoid regulation of hepatic glucose-6-phosphate dehydrogenase.
The effect of ethanol, alone and in combination with glucocorticoid and insulin, on glucose-6-phosphate dehydrogenase (G6PDH; EC 126.96.36.199) was studied in primary cultures of rat hepatocytes maintained in a chemically defined medium. Maintenance of hepatocytes from fasted animals in a culture medium devoid of hormones and ethanol resulted in a 2.5-fold increase in G6PDH activity in 48 hr. Parallel cultures treated with glucocorticoid and insulin or glucocorticoid, insulin and ethanol stimulated enzyme activity 6- and 9-fold, respectively in 48 hr. Treatment with ethanol for 48 hr potentiated basal and glucocorticoid plus insulin-induced enzyme activity 1.4-fold. The activity of G6PDH mRNA, estimated by cell-free translation of hepatic mRNA in a mRNA-dependent reticulocyte lysate and by RNA dot-blot hybridization, was compared with enzyme activity and relative rate of G6PDH synthesis. The increases in enzyme activity observed in response to glucocorticoid and insulin or ethanol, alone or in combination with glucocorticoid and insulin, were paralleled by comparable increases in the rate of synthesis and mRNA levels of G6PDH. The results of this study show that the glucocorticoids, insulin and ethanol interact to stimulate the synthesis of G6PDH primarily by increasing the concentration of G6PDH mRNA.


Impairment of opioid control of luteinizing hormone secretion in menstrual disorders.
With the aim of examining central opioid influences on the control of luteinizing hormone (LH) secretion, we evaluated the LH response to naloxone, an opioid receptor antagonist, in patients affected by normo-, hyper-, and hypogonadotropic amenorrhea, polycystic ovarian disease and hyperprolactinemia. The results indicate that opioid influences are altered in well-defined pathologic conditions (hyperprolactinemia, obesity), in addition to being modified by gonadal steroids.


SCFOsFBK1 E3 ligase mediates jasmonic acid-induced turnover of OsATL53 and OsCCR14 to regulate lignification of rice anthers and roots.
The rice F-box protein OsFBK1, which mediates the turnover of a cinnamoyl CoA-reductase, OsCCR14, has previously been shown to regulate anther and root lignification. Here, we identify OsATL53, a member of the ATL family of RING-H2 proteins that interacts with OsCCR14 in the cytoplasm. OsATL53 was identified in the same yeast two-hybrid library screening as reported previously for OsCCR14, and we show it to have cytoplasmic localization and E3 ligase ubiquitination properties. SCFOsFBK1 mediates turnover of OsATL53 in the cytoplasm and the nucleus, and that of OsCCR14 only in the nucleus, as shown by cell-free degradation assays. Confocal fluorescence lifetime imaging microscopy analyses demonstrate that in presence of jasmonic acid (JA), which plays a role in anther dehiscence, OsATL53-OsCCR14 undergoes conformational changes that trigger the complex to accumulate around the nuclear periphery and signals OsFBK1 to initiate degradation of the proteins in the respective cellular compartments. OsATL53 decreases the enzymatic activity of OsCCR14 and sequesters it in the cytoplasm, thereby regulating the lignification process. Transgenic rice with knockdown of OsATL53 display increased lignin deposition in the anthers and roots compared to the wild type, whilst knockdown of OsCCR14 results in decreased lignin content. Our results show that OsATL53 affects the activity of OsCCR14, and that their JA-induced degradation by SCFOsFBK1 regulates lignification of rice anthers and roots.


Prognostic value of tissue Doppler imaging in patients with chronic congestive heart failure.
The prognostic value of tissue Doppler imaging (TDI) in patients with chronic congestive heart failure (CHF) has not been compared against conventional measures of systolic, diastolic and overall left ventricular LV performance. The aim of this study was to assess the prognostic value of TDI-derived parameters in patients with CHF. One hundred thirty-two subjects with chronic CHF [due to ischemic (n=82) or dilated (n=50) cardiomyopathy, 101 males, mean age 57+/-11 years] underwent conventional two-dimensional/Doppler echocardiography and assessment of the Tei-index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic, early and late diastolic mitral annular velocities (S', E' and A') were derived from pulsed TDI. A cardiac event (cardiac death, urgent cardiac transplantation or hospitalization due to decompensated CHF) was defined as the combined study endpoint. The patients were followed for a mean of 224+/-123 days. Thirty-one patients suffered an event (cardiac death, n=5; urgent cardiac transplantation, n=2; hospitalization due to CHF, n=24). In patients with event, ejection fraction was lower (25+/-10 vs. 32+/-9%), mitral deceleration time was shorter (138+/-58 vs. 193+/-72 ms), and the peak mitral E/E'-ratio (16.1+/-6.6 vs. 10.6+/-5.0) was significantly elevated as compared to patients free of events (p<0.001 for all comparisons). In those patients, the Tei-index was elevated (1.09+/-0.39 vs. 0.86+/-0.26, p<0.01), and a restrictive mitral filling pattern was more frequent (51.6 vs. 17.5%, p<0.001). Stepwise multivariate analysis identified the mitral E/E'-ratio (p<0.001) and the Tei-index (p=0.019) as the only independent predictors of a combined event. E/E'-ratio was the best predictor of hospitalization due to CHF also. In patients with mitral E/E'-ratio>12.5 or Tei-index>0.90, outcome was poor. In subjects with chronic CHF, the mitral E/E'-ratio is a stronger predictor of future cardiac events than conventional parameters of systolic, diastolic or overall LV performance. The E/E'-ratio may be a useful addition in the routine follow-up of such patients.


The relationship between plasma prolactin and testosterone levels in male hypogonadism.
Fifty seven male patients either complaining of poor sexual development, gynecomastia or dwarfism and signs of sexual infantilism were studied. Plasma prolactin (PRL) and testosterone (T) were estimated in all patients while 33 of them were also subjected to full pituitary function tests. Twelve of the latter had an elevated basal plasma cortisol or growth hormone which suggested the patient may have been "stressed"; the results were analyzed both excluding and including these patients. The remaining patients were divided into those with a plasma T less than 8.0 nmol/l (Group A, 25 patients) and those with a plasma T greater than 8.0 nmol/l (Group B, 20 patients). The results were compared with those from 18 normal men (Group C). The mean plasma PRL in group A (108.1 mU/l) was significantly lower than that in group B (181.5 mU/l, p less than 0.005) or group C (255.7 mU/l, p less than 0.001). The difference between groups A and B became much less (p less than 0.01) when results from the "stressed" patients were included but this did not affect the difference with group C. The mean plasma PRL in group B was also significantly lower (p less than 0.05) than that in group C but the significance of the difference disappeared when all the patients were included (p less than 0.2). In the patients there was a significant correlation between plasma and PRL plasma T (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Differential regulation of AQP2 trafficking in endosomes by microtubules and actin filaments.
Vasopressin-induced trafficking of aquaporin-2 (AQP2) water channels in kidney collecting duct cells is critical to regulate the urine concentration. To better understand the mechanism of subcellular trafficking of AQP2, we examined MDCK cells expressing AQP2 as a model. We first performed double-immunolabeling of AQP2 with endosomal marker proteins, and showed that AQP2 is stored at a Rab11-positive subapical compartment. After the translocation to the plasma membrane, AQP2 was endocytosed to EEA1-positive early endosomes, and then transferred back to the original Rab11-positive compartment. When Rab11 was depleted by RNA interference, retention of AQP2 at the subapical storage compartment was impaired. We next examined the role of cytoskeleton in the AQP2 trafficking and localization. By the treatment with microtubule-disrupting agent such as nocodazole or colcemid, the distribution of AQP2 storage compartment was altered. The disruption of actin filaments with cytochalasin D or latrunculin B induced the accumulation of AQP2 in EEA1-positive early endosomes. Altogether, our data suggest that Rab11 and microtubules maintain the proper distribution of the subapical AQP2 storage compartment, and actin filaments regulate the trafficking of AQP2 from early endosomes to the storage compartment.


Quality of life for adult women born with bladder and cloacal exstrophy: a long-term follow up.
To assess the quality of life of 23 female patients over 18 years of age treated and followed in the same institution. Fifty questions were sent to this group of patients covering their uro-gynaecological history, education and profession, social life and related psychological issues, sexual life and fertility. All replies were kept anonymous. Seventeen patients (74%) replied. Urine incontinence at various degrees was found in 65%. Genital prolapse was reported in 29.5%. Students accounted for 41%; 59% were actively working with a satisfactory professional life in 82% of cases. Seventy-six per cent did not consider that exstrophy affected their professional life, and 76% were happy with their social life. Psychological distress was reported by 41%, and the symptoms are detailed. Sixty-four per cent were married or had a stable partner. Seventy-six per cent were active sexually, all declaring heterosexual relations. Eighty-eight per cent had periods. Four pregnancies were reported and morbidity during gestation is described. All children were born by Caesarean section and were normal. These results are discussed and compared with the literature. Despite many hurdles, this group of patients can expect a subnormal social, family and professional life. Urinary incontinence and poor body image were the most important factors altering quality of life.


Case Report: Bilateral symmetrical primary kaposiform hemangioendothelioma of the femur.
Kaposiform hemangioendothelioma (KHE) is a rare borderline vascular tumor that usually presents as a mass of skin or deep soft tissue. We report a unique case of an 8-year-old KHE patient with bilateral symmetrical sites involving both femurs. The laboratory, radiographic, and pathological findings of the patient were minutely described. During the 6-month follow-up, the symptoms of pain and dysfunction of this patient were relieved. This study aimed to arouse clinicians' concern about the symmetrical sites of KHE patients.


Plasma cell granuloma of the larynx (case report and review of the literature).
A case is reported of Plasma Cell Granuloma of the larynx treated successfully with steroids and antibiotics.


Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.
To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.


Adenohypophysis placodal precursors exhibit distinctive features within the rostral preplacodal ectoderm.
Placodes are discrete thickenings of the vertebrate cranial ectoderm that generate morpho-functionally distinct structures, such as the adenohypophysis, olfactory epithelium and lens. All placodes arise from a horseshoe-shaped preplacodal ectoderm in which the precursors of individual placodes are intermingled. However, fate-map studies indicated that cells positioned at the preplacodal midline give rise to only the adenohypophyseal placode, suggesting a unique organization of these precursors within the preplacode. To test this possibility, we combined embryological and molecular approaches in chick embryos to show that, at gastrula stage, adenohypophyseal precursors are clustered in the median preplacodal ectoderm, largely segregated from those of the adjacent olfactory placode. Median precursors are elongated, densely packed and, at neurula stage, express a molecular signature that distinguishes them from the remaining preplacodal cells. Olfactory placode precursors and midline neural cells can replace ablated adenohypophyseal precursors up to head-fold stage, although with a more plastic organization. We thus propose that adenohypophyseal placode precursors are unique within the preplacodal ectoderm possibly because they originate the only single placode and the only one with an endocrine character.


Predictability in orbital reconstruction: A human cadaver study. Part II: Navigation-assisted orbital reconstruction.
Preformed orbital reconstruction plates are useful for treating orbital defects. However, intraoperative errors can lead to misplaced implants and poor outcomes. Navigation-assisted surgery may help optimize orbital reconstruction. We aimed to explore whether navigation-assisted surgery is more predictable than traditional orbital reconstruction for optimal implant placement. Pre-injury computed tomography scans were obtained for 10 cadaver heads (20 orbits). Complex orbital fractures (Class III-IV) were created in all orbits, which were reconstructed using a transconjunctival approach with and without navigation. The best possible fit of the stereolithographic file of a preformed orbital mesh plate was used as the optimal position for reconstruction. The accuracy of the implant positions was evaluated using iPlan software. The consistency of orbital reconstruction was lower in the traditional reconstructions than in the navigation group in the parameters of translation and rotation. Implant position also differed significantly in the parameters of translation (p = 0.002) and rotation (pitch: p = 0.77; yaw: p < 0.001; roll: p = 0.001). Compared with traditional orbital reconstruction, navigation-assisted reconstruction provides more predictable anatomical reconstruction of complex orbital defects and significantly improves orbital implant position.


Leptospirosis kidney disease: Evolution from acute to chronic kidney disease.
Leptospirosis is a neglected bacterial disease caused by leptospiral infection that carries a substantial mortality risk in severe cases. Research has shown that acute, chronic, and asymptomatic leptospiral infections are closely linked to acute and chronic kidney disease (CKD) and renal fibrosis. Leptospires affect renal function by infiltrating kidney cells via the renal tubules and interstitium and surviving in the kidney by circumventing the immune system. The most well-known pathogenic molecular mechanism of renal tubular damage caused by leptospiral infection is the direct binding of the bacterial outer membrane protein LipL32 to toll-like receptor-2 expressed in renal tubular epithelial cells (TECs) to induce intracellular inflammatory signaling pathways. These pathways include the production of tumor necrosis factor (TNF)-α and nuclear factor kappa activation, resulting in acute and chronic leptospirosis-related kidney injury. Few studies have investigated the relationship between acute and chronic renal diseases and leptospirosis and further evidence is necessary. In this review, we intend to discuss the roles of acute kidney injury (AKI) to/on CKD in leptospirosis. This study reviews the molecular pathways underlying the pathogenesis of leptospirosis kidney disease, which will assist in concentrating on potential future research directions.


De novo 22q11.2 deletions and auricular findings in two Chinese patients with microtia.
Congenital microtia is a common craniofacial malformation resulting from both environmental and genetic factors. Recurrent chromosomal imbalances were observed in patients with microtia. The 22q11.2 deletion is one of the most common microdeletions in human beings. The cell division cycle 45 gene (CDC45) embedded in the proximal 22q11.2 deleted region is involved in craniofacial development. However, only a few studies have focused on the 22q11.2 deletion as genetic etiology in microtia patients and studied its associated external ear deformity characteristics in detail. In this research, a total of 65 patients from north China with sporadic microtia were studied. Copy number variations of CDC45 were screened using AccuCopy assay. The 22q11.2 deletion harboring CDC45 was identified by whole-genome sequencing and targeted next-generation sequencing. A parental test was carried out to determine the origin of the deletion. CDC45 copy number loss was identified in two patients with microtia. A set of qPCR assays demonstrated two patients carried a typical proximal 22q11.2 deletion between the low-copy repeats on chromosome 22q11.2 (LCR22A and LCR22D), encompassing CDC45. The 22q11.2 deletions were de novo in each patient. In-depth auricular phenotype assessment showed these two patients have a distinct concha-type ear malformation while other microtia patients have lobule-type microtia among the 65 microtia patient cohort in this study. Here we present two additional Chinese microtia patients with de novo 22q11.2 proximal deletion harboring CDC45 and further report these patients' distinct ear malformation.


Management of upper limb amputations.
Acquired upper extremity amputations beyond the finger can have substantial physical, psychological, social, and economic consequences for the patient. The hand surgeon is one of a team of specialists in the care of these patients, but the surgeon plays a critical role in the surgical management of these wounds. The execution of a successful amputation at each level of the limb allows maximum use of the residual extremity, with or without a prosthesis, and minimizes the known complications of these injuries. This article reviews current surgical options in performing and managing upper extremity amputations proximal to the finger.


The flat spot of the proximal ulna: a useful anatomic landmark in total elbow arthroplasty.
The relationship between the flat subcutaneous dorsal surface (flat spot) of the ulna and the anatomic flexion axis of the elbow was investigated in 68 cadaveric ulnae. The flat spot and the guiding ridge of the greater sigmoid notch were digitized with an electromagnetic tracking device. The area of the flat spot, as well as its angle with the plane of the greater sigmoid notch, was calculated. The size of the flat spot was variable but was found to be nearly perpendicular to the plane of the greater sigmoid notch (mean, 89.8 degrees +/- 6.5 degrees ). This indicates that the subcutaneous dorsal surface of the proximal ulna is a useful landmark to assist the surgeon intraoperatively to orient the ulnar component axially in total elbow arthroplasty.


[Participation of the immigrant population in breast cancer screening in Tarragona, Spain].
To evaluate the differences between autochthonous and allochthonous women's participation in a breast cancer screening programme. Retrospective study based on data from the Breast Cancer Screening Programme of the province of Tarragona (2008-2015). The sample is the target population of the programme with known country of origin. Cohort of 40,824 women. Allochthonous women participate less than autochthonous women (41.8% vs. 72.3%) although they have a similar global detection rate to the latter but with differences according to the human development index of their country of origin. Both groups present similar tumour stages on detection (p=.59). Strategies specifically aimed at the immigrant population are required to improve their participation in breast cancer screening.


Phosphate on ceria with controlled active sites distribution for wide temperature NH3-SCR.
Practical catalysts that work well at a wide operation window for selective catalytic reduction of NOx by NH3 (NH3-SCR) are essential for the purification of non-isothermal emission such as vehicle exhaust. However, NH3-SCR catalyst with high low-temperature performance has excellent NO activation and oxidation ability, leading inevitably to NH3-intermediates over-oxidation and N2 selectivity deterioration at high operation temperatures. By far the best performance ceria-based catalyst with a super-wide temperature window of 175-400 oC for 90% NOx conversion in ideal environment and 225-475 oC for 90% NOx conversion by addition of 50 ppm SO2 and 5% H2O is obtained via distributing phosphate over the outer of ceria. NH3 protection strategy is the key for keeping high-temperature activity. Brønsted acidity surged as the formation of P-OH network via a charge compensatory mechanism of phosphate. NH3 was prone to be captured by the surface P-OH network, forming NH4+ species, avoiding being oxidized and contributing to both low and high temperature activity. NO can also be readily absorbed and oxidized to the absorbed NO2(ad) species over phosphate as reflected by in situ DRIFTS and DFT calculation, providing a facile pathway for 'fast SCR' by reacting with NH4+ species to form N2 and H2O. The reaction followed the L-H mechanism and contributed to catalytic activity under 300 oC. This directional structure fabricate strategy helps to increases the NOx conversion and N2 selectivity under a broaden temperature window. The enriched Brønsted acid sites over phosphate treated ceria were also demonstrated to have largely suppressed SO2 adsorption, which significantly slowed down the catalyst poisoning. A dynamic equilibrium between the poisoning and regeneration process can be achieved according to the shrinking-core model for each nanosphere, leading to the excellent resistance.


Molecular analysis of the hemagglutinin genes of Australian H7N7 influenza viruses: role of passerine birds in maintenance or transmission?
In 1985 a fowl plague-like disease occurred in chickens in Lockwood, Victoria, Australia and caused high mortality. An H7N7 influenza virus was isolated from the chickens (A/Chicken/Victoria/1/85); additionally, an antigenically similar virus was isolated from starlings (A/Starling/Victoria/5156/85) and serological evidence of H7N7 virus infection was found in sparrows. Antigenic analysis with monoclonal antibodies to H7, oligonucleotide mapping of total vRNA, and sequence analysis of the HA genes established that the chicken and starling influenza viruses were closely related and probably came from the same source. There was high nucleotide sequence homology (95.3%) between the HA genes of A/Chick/Vic/85 and a fowl plague-like virus isolated from chickens in Victoria 9 years earlier [A/Fowl/Vic/76 (H7N7)]. The sequence homologies indicated that the A/Chick/Vic/85 and A/Fowl/Vic/76 were derived from a common recent ancestor, while another recent H7N7 virus, Seal/Mass/1/80 originated from a different evolutionary lineage. Experimental infection of chickens and starlings with A/Chick/Vic/1/85 (H7N7) was associated with high mortality (100%), transmission to contact birds of the same species, and virus in all organs. In sparrows one-third of the birds died after infection and virus was isolated from most organs; transmission to contact sparrows did not occur. In contrast, the H7N7 virus replicated in ducks and spread to contact ducks but caused no mortality. These studies establish that the host species plays a role in determining the virulence of avian influenza viruses, and provide the first evidence for transmission of virulent influenza viruses between domestic poultry and passerine birds. They support the hypothesis that potentially virulent H7N7 influenza viruses could be maintained in ducks where they cause no apparent disease and may sometimes spread to other wild birds and domestic poultry.


Significance of QRS duration changes in the evaluation of ST-segment depression presenting exclusively during the postexercise recovery period.
The aim of this study was to evaluate the contribution of QRS prolongation in the diagnosis of coronary artery disease (CAD) in patients with exercise-induced ST-segment depression exclusively during the recovery period. The study population consisted of 107 patients (90 males and 17 females) aged 39-70 (mean 59 +/- 7) years who underwent a treadmill exercise test using Bruce protocol and presented ST-segment depression limited to the recovery period. Angiographic data were available for all studied patients. Among studied patients, 74 (69%) were found to have hemodynamically significant CAD, while the remaining 33 (31%) had normal coronary arteries. Concomitant QRS prolongation was revealed in 61 (82%) of the patients with angiographically documented CAD, while in 13 (18%) patients QRS duration remained unchanged. On the contrary, only 4 (12%) of the 33 patients with normal coronary arteries showed prolonged QRS duration during ST depression, while in the remaining 29 (88%) QRS duration remained unchanged. The evaluation of the concomitant QRS duration changes may discriminate patients with truly ischemia-induced ST-segment depression limited to the recovery period.


Inhibition of breast cancer cell growth and induction of cell death by 1,1-bis(3'-indolyl)methane (DIM) and 5,5'-dibromoDIM.
1,1-Bis(3'-indolyl)methane (DIM) and the 5,5'-dibromo ring substituted DIM (5,5'-diBrDIM) inhibited growth of MCF-7 and MDA-MB-231 breast cancer cells, and IC50 values were 10-20 and 1-5 microM, respectively, in both cell lines. DIM and 5,5'-diBrDIM did not induce p21 or p27 protein levels or alter expression of Sp1 or Sp3 proteins in either cell line. In contrast, 10 microM 5,5'-diBrDIM downregulated cyclin D1 protein in MCF-7 and MDA-MB-231 cells 12 and 24 h after treatment. DIM (20 microM) also decreased cyclin D1 in MCF-7 (24 h) and MDA-MB-231 (12 h), and the DIM/5,5'-diBrDIM-induced degradation of cyclin D1 was blocked by the proteasome inhibitor MG132. Both DIM and 5,5'-diBrDIM induced apoptosis in MCF-7 cells and this was accompanied by decreased Bcl-2, release of mitochondrial cytochrome c, and decreased mitochondrial membrane potential as determined by the red/green fluorescence of JC-1. DIM and 5,5'-diBrDIM induced extensive necrosis in MDA-MB-231 cells; however, this was accompanied by decreased mitochondrial membrane potential primarily in cells treated with 5,5'-diBrDIM but not DIM. Thus, DIM and 5,5'-diBrDIM induce cell death in MCF-7 and MDA-MB-231 cells by overlapping and different pathways, and the ring-substituted DIM represents a novel class of uncharged mitochondrial poisons that inhibit breast cancer cell and tumor growth.


Retrolental fibroplasia. Cases seen at the Helsinki University Eye Hospital 1956-1974.
In the period 1956-1974, 31 new cases of retrolental fibroplasia (RLF) were diagnosed at the Helsinki University Eye Hospital. All were alive in 1974. 90% weighed less than 1500 g at birth and the gestational age of less than 30 weeks at birth was present in 85%. All patients had required supplementary oxygen during the first weeks of life. 84% of the eyes had visual acuity of finger counting 1 m or less and when classified according to the corrected visual acuity in the better eye, 71% of the patients were practically blind according to the classification by Rintelen. 81% of the eyes showed one of the cicatricial stages of RLF, III to V, and 45% showed the grade V of the disease. 11% of the eyes showed corneal opacities, 44% a flat or absent anterior chamber, 11% had intraocular pressure of greater than or equal to 30 mmHg and 21% showed lenticular opacities. When the period of the observation was surveyed, it was found that during the latter half of the observation period, twice as many new cases of RLF were born. At a rough estimate it was calculated that in 1956-1974 at least 50 new cases of RLF developed in Finland.


Radioactive iodine dose and survival in cats with hyperthyroidism (2015-2020).
Radioactive iodine (131I) is the preferred treatment for feline hyperthyroidism but neither the optimal 131I dose nor consistent predictors of post-treatment azotaemia have been determined. The aims of the study were to evaluate the relationships between: (1) 131I dose and survival; and (2) pretreatment and post-treatment serum creatinine concentration. Medical records of hyperthyroid cats treated with 131I at a single referral hospital were reviewed. Information regarding signalment, body weight, pretreatment and post-treatment serum total thyroxine concentration (TT4), serum creatinine concentration, 131I dose and survival were determined. Multivariable Cox proportional hazards analysis was used to identify variables associated with survival. Multivariable linear regression analysis was used to identify variables associated with post-treatment serum creatinine concentration. One hundred and ninety-eight (79 male, 119 female) cats were treated for hyperthyroidism with 131I (median dose 138 MBq; interquartile range 92-168). Median survival time was 1153 days (range 16-1871). Post-treatment serum creatinine (P <0.001) and age (P = 0.049) were significantly associated with survival. Every 10 µmol/l increase in post-treatment serum creatinine concentration and every year increase in age was associated with a 1.07-fold (confidence interval [CI] 1.04-1.11) and 1.17-fold (CI 1.00-1.37) increase in the daily hazard of death, respectively. Pretreatment serum creatinine concentration was directly, and post-treatment serum TT4 concentration was inversely, associated with post-treatment serum creatinine concentration. Every 1 μmol/l increase in pretreatment serum creatinine concentration was associated with an increase in post-treatment serum creatinine concentration of 0.7 μmol/l (SE 0.17; P <0.001). Conversely, every 1 nmol/l decrease in post-treatment serum TT4 concentration was associated with a 1.2 μmol/l (SE 0.61; P <0.001) increase in post-treatment serum creatinine concentration. Post-treatment serum TT4 concentration was associated with post-treatment azotaemia, which was associated with survival. Although 131I dose was not directly associated with survival, dosing strategies that minimise post-treatment hypothyroidism and azotaemia could improve patient survival.


Growth Behavior, Biomass Composition and Fatty Acid Methyl Esters (FAMEs) Production Potential of Chlamydomonas reinhardtii, and Chlorella vulgaris Cultures.
The production of biomolecules by microalgae has a wide range of applications in the development of various materials and products, such as biodiesel, food supplements, and cosmetics. Microalgae biomass can be produced using waste and in a smaller space than other types of crops (e.g., soja, corn), which shows microalgae's great potential as a source of biomass. Among the produced biomolecules of greatest interest are carbohydrates, proteins, lipids, and fatty acids. In this study, the production of these biomolecules was determined in two strains of microalgae (Chlamydomonas reinhardtii and Chlorella vulgaris) when exposed to different concentrations of nitrogen, phosphorus, and sulfur. Results show a significant microalgal growth (3.69 g L-1) and carbohydrates (163 mg g-1) increase in C. reinhardtii under low nitrogen concentration. Also, higher lipids content was produced under low sulfur concentration (246 mg g-1). It was observed that sulfur variation could affect in a negative way proteins production in C. reinhardtii culture. In the case of C. vulgaris, a higher biomass production was obtained in the standard culture medium (1.37 g L-1), and under a low-phosphorus condition, C. vulgaris produced a higher lipids concentration (248 mg g-1). It was observed that a low concentration of nitrogen had a better effect on the accumulation of fatty acid methyl esters (FAMEs) (C16-C18) in both microalgae. These results lead us to visualize the effects that the variation in macronutrients can have on the growth of microalgae and their possible utility for the production of microalgae-based subproducts.


[Treatment of falciparum malaria with artemether-lumefantrine according to a 5-day schedule: results of a study in 21 patients and recommendations].
To describe the outcome of 21 successive patients with falciparum malaria treated with artemether-lumefantrine in 6 oral doses of 80-480 mg in 96 hrs (5-day schedule). Retrospective cohort study. The data on all successive patients with falciparum malaria that were treated with artemether-lumefantrine in the Leiden University Medical Centre (n = 15) and the Bronovo Hospital (n = 6), the Netherlands, during the period from August 2003 to February 2006 were evaluated. Ten patients with uncomplicated falciparum malaria were treated exclusively with artemether-lumefantrine; time to parasitological clearance was less than 48 hrs in 5 out of 6 tested patients. The mean admission time was 1.3 days (95% CI: 0.7-1.9). 6 patients with non-severe falciparum malaria were initially treated with intravenous quinine because of vomiting; artemether-lumefantrine was started after an average of 0.9 days. Parasite clearance required more than 48 hrs in all patients. The mean admission time was 3.8 days (95% CI: 2.7-4.9). 5 patients had severe falciparum malaria. They received artemether-lumefantrine 4-24 hrs after starting quinine therapy. The parasite count was < 0.1% after an average of 1.5 days (95% CI: 0.3-2.7). The mean admission time was 4.2 days (95% CI: 2.2-5.2). The serum level of lumefantrine was > or = 500 microg/l (target value) in 9 out of 10 tested patients. Treatment of falciparum malaria with artemether-lumefantrine according to a 5-day schedule resulted in a swift recovery and short admissions. No relapses were reported.


Identification of amygdalin and its major metabolites in rat urine by LC-MS/MS.
Amygdalin and its metabolites in rat urine were identified using liquid chromatography-electrospray ionization (ESI) tandem ion-trap mass spectrometry. The purified rat urine sample was separated using a reversed-phase C18 column with 10 mM sodium phosphate buffer (pH 3.1) containing 30% methanol as the mobile phase, amygdalin and its metabolites were detected by on-line mass detector in selected ion monitoring (SIM) mode. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (DeltaM), retention times and MS(2) spectral patterns of metabolites with those of parent drug. At least seven metabolites and the parent drug were found in rat urine after i.v. injection of 100 mg/kg doses of amygdalin. Among them, six metabolites were reported for the first time.


Liver transplantation with preservation of the inferior vena cava: lessons learned through 2,000 cases.
We aim to demonstrate the utility and efficacy of the "piggyback technique" (PBT); liver transplant (LT) with caval preservation. Adult LTs were performed with intent to use the PBT except in cases of juxtacaval malignancy or technical difficulty. Hepatic venous outflow was established between the donor suprahepatic cava and the joined ostia of all recipient suprahepatic veins. Technical variants with the donor cava and recipient retrohepatic cava were used as needed. The experience was divided into 2 eras: E1 (1994-2002), E2 (2002-2010). We completed 945 of 1080 LTs in E1 (87.5%) and 851 of 920 LTs in E2 (92.5%) using the PBT. Thirty day mortality was 4.6% in E1, 3% in E2 (p = 0.02) with 2 intra-operative deaths in E1. One, 3, 5 year patient survival was 83.7, 75.6, 69.3% in E1 vs. 86, 78.4, 73.8% in E2 (p = 0.057). Graft survival was 77.7, 69, 62.3% in E1 vs. 84, 76.2, 71.2% in E2 (p < 0.0001). Median operative time and hospital length of stay improved in E2 (p < 0.0001, 0.0001). Outflow variants were used more frequently in E2 (11.3% vs. 6.1%). Nine patients (0.5%) developed outflow obstruction, 6 in E1, and 3 in E2. Twice, it was recognized and corrected intraoperatively. Seven patients presented with refractory ascites. Six were successfully treated (4 balloon dilatation, 2 surgical revision), one patient died after attempted dilatation. The PBT can be used as the preferred technique in adult LT. With experience, the technique was used more frequently, with more variants, with improved outcomes. Outflow obstruction was a rare complication.


The prostacyclin analog beraprost sodium augments the efficacy of therapeutic angiogenesis induced by autologous bone marrow cells.
Implantation of autologous bone marrow (BM) mononuclear cells (MNCs) has been shown to augment neovascular formation in ischemic tissues in experimental animals and in humans. Prostaglandin derivatives improve the symptoms of patients with critical limb ischemia, possibly by their vasodilating and antiplatelet actions. We therefore examined whether therapeutic angiogenesis by implantation of autologous BM-MNCs would be enhanced by beraprost sodium (BPS), using a rabbit ischemic hindlimb model. Ischemia was induced by surgical resection of the left femoral artery. Twenty-five New Zealand white rabbits were divided into four groups. The first group (BM group, n = 4) received autologous BM-MNCs (2 x 10(6)/animal) implanted into the ischemic tissue 1 week after limb ischemia. The second group (BM+BPS group, n = 8) received BPS injected into the dorsal skin (300 microg/kg daily) starting 1 week before limb surgery. This group received BM-MNC implantation 1 week after surgery. Daily injection of BPS was continued until the end of the protocol. The third group (BPS group, n = 8) received BPS injected into the dorsal skin (600 microg/kg daily) starting 1 week before limb surgery. The fourth group received saline as a control (n = 4). The extent of angiogenesis in the ischemic hindlimb was assessed using the angiographic score (AS), ischemic/normal limb calf blood pressure ratio (CBPR), and tissue capillary density. Four weeks after limb ischemia, the ischemic/normal CBPR was highest in the BM+BPS group, followed by the BPS, BM, and control groups (0.56 +/- 0.16, 0.51 +/- 0.25, 0.44 +/- 0.15, and 0.30 +/- 0.10, respectively). The AS was also the greatest in the BM+BP group, followed by the BM, BP, and S group (1.63 +/-0.21, 1.31 +/- 0.25, 1.26 +/- 0.21 and 0.80 +/- 0.10, respectively). The TCD was greatest in the BM+BP group, followed in by the BM, BP, and S group? (46 +/- 4.1, 34 +/- 0.7, 33 +/- 6.9, and 19 +/- 1.8 per field, respectively). BP treatment is an effective means to enhance the efficacy of therapeutic angiogenesis induced by autologous BM-MNCs implantation in ischemic hindlimb tissues.


Environmental implications of interaction between humic substances and iron oxide nanoparticles: A review.
Goethite, hematite, ferrihydrite, and other iron oxides bind through various sorption reactions with humic substances (HS) in soils creating nano-, micro-, and macro-aggregates with a specific nature and stability. Long residence times of soil organic matter (SOM) have been attributed to iron-humic substance (Fe-HS) complexes due to physical protection and chemical stabilization at the organic-mineral interface. Humic acids (HA) and fulvic acids (FA) contain many acidic functional groups that interact with Fe oxides through different mechanisms. Due to the numerous interactions between mineral Fe and natural SOM, much research has led into a better identification and definition of HS. In this review, we first focus on the surface colloidal properties of Fe oxides and their reactivity toward HS. These minerals can be efficiently identified by usual techniques, such as XRD, FTIR spectroscopy, XAS, Mössbauer, diffuse reflectance spectroscopies (DRS), HRTEM, ATM, NanoSIMS. Second, we present the recent state of art regarding the adsorption/precipitation of HS onto iron mineral surfaces and their effects on binding metalloid and trace elements. Finally, we consider future research directions based on recent scientific literature, with particular focus on the ability of Fe nano-particles to increase Fe bioavailability, improve carbon sequestration, reduce greenhouse gas emissions, and decrease the impact of persistent organic and inorganic pollutants. The methodology in this field has rapidly developed over the last decade. However, new procedures to estimate the nature of Fe-HA bonds will be important contributions in clarifying the role of natural iron oxides in soil for carbon stabilization.


Inter-strain comparison by pyrolysis mass spectrometry in the investigation of Staphylococcus aureus nosocomial infection.
Pyrolysis mass spectrometry (PyMS) was used to examine isolates of Staphylococcus aureus from an outbreak of wound infections on a cardiothoracic surgical unit, some of which were thought to have been related to a point-source in the operating theatre. The PyMS results were compared with the results of phage typing. Both methods suggested that a single strain of S. aureus, of phage pattern 29/52/52A/79/80/81, was responsible for some of the wound infections, but PyMS also identified two patients with phage non-typable isolates. Phage typing indicated four staff members as possible carriers of the epidemic strain, but PyMS indicated only two. Epidemiological enquiry confirmed that one of the two members of staff identified by both methods was likely to have been the source of the theatre-based infection. PyMS is a rapid and relatively inexpensive technique for the investigation of nosocomial S. aureus infection and was more discriminatory than phage typing in this instance.