Bioavailability of zinc from defatted soy flour, soy hulls and whole eggs as determined by intrinsic and extrinsic labeling techniques.
Bioavailability of zinc from diets prepared from intrinsically and extrinsically labeled autoclaved, defatted soy flour and scrambled, freeze-dried egg was investigated in male rats marginally depleted in zinc. In one study, retention of zinc from intrinsically labeled soybean flour (73%) was significantly less than from 65ZnCl2 extrinsically added to a soy flour-based diet (80%). Zinc from intrinsically labeled soybean hulls and from soy flour diets containing 10% soybean hulls extrinsically labeled with 65ZnCl2 was as available as the zinc from the extrinsically labeled soy flour diet. In a second study, extrinsic and intrinsic labeling techniques gave a similar assessment of bioavailability of zinc from egg- and soy flour-based diets when extrinsic labeling was accomplished by thoroughly mixing 65ZnCl2 with the protein source prior to incorporation into the diet. Absorption of 65Zn was greater from egg diets than from soy flour diets and of intermediate value from mixed soy flour and egg (50:50, wt/wt) diets regardless of which protein source was labeled, indicating that the zinc entered a common pool.


N-terminal pro-brain natriuretic peptide and outcomes in patients undergoing surgical ventricular restoration.
N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels have been shown to be increased at baseline in patients undergoing surgical ventricular restoration (SVR) of the left ventricle. However, changes in the values of this marker in the early postoperative period and its prognostic significance remain less known in these patients. We evaluated 31 consecutive patients undergoing SVR who had NT-pro-BNP determined a day before SVR and from postoperative days 0 to 4. Major morbidity was defined as > or =1 of the following: ventilation >48 hours, stroke, acute renal failure, low cardiac output, reoperation, or mediastinitis. The association of preoperative NT-pro-BNP with perioperative outcomes was assessed using multivariable logistic regression analysis. Receiver operating characteristic curve was used to test its discrimination power. Major morbidity occurred in 16 patients (52%) with only 1 death within 30 days of SVR. Mean preoperative NT-pro-BNP was 4.5-fold higher in patients with postoperative major morbidity than in those without it (3,022 +/- 2,981 vs 676 +/- 533 pg/ml, p = 0.007). On multivariate analysis, preoperative NT-pro-BNP was independently associated with major morbidity after adjusting for baseline confounding, particularly age, ejection fraction, and European System for Cardiac Operative Risk Evaluation (odds ratio 1.002, 95% confidence interval 1.001 to 1.003, p = 0.032). Preoperative NT-pro-BNP had a high discrimination power on receiver operating characteristic analysis for major morbidity (area under the curve 0.84, sensitivity 68%, and specificity 88% for 1,304 pg/ml). Although NT-pro-BNP levels decreased after SVR in patients without major morbidity, their levels remained persistently increased in those with it. In conclusion, preoperative NT-pro-BNP determination may be of value in stratifying the risk for major morbidity after SVR.


Functional analysis of a transrepressor domain in the hepatitis C virus core protein.
Hepatitis C virus (HCV) is one of the major causative agents of chronic liver disease with the potential for development of hepatocellular carcinoma. The putative core protein of the virus has many intriguing properties, including transcriptional regulation of cellular and unrelated viral promoters. To further characterize the transregulatory function, a number of chimeric constructs were made by fusion of the core gene to the DNA binding domain of the yeast transactivator factor GAL4. The fusion protein exhibited a repressor activity on the herpes simplex virus thymidine kinase promoter via the upstream GAL4 DNA binding sites. A structure /function analysis of HCV core mutants in the context of the GAL4 DNA binding domain revealed that the transcriptional repressor activity was located near the N-terminus (amino acids 26 85). Transcription was strongly inhibited upon transfer of this repressor domain to a heterologous activation domain, (3CGln) of Epstein Barr virus transcription factor EBNA3C. Results from this study suggest that the HCV core protein contains an overall repressor activity, and that the repressor domain is located near the N-terminus.


Decrease of memory retention in a parasitic wasp: an effect of host manipulation by Wolbachia?
Several factors, such as cold exposure, aging, the number of experiences and viral infection, have been shown to affect learning ability in different organisms. Wolbachia has been found worldwide as an arthropod parasite/mutualist symbiont in a wide range of species, including insects. Differing effects have been identified on physiology and behavior by Wolbachia. However, the effect of Wolbachia infection on the learning ability of their host had never previously been studied. The current study carried out to compare learning ability and memory duration in 2 strains of the parasitoid Trichogramma brassicae: 1 uninfected and 1 infected by Wolbachia. Both strains were able to associate the novel odors with the reward of an oviposition into a host egg. However, the percentage of females that responded to the experimental design and displayed an ability to learn in these conditions was higher in the uninfected strain. Memory duration was longer in uninfected wasps (23.8 and 21.4 h after conditioning with peppermint and lemon, respectively) than in infected wasps (18.9 and 16.2 h after conditioning with peppermint and lemon, respectively). Memory retention increased in response to the number of conditioning sessions in both strains, but memory retention was always shorter in the infected wasps than in the uninfected ones. Wolbachia infection may select for reduced memory retention because shorter memory induces infected wasps to disperse in new environments and avoid competition with uninfected wasps by forgetting cues related to previously visited environments, thus increasing transmission of Wolbachia in new environments.


Molecular characterization of the levansucrase gene from the endophytic sugarcane bacterium Acetobacter diazotrophicus SRT4.
The Acetobacter diazotrophicus SRT4 gene encoding levansucrase (EC 220.127.116.11) (IsdA) was isolated from a genomic library. The nucleotide sequence of a 2.3 kb DNA fragment sufficient for complementation of a levansucrase-deficient mutant (obtained by EMS treatment) was determined. The IsdA gene (1751 bp) coded for a polypeptide of molecular mass 64.9 kDa with an isoelectric point of 5.2. The N-terminal amino acid sequence of the extracellular levansucrase indicated the presence of a precursor protein with a putative signal sequence of 51 residues which is possibly cleaved in two successive steps. Expression of the IsdA gene from the lac promoter in Escherichia coli resulted in the production of a protein with levansucrase activity. The deduced amino acid sequence of the IsdA gene was 48% and 46% identical with the levansucrases from the Gram-negative bacteria Zymomonas mobilis and Erwinia amylovora, respectively, but only 28-31% identical with levansucrases from Gram-positive bacteria. Multiple alignments of published levansucrase sequences from Gram-negative and Gram-positive bacteria revealed eight conserved motifs. A comparison of the catalytic properties and the sequence of the A. diazotrophicus levansucrase with those of the Bacillus subtilis levansucrase suggested that one of these motifs may be involved in the specificity of the synthetized product. Disruption of the IsdA gene in the genome of A. diazotrophicus resulted in a mutant lacking both levansucrase activity and the ability to utilize sucrose as a carbon source, suggesting that levansucrase is the key enzyme in sucrose metabolism of A. diazotrophicus.


Interventional treatment of pulmonary arteriovenous malformations.
Pulmonary arteriovenous malformations (PAVM) are congenital vascular communications in the lungs. They act as right to left shunts so that the blood running through these malformations is not oxygenated or filtered. These patients are typically hypoxaemic with exercise intolerance and are at high risk of paradoxical emboli to the brain and other organs. These malformations are most commonly seen in hereditary haemorrhagic telangiectasia (HHT) (Mb. Osler-Weber-Rendu syndrome). Nowadays, the generally accepted treatment strategy of first choice is embolization of the afferent arteries to the arteriovenous malformations. It is a minimally invasive procedure and at the same time a lung preserving treatment with a very high technical success, high effectiveness and low morbidity and mortality. Embolization prevents cerebral stroke and abscess as well as pulmonary haemorrhage and further raises the functional level. Embolization is a well-established method of treating PAVM, with a significant effect on oxygenation of the blood. Screening for PAVM in patients at risk is recommended, especially in patients with HHT.


Dilatation of the parous non-pregnant cervix.
In vitro cervical dilatations were carried out on 33 uteri removed by hysterectomy for conditions not involving the cervix from parous women in their reproductive span of life. A specially designed force measuring dilator was used for all the tests. The analysis of the results involved the application of a thick-walled cylindrical stress determination technique. Using this approach it was possible to calculate quasi-elastic moduli for different degrees of dilatation and obtain theoretical distributions of radial and circumferential stress across the cervical wall. These results indicated a yielding of the cervical tissue at about 9 to 11 mm. dilatation in a significant number of cases.


Influence of Target-Substrate Distance on the Transport Process of Sputtered Atoms: MC-MD Multiscale Coupling Simulation.
A Monte Carlo (MC) and molecular dynamics (MD) coupling simulation scheme for sputtered particle transport was first proposed in this work. In this scheme, the MC method was utilized to model the free-flight process of sputtered atoms, while the MD model was adopted to simulate the collision between the sputtered atom and background gas atom so as to self-consistently calculate the post-collision velocity of the sputtered atom. The reliability of the MD collision model has been verified by comparing the computation results of the MD model and of an analytical model. This MC-MD coupling simulation scheme was used to investigate the influence of target-substrate distance on the transport characteristic parameters of sputtered Cu atoms during magnetron sputtering discharge. As the target-substrate distance increased from 30 to 150 mm, the peak energy of the incident energy distribution of deposited Cu atoms decreased from 2 to 1 eV due to the gradual thermalization of sputtered atoms. The distribution of differential deposition rate in unit solid angle firstly became more forward-peaked and then reversely approached the cosine distribution, which was agreed with the existing experimental observations. This work is expected to provide a more realistic simulation scheme for sputtered particle transport, which can be further combined with the MD simulation of sputtered film growth to explore the influence mechanism of process parameters on the properties of sputtered film.


Exploring effective approaches for haplotype block phasing.
Knowledge of phase, the specific allele sequence on each copy of homologous chromosomes, is increasingly recognized as critical for detecting certain classes of disease-associated mutations. One approach for detecting such mutations is through phased haplotype association analysis. While the accuracy of methods for phasing genotype data has been widely explored, there has been little attention given to phasing accuracy at haplotype block scale. Understanding the combined impact of the accuracy of phasing tool and the method used to determine haplotype blocks on the error rate within the determined blocks is essential to conduct accurate haplotype analyses. We present a systematic study exploring the relationship between seven widely used phasing methods and two common methods for determining haplotype blocks. The evaluation focuses on the number of haplotype blocks that are incorrectly phased. Insights from these results are used to develop a haplotype estimator based on a consensus of three tools. The consensus estimator achieved the most accurate phasing in all applied tests. Individually, EAGLE2, BEAGLE and SHAPEIT2 alternate in being the best performing tool in different scenarios. Determining haplotype blocks based on linkage disequilibrium leads to more correctly phased blocks compared to a sliding window approach. We find that there is little difference between phasing sections of a genome (e.g. a gene) compared to phasing entire chromosomes. Finally, we show that the location of phasing error varies when the tools are applied to the same data several times, a finding that could be important for downstream analyses. The choice of phasing and block determination algorithms and their interaction impacts the accuracy of phased haplotype blocks. This work provides guidance and evidence for the different design choices needed for analyses using haplotype blocks. The study highlights a number of issues that may have limited the replicability of previous haplotype analysis.


Loss of stress response as a consequence of viral infection: implications for disease and therapy.
Herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. Having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. Host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. In the case of Newcastle disease virus, the effects of viral infection on heat shock proteins may be leveraged as a therapy for cancer. Finally, the search for a specific virus being responsible for a condition like chronic fatigue syndrome may not be worthwhile if the disease is simply a nonspecific response to viral infection.


Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.
Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.


Function and redundancy of the chaplin cell surface proteins in aerial hypha formation, rodlet assembly, and viability in Streptomyces coelicolor.
The chaplins are a family of eight secreted proteins that are critical for raising aerial hyphae in Streptomyces coelicolor. These eight chaplins can be separated into two main groups: the long chaplins (ChpA to -C) and the short chaplins (ChpD to -H). The short chaplins can be further subdivided on the basis of their abilities to form intramolecular disulfide bonds: ChpD, -F, -G, and -H contain two Cys residues, while ChpE has none. A "minimal chaplin strain" containing only chpC, chpE, and chpH was constructed and was found to raise a substantial aerial mycelium. This strain was used to examine the roles of specific chaplins. Within this strain, the Cys-containing ChpH was identified as the major polymerization unit contributing to aerial hypha formation and assembly of an intricate rodlet ultrastructure on the aerial surfaces, and the two Cys residues were determined to be critical for its function. ChpC augmented aerial hypha formation and rodlet assembly, likely by anchoring the short chaplins to the cell surface, while ChpE was essential for the viability of wild-type S. coelicolor. Interestingly, the lethal effects of a chpE null mutation could be suppressed by the loss of the other chaplins, the inactivation of the twin arginine translocation (Tat) secretion pathway, or the loss of the rodlins.


Resistance of mouse primary microglia and astrocytes to acrylonitrile-induced oxidative stress.
Acrylonitrile (ACN) is a widely used chemical in the production of plastics, resin, nitrile, acrylic fibers, synthetic rubber, and acrylamide. ACN is considered a Group 2B possible carcinogen in humans and is known to cause gliomas in rats. These gliomas are predominantly composed of microglia and not astrocytes. Interestingly, ACN treatment does not cause gliomas in mice, suggesting that mouse astrocytes and microglia may be resistant to ACN. We investigated the effects of ACN treatment on primary mouse microglia and astrocytes to investigate their sensitivity to the chemical. Cell viability, ACN uptake, glutathione (GSH) levels and the expression of NF-E2-related factor 2 (Nrf2) were evaluated in primary mouse microglia and astrocytes following ACN treatment. Our results indicate that mouse glial cells are resistant to ACN-induced oxidative stress. Both cell types accumulated ACN; however, there was a minor effect of ACN on cell viability in astrocytes and microglia. Nrf2 and GSH levels were unchanged in ACN-treated as compared to the untreated cells. These observations suggest that primary mouse glial cells are resistant to ACN.


Cytodiagnosis of classic lobular carcinoma and its variants.
The well-known cytologic features of lobular carcinoma traditionally consist of modest cellularity and small, atypical cells lying singly or in small groups. However, lobular carcinoma is a common pitfall in the cytodiagnosis of breast lesions. Knowledge of its varied histologic appearance can help to prevent diagnostic difficulties. Among 55 consecutive cases of breast needle aspirates with histologic follow-up, 9 lobular carcinomas were identified. The surgical material was examined for the following histologic variants: (1) classic, (2) solid, (3) alveolar, and (4) mixed; it was correlated with the cytologic findings. Pure, classic lesions were the most likely cause of false-negative diagnoses. Two of nine lobular carcinomas were diagnosed as benign due to scant cellularity and cell smallness. Four of nine were cytologically misclassified as ductal type due to more abundant cellularity and larger cells. This could be attributed to the predominant alveolar or solid patterns present in three cases. Only three of nine were accurately classified as lobular carcinoma, and all had a significant classic histologic element. Another important feature that is highly suggestive of lobular carcinoma is the presence of cytoplasmic vacuoles. They were overlooked in three of four cases. This study suggested that the traditional cytologic features of lobular carcinoma are present only in tumors with a predominantly classic histologic pattern. Awareness of the variant patterns and their cytologic features, including more abundant cellularity, larger cells and clusters, and cytoplasmic vacuoles, will aid in correct classification.


Prevalence of spontaneous reperfusion and associated myocardial salvage in patients with acute myocardial infarction.
This study sought to determine the prevalence of spontaneous reperfusion of an infarct-related artery (IRA) and associated myocardial salvage in the absence of thrombolysis or angioplasty. Twenty-one patients with acute myocardial infarction received only heparin and aspirin. At a median of 18 hours after presentation, 12 patients (57%) had angiographic patency of the IRA. Technetium-99m sestamibi was injected acutely on presentation and again at hospital discharge. Acute and final perfusion defect sizes were measured. Their difference, myocardial salvage, was calculated along with salvage index (myocardial salvage/acute defect). Comparing patients with a patent versus occluded IRA, myocardium at risk was similar (16% +/- 12% vs 12% +/- 9% left ventricle, p = NS); however, myocardial salvage (9% +/- 9% vs -2% +/- 7% left ventricle, p = 0.01), and salvage index (0.62 +/- 0.37 vs 0.19 +/- 0.33, p = 0.01) were greater in patients with spontaneous reperfusion. Resolution of chest pain was greater in patients with a patent IRA (100% vs 55%, p = 0.003). Spontaneous reperfusion of the IRA occurs frequently in patients with acute myocardial infarction and is associated with significant myocardial salvage.


Silver nanoparticles coated with thioxanthone derivative as hybrid photoinitiating systems for free radical polymerization.
A new type of photoinitiator for free radical polymerization was synthesized and characterized. 2-(11-Mercaptoundecyloxy)thioxanthone (1) was anchored at the surface of silver nanoparticles (NPs), and the interaction of plasmon field generated in the immediate vicinity of Ag NPs carrying the chromophores was evaluated. The optical features and structure of the silver-initiator nanoassemblies (Ag@1) were characterized by UV-vis and fluorescence spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). TEM and XRD studies revealed the presence of ca. 5-6 nm diameter Ag NPs, and XPS also confirmed the successful anchorage of 1 at their periphery. The nanoassemblies Ag@1 were successfully used as macroinitiator for radical polymerization of acrylate monomers, triggered photochemically, to obtain Ag(0)-polyacrylate nanocomposite materials. The nanocomposite materials synthesized with the use of Ag@1 exhibit attractive possibilities for patterning the surface of thin films.


Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden.
A first episode of depression after 65 years of age has long been associated with both severe macrovascular and small microvascular pathology. Among the three more frequent forms of depression in old age, post-stroke depression has been associated with an abrupt damage of cortical circuits involved in monoamine production and mood regulation. Late-onset depression (LOD) in the absence of stroke has been related to lacunes and white matter lesions that invade both the neocortex and subcortical nuclei. Recurrent late-life depression is thought to induce neuronal loss in the hippocampal formation and white matter lesions that affect limbic pathways. Despite an impressive number of magnetic resonance imaging (MRI) studies in this field, the presence of a causal relationship between structural changes in the human brain and LOD is still controversial. The present article provides a critical overview of the contribution of neuropathology in post-stroke, late-onset, and late-life recurrent depression. Recent autopsy findings challenge the role of stroke location in the occurrence of post-stroke depression by pointing to the deleterious effect of subcortical lacunes. Despite the lines of evidences supporting the association between MRI-assessed white matter changes and mood dysregulation, lacunes, periventricular and deep white matter demyelination are all unrelated to the occurrence of LOD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of aging-related neurodegenerative changes in the human brain. However, they also provide data in favor of the neurotoxic theory of depression by showing that neuronal loss occurs in the hippocampus of chronically depressed patients. These three paradigms are discussed in the light of the complex relationships between psychosocial determinants and biological vulnerability in affective disorders.


In silico assessment of human Calprotectin subunits (S100A8/A9) in presence of sodium and calcium ions using Molecular Dynamics simulation approach.
Calprotectin is a heterodimeric protein complex which consists of two subunits including S100A8 and S100A9. This protein has a major role in different inflammatory disease and various types of cancers. In current study we aimed to evaluate the structural and thermodynamic changes of the subunits and the complex in presence of sodium and calcium ions using molecular dynamics (MD) simulation. Therefore, the residue interaction network (RIN) was visualized in Cytoscape program. In next step, to measure the binding free energy, the potential of mean force (PMF) method was performed. Finally, the molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method was applied as an effective tool to calculate the molecular model affinities. The MD simulation results of the subunits represented their structural changes in presence of Ca2+. Moreover, the RIN and Hydrogen bond analysis demonstrated that cluster interactions between Calprotectin subunits in presence of Ca2+ were greater in comparison with Na+. Our findings indicated that the binding free energy of the subunits in presence of Ca2+ was significantly greater than Na+. The results revealed that Ca2+ has the ability to induce structural changes in subunits in comparison with Na+ which lead to create stronger interactions between. Hence, studying the physical characteristics of the human proteins could be considered as a powerful tool in theranostics and drug design purposes.


Neck Rejuvenation through the Lateral Platysma Window: A Key Component of Face-Lift Surgery.
Rejuvenating an aged face relies on maintaining facial harmony to provide optimal aesthetic results. Restoration of more youthful facial contours is dependent on blending the aesthetic facial topographic units. Many authors continue to debate the best approach for neck rejuvenation through a medial approach, a lateral approach, or a combination of the two. The authors present their approach to neck rejuvenation through medial platysma plication, inferior release, and lateral platysma window.


Enhancing functional abilities and cognitive integration of the lower limb prosthesis.
Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.


Synthetic pulmonary surfactant preparations: new developments and future trends.
Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration. Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material. In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed.


Physical activity and cognitive changes in younger women after breast cancer treatment.
Studies indicate women aged 25-49 years previously treated for cancer report cognitive alterations. Good evidence indicates physical activity can be beneficial after cancer and might additionally benefit cognitive function. This short report presents data from a substudy of the Younger Women's Wellness after Cancer Program (YWWACP), which explored cognitive alterations and investigated potential associations between physical activity and cognitive function in participants in the YWWACP. The primary aim of this substudy was to determine in younger women previously treated for breast cancer (1) whether subjectively reported cognitive function changed over time and (2) if physical activity is associated with subjectively reported cognitive function, and if time had an impact on this. All participants had completed breast cancer treatment. Data were collected at baseline (n=41) and at 12 weeks. Measures assessed demographics, self-reported physical activity, cognitive function, sleep quality, stress, anxiety and depression using validated and reliable, subjectively reported instruments. Cognitive function and physical activity scores increased across the time points, with cognitive function revealing a statistically significant increase over time (p=0.004). Statistical testing revealed that physical activity was not correlated with cognitive function and that change in physical activity was not correlated with change in cognitive function. These data provide early evidence that cognitive function and physical activity improved over time in this sample. However, interpretations of a correlation between physical activity and cognitive function should be made with caution, and future research would benefit from larger samples.


Carotid Intima-Media Thickness Score, Positive Coronary Artery Calcium Score, and Incident Coronary Heart Disease: The Multi-Ethnic Study of Atherosclerosis.
Common carotid artery and internal carotid artery intima-media thicknesses (IMT) are associated with coronary heart disease (CHD) and increase with age. Using age, sex, and race/ethnicity IMT percentiles may improve CHD prediction when added to Framingham risk factors and coronary artery calcium score. We study these possibilities in the Multi-Ethnic Study of Atherosclerosis (MESA), a multi-ethnic cohort of whites, Chinese, blacks, and Hispanics. IMT data were acquired in the age range 45 to 84 years. Common carotid artery and internal carotid artery IMT, sex, and race/ethnic specific normative values were calculated for each MESA participant and combined as an IMT score. Multivariable Cox-proportional hazards models and logistic regression models were generated with CHD as outcome adding the IMT score to (1) a base model with Framingham risk factors, sex, race/ethnicity and (2) the base model with coronary artery calcium added. Harrell's C-statistics and area under the curve were estimated. Median follow-up was 10.2 years (interquartile range: 9.7, 10.7 years) with 429 first-time CHD events. Mean age was 62.1 years and 52.6% of participants were women. IMT score increased the base area under the curve from 0.7210 to 0.7396 (P=0.0008) and with positive coronary artery calcium score added to the model, from 0.7627 to 0.7714 (P=0.02). A carotid IMT score based on normative data incrementally adds to Framingham risk factors and a positive calcium score in predicting first-time CHD in an ethnically diverse cohort.


Molecular characterization of respiratory syncytial viruses circulating in a paediatric cohort in Amman, Jordan.
Respiratory syncytial viruses (RSVs) are an important cause of mortality worldwide and a major cause of respiratory tract infections in children, driving development of vaccine candidates. However, there are large gaps in our knowledge of the local evolutionary and transmission dynamics of RSVs, particularly in understudied regions such as the Middle East. To address this gap, we sequenced the complete genomes of 58 RSVA and 27 RSVB samples collected in a paediatric cohort in Amman, Jordan, between 2010 and 2013. RSVA and RSVB co-circulated during each winter epidemic of RSV in Amman, and each epidemic comprised multiple independent viral introductions of RSVA and RSVB. However, RSVA and RSVB alternated in dominance across years, potential evidence of immunological interactions. Children infected with RSVA tended to be older than RSVB-infected children [30 months versus 22.4 months, respectively (P value = 0.02)], and tended to developed bronchopneumonia less frequently than those with RSVB, although the difference was not statistically significant (P value = 0.06). Differences in spatial patterns were investigated, and RSVA lineages were often identified in multiple regions in Amman, whereas RSVB introductions did not spread beyond a single region of the city, although these findings were based on small sample sizes. Multiple RSVA genotypes were identified in Amman, including GA2 viruses as well as three viruses from the ON1 sub-genotype that emerged in 2009 and are now the dominant genotype circulating worldwide. As vaccine development advances, further sequencing of RSV is needed to understand viral ecology and transmission, particularly in under-studied locations.


THE TOXICOLOGY OF CHEMOSTERILANTS.
Sterilization of males can in certain circumstances be more efficient than killing as a method for control of insects and perhaps other pests. A number of chemicals (chemosterilants) show promise of producing sexual sterility in insects without some of the practical limitations of radiation. The most important compounds are alkylating agents. These have little immediate pharmacological action, but are notable for their selective action against haematopoietic and some other proliferating tissues. A number of alkylating agents have been shown to be mutagens in insects, bacteria, fungi, and higher plants; carcinogens in mammals; and teratogens in insects, birds, and mammals. Some produce sexual sterility, possibly in mammals as well as in insects, at doses too low to produce the other effects. Some have an established reputation as drugs for palliative treatment of leukaemia and other neoplasms.The development of insect sterilization as a vector control technique has been handicapped in part by lack of scientific information on the acute and long-term hazards that might be associated with the use of chemosterilants. In this paper the author brings together the available knowledge on the toxicology of the alkylating agents.


Interleukin-2 receptor downstream events in regulatory T cells: implications for the choice of immunosuppressive drug therapy.
Naturally occurring CD4+CD25(high)FOXP3+ regulatory T cells (Tregs) constitute a powerful mechanism of immune regulation and therefore, have important therapeutic potential for disorders such as autoimmune diseases, allograft rejection and graft-versus-host disease. Disruption of the IL-2R signalling pathway by genetic defects of the interleukin (IL)-2 gene or components of the IL-2 receptor (R) complex results in severe T cell-mediated autoimmunity rather than immunodeficiency, indicating a crucial role for IL-2R signalling for Treg development and function. Signalling downstream of the IL-2R can act through the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway, the Janus kinase (JAK)/Signal transducers and Activators of Transcription (STAT) pathway and the mitogen-activated protein kinase (MAPK) pathway. In this report we focus on the relevance of these pathways as well as the impact of immunosuppressive drugs that may affect or enhance Treg function by targeting IL-2R signalling.


Same size--same niche? Foraging niche separation between sympatric juvenile Galapagos sea lions and adult Galapagos fur seals.
1. In vertebrates, patterns of resource utilization change throughout development according to age- and or size-specific abilities and requirements. Thus, interspecific competition affects different age classes differently. 2. Adults of sympatric species often show distinct foraging niche segregation, but juvenile resource use might overlap with adult competitors of similar body size. Resultant negative effects on juveniles can have important consequences for population dynamics, yet such interactions have received little attention in studies of mammalian communities. 3. Using GPS tracking devices, time-depth recorders and stable isotope data, we compared diving depth, activity time, trophic position and foraging habitat characteristics to investigate foraging niche overlap between similar-sized sympatric juvenile Galapagos sea lions (Zalophus wollebaeki) and adult Galapagos fur seals (Arctocephalus galapagoensis) and compared each group with much larger-bodied adult Galapagos sea lions. 4. We found little indication for direct competition but a complex pattern of foraging niche segregation: juvenile sea lions and adult fur seals dived to shallow depths at night, but foraged in different habitats with limited spatial overlap. Conversely, juvenile and adult sea lions employed different foraging patterns, but their foraging areas overlapped almost completely. 5. Consistency of foraging habitat characteristics between juvenile and adult sea lions suggests that avoidance of competition may be important in shaping foraging habitat utilization. Resultant specialization on a limited habitat could contribute to low sea lion numbers that contrast with high fur seal abundance. Our data suggest that exploitation by multiple predators within spatially restricted foraging ranges of juveniles might negatively impact juvenile foraging success and ultimately influence population dynamics.


The role of capsule endoscopy in the detection of small bowel disease.
Videocapsule endoscopy (VCE) can identify lesions in the small bowel which would otherwise be hard to detect. We have selected 53 patients with digestive symptoms in which upper and lower endoscopy had provided no findings. Patients were classified into three groups, based on their main indication for VCE exploration: group one--obscure gastrointestinal bleeding (OGIB); group two--unspecific abdominal symptoms; group 3--monitoring of a prior known pathology. We found that VCE has high predictive values, sensibility and specificity in the diagnosis of OGIB. VCE was also useful in the detection and extent evaluation of lesions in Crohn's and celiac disease. VCE is also able to detect tumors of the small bowel with sufficient accuracy, and can be used to monitor patients with hereditary pre-malignant diseases such as FAP. There were few light adverse effects and no major complications. We conclude that VCE is a safe and effective procedure for the detection of small bowel lesions.


Glycogen storage disease-like phenotype with central nervous system involvement in a PGM1-CDG patient.
A 10-year-old boy presented with cleft palate, hepatopathy, cholecystolithiasis, myopathy, coagulopathy, hyperlipidemia, hypoglycemia, hyperuricemia, short stature, obesity, hypothyroidism, microcephaly and mild intellectual disability. The multi-systemic manifestation involving certain distinct clinical features prompted us to search for a subtype of congenital disorders of glycosylation (CDG). The patient was screened for CDG by examining the distribution of transferrin (TRF) and apolipoprotein C-III (ApoC-III) sialylated isoforms using isoelectric focusing of serum. This was followed by spectrophotometric measurement of phosphoglucomutase 1 (PGM1) activity in fibroblasts and molecular analysis including sequencing and PCR-RFLP of PGM1 gene. Selected bioinformatics tools were used to evaluate the data. Increased relative levels of di-, mono- and asialotransferrin reflected a defect of N-glycosylation in the patient. Markedly decreased activity of PGM1 corresponding to less than 5% of control´s was found. Sequencing of PGM1 gene revealed the presence of two heterozygous missense mutations c.1010C>T (p.T337M) and c.1508G>A (p.R503Q), whose pathogenicity was confirmed by in silico analysis. We report the first Czech patient with a glycosylation disorder due to PGM1 deficiency. Compared to the described cases, no dilated cardiomyopathy was noted in our patient. However, he suffered from a mild neurological impairment, which is an uncommon feature that extends the phenotype associated with PGM1-CDG. Lactose-rich diet, which was previously reported to have ameliorated the clinical symptoms in some PGM1-CDG patients, did not result in any improvement in our patient.


An integrated method for understanding the function of macro-lithic tools. Use wear, 3D and spatial analyses of an Early Upper Palaeolithic assemblage from North Eastern Italy.
The article presents an original analysis which combines use-wear, 3D modelling and spatial analyses to experimental archaeology in order to investigate Early Upper Palaeolithic flint-knapping gestures and techniques involving the use of macro-lithic tools. In particular, the methodological framework proposed in this paper was applied to the study of Protoaurignacian and Aurignacian macro-tools from Fumane Cave (Verona, Italy). Combining spatial analysis and use wear investigation, both at low and high magnifications, permitted the identification and detailed description of the use-related traces affecting both the hammerstones and retouchers which, at Fumane Cave, were used at different stages during flint tool production. Several experimental activities were performed including core reduction, maintenance, and blank production together with different types of edge retouching. From a methodological perspective, the protocol of analysis permitted to codify specific traces and to produce quantitative data related to their geometry and distribution over the tool's surface, according to the activities and gestures performed. The results obtained allowed a careful investigation of the function and the gestures associated to the use of the macro-lithic tools coming from the Protoaurignacian and Aurignacian levels of Fumane Cave while providing a methodological tool for interpreting different archaeological samples.


Understanding Alcohol Use Discourse and Stigma Patterns in Perinatal Care on Twitter.
(1) Background: perinatal alcohol use generates a variety of health risks. Social media platforms discuss fetal alcohol spectrum disorder (FASD) and other widespread outcomes, providing personalized user-generated content about the perceptions and behaviors related to alcohol use during pregnancy. Data collected from Twitter underscores various narrative structures and sentiments in tweets that reflect large-scale discourses and foster societal stigmas; (2) Methods: We extracted alcohol-related tweets from May 2019 to October 2021 using an official Twitter search API based on a set of keywords provided by our clinical team. Our exploratory study utilized thematic content analysis and inductive qualitative coding methods to analyze user content. Iterative line-by-line coding categorized dynamic descriptive themes from a random sample of 500 tweets; (3) Results: qualitative methods from content analysis revealed underlying patterns among inter-user engagements, outlining individual, interpersonal and population-level stigmas about perinatal alcohol use and negative sentiment towards drinking mothers. As a result, the overall silence surrounding personal experiences with alcohol use during pregnancy suggests an unwillingness and sense of reluctancy from pregnant adults to leverage the platform for support and assistance due to societal stigmas; (4) Conclusions: identifying these discursive factors will facilitate more effective public health programs that take into account specific challenges related to social media networks and develop prevention strategies to help Twitter users struggling with perinatal alcohol use.


Preoperative diagnosis of hiatal hernia: barium swallow X-ray, high-resolution manometry, or endoscopy?
The assessment of hiatal hernias (HH) is typically done with barium swallow X‑ray, upper endoscopy, and by high-resolution esophageal manometry (HRM). The aim of this study was to assess the clinical utility of these methods in terms of HH detection and their correlation to gastroesophageal reflux disease (GERD). A retrospective comparative analysis of patients with symptoms of GERD was carried out. The performance of endoscopy and HRM in diagnosing HH was assessed, taking barium swallow X‑ray as a reference. Furthermore, statistically comparative analysis between detected hernias and the presence of reflux disease in ambulatory impedance-pH monitoring (MII) was performed. Overall, 112 patients were analyzed. Barium swallow X‑ray showed no correlation either to HR manometrically or to endoscopically assessed HH. Significant accordance in the detection rate of HH was proved between HRM and gastroesophagoscopy (p < 0.001). Only endoscopically assessed HH showed a significant correlation with GERD (p = 0.047). No correlation between detected hernias and GERD could be found either with HRM or with barium swallow X‑ray. Barium swallow X‑ray provided the highest rate of HH detection (76.8%). For the reliable exclusion of HH prior to treatment, all three mentioned investigations appear to be necessary in order of low conformity.


Stored and neosynthesized mRNA in Arabidopsis seeds: effects of cycloheximide and controlled deterioration treatment on the resumption of transcription during imbibition.
Dry seeds accumulate translatable mRNAs as well as functional proteins for transcription and translation. They are possibly involved in early physiological responses after imbibition, however, their functions remain poorly understood. The aim of this study is to investigate the function of seed stored transcriptional machinery in resumption of gene expression after the onset of imbibition in Arabidopsis thaliana. First, we examined the characters of stored mRNAs in A. thaliana dry seeds using microarray data from non-dormant Columbia (Col) and dormant Cape Verde Islands (Cvi) accessions. Transcriptomes of Col and Cvi dry seeds resembled one another, suggesting that patterns of stored mRNA do not reflect either the degree of dormancy or germination potential, but rather reflect the developmental context, such as seed maturation. Upon imbibition, changes in mRNA abundance of many genes were initiated between 1- and 2-h after the onset of imbibition. RT-PCR expression analysis of imbibition-responsive genes indicates that early induction was not altered by treatment of cycloheximide. This suggests that de novo protein synthesis is not required for gene expression during early imbibition stages. Moreover, controlled deterioration treatment (CDT), which causes artificial damages on dry seeds, disrupted gene expression specifically during the first 3 h after the start of imbibition, suggesting that seed stored transcription factors play a pivotal role in gene expression during early imbibition periods. Furthermore, the negligible effect of CDT on germination indicates that early imbibition response is dispensable and de novo synthesized proteins compensate for the function of stored proteins for germination.


Pectin methylesterase, a regulator of pollen tube growth.
The apical wall of growing pollen tubes must be strong enough to withstand the internal turgor pressure, but plastic enough to allow the incorporation of new membrane and cell wall material to support polarized tip growth. These essential rheological properties appear to be controlled by pectins, which constitute the principal component of the apical cell wall. Pectins are secreted as methylesters and subsequently deesterified by the enzyme pectin methylesterase (PME) in a process that exposes acidic residues. These carboxyls can be cross-linked by calcium, which structurally rigidifies the cell wall. Here, we examine the role of PME in cell elongation and the regulation of its secretion and enzymatic activity. Application of an exogenous PME induces thickening of the apical cell wall and inhibits pollen tube growth. Screening a Nicotiana tabacum pollen cDNA library yielded a pollen-specific PME, NtPPME1, containing a pre-region and a pro-region. Expression studies with green fluorescent protein fusion proteins show that the pro-region participates in the correct targeting of the mature PME. Results from in vitro growth analysis and immunolocalization studies using antipectin antibodies (JIM5 and JIM7) provide support for the idea that the pro-region acts as an intracellular inhibitor of PME activity, thereby preventing premature deesterification of pectins. In addition to providing experimental data that help resolve the significance and function of the pro-region, our results give insight into the mechanism by which PME and its pro-region regulate the cell wall dynamics of growing pollen tubes.


Noggin-Mediated Retinal Induction Reveals a Novel Interplay Between Bone Morphogenetic Protein Inhibition, Transforming Growth Factor β, and Sonic Hedgehog Signaling.
It has long been known that the depletion of bone morphogenetic protein (BMP) is one of the key factors necessary for the development of anterior neuroectodermal structures. However, the precise molecular mechanisms that underlie forebrain regionalization are still not completely understood. Here, we show that Noggin1 is involved in the regionalization of anterior neural structures in a dose-dependent manner. Low doses of Noggin1 expand prosencephalic territories, while higher doses specify diencephalic and retinal regions at the expense of telencephalic areas. A similar dose-dependent mechanism determines the ability of Noggin1 to convert pluripotent cells in prosencephalic or diencephalic/retinal precursors, as shown by transplant experiments and molecular analyses. At a molecular level, the strong inhibition of BMP signaling exerted by high doses of Noggin1 reinforces the Nodal/transforming growth factor (TGF)β signaling pathway, leading to activation of Gli1 and Gli2 and subsequent activation of Sonic Hedgehog (SHH) signaling. We propose a new role for Noggin1 in determining specific anterior neural structures by the modulation of TGFβ and SHH signaling.


An Australian audit of ED pain management patterns.
Timely and appropriate pain management is an important quality indicator of ED performance. Emergency health care workers are well positioned to become active leaders and innovatively responsive in reducing human suffering. A pain management audit was conducted to determine Australia practice patterns. A 12-month retrospective descriptive cohort audit was undertaken. Through the randomization process a medical record audit tool was completed for each record identified. Ethical approval for the study was obtained. Seventy-four hospitals agreed to conduct the audit, 36 (48%) provided data. The total number of patient notes reviewed was 2,066. Ninety-five percent (1,966) of patients arrived by ambulance. Of the patients (n=547; 56.4%) with a documented triage pain score the majority arrived in severe pain (n=300; 41.3%). Of the total number of patients (1,966) documented arriving in pain 1,473 (74.9%) received an analgesic. Six hundred and forty-four (32.7%) patients received an opioid. From time of emergency department arrival, the median time for analgesic administration was 70 minutes (IQR 58 minutes to 92 minutes). Twenty-five emergency departments (69.4%) had pain management policies that enabled nurses to initiate a pharmacological analgesia without medical consultation. The Australian pain management audit highlighted current practices and potential areas for further research. While the audit demonstrated that nurse initiated pain management interventions promoted better analgesic response, greater consistency of triage pain assessment, code allocation, and documentation of pain scores may go some way to improving the timeliness of analgesia.


Effects of aspirin and propranolol on feline platelet aggregation.
Three groups of cats were given aspirin in single dosages of 5, 10, and 25 mg/kg. A 4th group was given 2 dosages of 25 mg/kg, 3 days between doses. The degree of inhibition of platelet function and the duration of antagonism to platelet aggregation were studied. The dosage of 25 mg/kg (single and repeated) consistently inhibited platelet function, and the effects lasted 3 to 5 days. Additive drug effect was not noted in group 4, since the 2nd dosage antagonized platelet function to a degree and duration similar to the effects of the 1st. The dosage of aspirin recommended for antiplatelet activity in the average-sized cat (3 kg) equals approximately 1 pediatric aspirin (90 mg) given twice a week. Propranolol, given to cats at dosages of 2.5 to 15 mg had no effect on platelet aggregation.


The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.
Before S phase, cells license replication origins for initiation by loading them with Mcm2-7 heterohexamers. This process is dependent on Cdc6, which is recruited to unlicensed origins. Using Xenopus egg extracts we show that although each origin can load many Mcm2-7 hexamers, the affinity of Cdc6 for each origins drops once it has been licensed by loading the first hexamers. This encourages the distribution of at least one Mcm2-7 hexamer to each origin, and thereby helps to ensure that all origins are licensed. Although Cdc6 is not essential for DNA replication once licensing is complete, Cdc6 regains a high affinity for origins once replication forks are initiated and Mcm2-7 has been displaced from the origin DNA. We show that the presence of Cdc6 during S phase is essential for the checkpoint kinase Chk1 to become activated in response to replication inhibition. These results show that Cdc6 plays multiple roles in ensuring precise chromosome duplication.


Mechanism of Interferon-Stimulated Gene Induction in HIV-1-Infected Macrophages.
Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum. The second, dominant, and persistent phase (>48 hpi) was induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by small interfering RNA (siRNA) and the inhibition of both the initiation and elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional silencing. We further define the induction pathway, showing sequential HIV RNA stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA knockdown. IRF1 also plays a key role in the first phase. We also show that the ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious virus. All induced antiviral ISGs probably lead to restriction of HIV replication in macrophages, contributing to a persistent, noncytopathic infection, while the inhibition of interferon facilitates spread to adjacent cells. Both may influence the size of macrophage HIV reservoirs in vivo Elucidating the mechanisms of ISG induction may help in devising immunotherapeutic strategies to limit the size of these reservoirs.IMPORTANCE HIV, like other viruses, manipulates the antiviral interferon and interferon-stimulated gene (ISG) system to facilitate its initial infection and establishment of viral reservoirs. HIV specifically inhibits all type I and III interferons in its target cells, including macrophages, dendritic cells, and T cells. It also induces a subset of over 20 ISGs of differing compositions in each cell target. This occurs in two temporal phases in macrophages. Extracellular vesicles contained within the inoculum induce the first, transient phase of ISGs. Newly transcribed HIV RNA induce the second, dominant ISG phase, and here, the full induction pathway is defined. Therefore, HIV nucleic acids, which are potent inducers of interferon and ISGs, are initially concealed, and antiviral ISGs are not fully induced until replication is well established. These antiviral ISGs may contribute to persistent infection in macrophages and to the establishment of viral reservoirs in vivo.


Gram-negative septicemia and shock.
Gram-negative septicemia is an old disease with dramatic changes in the arena of modern medicine. Whereas it was most often the domain of the infectious disease specialist and the abdominal surgeon 25 years ago, it is now managed in most medical practice specialties. It requires thorough understanding by all practitioners. Its physiology is increasingly well understood. The relationships between sepsis and host underlying diseases are important. Nonspecific therapies are important for early management of septicemia and impending shock, but specific application of immunotherapy in the form of antibody or vaccines, antibiotics selected for the most likely organism, and perhaps even pharmacotherapy directed at recognized intrinsic mediators of host responses to bacteremia, hold the greatest promise for a successful outcome.


What are the consistent predictors of generic and specific post-stroke health-related quality of life?
In order to improve post-stroke health-related quality of life (HRQOL), it is crucial to focus scarce health care and research resources towards its consistent determinants. Disparities in reported determinants of post-stroke HRQOL may be due to the use of different instruments (generic or specific) in different populations. This is the first study to identify factors which consistently influenced both generic and specific post-stroke HRQOL in the same study population. One hundred consecutive consenting stroke survivors were assessed using the stroke levity scale (SLS), modified Rankin scale (mRS), SF-36 and HRQOL in stroke patients (HRQOLISP) measure. Employing multiple regression analysis (R(2) = 0.63), potential predictors were sought among age, gender, socioeconomic class (SEC), aphasia, post-stroke duration, side, type and number of strokes, SLS, mRS, social support and Likert scale-graded responses to laughter and negative-feeling frequency. Gender, SEC and stroke type had no significant impact on HRQOL. The consistent independent statistical predictors of several facets of generic and stroke-specific HRQOL were stroke severity, disability, laughter and negative-feeling frequencies. While stroke severity, a component of physical health, impaired psychological health, psychological dysfunction in turn negatively influenced physical and other domains of health, thereby creating a vicious cycle. These multidirectional interactions may involve neural, social and existential mechanisms which remain to be confirmed, elucidated and exploited.


Ontario's attempt at primary care reform hits another snag.
Ontario is the latest province to step into the health care reform spotlight. Proponents hope its proposed series of primary care pilot projects, built around the concept of patient rostering, will improve the delivery of care. If the project goes ahead, doctors in 5 participating sites will be paid under a capitation system, with payments starting at $70.29 annually for men aged between 25 and 35.


Evaluation of the oxidative stress in chronic alcoholics.
The present study was conducted to assess the activity of Gamma Glutamyl Transferase (GGT) and its association with oxidative stress in alcoholics. Sixty male alcoholics with a history of alcohol abuse for more than five years were the subjects of this study. Twenty healthy male volunteers who matched in age and the socio-economic status, served as the control subjects. GGT, reduced glutathione (GSH, a key intra-cellular antioxidant) and malondialdehyde (MDA, a marker of the oxidative stress) were assayed in the plasma of the two groups, and the results were statistically analyzed. The activity of the plasma GGT, known as a marker of Alcoholic Liver Disease (ALD); was significantly higher in the alcoholics as compared to that in the healthy controls. There was a significant positive correlation between the enzyme activity and the plasma levels of MDA and this indicated that there was an increased release of this enzyme with enhanced oxidative damage, due to the generation of oxygen free radicals in the study group. There was a significantly increased level of MDA and a decrease in the level of GSH in the alcoholics as compared to those in the controls. Significant negative correlations between GGT and GSH, and between MDA and GSH were observed. The present study demonstrates that alcoholics have a compromised antioxidant defense system.


Rapid degradation and non-selectivity of Dakin's solution prevents effectiveness in contaminated musculoskeletal wound models.
Dakin's solution (buffered sodium hypochlorite) has been used as a topical adjunct for the treatment of invasive fungal infections in trauma patients. Prudent use of Dakin's solution (DS) for complex musculoskeletal wound management implies balancing antimicrobial efficacy and human tissue toxicity, but little empirical evidence exists to inform clinical practice. To identify potentially efficacious DS concentrations and application methods, we conducted two animal studies to evaluate the ability of DS to reduce bacterial burden in small and large animal models of contaminated musculoskeletal wounds. An established rat (Rattus norvegicus) contaminated femoral defect model was employed to evaluate the antimicrobial efficacy of DS as a topical adjunctive treatment for Staphylococcus aureus infection. A range of clinically-relevant DS concentrations (0.00025%-0.125%) were tested, both with and without periodic replenishment during treatment. Next, an established goat (Capra hircus) musculoskeletal wound model, consisting of a Pseudomonas aeruginosa contaminated proximal tibia cortical defect, muscle crush, and thermal injury, was utilized to evaluate the antimicrobial efficacy of dilute DS (0.0025% and 0.025%) as a surgical irrigant solution. In situ reactive chlorine concentrations were monitored throughout each treatment using an automated iodometric titration approach. In a rat wound model, DS treatment did not significantly reduce S. aureus bioburden after 14 days as compared to saline control. Two treatment groups (0.01% single application and 0.025% multiple application) exhibited significantly higher bacterial burden than control. In a goat musculoskeletal wound model, neither 0.0025% nor 0.025% DS significantly altered P. aeruginosa bioburden immediately following treatment or at 48 h post-treatment. Overall, DS applied to exposed soft tissue exhibited rapid degradation, e.g., 0.125% DS degraded 32% after 5 s progressing to 86% degradation after 15 min following single application. We did not observe evidence of a therapeutic benefit following Dakin's solution treatment for any tested concentration or application method in two contaminated musculoskeletal wound models. Despite confirmation of robust bactericidal activity in vitro, our findings suggest DS at current clinically-used concentrations does not kill tissue surface-attached bacteria, nor does it necessarily cause host tissue toxicity that exacerbates infection in the setting of complex musculoskeletal injury.


A gradient of silent substitution rate in the human pseudoautosomal region.
It has been demonstrated that recombination in the human p-arm pseudoautosomal region (p-PAR) is at least twenty times more frequent than the genomic average of approximately 1 cM/Mb, which may affect substitution patterns and rates in this region. Here I report the analysis of substitution patterns and rates in 10 human, chimpanzee, gorilla, and orangutan genes across the p-PAR. Between species silent divergence in the p-PAR forms a gradient, increasing toward the telomere. The correlation of silent divergence with distance from the p-PAR boundary is highly significant (rho = 0.911, P < 0.001). After exclusion of the CpG dinucleotides this correlation is still significant (rho = 0.89, P < 0.01), thus the substitution rate gradient cannot be explained solely by the differences in the extent of methylation across the p-PAR. Frequent recombination in the PAR may result in a relatively strong effect of biased gene conversion (BGC), which, because of the increased probability of fixation of the G or C nucleotides at (A or T)/(G or C) segregating sites, may affect substitution rates. BGC, however, does not seem to be the factor creating the substitution rate gradient in the p-PAR, because the only gradient is still detactable if only A<-->T and G<-->C substitutions are taken into account (rho = 0.82, P < 0.01). I hypothesize that the substitution rate gradient in the p-PAR is due to the mutagenic effect of recombination, which is very frequent in the distal human p-PAR and might be lower near the p-PAR boundary.


[Dynamics of various electrophysiologic indices in patients with mild acute closed craniocerebral injuries during complex treatment using reflexotherapy].
An analysis of 117 cases of acute closed craniocerebral trauma (CCCT) of a mild degree, the time-course of the EEG, EchoEG and REG findings in the process of treatment has shown that mild CCCT was expressed clinically in CSF hypertension, as well as vegetovascular and asthenoneurotic syndromes. The detection at the early stages of the injury of the leading clinical syndrome contributes to the conduction of purposeful therapeutic measures. A positive time-course of some electrophysiological parameters indicates the normalization of vegetovascular dysfunctions under the impact of acupuncture, which permits the use of this method in the multiple modality treatment of CCCT in the acute period.


Dilemma Facing Patients Aged 75 Years and Older on Fluid Restriction When Drug Package Inserts Advise Use of a Lot of Water: A Cross-Sectional, Descriptive, and Hypothesis-Generating Study Using a Large Claims Database.
Several oral drugs are recommended to be taken with large amounts of water for reasons such as peptic ulcer prophylaxis. On the other hand, there are many patients with diseases that restrict water intake, and the actual frequency of patients receiving prescriptions in these conflicting situations is not clear. Using a large claims database in Japan, this study aimed to determine the proportion of patients aged ≥ 75 years on fluid restriction who received drugs whose drug package insert mentioned "a large amount of water intake is needed when taking the drug". We performed a prescription survey of older patients over 75 years of age using the Japan Medical Data Centre (JMDC) claims database. Out of approximately 8800 oral drugs used in Japan, we defined 29 drugs for which package inserts noted that a large amount of water intake is recommended during drug administration. We defined diagnosis codes for some common diseases for which restricted water intake is likely recommended: heart failure (NYHA class III or IV), liver cirrhosis with ascites, and chronic kidney disease stage 5, including dialysis patients. Of 5968 patients aged ≥ 75 years (men 47.7%), 320 (5.4%) patients with heart failure (2.8%, n = 170), liver cirrhosis (0.7%, n = 40), or chronic kidney disease (1.9%, n = 113), diagnoses likely associated with the need for fluid restriction, were prescribed drugs for which abundant fluid at intake was recommended. Among 29 identified drugs, 15 drugs were administered to older patients over 75 years with fluid restriction due to said diseases. Of patients 75 years and older with disease likely requiring water restriction, 5.4% faced the dilemma of following advice to restrict fluid intake due to their diagnoses or to adhere to instructions in drug package inserts to have abundant fluid intake when taking the drug. Our study raises awareness regarding the dilemma of water restriction and intake in clinical settings, highlighting the importance of considering individual patient needs. These real-world findings emphasize the need for information and guidelines to assist healthcare professionals in navigating this dilemma and making informed decisions for the benefit of their patients.


Designing a National Disaster Medical System.
The National Disaster Medical System (NDMS) is a partnership of private and public sectors to provide care to the victims of great disasters. The system is being developed as a voluntary cooperative effort of four major Federal agencies, State and local governments, and the American professional and hospital communities. A medical response component will include 150 disaster medical assistance units capable of clearing or staging operations in a disaster. Each unit will comprise three 29-person teams containing physicians, nurses, medical technicians, and support personnel and will include a 16-person unit command and support element. An evacuation component will be founded on the military aeromedical evacuation system, augmented by civilian aircraft and other transportation resources. A hospital component will enroll 100,000 pre-committed beds in hospitals throughout the nation. The system is designed to care for up to 100,000 casualties arising from a massive peacetime disaster or an overseas conventional military conflict. The National Disaster Medical System will be implemented over a period of 3 to 5 years. The authors recommend that all parts of the American health care community join in support of the system.


Breast Cancer Estrogen Receptor Status According to Biological Generation: US Black and White Women Born 1915-1979.
Evidence suggests that contemporary population distributions of estrogen-receptor (ER) status among breast cancer patients may be shaped by earlier major societal events, such as the 1965 abolition of legal racial discrimination in the United States (state and local "Jim Crow" laws) and the Great Famine in China (1959-1961). We analyzed changes in ER status in relation to Jim Crow birthplace among the 46,417 black and 339,830 white US-born, non-Hispanic women in the Surveillance, Epidemiology, and End Results (SEER) 13 Registry Group who were born between 1915 and 1979 and diagnosed (ages 25-84 years, inclusive) during 1992-2012. We grouped the cases according to birth cohort and quantified the rate of change using the haldane (which scales change in relation to biological generation). The percentage of ER-positive cases rose according to birth cohort (1915-1919 to 1975-1979) only among women diagnosed before age 55. Changes according to biological generation were greater among black women than among white women, and among black women, they were greatest among those born in Jim Crow (versus non-Jim Crow) states, with this group being the only group to exhibit high haldane values (>|0.3|, indicating high rate of change). Our study's analytical approach and findings underscore the need to consider history and societal context when analyzing ER status among breast cancer patients and racial/ethnic inequities in its distribution.


Reliable quantification of phthalates in environmental matrices (air, water, sludge, sediment and soil): a review.
Because of their widespread application, phthalates or phthalic acid esters (PAEs) are ubiquitous in the environment. Their presence has attracted considerable attention due to their potential impacts on ecosystem functioning and on public health, so their quantification has become a necessity. Various extraction procedures as well as gas/liquid chromatography and mass spectrometry detection techniques are found as suitable for reliable detection of such compounds. However, PAEs are ubiquitous in the laboratory environment including ambient air, reagents, sampling equipment, and various analytical devices, that induces difficult analysis of real samples with a low PAE background. Therefore, accurate PAE analysis in environmental matrices is a challenging task. This paper reviews the extensive literature data on the techniques for PAE quantification in natural media. Sampling, sample extraction/pretreatment and detection for quantifying PAEs in different environmental matrices (air, water, sludge, sediment and soil) have been reviewed and compared. The concept of "green analytical chemistry" for PAE determination is also discussed. Moreover useful information about the material preparation and the procedures of quality control and quality assurance are presented to overcome the problem of sample contamination and these encountered due to matrix effects in order to avoid overestimating PAE concentrations in the environment.


Do We Know How to Avoid OASIs in Non-Supine Birth Positions? A Retrospective Cohort Analysis.
To evaluate the association between the upright and supine maternal positions for birth and the incidence of obstetric anal sphincter injuries (OASIs). Retrospective cohort study analyzed the data of 1,728 pregnant women who vaginally delivered live single cephalic newborns with a birth weight of 2,500 g. Multiple regression analyses were used to investigate the effect of the supine and upright positions on the incidence of OASIs after adjusting for risk factors and obstetric interventions. In total, 239 (13.8%) births occurred in upright positions, and 1,489 (86.2%) in supine positions. Grade-III lacerations occurred in 43 (2.5%) patients, and grade-IV lacerations occurred in 3 (0.2%) women. Supine positions had a significant protective effect against severe lacerations, odds ratio [95% confidence interval]: 0,47 [0.22-0.99], adjusted for the use of forceps 4.80 [2.15-10.70], nulliparity 2.86 [1.44-5.69], and birth weight 3.30 [1.56-7.00]. Anesthesia (p < 0.070), oxytocin augmentation (p < 0.228), shoulder dystocia (p < 0.670), and episiotomy (p < 0.559) were not associated with the incidence of severe lacerations. Upright birth positions were not associated with a lower rate of perineal tears. The interpretation of the findings regarding these positions raised doubts about perineal protection that are still unanswered.


Effectiveness of Helmet therapy for infants with moderate to severe positional plagiocephaly.
The use of helmet treatment for positional plagiocephaly has increased recently; however, its effect is unknown in Korea. This study aimed to investigate the effectiveness of helmet therapy and identify its influencing factors. Ninety pediatric patients diagnosed with moderate to severe positional plagiocephaly received helmet therapy. Severity of moderate to severe positional plagiocephaly was defined as cranial vault asymmetry (CVA) > 10 mm or CVA index (CVAI) >6%. Patients were categorized by age, severity, and daily helmet wear. Multiple regression analysis controlled for factors like sex and prematurity. Treatment success was assessed by comparing pre/post- helmet theray CVA and CVAI, considering normalization or decrease to mild plagiocephaly (CVA ≤ 10 mm or CVAI ≤ 6%). A total of 90 participants were enrolled (mean age, 5.6±1.6 months; male, 53 [58.9%]). The mean helmet therapy duration was 6.4±2.7 months, while the mean daily wear time was 18.4±2.7 hours. Among the 90 patients, 66 (73.3%) had moderate disease and 24 (26.7%) had severe disease. The mean CVA and CVAI decreased by 6.3±2.7 mm and 4.3±1.8% after versus before treatment (P<0.001). Treatment was successful in 76 infants (84.4%). The most effective changes in CVA and CVAI were noted in those who began treatment before 9 months of age (6.2±2.5 mm and 5.0±1.9%, P<0.001), had high compliance (6.2±2.4 mm and 4.9±1.9%, P<0.001), and had high severity (8.0±2.3 mm and 6.6±1.7%, P<0.001). Starting helmet treatment before 9 months and wearing it over 15 hours daily yielded better outcomes.


Clinical evaluation of the determination of plasma concentrations of darunavir, etravirine, raltegravir and ritonavir in dried blood spot samples.
Measurement of drug levels in plasma is currently the gold standard for pharmacological studies. However, venous sampling is not feasible in some populations (e.g., neonates) or may be difficult in certain situations, such as nonhospital-based settings. Dried blood spots (DBS) can be obtained by a simple fingerprick and the subsequent collection of blood on a filter card, allowing patient-friendly sample collection in non-hospital-based settings. Despite these advantages, thus far no clinical evaluation has been performed for the use of DBS concentrations as surrogates for plasma levels. Our purpose was to clinically evaluate DBS sampling for the determination of plasma concentrations for the novel antiretroviral drugs etravirine, darunavir/ritonavir and raltegravir. DBS concentrations were measured in 11 HIV-infected patients using LC-MS/MS. DBS concentrations were proportional to plasma concentrations. All drug concentrations were higher in DBS than in plasma samples. The plasma:DBS ratio and the respective relative standard error of estimate (RSE) of darunavir, etravirine, raltegravir and ritonavir were 0.632 (4.97% RSE), 0.523 (4.84% RSE), 0.617 (14.9% RSE) and 0.592 (2.99% RSE), respectively. Hematocrit did not explain variability in our study. DBS are reproducibly correlated to plasma levels and can be used for monitoring antiretroviral drug exposure in HIV-infected patients.


MonoEF: Extrinsic Parameter Free Monocular 3D Object Detection.
Monocular 3D object detection is an important task in autonomous driving. It can be easily intractable where there exists ego-car pose change w.r.t. ground plane. This is common due to the slight fluctuation of road smoothness and slope. Due to the lack of insight in industrial application, existing methods on open datasets neglect the camera pose information, which inevitably results in the detector being susceptible to camera extrinsic parameters. The perturbation of objects is very popular in most autonomous driving cases for industrial products. To this end, we propose a novel method to capture camera pose to formulate the detector free from extrinsic perturbation. Specifically, the proposed framework predicts camera extrinsic parameters by detecting vanishing point and horizon change. A converter is designed to rectify perturbative features in the latent space. By doing so, our 3D detector works independent of the extrinsic parameter variations and produces accurate results in realistic cases, e.g., potholed and uneven roads, where almost all existing monocular detectors fail to handle. Experiments demonstrate our method yields the best performance compared with the other state-of-the-arts by a large margin on both KITTI 3D and nuScenes datasets.


Anhydrobiosis in yeast: influence of calcium and magnesium ions on yeast resistance to dehydration-rehydration.
The influence of calcium and magnesium ions on resistance to dehydration in the yeast, Saccharomyces cerevisiae, was investigated. Magnesium ion availability directly influenced yeast cells' resistance to dehydration and, when additionally supplemented with calcium ions, this provided further significant increase of yeast resistance to dehydration. Gradual rehydration of dry yeast cells in water vapour indicated that both magnesium and calcium may be important for the stabilization of yeast cell membranes. In particular, calcium ions were shown for the first time to increase the resistance of yeast cells to dehydration in stress-sensitive cultures from exponential growth phases. It is concluded that magnesium and calcium ion supplementations in nutrient media may increase the dehydration stress tolerance of S. cerevisiae cells significantly, and this finding is important for the production of active dry yeast preparations for food and fermentation industries.


Effects of a novel biodegredable implant system on a rat tibia fracture model.
This study aimed to determine the effects of a novel biodegradable implant releasing platelet-derived growth factor (PDGF) at the fracture site on fracture healing in a rat tibia fracture model. In this study, 35 male Sprague-Dawley rats weighing between 300 and 350 g were used. The rats were divided into four groups: Group A (control group without any treatment, n=10), Group B (spacer without PDGF Group, n=10), Group C (spacer with PDGF group, n=10), and Group D (healthy rat Group, n=5). Standardized fractures were created in the right tibias of rats, and then biodegradable implants made of poly-β-hydroxybutyrate-co-3-hydroxy valerate were implanted at the fracture sites in Groups B and C. In Group C, implants were loaded with 600 ng of PDGF. Animals were sacrificed 30 days after the operation, and fracture healing in each group was assessed radiologically based on the Goldberg score. Furthermore, the anteroposterior (AP) and mediolateral (ML) callus diameters were measured macroscopically, and fracture sites were mechanically tested. In the radiological assessment, Group C showed higher fracture healing rate than Groups A and B (p=0.001), whereas no significant difference was found between group C and Group D (p>0.05). In the macroscopic assessment, while Group C exhibited the thickest AP callus diameter (p=0.02), no significant differences in ML callus diameters existed among the groups (p>0.05). Mechanical testing revealed that Group C had higher torsional strength (p=0.001) and stiffness than Groups A and B (p=0.001) while there was no significant difference between Groups C and D (p>0.05). Biodegradable implant releasing PDGF may have positive effects on fracture healing.


Objective analysis of ambisonics for hearing aid applications: Effect of listener's head, room reverberation, and directional microphones.
Recently, an increased interest has been demonstrated in evaluating hearing aids (HAs) inside controlled, but at the same time, realistic sound environments. A promising candidate that employs loudspeakers for realizing such sound environments is the listener-centered method of higher-order ambisonics (HOA). Although the accuracy of HOA has been widely studied, it remains unclear to what extent the results can be generalized when (1) a listener wearing HAs that may feature multi-microphone directional algorithms is considered inside the reconstructed sound field and (2) reverberant scenes are recorded and reconstructed. For the purpose of objectively validating HOA for listening tests involving HAs, a framework was developed to simulate the entire path of sounds presented in a modeled room, recorded by a HOA microphone array, decoded to a loudspeaker array, and finally received at the ears and HA microphones of a dummy listener fitted with HAs. Reproduction errors at the ear signals and at the output of a cardioid HA microphone were analyzed for different anechoic and reverberant scenes. It was found that the diffuse reverberation reduces the considered time-averaged HOA reconstruction errors which, depending on the considered application, suggests that reverberation can increase the usable frequency range of a HOA system.


Surgical treatment of male breast cancer metastasis to thoracic spine: A case report.
We present a rare clinical case of a metastatic spinal tumor in the 7th thoracic spine from male breast cancer (MBC). A 62-year-old man was referred as an outpatient, complaining of continuous pain in the back and right flank that began 2 weeks earlier. The patient had no neurologic signs or symptoms but had a medical history of left breast modified radical mastectomy because of MBC. Computed tomography and magnetic resonance imaging showed metastasis in the T7 vertebra and no other metastasis on positron emission tomography/computed tomography or bone scan. Separation surgery was performed with posterior corpectomy of T7 (en bloc excision), followed by stabilization with an expandable titanium cage and pedicle screws. The pathological examination of the excised T7 vertebra confirmed metastatic carcinoma with neuroendocrine differentiation from the breast. Adjuvant chemo-radiotherapy was performed after surgery. The patient had no symptoms at the 21-month follow-up. Radiologic studies showed no evidence of recurrent or metastatic lesions. MBC is extremely rare, with fewer cases of spinal metastases. Among these, patients who undergo separation surgery are even rarer. This case shows that radical surgery can be an option for MBC with spine metastasis if indicated.


Reactive Oxygen Species Production Is a Major Factor Directing the Postantibiotic Effect of Fluoroquinolones in Streptococcus pneumoniae.
We studied the molecular mechanisms involved in the postantibiotic effect of the fluoroquinolones levofloxacin and moxifloxacin in Streptococcus pneumoniae Wild-type strain R6 had postantibiotic effects of 2.05 ± 0.10 h (mean ± standard deviation [SD]) and 3.23 ± 0.45 h at 2.5× and 10× MIC of levofloxacin, respectively. Moxifloxacin exhibited lower effects of 0.87 ± 0.1 and 2.41 ± 0.29 h at 2.5× and 10× MIC, respectively. Fluoroquinolone-induced chromosome fragmentation was measured at equivalent postantibiotic effects for levofloxacin (2.5× MIC) and moxifloxacin (10× MIC). After 2 h of drug removal, reductions were approximately 7-fold for levofloxacin and 3-fold for moxifloxacin, without further decreases at later times. Variations in reactive oxygen species production were detected after 4 to 6 h of drug withdrawals, with decreases ≥400-fold for levofloxacin and ≥800-fold for moxifloxacin at 6 h. In accordance, after 4 to 6 h of drug withdrawal, the levofloxacin-induced upregulation of the fatCDEB operon, introducing iron in the bacteria, decreased up to 2- to 3-fold, and the moxifloxacin-induced upregulation of several genes involved in the production of pyruvate was reduced 3- to 7-fold. In accordance, lower postantibiotic effects (up to 1 h) were observed in strain R6 ΔspxB, lacking the main enzyme involved in oxygen peroxide production, than in R6. Although no change in the recovery of chromosome fragmentation was observed between R6 and R6 ΔspxB, 3.5 × 103-fold lower reactive oxygen species production was observed in R6 ΔspxB, without changes after drug removal. These results show that reactive oxygen species are the main factors directing the postantibiotic effect of levofloxacin and moxifloxacin in S. pneumoniae.


Breast reconstruction in women under 30: a 10-year experience.
The number of women diagnosed with breast cancer at a young age (≤30years) continues to rise. As young women present for breast cancer management with greater frequency, an accurate characterization of the differences in cancer treatments and reconstruction techniques is imperative to optimize care. Here, we sought to identify the reconstruction trends in this population of women ≤30years at time of breast cancer diagnosis. We retrospectively reviewed the charts of women aged ≤30years who underwent breast reconstruction at The University of Texas M.D. Anderson Cancer Center. We extracted data on the patients' diagnosis, adjuvant therapy, reconstructive choice, reason for reconstructive choice, and decision for contralateral prophylactic mastectomy (CPM). Over a 10-year period, 54 patients aged ≤30years underwent 77 breast reconstructions, including 30 microsurgical autologous tissue reconstructions and 34 tissue expander-based reconstructions. Donor site limitations, including insufficient abdominal tissue, restricted the number of patients eligible for abdominal based reconstruction despite the patients' interest in the latter. The rate of CPM was 43%, which was significantly higher than the national average of 8%, further complicating the possibility of total autologous reconstruction. Because of the high rate of bilateral mastectomy and innate donor tissue limitations, young, healthy women who are otherwise ideal candidates for free tissue transfer using the abdominal donor site undergo significantly more tissue expander reconstructions than expected. Implant-based reconstruction or donor sites other than the abdomen must be considered in this unique population.


Pediatric phase I trial and pharmacokinetic study of trimetrexate.
Trimetrexate, a new nonclassical antifolate, was evaluated in a phase I trial in children with refractory cancer including nine with acute leukemia and 21 with solid tumors. The drug was administered as an i.v. bolus injection weekly for three doses, and courses were repeated every 28 days. The dose ranged from 35 to 145 mg/m2. Thirty patients who received a total of 33 courses were evaluable for toxicity, including 19 who were evaluable for hematological toxicity. The maximally tolerated dose for patients with a solid tumor and leukemia was 110 mg/m2. The dose-limiting toxicities were myelosuppression, mucositis and a pruritic, diffuse maculopapular rash. Other side effects observed included transient, mild elevations of serum transaminases, mild nausea and vomiting, and a local phlebitis at the site of injection at higher dose levels. A single patient with delayed drug clearance had evidence of renal toxicity with a transient increase in serum creatinine. The pharmacokinetics of trimetrexate were studied in 25 patients over the entire dose range. There was considerable interpatient variability in total drug clearance (range 9.2 to 215 ml/min/m2) and half-life (2.1 to 20 h). There was a suggestion of a correlation between plasma concentration at 24 h and the development of hematological toxicity at the highest dose level. Trimetrexate was cleared primarily by biotransformation with renal clearance accounting for only 10% of total clearance. Two metabolites of trimetrexate which inhibit the enzyme dihydrofolate reductase were identified in the urine. One of these appears to be a glucuronide conjugate.


Assessment of personal protective equipment use among farmers in eastern North Carolina: a cross-sectional study.
Agriculture consistently ranks among the top hazardous occupations, accounting for a significant number of injuries and fatalities in the workplace. Eastern North Carolina has a significant number of small, independent, family-run, owned, and operated farms. However, little is known about perception, behavior, training, accessibility, or purchasing personal protective equipment (PPE) for safety among farmers in the region. In this study, telephone interviews were conducted among participating farmers between March and June 2012 (N = 129). Univariate and bivariate analyses were conducted to examine associations between PPE behavior and workplace hazards, health-related concerns, and wearing and purchasing PPE. Findings indicated that personal behavior of wearing hearing protection devices (HPDs) and protection from the sun among farmers was low. However, a relatively high percentage of farmers reported wearing PPE when working with agricultural chemicals. Most farmers received training from agricultural extension offices. The findings indicate that, in general, farmers are well aware of the risks associated with occupational hazards and recognize concern for health and safety protection in the workplace. Transitioning these concerns into preventative action remains a challenge and priority for the agricultural health professional.


Magnetic chains of Fe3 clusters in the {Fe3YO2} butterfly molecular compound.
The "butterfly" molecule [Fe3Y(μ3-O)2(CCl3COO)8(H2O)(THF)3] (in brief {Fe3YO2}) includes three Fe3+ ions which build a robust Fe3 cluster with a strong intracluster antiferromagnetic exchange and a total spin S = 5/2. It represents the starting magnetic system to study further interactions with magnetic rare earths when Y is replaced with lanthanides. We present heat capacity and equilibrium susceptibility measurements below 2 K, which show that each cluster has a sizeable magnetic anisotropy pointing to the existence of intercluster interactions. However, no phase transition to a long-range magnetically ordered phase is observed down to 20 mK. The intercluster interaction is analysed in the framework of the one-dimensional Blume-Capel model with an antiferromagnetic chain interaction constant J/kB = -40(2) mK between Fe3 cluster spins, and a uniaxial anisotropy with parameter D/kB = -0.56(3) K. This is associated to single chains of Fe3 clusters oriented along the shortest intercluster distances displayed by the crystal structure of {Fe3YO2}. Ac susceptibility measurements reveal that the magnetic relaxation is dominated by a quantum tunnelling process below 0.2 K, and by thermally activated processes above this temperature. The experimental activation energy of this single chain magnet, Ea/kB = 3.4(6) K, can be accounted for by the combination of contributions arising from single-molecule magnetic anisotropy and spin-spin correlations along the chains.


Gene expression changes in honey bees induced by sublethal imidacloprid exposure during the larval stage.
Honey bee larvae exposed to sublethal doses of imidacloprid show behavioural abnormalities as adult insects. Previous studies have demonstrated that this phenomenon originates from abnormal neural development in response to imidacloprid exposure. Here, we further investigated the global gene expression changes in the heads of newly emerged adults and observed that 578 genes showed more than 2-fold changes in gene expression after imidacloprid exposure. This information might aid in understanding the effects of pesticides on the health of pollinators. For example, the genes encoding major royal jelly proteins (MRJPs), a group of multifunctional proteins with significant roles in the sustainable development of bee colonies, were strongly downregulated. These downregulation patterns were further confirmed through analyses using quantitative reverse transcription-polymerase chain reaction on the heads of 6-day-old nurse bees. To our knowledge, this study is the first to demonstrate that sublethal doses of imidacloprid affect mrjp expression and likely weaken bee colonies.


Recurrent positive selection and heterogeneous codon usage bias events leading to coexistence of divergent pigeon circoviruses.
The capsid genes from 14 pigeon circovirus (PiCV) sequences, collected from Taiwan between 2009 and 2010, were sequenced and compared with 14 PiCV capsid gene sequences from GenBank. Based on pairwise comparison, PiCV strains from Taiwan shared 73.9-100% nucleotide identity and 72-100% amino acid identity with those of the 14 reported PiCV sequences. Phylogenetic analyses revealed that Taiwanese PiCV isolates can be grouped into two clades: clade 1 comprising isolates from Belgium, Australia, USA, Italy and China, and clade 2 showing close relation to isolates from Germany and France. Recurrent positive selection was detected in clade 1 PiCV lineages, which may contribute to the diversification of predominant PiCV sequences in Taiwan. Further observations suggest that synonymous codon usage variations between PiCV clade 1 and clade 2 may reflect the adaptive divergence on translation efficiency of capsid genes in infectious hosts. Variation in selective pressures acting on the evolutionary divergence and codon usage bias of both clades explains the regional coexistence of virus sequences congeners prevented from competitive exclusion within an island such as Taiwan. Our genotyping results also provide insight into the aetiological agents of PiCV outbreak in Taiwan and we present a comparative analysis of the central coding region of PiCV genome. From the sequence comparison results of 28 PiCVs which differs in regard to the geographical origin and columbid species, we identified conserved regions within the capsid gene that are likely to be suitable for primer selection and vaccine development.