Maternal serum vitamin D levels in pregnancies complicated by neural tube defects.
The association between vitamin D deficiency and abnormal neural development has been proposed previously. We aimed to evaluate maternal serum vitamin D levels in pregnancies complicated by neural tube defects (NTDs) and compared them with healthy pregnant women. A total of 60 pregnant women were included in this controlled cross-sectional study. Thirty of the patients whose pregnancies were complicated by meningocele, meningomyelocele, encephalocele, anencephaly and fetal acrania constituted the study group, whereas 30 normal pregnant women constituted the control group. The main parameters recorded for each woman were as follows: age, body mass index (BMI), gestational week (GW), gravidity, abortion, co-morbidities, dressing style, consumption of milk and dairy products and serum levels of 25(OH)VitD3, calcium, albumin and total protein. The mean maternal serum 25(OH)VitD3 level was 6.2 ± 5.0 ng/ml in the study group and 9.1 ± 7.3 ng/ml in the control group (p: 0.071). The mean maternal serum calcium level was statistically significantly higher in the control group, and calcium-rich dietary intake was also more common in this group (p < 0.05). There was no statistically significant difference between groups in terms of age, BMI, GW, dressing style and serum levels of albumin and total protein. Vitamin D deficiency is common among pregnant women, and maternal serum calcium levels were lower in pregnancies complicated by NTD than healthy pregnant women. Larger further studies are required to evaluate the effects of calcium-rich dietary sources or vitamin D and calcium in the development of NTDs.


Body composition and mortality in men receiving prostate radiotherapy: A pooled analysis of NRG/RTOG 9406 and NRG/RTOG 0126.
To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality. Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death. Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area. This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.


DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67 status of estrogen receptor-positive breast cancers.
Breast tumor heterogeneity is related to risk factors that lead to worse prognosis, yet such heterogeneity has not been well studied. To predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer patients via analysis of tumor heterogeneity with subgroup identification based on patterns of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Retrospective study. Seventy-seven breast cancer patients with ER-positive breast cancer were investigated, of whom 51 had low Ki-67 expression. T1 -weighted 3.0T DCE-MR images. Each tumor was partitioned into multiple subregions using three methods based on patterns of dynamic enhancement: 1) time to peak (TTP), 2) peak enhancement rate (PER), and 3) kinetic pattern clustering (KPC). In each tumor subregion, 18 texture features were computed. Univariate and multivariate logistic regression analyses were performed using a leave-one-out-based cross-validation (LOOCV) method. The partitioning results were compared with the same feature extraction methods across the whole tumor. In the univariate analysis, the best-performing feature was the texture statistic of sum variance in the tumor subregion with early TTP for differentiating between patients with high and low Ki-67 expression (area under the receiver operating characteristic curves, AUC = 0.748). Multivariate analysis showed that features from the tumor subregion associated with early TTP yielded the highest performance (AUC = 0.807) among the subregions for predicting the Ki-67 status. Among all regions, the tumor area with high PER at a precontrast MR image achieved the highest performance (AUC = 0.722), while the subregion that exhibited the highest overall enhancement rate based on KPC had an AUC of 0.731. These three models based on intratumoral texture analysis significantly (P < 0.01) outperformed the model using features from the whole tumor (AUC = 0.59). Texture analysis of intratumoral heterogeneity has the potential to serve as a valuable clinical marker to enhance the prediction of breast cancer prognosis. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.


Type VI secretion TssK baseplate protein exhibits structural similarity with phage receptor-binding proteins and evolved to bind the membrane complex.
The type VI secretion system (T6SS) is a multiprotein machine widespread in Gram-negative bacteria that delivers toxins into both eukaryotic and prokaryotic cells. The mechanism of action of the T6SS is comparable to that of contractile myophages. The T6SS builds a tail-like structure made of an inner tube wrapped by a sheath, assembled under an extended conformation. Contraction of the sheath propels the inner tube towards the target cell. The T6SS tail is assembled on a platform-the baseplate-which is functionally similar to bacteriophage baseplates. In addition, the baseplate docks the tail to a trans-envelope membrane complex that orients the tail towards the target. Here, we report the crystal structure of TssK, a central component of the T6SS baseplate. We show that TssK is composed of three domains, and establish the contribution of each domain to the interaction with TssK partners. Importantly, this study reveals that the N-terminal domain of TssK is structurally homologous to the shoulder domain of phage receptor-binding proteins, and the C-terminal domain binds the membrane complex. We propose that TssK has conserved the domain of attachment to the virion particle but has evolved the reception domain to use the T6SS membrane complex as receptor.


Reticulospinal neurons with and without monosynaptic inputs from cerebellar nuclei.
An account is given of the responses of 557 medial reticular neurons with axons projecting down the spinal cord. All 30 experiments were on decerebrated unanesthetized cats paralyzed by Flaxedil. Recording from single neurons was by extracellular glass microelectrodes. Identification was first by location (confirmed by subsequent histology) in the medial reticular nucleus of medulla or pons, and second by antidromic activation from cord stimulation at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between L2 and C2 antidromic responses, and were usually in the range of 90-140 m/s; but about 25% were slower, ranging down to 30 m/s. Stimulation by electrodes in the ipsilateral and contralateral fastigial nuclei differentiated reticulospinal neurons into two classes according to whether they did or did not receive monosynaptic inputs, the respective populations of fully investigated neurons being 270 and 174. The fastigioreticular neurons were distinguished by a higher background frequency with mean values of 28 as against 15/s. There were also significant diffences in both the excitatory and inhibitory responses to afferent volleys from forelimb and hindlimb nerves. Comparison of the respective latency histograms showed that the responses of neurons with a fastigial input had an excess of latencies in the ranges that can be correlated with the latency histograms observed for fastigial responses. Thus, there is evidence for the effectiveness of the fastigial input and so for the pathway with monosynaptic linkage: Purkinje cells of cerebellar vermis yields fastigial neurons yields medial reticular neurons projecting down the spinal cord. Adequate stimulation of cutaneous receptors by pad taps and air-jet stimulation of hairy skin in a disppointingly small action when compared with fastigical responses. Explanations of this deficiency are suggested. Another discrpancy from the fastigial responses is that the medial reticular neurons have much wider receptive fields with little discrimination between ipsilateral and contralateral and between forelimb and hindlimb. Stimulation of the ipsilateral tegmental tract was tested on 183 reticulospinal neurons, 112 being with fastigial inputs. In about half there was a powerful monosynaptic excitation, which would identify such neurons as being on the pathway from mesencephalic and diencephalic centers to the spinal cord. There is a general discussion of transmission across successive synaptic relays, where specificity is sacrificed to integration.


Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations in major antigenic sites of the hemagglutinin molecule analogous to those for human influenza virus.
H5N1 highly pathogenic avian influenza virus has been endemic in poultry in Egypt since 2008, notwithstanding the implementation of mass vaccination and culling of infected birds. Extensive circulation of the virus has resulted in a progressive genetic evolution and an antigenic drift. In poultry, the occurrence of antigenic drift in avian influenza viruses is less well documented and the mechanisms remain to be clarified. To test the hypothesis that H5N1 antigenic drift is driven by mechanisms similar to type A influenza viruses in humans, we generated reassortant viruses, by reverse genetics, that harbored molecular changes identified in genetically divergent viruses circulating in the vaccinated population. Parental and reassortant phenotype viruses were antigenically analyzed by hemagglutination inhibition (HI) test and microneutralization (MN) assay. The results of the study indicate that the antigenic drift of H5N1 in poultry is driven by multiple mutations primarily occurring in major antigenic sites at the receptor binding subdomain, similarly to what has been described for human influenza H1 and H3 subtype viruses.


Ultrafast chemistry: using time-resolved vibrational spectroscopy for interrogation of structural dynamics.
Time-resolved infrared (IR) and Raman spectroscopy elucidates molecular structure evolution during ultrafast chemical reactions. Following vibrational marker modes in real time provides direct insight into the structural dynamics, as is evidenced in studies on intramolecular hydrogen transfer, bimolecular proton transfer, electron transfer, hydrogen bonding during solvation dynamics, bond fission in organometallic compounds and heme proteins, cis-trans isomerization in retinal proteins, and transformations in photochromic switch pairs. Femtosecond IR spectroscopy monitors the site-specific interactions in hydrogen bonds. Conversion between excited electronic states can be followed for intramolecular electron transfer by inspection of the fingerprint IR- or Raman-active vibrations in conjunction with quantum chemical calculations. Excess internal vibrational energy, generated either by optical excitation or by internal conversion from the electronic excited state to the ground state, is observable through transient frequency shifts of IR-active vibrations and through nonequilibrium populations as deduced by Raman resonances.


How might we motivate uptake of the Dual Prevention Pill? Findings from human-centered design research with potential end users, male partners, and healthcare providers.
Multipurpose prevention technologies (MPTs) combining contraception with HIV prevention offer a promising solution to uptake and adherence challenges faced with oral pre-exposure prophylaxis (PrEP). The Dual Prevention Pill (DPP), which combines oral PrEP with an oral contraceptive pill (OCP), could address unmet need for family planning (FP) and HIV prevention. This study aimed to identify barriers and motivators for DPP uptake to inform the development of a DPP demand generation strategy and broader introduction efforts for MPTs. Qualitative, ethnographic research employing human-centered design techniques was conducted in Kenya, South Africa, and Zimbabwe. A research consortium conducted 45 immersions, 34 key informant interviews, and 12 friendship circles with potential end users, male romantic partners, healthcare providers (HCPs), and cultural commentators. Creative concepts were subsequently co-created and validated in workshops with end users, male partners, and HCPs. Four major themes emerged. Women struggled to balance personal motivations with societal expectations. Relationship goals strongly influenced sexual and reproductive health decisions, particularly related to financial security and social status. Negative experiences, such as untrustworthy partners, were significant triggers for OCP and PrEP use. Lastly, male partners were concerned about the DPP upending gender norms but held more positive individual attitudes. Five initial audience segments for the DPP were identified: women seeking enjoyment outside of their primary relationship; new mothers adhering to social norms; women wanting to maintain romantic relationships; women at risk of unintended pregnancy; and women with unfaithful partners. Segments informed the development of three communication themes, with the preferred route highlighting the DPP as a tool to prepare for life's unpredictability. To effectively generate demand for the DPP, several strategies should be considered. Connecting with women's diverse identities and goals and celebrating their individuality is crucial. Linking the DPP to relationship goals reframes it as a means to protect relationships rather than a risk. Leveraging negative triggers through targeted media campaigns empowers women to take control of their sexual health during challenging moments. A balance in channel placement is necessary to raise public awareness while using more discrete channels for potentially controversial messages with male partners and wider communities.


Evaluation of a Computer-Aided Diagnosis System in the Classification of Lesions in Breast Strain Elastography Imaging.
Purpose: Evaluation of the performance of a computer-aided diagnosis (CAD) system based on the quantified color distribution in strain elastography imaging to evaluate the malignancy of breast tumors. Methods: The database consisted of 31 malignant and 52 benign lesions. A radiologist who was blinded to the diagnosis performed the visual analysis of the lesions. After six months with no eye contact on the breast images, the same radiologist and other two radiologists manually drew the contour of the lesions in B-mode ultrasound, which was masked in the elastography image. In order to measure the amount of hard tissue in a lesion, we developed a CAD system able to identify the amount of hard tissue, represented by red color, and quantify its predominance in a lesion, allowing classification as soft, intermediate, or hard. The data obtained with the CAD system were compared with the visual analysis. We calculated the sensitivity, specificity, and area under the curve (AUC) for the classification using the CAD system from the manual delineation of the contour by each radiologist. Results: The performance of the CAD system for the most experienced radiologist achieved sensitivity of 70.97%, specificity of 88.46%, and AUC of 0.853. The system presented better performance compared with his visual diagnosis, whose sensitivity, specificity, and AUC were 61.29%, 88.46%, and 0.829, respectively. The system obtained sensitivity, specificity, and AUC of 67.70%, 84.60%, and 0.783, respectively, for images segmented by Radiologist 2, and 51.60%, 92.30%, and 0.771, respectively, for those segmented by the Resident. The intra-class correlation coefficient was 0.748. The inter-observer agreement of the CAD system with the different contours was good in all comparisons. Conclusions: The proposed CAD system can improve the radiologist performance for classifying breast masses, with excellent inter-observer agreement. It could be a promising tool for clinical use.


Deep generative design with 3D pharmacophoric constraints.
Generative models have increasingly been proposed as a solution to the molecular design problem. However, it has proved challenging to control the design process or incorporate prior knowledge, limiting their practical use in drug discovery. In particular, generative methods have made limited use of three-dimensional (3D) structural information even though this is critical to binding. This work describes a method to incorporate such information and demonstrates the benefit of doing so. We combine an existing graph-based deep generative model, DeLinker, with a convolutional neural network to utilise physically-meaningful 3D representations of molecules and target pharmacophores. We apply our model, DEVELOP, to both linker and R-group design, demonstrating its suitability for both hit-to-lead and lead optimisation. The 3D pharmacophoric information results in improved generation and allows greater control of the design process. In multiple large-scale evaluations, we show that including 3D pharmacophoric constraints results in substantial improvements in the quality of generated molecules. On a challenging test set derived from PDBbind, our model improves the proportion of generated molecules with high 3D similarity to the original molecule by over 300%. In addition, DEVELOP recovers 10× more of the original molecules compared to the baseline DeLinker method. Our approach is general-purpose, readily modifiable to alternate 3D representations, and can be incorporated into other generative frameworks. Code is available at https://github.com/oxpig/DEVELOP.


Melatonin in ventricular and subarachnoid cerebrospinal fluid: Its function in the neural glymphatic network and biological significance for neurocognitive health.
The central nervous system (CNS) is endowed with a specialized cerebrospinal fluid (CSF)/lymph network which removes toxic molecules and metabolic by-products from the neural parenchyma; collectively, this has been named the glymphatic system. It allows CSF located in the subarachnoid space which surrounds the CNS to enter the depths of the brain and spinal cord by means of Virchow-Robin perivascular and perivenous spaces. CSF in the periarterial spaces is transferred across the astrocytic end feet which line these spaces aided by AQ4 channels; in the interstitium, the fluid moves via convection through the parenchyma to be eventually discharged into the perivenous spaces. As it passes through the neural tissue, the interstitial fluid flushes metabolic by-products and extracellular toxins and debris into the CSF of the perivenous spaces. The fluid then moves to the surface of the CNS where the contaminants are absorbed into true lymphatic vessels in the dura mater from where it is shunted out of the cranial vault to the cervical lymph nodes. Pineal melatonin released directly into the CSF causes the concentration of this molecule to be much higher in the CSF of the third ventricle than in the blood. After the ventricular melatonin enters the subarachnoid and Virchow-Robin spaces it is taken into the neural tissue where it functions as a potent antioxidant and anti-inflammatory agent. Experimental evidence indicates that it removes pathogenic toxins, e.g., amyloid-β and others, from the brain to protect against neurocognitive decline. Melatonin levels drop markedly during aging, coincident with the development of several neurodegenerative diseases and the accumulation of the associated neurotoxins.


Facile Preparation of Super Absorbent from Calcium-Aluminum Waste Residue and Its Application for Adsorption of Congo Red.
A super absorbent was synthesized from calcium-aluminum waste residue of aluminum industrial using a facile hydrothermal method. The XRD results revealed that the main phase of hydrothermal product at 120 °C is CaSO₄ ·2H₂O, with a small amount of Al(OH)₃. The as-prepared products were used to investigate the adsorptive applications in Congo red (CR) removal, and the results showed that the products treated at 120 °C had the best adsorption properties. The maximum adsorption capacity reaches about 1860.11 mg/g with a removal rate of 99.75%. Furthermore, the used adsorbent could be regenerated for at least four cycles through a calcination procedure, indicating its potential as an excellent adsorbent for the removal of CR dye from wastewater. The adsorption behavior was analyzed by Langmuir, Freundlich and Sips isotherms, and the adsorption proved to be a multilayer adsorption. This facile method presented here may provide promise synthesis of high-effective and low-cost adsorbents from industrial solid waste and achieve the goal of "using waste to treat waste" in the future.


Reversal of Aged Muscle Stem Cell Dysfunction.
The loss of muscle stem cell (MuSC) numbers and function in the elderly results in a dramatic delay or incomplete repair of muscle following injury or surgery. Prolonged immobility can exacerbate the loss of muscle mass with increased morbidity of affected patients. Stem cells and their niche cooperate to regulate the activation, self-renewal, differentiation, and return to quiescence of MuSCs. Extracellular matrix fibronectin (FN) and MuSC β1-integrin have been identified as critical factors in the dysfunction of aging muscle. Reduced amounts and/or function of β1-integrin and fibronectin are critical factors in the decline in MuSC regeneration and homeostasis with aging. Replacement of fibronectin and/or stimulation of β1-integrin may provide a novel means to augment the decline in MuSC function with age.


Determination of the coenzyme Q10 status in a large Caucasian study population.
Coenzyme Q10 (CoQ10 ) exists in a reduced (ubiquinol) and an oxidized (ubiquinone) form in all human tissues and functions, amongst others, in the respiratory chain, redox-cycles, and gene expression. As the status of CoQ10 is an important risk factor for several diseases, here we determined the CoQ10 status (ubiquinol, ubiquinone) in a large Caucasian study population (n = 1,911). The study population covers a wide age range (age: 18-83 years, 43.4% men), has information available on more than 10 measured clinical phenotypes, more than 30 diseases (presence vs. absence), about 30 biomarkers, and comprehensive genetic information including whole-genome SNP typing (>891,000 SNPs). The major aim of this long-term resource in CoQ10 research is the comprehensive analysis of the CoQ10 status with respect to integrated health parameters (i.e., fat metabolism, inflammation), disease-related biomarkers (i.e., liver enzymes, marker for heart failure), common diseases (i.e., neuropathy, myocardial infarction), and genetic risk in humans. Based on disease status, biomarkers, and genetic variants, our cohort is also useful to perform Mendelian randomisation approaches. In conclusion, the present study population is a promising resource to gain deeper insight into CoQ10 status in human health and disease.


Two-dimensional NaxSiS as a promising anode material for rechargeable sodium-based batteries: ab initio material design.
The rapidly rising demand for energy storage systems presents an imperative need to develop sodium-ion batteries with high energy density, high conductivity, and low barrier energy. In this work, we present a Density Functional study on the properties of two-dimensional NaxSiS as a promising anode material for rechargeable sodium-ion batteries. Energetically stable structures of Na-adsorbed silicene sulfide NaxSiS with various Na contents were explored. It is found that the adsorption energy of a Na atom is higher than -0.4 eV and it decreases with increasing Na content. The electronic structure of pristine silicene sulfide shows semiconductor behaviour with a bandgap of 0.99 eV, while the Na-adsorbed SiS exhibits metallic characteristics. The highest theoretical capacity of 187.2 mA h g-1, which is higher than that of well-known two dimensional materials, is found in the fully intercalated phase of SiS Na0.5SiS which corresponds to per side layer. Furthermore, Na ions can diffuse along two typical pathways on the surface of SiS with a small barrier of 183 meV which is much smaller than that of the two dimensional LixSiS, NaxTiS2, and NaxMoS2. All these characteristics suggest that silicene sulfide SiS can be expected to be a promising anode material for sodium ion batteries.


Ophthalmological findings in patients with spinocerebellar ataxia type 1 are not correlated with neurological anticipation.
Optic atrophy, attenuation of the oscillatory potentials (OPs) of the electroretinogram (ERG), and enlargement of corneal endothelial cells, have been reported in patients with spinocerebellar ataxia type 1 (SCA1). These patients have a trinucleotide repeat expansion in the SCA1 gene and show neurological anticipation. The purpose of this study was to determine whether the ophthalmological findings are correlated with the neurological disorders, and whether ophthalmological anticipation is present in patients with SCA1. The visual acuity, ERGs, and corneal endothelial cell density were examined in 14 patients whose DNA analysis revealed an expanded trinucleotide repeat in an allele of the SCA1 gene. The results of the tests were compared with the trinucleotide repeat number and the duration of the neuronal disease. The neurological disorders in the patients showed anticipation. The negative correlation between the trinucleotide repeat number and the neurological disorder was statistically significant (P<0.0001). However, the correlations between trinucleotide repeat number and visual acuity, amplitude of OPs, and corneal endothelial cell density were not significant. Statistically significant correlations were found between the duration of the neuronal disease and the visual acuity, OPs, and corneal endothelial cell density (P<0.0001, P=0.0004, and P<0.0001, respectively). The ophthalmological disorders were prominent in patients who had neuronal disease for more than 10 years. Unlike the neurological findings, the ophthalmological disorders in patients with SCA1 were not correlated with the trinucleotide repeat number of the SCA1 gene. The ophthalmological findings were most highly correlated with the duration of the neuronal disease.


Influence of population selection on the 99th percentile reference value for cardiac troponin assays.
We sought to determine the effect of patient selection on the 99th reference percentile of 2 sensitive and 1 high-sensitivity (hs) cardiac troponin assays in a well-defined reference population. Individuals>45 years old were randomly selected from 7 representative local community practices. Detailed information regarding the participants was collected via questionnaires. The healthy reference population was defined as individuals who had no history of vascular disease, hypertension, or heavy alcohol intake; were not receiving cardiac medication; and had blood pressure<140/90 mmHg, fasting blood glucose<110 mg/dL (approximately 6 mmol/L), estimated creatinine clearance>60 mL·min(-1)·(1.73 m2)(-1), and normal cardiac function according to results of echocardiography. Samples were stored at -70 °C until analysis for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide. Application of progressively more stringent population selection strategies to the initial baseline population of 545 participants until the only individuals who remained were completely healthy according to the study criteria reduced the number of outliers seen and led to a progressive decrease in the 99th-percentile value obtained for the Roche hs-cTnT assay and the sensitive Beckman cTnI assay but not for the sensitive Siemens Ultra cTnI assay. Furthermore, a sex difference found in the baseline population for the hs-cTnT (P=0.0018) and Beckman cTnI assays (P<0.0001) progressively decreased with more stringent population selection criteria. The reference population selection strategy significantly influenced the 99th percentile reference values determined for troponin assays and the observed sex differences in troponin concentrations.


Tools for the body (schema).
What happens in our brain when we use a tool to reach for a distant object? Recent neurophysiological, psychological and neuropsychological research suggests that this extended motor capability is followed by changes in specific neural networks that hold an updated map of body shape and posture (the putative "Body Schema" of classical neurology). These changes are compatible with the notion of the inclusion of tools in the "Body Schema", as if our own effector (e.g. the hand) were elongated to the tip of the tool. In this review we present empirical support for this intriguing idea from both single-neuron recordings in the monkey brain and behavioural performance of normal and brain-damaged humans. These relatively simple neural and behavioural aspects of tool-use shed light on more complex evolutionary and cognitive aspects of body representation and multisensory space coding for action.


The African Green Monkey model for cutaneous and visceral leishmaniasis.
Non-human primates are valuable models for biomedical research because of their similarities to human anatomy, immunology and physiology. Leishmaniasis, a disease caused by protozoan parasites, has a worldwide distribution and results in high morbidity and mortality. Availability of a non-human primate model of leishmaniasis would facilitate the study of different aspects of this disease and would accelerate the development of vaccines and new drugs. In this article, some interesting features of the vervet monkey (African Green monkey) model of human cutaneous and visceral leishmaniasis are discussed.


[Hypocortisolemia with neither signs nor symptoms of cortisol deficiency: research on transcortin characteristics].
Low plasma levels of cortisol, as a result of primary or secondary adrenal hypofunction, is usually associated to findings of hypocortisolism. Low plasma cortisol levels without clinical manifestations have been observed in patients in which cortisol binding capacity (CBG) is altered. In this paper we report a clinically normal patient, with very low plasma cortisol levels. We investigated a possible CBG defect or the presence of a CBG binding substance as an explanation of the clinical findings. We found a normal CBG and no competing substance. Therefore, the presence of low cortisol levels suggests the presence in this patient of a receptor with increased sensitivity to cortisol, or another molecule that can be recognized as glucocorticoid by the cortisol receptor.


Experimental evidence of icosahedral and decahedral packing in one-dimensional nanostructures.
The packing of spheres is a subject that has drawn the attention of mathematicians and philosophers for centuries and that currently attracts the interest of the scientific community in several fields. At the nanoscale, the packing of atoms affects the chemical and structural properties of the material and, hence, its potential applications. This report describes the experimental formation of 5-fold nanostructures by the packing of interpenetrated icosahedral and decahedral units. These nanowires, formed by the reaction of a mixture of metal salts (Au and Ag) in the presence of oleylamine, are obtained when the chemical composition is specifically Ag/Au = 3:1. The experimental images of the icosahedral nanowires have a high likelihood with simulated electron micrographs of structures formed by two or three Boerdijk-Coxeter-Bernal helices roped on a single structure, whereas for the decahedral wires, simulations using a model of adjacent decahedra match the experimental structures. To our knowledge, this is the first report of the synthesis of nanowires formed by the packing of structures with 5-fold symmetry. These icosahedral nanowire structures are similar to those of quasicrystals, which can only be formed if at least two atomic species are present and in which icosahedral and decahedral packing has been found for bulk crystals.


Neurological event rates and associated risk factors in acute type B aortic dissections treated by thoracic aortic endovascular repair.
Thoracic endovascular aortic repair is the method of choice in patients with complicated type B acute aortic dissection. However, thoracic endovascular aortic repair carries a risk of periprocedural neurological events including stroke and spinal cord ischemia. We aimed to look at procedure-related neurological complications within a large cohort of patients with type B acute aortic dissection treated by thoracic endovascular aortic repair. Between 1996 and 2021, the International Registry of Acute Aortic Dissection collected data on 3783 patients with type B acute aortic dissection. For this analysis, 648 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair were included (69.4% male, mean age 62.7 ± 13.4 years). Patients were excluded who presented with a preexisting neurologic deficit or received adjunctive procedures. Demographics, clinical symptoms, and outcomes were analyzed. The primary end point was the periprocedural incidence of neurological events (defined as stroke, spinal cord ischemia, transient neurological deficit, or coma). Predictors for perioperative neurological events and follow-up outcomes were considered as secondary end points. Periprocedure neurological events were noted in 72 patients (11.1%) and included strokes (n = 29, 4.6%), spinal cord ischemias (n = 21, 3.3%), transient neurological deficits (n = 16, 2.6%), or coma (n = 6, 1.0%). The group with neurological events had a significantly higher in-hospital mortality (20.8% vs 4.3%, P < .001). Patients with neurological events were more likely to be female (40.3% vs 29.3%, P = .077), and aortic rupture was more often cited as an indication for thoracic endovascular aortic repair (38.8% vs 16.5%, P < .001). In patients with neurological events, more stent grafts were used (2 vs 1 stent graft, P = .002). Multivariable logistic regression analysis showed that aortic rupture (odds ratio, 3.12, 95% confidence interval, 1.44-6.78, P = .004) and female sex (odds ratio, 1.984, 95% confidence interval, 1.031-3.817, P = .040) were significantly associated with perioperative neurological events. In this highly selected group from dedicated aortic centers, more than 1 in 10 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair had neurological events, in particular women. Further research is needed to identify the causes and presentation of these events after thoracic endovascular aortic repair, especially among women.


A breakthrough-like effect of metformin reduces peripheral resistance to triiodothyronine in euthyroid, non-insulin-resistant, type 2 diabetic patients.
Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well. In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line. Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect. Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.


Single HERG delayed rectifier K+ channels expressed in Xenopus oocytes.
HERG is a K+ channel with properties similar to the rapidly activating component (I(Kr)) of delayed rectifier K+ current, which is important for repolarization of human cardiac myocytes. In this study, we have characterized the single-channel properties of HERG expressed in Xenopus oocytes. Currents were measured in cell-attached patches with an extracellular K concentration of 120 mM. The single HERG channel conductance, determined at test potentials between -50 and -110 mV, was 12.1 +/- 0.6 pS. At positive test potentials (+40 to +80 mV), the probability of channel opening was low and slope conductance was 5.1 +/- 0.6 pS. The mean channel open times at -90 mV were 2.9 +/- 0.5 and 11.8 +/- 1.0 ms, and the mean channel closed times were 0.54 +/- 0.02 and 14.5 +/- 5.3 ms. Single HERG channels were blocked by MK-499, a class III antiarrhythmic agent that blocks I(Kr) in cardiac myocytes. The development of block was more rapid in inside-out patches than in cell-attached patches or in whole cell recordings, indicating that block occurs from the cytoplasmic side of the membrane. The single-channel properties of HERG are similar to I(Kr) channels of isolated cardiac myocytes, which provides further evidence that HERG proteins coassemble to form I(Kr) channels.


Monoclonal gammopathy among patients with chronic hepatitis C virus infection.
An association between monoclonal gammopathies and chronic liver diseases has been previously reported. Hence, the objective of this study was to determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection in Egypt. This is a prospective study of 200 HCV-positive and 100 HCV-negative patients with chronic liver diseases recruited consecutively at the Kasr El Aini Hospital Departments of Internal Medicine and Hematology, Cairo University. Clinical data were gathered, serum protein electrophoresis was performed and immunoelectrophoresis was carried out for the detection of monoclonal component. Histological examination of bone marrow was performed in patients with monoclonal gammopathy. A monoclonal band was detected in 2% of the HCV-positive patients and in 0% of the HCV-negative patients (P > 0.05). In this study, 4 cases of monoclonal gammopathy of undetermined significance were observed in the HCV-positive group, whereas none was observed in the HCV-negative group, which supports prior observations that HCV infection is associated with an excess risk for monoclonal gammopathy of undetermined significance.


Swine Dialyzable Spleen Extract as Antiviral Prophylaxis.
Worldwide, the most highly consumed meat is of porcine origin. The production and distribution of swine meat are affected by diverse health matters, such as influenza and diarrhea, which cause head losses and require the use of antibiotics and other drugs in hog farms. To stimulate newborn piglet immune responses and increase resistance to infections, we developed a spray-drying technique to produce dried swine dialyzable spleen extract (sDSE), an immunomodulator. Based on the size-exclusion ultra performance liquid chromatography quantitative analysis, it was possible to recover up to 58% of the product after the drying process. The biological activity of orally administered dried sDSE increased mouse survival and induced cytokine production in a herpes infection model.


Use of animation video in surgical decision-making for treatment of early breast cancer in Indian women.
Surgical decision-making in early breast cancer is difficult for the patient and also for the treating clinician, especially when the patient is not completely aware of the available options. Adjuncts such as animation video with case scenarios can be helpful in this regard. We used an animation video to help in decision-making and evaluated the effect of such adjunct in Indian women with early breast cancer. An animation video of running time of 4 min and 11 s was shown to forty patients with early breast cancer, who filled in a patient satisfaction multimedia questionnaire at the end of the animation. Seventeen (42.5%) patients underwent breast-conserving surgery (BCS) while the rest 23 (57.5%) patients underwent the mastectomy. All forty patients were satisfied with the animation video. The mean score of the utility of the video to improve understanding of the disorder, better organization of treatment, stimulated interest in the relations, and saved unnecessary discussion was 88.50, 88.50,88.3, and 90.3, respectively. Age and literacy status did not significantly affect the scores. All the patients found the video useful and most patients made the decision on the first attempt. Patients' perspective about BCS is influenced by the fear of recurrence, fear of multiple surgeries, complications, and also the counseling provided by the surgeon. In this situation, such animation videos provide an unbiased view on the operative procedure and help in decision-making.


Multi-source synthesis of data to inform health policy.
To propose a new method for comparing and integrating original qualitative data with systematic reviews of quantitative and qualitative studies, demonstrated by a study of the psychosocial needs of chronic fatigue syndrome (CFS) sufferers in Québec. A systematic literature review was performed across various databases for English and French language studies, on the psychosocial aspects of CFS. Qualitative, quantitative, and mixed method studies published between January 1994 and July 2008 were included. Unpublished literature and reference lists of included studies were also searched. Themes identified in the literature were used to guide semi-structured interviews with seventeen CFS-sufferers, mostly recruited from a large specialist practice in Montreal. Interviews were transcribed verbatim and validated by a research assistant. Transcripts were coded using the identified themes. New codes were created when new issues arose. All themes were subsequently synthesized into overall categories using a constant comparative method. The literature search yielded thirty-one papers: twenty-eight primary studies and three systematic reviews. Twelve themes were identified and synthesized into four overall problem categories, such as "Lack of professional recognition." Interviews confirmed findings from the literature, but also revealed unidentified needs specific to CFS-sufferers in Québec. Policy recommendations were provided to address these needs. Multi-Source Synthesis provides a systematic method for synthesizing data from original studies with literature findings, thereby broadening the knowledge base and the local relevance of decisions concerning specific patient populations.


Large area films of alternating graphene-carbon nanotube layers processed in water.
We report the preparation of hybrid paperlike films consisting of alternating layers of graphene (or graphene oxide) and different types of multiwalled carbon nanotubes (N-doped MWNTs, B-doped MWNTs, and pristine MWNTs). We used an efficient self-assembly method in which nanotubes were functionalized with cationic polyelectrolytes in order to make them dispersible in water, and subsequently these suspensions were mixed with graphene oxide (GO) suspensions, and the films were formed by casting/evaporation processes. The electronic properties of these films (as produced and thermally reduced) were characterized, and we found electrical resistivities as low as 3 × 10(-4) Ω cm. Furthermore, we observed that these films could be used as electron field emission sources with extraordinary efficiencies; threshold electric field of ca. 0.55 V/μm, β factor as high as of 15.19 × 10(3), and operating currents up to 220 μA. These values are significantly enhanced when compared to previous reports in the literature for other carbon nanostructured filmlike materials. We believe these hybrid foils could find other applications as scaffolds for tissue regeneration, thermal and conducting papers, and laminate composites with epoxy resins.


Morphological regionalization using fetal magnetic resonance images of normal developing brains.
Regional differences in human brain development during infancy have been studied for many years, but little is known about how regionalization of the brain proceeds during intrauterine life. We investigated the regionalization of cerebral volume and cortical convolutions based on the volumetric magnetic resonance images (MRIs) of 43 fetuses, ranging from 21 to 37 weeks of gestation. Two plausible parcellations of MRI are proposed, and curvature index together with gyrification index are used to quantify the regional cortical convolutions. Our results elucidate that the cortical foldings among different brain regions develop at comparable rates, suggesting a similar uniformity of changes in size of the cortical sheet in these regions over time. On the contrary, the growth of the cerebral volume presents regional difference, with the frontal and parieto-temporal regions growing significantly faster than other regions due to the contribution from expansion of basal ganglia. This quantitative regional information suggests that cerebral volume is not a relevant parameter to measure in relation to gyrification, and that the size of the cortical sheet is more likely to be directly related to cortical folding. The availability of quantitative regional information on normal fetal brains in utero will allow clinical application of this information when probing neurodevelopmental disorders in the future.


Recruitment of exogenous macrophages into metastases at different stages of tumor growth.
The endogenous tumor-associated macrophage content and recruitment of labeled peritoneal exudate cells into experimental murine B16 melanoma metastases has been examined at different stages in the progressive growth of metastatic lesions. The recruitment of thioglycollate-elicited peritoneal exudate cells and peritoneal exudate cells activated in vitro with muramyl dipeptide was studied. Tumor-associated macrophages and labeled peritoneal exudate cells were identified in paraffin sections by specific histochemical staining and their density in individual metastases measured morphometrically. The density of tumor-associated macrophages and exogenously recruited peritoneal exudate cells was high in very small lesions but decreased rapidly as a function of enlargement of metastases, MD:An; where MD is macrophage density, A is the cross-sectional area of the lesion and n is a negative number. No significant difference was observed in the recruitment of activated and nonactivated peritoneal exudate cells. These results suggest that decreased recruitment of macrophages from the circulation may explain the decrease in the density of tumor-associated macrophages as metastases grow and indicate that macrophage activation is not accompanied by enhanced localization and/or uptake of macrophages into metastases.


Mutations in the capsid protein of Brome mosaic virus affecting encapsidation eliminate vesicle induction in planta: implications for virus cell-to-cell spread.
Positive-strand RNA viruses are known to rearrange the endomembrane network to make it more conducive for replication, maturation, or egress. Our previous transmission electron microscopic (TEM) analysis showed that ectopic expression of wild-type (wt) capsid protein (CP) of Brome mosaic virus (BMV) has an intrinsic property of modifying the endoplasmic reticulum (ER) to induce vesicles similar to those present in wt BMV infection. In this study, we evaluated the functional significance of CP-mediated vesicle induction to the BMV infection cycle in planta. Consequently, the cytopathologic changes induced by wt CP or its mutants defective in virion assembly due to mutations engineered in either N- or C-proximal domains were comparatively analyzed by TEM in two susceptible (Nicotiana benthamiana and Chenopodium quinoa) and one nonhost (N. clevelandii) plant species. The results showed that in susceptible hosts, CP-mediated ER-derived vesicle induction is contingent on the expression of encapsidation-competent CP. In contrast, unlike in N. benthamiana and C. quinoa, transient expression of wt CP in nonhost N. clevelandii plants eliminated vesicle induction. Additionally, comparative source-to-sink analysis of virus spread in leaves of N. benthamiana and N. clevelandii coexpressing wt BMV and Cucumber mosaic virus (CMV) showed that despite trans-encapsidation, CMV failed to complement the defective cell-to-cell movement of BMV. The significance and relation of CP-mediated vesicle induction to virus cell-to-cell movement are discussed.


Comparison of three different methods of monitoring unwanted effects during antihypertensive therapy.
In a double-blind, randomized, crossover, multicenter study performed in 227 hypertensive outpatients, two antihypertensive drugs, oxprenolol and chlorthalidone, were investigated to determine unwanted effects. Three main methodologic procedures were applied: the conventional evaluation of unwanted effects by the physician and involving the whole patient population, the checklist, and the free questionnaire. The latter two were assigned by randomization to the patients themselves. The study showed that unwanted effects seem to be frequently overreported when a checklist is used, whereas the free questionnaire gives more information about the symptoms of the disease than about the tolerance of the drug. The conventional method, when physicians are well-informed and sensitized to the problem, seems to provide more reliable information about unwanted effects of a drug.


Blood coagulation, fibrinolysis and lipid profile in patients with primary hyperparathyroidism: increased plasma factor VII and X activities and D-Dimer levels.
Primary hyperparathyroidism (PHPT) is associated with an increased cardiovascular mortality and morbidity rate. However, the exact role of PTH and/or calcium in the development of cardiovascular disease (CVD) is still controversial. The influence of PHPT on hemostasis is yet unknown. Therefore, the main purpose of this study was to investigate the markers of endogenous coagulation/fibrinolysis and to evaluate the relationships between these hemostatic parameters, serum lipid profile and serum calcium and PTH in patients with PHPT. Twenty-three patients with PHPT and 20 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX and X activities, von Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipoprotein variables, were measured. The relationships between biochemical parameters and these hemostatic parameters were examinated. Compared with the control subjects, platelet count, FVII, FX activities, and D-Dimer levels were significantly increased in patients with PHPT (p<0.001, p<0.05, p<0.001, and p<0.05, respectively). Among the lipids, the levels of TC, TG and LDL-C were significantly increased in patients with PHPT (p<0.01, p<0.001, p<0.001, respectively) than those in controls. In patients with PHPT, we showed a positive correlation between urinary phosphorus excretion and factors VIII, IX, and X (r: 0.572, p<0.01; r: 0.543, p<0.01; r: 0.532, p<0.01, respectively). F IX activity was positively correlated with TC (r: 0.463, p<0.05) and LDL-C (r: 0.549, p<0.01) There was a positive correlation between serum ALP and PAI-1 levels (r: 0.451, p<0.05). ApoB was positively correlated with D-Dimer (r: 0.421, p<0.05). We did not find any significant correlation between iPTH and serum calcium and the hemostatic parameters that we measured. In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased platelet count, F VII and FX activities and D-Dimer levels in patients with PHPT represent a potential hypercoagulable state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality rate due to CVD in patients with PHPT.


Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients.
Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.


Hemodynamics in the Left Atrium and Its Effect on Ventricular Flow Patterns.
In the present study, we investigate the hemodynamics inside left atrium (LA) and understand its impact on the development of ventricular flow patterns. We construct the heart model using dynamic-computed tomographic images and perform simulations using an immersed boundary method based flow solver. We show that the atrial hemodynamics is characterized by a circulatory flow generated by the left pulmonary veins (LPVs) and a direct stream from the right pulmonary veins (RPVs). The complex interaction of the vortex rings formed from each of the PVs leads to vortex breakup and annihilation, thereby producing a regularized flow at the mitral annulus. A comparison of the ventricular flow velocities between the physiological and a simplified pipe-based atrium model shows that the overall differences are limited to about 10% of the peak mitral flow velocity. The implications of this finding on the functional morphology of the left heart as well the computational and experimental modeling of ventricular hemodynamics are discussed.


Riding in shopping carts and exposure to raw meat and poultry products: prevalence of, and factors associated with, this risk factor for salmonella and campylobacter infection in children younger than 3 years.
Riding in a shopping cart next to raw meat or poultry is a risk factor for Salmonella and Campylobacter infections in infants. To describe the frequency of, and factors associated with, this behavior, we surveyed parents of children aged younger than 3 years in Foodborne Disease Active Surveillance Network sites. We defined exposure as answering yes to one of a series of questions asking if packages of raw meat or poultry were near a child in a shopping cart, or if a child was in the cart basket at the same time as was raw meat or poultry. Among 1,273 respondents, 767 (60%) reported that their children visited a grocery store in the past week and rode in shopping carts. Among these children, 103 (13%) were exposed to raw products. Children who rode in the baskets were more likely to be exposed than were those who rode only in the seats (odds ratio [OR], 17.8; 95% confidence interval [CI], 11.0 to 28.9). In a multivariate model, riding in the basket (OR, 15.5; 95% CI, 9.2 to 26.1), income less than $55,000 (OR, 1.8; 95% CI, 1.0 to 3.1), and Hispanic ethnicity (OR, 2.3; 95% CI, 1.2 to 4.5) were associated with exposure. Our study shows that children can be exposed to raw meat and poultry products while riding in shopping carts. Parents should separate children from raw products and place children in the seats rather than in the baskets of the cart. Retailer use of leak-proof packaging, customer placement of product in a plastic bag and on the rack underneath the cart, use of hand sanitizers and wipes, and consumer education may also be helpful.


[Validation of the meaning of terms identified in the CIPESC project for the axis focus of nursing practice of ICNP].
This work aims at continuing the contribution of Brazilian nursing in the elaboration of ICNPâ, which is being constructed by the coordination of ICN. It has two main objectives which are: 1) the definition of the terms identified in the CIPESC project and classified in the axis focus of nursing practice of the Nursing Phenomena Classification of ICNPâ-Beta Version; 2) the validation of these definitions within a group of judges composed of professionals who were previously involved in the execution of the CIPESC project, or who were teachers or nurse assistants in the area of community health nursing. The process was carried out in two phases, considering that the definitions that had a 0.80 rate of Agreement (RA) within the group of judges were validated. Ninety-nine definitions of the terms were validated: 26 attained a RA equal to 1.00; 56 attained a RA between 0.90-0.99 and, 17 attained a RA between 0.80 an 0.89. The definition of one term was not validated.


Transposable elements promote the evolution of genome streamlining.
Eukaryotes and prokaryotes have distinct genome architectures, with marked differences in genome size, the ratio of coding/non-coding DNA, and the abundance of transposable elements (TEs). As TEs replicate independently of their hosts, the proliferation of TEs is thought to have driven genome expansion in eukaryotes. However, prokaryotes also have TEs in intergenic spaces, so why do prokaryotes have small, streamlined genomes? Using an in silico model describing the genomes of single-celled asexual organisms that coevolve with TEs, we show that TEs acquired from the environment by horizontal gene transfer can promote the evolution of genome streamlining. The process depends on local interactions and is underpinned by rock-paper-scissors dynamics in which populations of cells with streamlined genomes beat TEs, which beat non-streamlined genomes, which beat streamlined genomes, in continuous and repeating cycles. Streamlining is maladaptive to individual cells, but improves lineage viability by hindering the proliferation of TEs. Streamlining does not evolve in sexually reproducing populations because recombination partially frees TEs from the deleterious effects they cause. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.


A recombinant foot-and-mouth disease virus antigen inhibits DNA replication and triggers the SOS response in Escherichia coli.
The 3D gene of foot-and-mouth disease virus encodes the viral RNA dependent RNA polymerase, also called virus infection associated (VIA) antigen, which is the most important serological marker of virus infection. This 3D gene from a serotype C1 virus has been cloned and overexpressed in Escherichia coli under the control of the strong lambda lytic promoters. The resulting 51 kDa recombinant protein has been shown to be immunoreactive with sera from infected animals. After induction of gene expression, an immediate and dramatic arrest of cell DNA synthesis occurs, similar to that produced by genotoxic doses of the drug mitomycin C. This effect does not occur during the production of either a truncated VIA antigen or other related and non-related viral proteins. The inhibition of DNA replication results in a subsequent induction of the host SOS DNA-repair response and in an increase of the mutation frequency in the surviving cells.


Comparison of M and N gene sequences distinguishes variation amongst equine arteritis virus isolates.
cDNA copies of the M and N genes of equine arteritis virus (EAV) isolates were synthesized by reverse transcription followed by polymerase chain reaction amplification. The cDNA was subjected to a cycle sequencing strategy using Taq polymerase, and the nucleotide and derived amino acid sequences of 10 virus isolates were compared. The M and N genes of all isolates had the same initiation and termination sites as the prototype Bucyrus strain and the encoded proteins were conserved between viruses. Comparison of nucleotide sequence homologies and phylogenetic tree analysis implied the existence of three EAV variants originating from the U.S.A. (Bucyrus), Austria (Vienna) and Switzerland (Bibuna), and suggested that RNA recombination between EAV isolates may have occurred.


[Psoas fixation of the bladder. An efficient aid in cases of repeat surgery of the uretero-vesical junction].
We reviewed our experience with 6 patients (5 males, 1 female) aged 3 to 10 years in whom psoas hitch of the bladder was performed in the course of repeated surgery of the vesicoureteral junction. All patients had previously undergone an operation on the distal ureter and presented an evident shortening of its length. After ureteral reimplantation in 4 patients (3 were Hendren's procedure and 1 Cohen's reimplantation), the reflux either persisted or became worse and the remaining 2 patients (posterior urethral valves) underwent cutaneous distal ureterostomy. In all cases the psoas hitch procedure successfully resolved the ureteral defect, provided the bladder with a new surface for a submucosal tunnel of suitable length and diameter, and permitted reimplantation of the ureter without traction or possibility of bending. The psoas hitch procedure is a simple and effective alternative in the management of distal ureter length defects. Although it has precise indications, it can have broad applications when combined with other techniques (TUU). However, the approach should be one of caution in those cases that also require surgery of the contralateral distal ureter.


Neonatal mastitis: controversies in management.
To document the range of presentations, extent of investigations, and treatment choices of 'physicians treating' neonates with mastitis seen over a 9-year period at a tertiary care pediatric hospital. An email survey was sent to Emergency Department (ED) staff and fellows asking them how they would treat a well-looking neonate with localized mastitis. Secondly, a retrospective chart review of neonates presenting to the ED with a diagnosis of neonatal mastitis or breast engorgement from July 2000 to December 2009 was conducted to assess how such patients were actually treated. 46/107 surveys were returned, with a wide discrepancy in how clinicians would treat neonatal mastitis: 4.3% would perform a full sepsis work up, including lumbar puncture, followed by IV antibiotics and hospital admission; 28% chose discharge on oral antibiotics; and 28% suggested admission only if blood work was abnormal. From the chart review, 33 neonates were diagnosed with possible neonatal mastitis over a 9-year period: 12 met the inclusion criteria. Of these, 8 (66%) were admitted and treated with intravenous antibiotics, 2 (16.6%) were treated with oral antibiotics, and 2 (16.6%) did not receive antibiotics. None of the 12 patients had lumbar puncture performed. There is significant disagreement among clinicians regarding the best way to treat the well-looking neonate with localized mastitis. Most elect to perform blood tests and start treatment with IV antibiotics with good Staphylococcus aureus coverage, followed by oral antibiotics if cultures are negative.


Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).
Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors. Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole. Mean maternal age was 30 years, and median gestational age was 30+3 weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, P=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43-0.59), while only esomeprazole inhibited placental sFlt-1 release. Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.


Pathophysiological significance of fasciculations in the early diagnosis of ALS.
In amyotrophic lateral sclerosis (ALS), muscles with preserved strength can have fasciculation potentials (FPs) as the only abnormality. The FPs in strong muscles are predominantly simple and stable, and can often be recruited by a slight voluntary contraction. In weak and atrophic muscles, the FPs are generally complex and unstable, tend to have a slower firing rate and are not recruited by voluntary contraction. Macro-electromyography studies suggest that these FPs are part of a more complex motor unit, as opposed to simple FPs which can represent all the motor unit. FPs driven by transcranial magnetic stimulation (TMS) were observed in 13 ALS patients. TMS-driven fasciculations had a simple morphology and were stable. Complex potentials were never cortically driven. These observations strengthen the conviction that fasciculations in ALS can have different origins. Simple, stable FPs arise proximally and are probably related to excitotoxicity phenomena, while complex, unstable FPs are most likely to originate in distal axonal sprouts that are associated with the reinnervation process. Some ALS patients with fatigue and mild weakness can have profuse fasciculations at an early phase in the evolution of the disease. Patients with denervation localized in one region and diffuse FPs should be strongly suspected of having ALS. With this strategy it should be possible to shorten the diagnosis time.


US trends in quality-adjusted life expectancy from 1987 to 2008: combining national surveys to more broadly track the health of the nation.
We used data from multiple national health surveys to systematically track the health of the US adult population. We estimated trends in quality-adjusted life expectancy (QALE) from 1987 to 2008 by using national mortality data combined with data on symptoms and impairments from the National Medical Expenditure Survey (1987), National Health Interview Survey (1987, 1994-1995, 1996), Medical Expenditure Panel Survey (1992, 1996, 2000-2008), National Nursing Home Survey (1985, 1995, and 1999), and Medicare Current Beneficiary Survey (1992, 1994-2008). We decomposed QALE into changes in life expectancy, impairments, symptoms, and smoking and body mass index. Years of QALE increased overall and for all demographic groups-men, women, Whites, and Blacks-despite being slowed by increases in obesity and a rising prevalence of some symptoms and impairments. Overall QALE gains were large: 2.4 years at age 25 years and 1.7 years at age 65 years. Understanding and consistently tracking the drivers of QALE change is central to informed policymaking. Harmonizing data from multiple national surveys is an important step in building this infrastructure.


Targeting tumor ubiquitin-proteasome pathway with polyphenols for chemosensitization.
The development of tumor drug resistance is one of the biggest obstacles on the way to achieve a favorable outcome of chemotherapy. Among various strategies that have been explored to overcome drug resistance, the combination of current chemotherapy with plant polyphenols as a chemosensitizer has emerged as a promising one. Plant polyphenols are a group of phytochemicals characterized by the presence of more than one phenolic group. Mechanistic studies suggest that polyphenols have multiple intracellular targets, one of which is the proteasome complex. The proteasome is a proteolytic enzyme complex responsible for intracellular protein degradation and has been shown to play an important role in tumor growth and the development of drug resistance. Therefore, proteasome inhibition by plant polyphenols could be one of the mechanisms contributing to their chemosensitizing effect. Plant polyphenols that have been identified to possess proteasome-inhibitory activity include (-)-epigallocatechins-3-gallate (EGCG), genistein, luteolin, apigenin, chrysin, quercetin, curcumin and tannic acid. These polyphenols have exhibited an appreciable effect on overcoming resistance to various chemotherapeutic drugs as well as multidrug resistance in a broad spectrum of tumors ranging from carcinoma and sarcoma to hematological malignances. The in vitro and in vivo studies on polyphenols with proteasome-inhibitory activity have built a solid foundation to support the idea that they could serve as a chemosensitizer for the treatment of cancer. In-depth mechanistic studies and identification of optimal regimen are needed in order to eventually translate this laboratory concept into clinical trials to actually benefit current chemotherapy.


Algoriphagus zhangzhouensis sp. nov., isolated from mangrove sediment.
A Gram-negative, short-rod-shaped and non-motile bacterium, strain 12C11(T), was isolated from an oil-degrading consortium, enriched from the Fugong mangrove sediment, Fujian Province of China. Optimum growth was observed at 25 °C, at pH 7.5 and with 4 % (w/v) NaCl. Comparative 16S rRNA gene sequence analysis demonstrated that it shared highest similarity with members of the genus Algoriphagus (97.5-93.4 %), exhibiting 97.5 % sequence similarity to Algoriphagus ornithinivorans IMSNU 14014(T), followed by Algoriphagus vanfongensis KMM 6241(T) (97.2 %); it shared <96.0 % sequence similarity with other members of the genus. Levels of nucleotide sequence similarity between gyrB (DNA gyrase subunit B) genes of strain 12C11(T) and A. vanfongensis KMM 6241(T), A. ornithinivorans IMSNU 14014(T), Algoriphagus marincola SW-2(T) and Algoriphagus hitonicola 7-UAH(T) were 78.8, 78.6, 75.6 and 77.4 %, respectively. Phylogenetic trees based on these housekeeping genes showed that strain 12C11(T) and other Algoriphagus strains formed a distinct lineage. The dominant fatty acids were iso-C15 : 0 (32.1 %), C16 : 1ω7c/C16 : 1ω6c (11.6 %), iso-C17 : 1 I/anteiso-C17 : 1 B (10.1 %), iso-C17 : 0 3-OH (9.2 %) and iso-C17 : 1ω9c/C16 : 0 10-methyl (7.1 %), which accounted for 70.0 % of the total fatty acids. DNA-DNA hybridization showed that strain 12C11(T) shared low DNA-DNA relatedness with A. vanfongensis KMM 6241(T) and A. ornithinivorans IMSNU 14014(T) (30.7±0.9 and 30.5±1.8 %, respectively). The G+C content of the chromosomal DNA of strain 12C11(T) was 38.4 mol%. The major respiratory quinones were MK-7 (96.0 %) and MK-6 (4.0 %). According to its morphology, physiology, fatty acid composition and 16S rRNA gene sequence data, the novel strain most appropriately belongs to the genus Algoriphagus, but can readily be distinguished from known Algoriphagus species. The name Algoriphagus zhangzhouensis sp. nov. is proposed (type strain 12C11(T) = CGMCC 1.11027(T) = MCCC 1F01099(T) = DSM 25035(T)).


Development of an automated treatment planning approach for lattice radiation therapy.
Lattice radiation therapy (LRT) alternates regions of high and low doses within the target. The heterogeneous dose distribution is delivered to a geometrical structure of vertices segmented inside the tumor. LRT is typically used to treat patients with large tumor volumes with cytoreduction intent. Due to the geometric complexity of the target volume and the required dose distribution, LRT treatment planning demands additional resources, which may limit clinical integration. We introduce a fully automated method to (1) generate an ordered lattice of vertices with various sizes and center-to-center distances and (2) perform dose optimization and calculation. We aim to report the dosimetry associated with these lattices to help clinical decision-making. Sarcoma cancer patients with tumor volume between 100 cm3 and 1500 cm3 who received radiotherapy treatment between 2010 and 2018 at our institution were considered for inclusion. Automated segmentation and dose optimization/calculation were performed by using the Eclipse Scripting Application Programming Interface (ESAPI, v16, Varian Medical Systems, Palo Alto, USA). Vertices were modeled by spheres segmented within the gross tumor volume (GTV) with 1 cm/1.5 cm/2 cm diameters (LRT-1 cm/1.5 cm/2 cm) and 2 to 5 cm center-to-center distance on square lattices alternating along the superior-inferior direction. Organs at risk were modeled by subtracting the GTV from the body structure (body-GTV). The prescription dose was that 50% of the vertice volume should receive at least 20 Gy in one fraction. The automated dose optimization included three stages. The vertices optimization objectives were refined during optimization according to their values at the end of the first and second stages. Lattices were classified according to a score based on the minimization of body-GTV max dose and the maximization of GTV dose uniformity (measured with the equivalent uniform dose [EUD]), GTV dose heterogeneity (measured with the GTV D90%/D10% ratio), and the number of patients with more than one vertex inserted in the GTV. Plan complexity was measured with the modulation complexity score (MCS). Correlations were assessed with the Spearman correlation coefficient (r) and its associated p-value. Thirty-three patients with GTV volumes between 150 and 1350 cm3 (median GTV volume = 494 cm3 , IQR = 272-779 cm3 were included. The median time required for segmentation/planning was 1 min/21 min. The number of vertices was strongly correlated with GTV volume in each LRT lattice for each center-to-center distance (r > 0.85, p-values < 0.001 in each case). Lattices with center-to-center distance = 2.5 cm/3 cm/3.5 cm in LRT-1.5 cm and center-to-center distance = 4 cm in LRT-1 cm had the best scores. These lattices were characterized by high heterogeneity (median GTV D90%/D10% between 0.06 and 0.19). The generated plans were moderately complex (median MCS ranged between 0.19 and 0.40). The automated LRT planning method allows for the efficacious generation of vertices arranged in an ordered lattice and the refinement of planning objectives during dose optimization, enabling the systematic evaluation of LRT dosimetry from various lattice geometries.


Smooth muscle phenotypes in developing and atherosclerotic human arteries demonstrated by myosin expression.
Smooth muscle myosin heavy chains (MHC) exist in multiple isoforms. Rabbit smooth muscle contain at least three types of MHC isoforms; SM1 (204 kDa), SM2 (200 kDa) and SMemb (200 kDa). SM1 and SM2 are specific to smooth muscle, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta and in activated mesenchymal cells. We previously reported that these three MHC isoforms are differentially expressed in rabbit during normal vascular development and in experimental arteriosclerosis and demonstrated that MHC isoforms are excellent markers for smooth muscle phenotype. In order to clarify the clinical significance of MHC isoforms, this article will focus on the expression of smooth muscle MHC isoforms in normally developing and atherosclerotic human arteries, especially in coronary arteries. We recently isolated and characterized three cDNA clones encoding human SM1, SM2, and SMemb. The expression of SM2 mRNA in the human fetal aorta was significantly lower as compared to SM1 mRNA but the ratio of SM2- to SM1-mRNA was increased after birth. SMemb mRNA in the aorta was decreased after birth. Immunohistologically, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was not detected in fetal arteries of early gestational stage. SM2 was recognized in well-differentiated smooth muscle after perinatal stage. In the human aorta or coronary arteries, unlike in rabbit, SMemb was detected even in the adult. Mild diffuse intimal thickening in the major coronary arteries of the young was found to be composed of smooth muscle cells, reacting equally to three antibodies for MHC isoforms. In thickened but non-atheromatous intima, the expression of well-differentiated smooth muscle-specific MHC (SM2) was reduced, especially in the deeper layer. With progression of atherosclerosis, intimal smooth muscle diminished the expression of not only SM2 but also SM1, whereas alpha-smooth muscle actin was well preserved. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisms of atherosclerosis.


Predictors of hospital stay in normotensive acute pulmonary embolism: a retrospective pilot study.
Introduction: The aim of our study is to determine the clinical, biochemical, and imaging factors that affect the duration of hospital stay in patients admitted with normotensive acute pulmonary embolism. Methods: This was a single-center retrospective study conducted in a community hospital in New York metropolitan area for patients admitted from October 2015 to October 2017. Results: A total of 79 patients were included, the mean age was 55.76 (SD = 17.33), 29 cases were males (37%) and 50 cases were females (63%). Among all patients, 17 cases had short length of stay (LOS) (≤2 days) and 62 cases had long LOS (>2 days). There were statistically significant differences in age (p = .041), presence of lung disease (p = .036), number of comorbidities (p = .043), and pulmonary embolism severity index (PESI) scores (original and simplified; p = .002 and .001, respectively). Logistic regression analysis showed that PESI score significantly predicted long LOS (OR 1.067, 95% CI [1.001, 1.137], p = .048). Similarly, sPESI significantly predicted long LOS (OR 0.223, 95% CI [0.050, 0.999], p = .050). Both regression models were adjusted for age, lung disease, and number of comorbidities. Conclusion: Both original and simplified PESI scores were statistically significant predictors of duration of hospital stay. Patients with multiple comorbidities or with chronic lung disease were also likely to have prolonged hospital stay. None of the cardiac biomarkers affected the duration of hospital stay, neither did the presence of right ventricular dysfunction nor treatment modality.


Correlation of serum cholesteryl ester fatty acid composition with susceptibility to atherosclerosis in different species.
Fatty acid composition of serum cholesteryl esters (CEs) in Chinese and 9 species of laboratory animals was analysed. Polyunsaturated fatty acids (PUFAs) were the predominant fatty acids in CEs. A close correlation between PUFAs to saturated fatty acids ratio (P/S) in CEs and susceptibility to atherosclerosis (AS) was observed in different species. Animals with high P/S such as mice (13.0), tree shrews (9.0) and rats (9.0) were AS-resistant, and those with low P/S such as rabbits (2.9) were susceptible to AS. The P/S value in men (4.9) was between those of the above two kinds of animals, and similar to those of pigs (4.2) and monkeys (3.7). Marked physiological significance of the rich PUFAs in CEs may be expected. As the main constituent of low density lipoprotein (LDL), CEs may provide PUFAs for cells efficiently via LDL receptor. It is assumed that PUFAs in CEs may play an important role in the metabolism of cholesterol and the development of AS by regulating LDL receptor activity, platelet function and prostaglandin metabolism.


17O solid state NMR as a valuable tool for deciphering reaction mechanisms in mechanochemistry: the case study on the 17O-enrichment of hydrated Ca-pyrophosphate biominerals.
The possibility of enriching in 17O the water molecules within hydrated biominerals belonging to the Ca-pyrophosphate family was investigated, using liquid assisted grinding (LAG) in the presence of 17O-labelled water. Two phases with different hydration levels, namely triclinic calcium pyrophosphate dihydrate (Ca2P2O7·2H2O, denoted t-CPPD) and monoclinic calcium pyrophosphate tetrahydrate (Ca2P2O7·4H2O, denoted m-CPPT β) were enriched in 17O using a "post-enrichment" strategy, in which the non-labelled precursors were ground under gentle milling conditions in the presence of stoichiometric quantities of 17O-enriched water (introduced here in very small volumes ∼10 μL). Using high-resolution 17O solid-state NMR (ssNMR) analyses at multiple magnetic fields, and dynamic nuclear polarisation (DNP)-enhanced 17O NMR, it was possible to show that the labelled water molecules are mainly located at the core of the crystal structures, but that they can enter the lattice in different ways, namely by dissolution/recrystallisation or by diffusion. Overall, this work sheds light on the importance of high-resolution 17O NMR to help decipher the different roles that water can play as a liquid-assisted grinding agent and as a reagent for 17O-isotopic enrichment.


Lung cancer surgery. A critical review of the evidence.
Surgery is generally considered to be the treatment of choice for anatomically localized non-small-cell lung cancer, but its effectiveness remains unproven. Observational studies have been of limited value because the criteria by which patients are selected for surgery create substantial differences between patients who undergo surgery and those who do not. One small randomized trial of surgery vs radiotherapy was inconclusive, but several large trials of lung cancer screening have provided indirect evidence against a benefit from surgery. Two ongoing randomized trials, one on extensive vs limited resection and the other on the effect of surgery in more extensive disease, may provide further insight into the effectiveness of surgery in the treatment of localized non-small-cell lung cancer. Development of a large randomized trial to directly assess the effectiveness of surgery in the treatment of localized non-small-cell lung cancer has been precluded by ethical concerns, but may need to be reconsidered if indicated by the findings of the two ongoing studies.


A verification of psychostimulant-induced improvement in sustained attention in rats: effects of d-amphetamine, nicotine, and pemoline.
Previous studies from this laboratory have demonstrated that a variety of psychostimulant drugs can improve the performance of rats trained in a 2-choice stimulus detection task in which the correct responses are indicated by a briefly illuminated light. To enhance the construct validity of the task for assessing sustained attention, the procedure was modified so that the precue interval across trials varied unpredictably between 3, 7, and 11 s. After training rats (N = 17) so that their baseline accuracy levels stabilized between 75% and 88% correct, their performance was assessed after administration of d-amphetamine (0.125-0.75 mg/kg sc), nicotine (0.25-0.75 mg/kg sc), and pemoline (5.0-30.0 po). At certain doses all 3 drugs induced performance improvements in mean choice accuracy and choice response time. Because the precue intervals varied unpredictably and the cue durations used to maintain the rats' baseline accuracy levels were typically short (range = 70-500 ms), the task conforms to most conditions typically required for assessing sustained attention. Results verify the proposal that psychostimulant drugs can enhance the attentiveness of animals in a fashion similar to that documented in humans.


Mesenchymal stem cells to treat female infertility; future perspective and challenges: A review.
Infertility negatively impacts the overall health and social life of affected individuals and couples. Female infertility is their inability to perceive pregnancy. To date, polycystic ovary syndrome, primary ovarian insufficiency, fallopian tube obstruction, endometriosis, and intrauterine synechiae have been identified as the primary causes of infertility in women. However, despite the mutual efforts of clinicians and research scientists, the development of an effective treatment modality has met little success in combating female infertility. Intriguingly, significant research has demonstrated mesenchymal stem cells as an optimal source for treating infertility disorders. Therefore, here we attempted to capsulize to date available studies to summarize the therapeutic potential of mesenchymal stem cells in combating infertility in women by focusing on the underlying mechanism through which stem cells can reduce the effects of ovarian disorders. Furthermore, we also discussed the preclinical and clinical application of stem cell therapy, their limitation, and the future perspective to minimize these limitations.


Percutaneous treatment of common bile duct stones: results and complications in 110 consecutive patients.
Choledocholithiasis is a common complication of cholecystolithiasis, occurring in 15-20% of patients who have gallbladder stones. Endoscopic retrograde cholangio-pancreatography is the standard treatment. When this is not possible or not feasible, percutaneous transhepatic stone removal is an alternative treatment. In this retrospective study, we analyze 110 patients who were treated with percutaneous transhepatic removal of Common Bile Duct (CBD) stones. Between March 1998 and September 2013 110 patients (61 men, 49 women; aged 14-96, mean age 69.7 years) with confirmed bile duct stones were included. PTC was done using ultrasound and fluoroscopy. Balloon dilatation of the papilla was done with 8-12 mm balloons. If stone size exceeded 10 mm, mechanical lithotripsy was performed. Stones were then removed by percutaneous extraction or evacuation into the duodenum. In 104 patients (104/110; 94.5%) total stone clearance of the CBD was achieved. A total of 12 complications occurred (10.9%), graded with the Clavien-Dindo scale as IVa, IVb, and V, respectively; hypoxia requiring resuscitation, sepsis and death due to ongoing cholangiosepsis (n = 1, 4, 1). Minor complications I, II, and IIIa included: small liver abscess, pleural empyema, transient hemobilia and mild fever (n = 1, 1, 2, 2). Percutaneous removal of CBD stones is an effective alternative treatment, when endoscopic treatment is contra-indicated, fails or is not feasible. It is effective, has a low complication rate and using deep sedation potentially requires only a very limited number of treatment sessions.


Photon capture and signalling by melanopsin retinal ganglion cells.
A subset of retinal ganglion cells has recently been discovered to be intrinsically photosensitive, with melanopsin as the pigment. These cells project primarily to brain centres for non-image-forming visual functions such as the pupillary light reflex and circadian photoentrainment. How well they signal intrinsic light absorption to drive behaviour remains unclear. Here we report fundamental parameters governing their intrinsic light responses and associated spike generation. The membrane density of melanopsin is 10(4)-fold lower than that of rod and cone pigments, resulting in a very low photon catch and a phototransducing role only in relatively bright light. Nonetheless, each captured photon elicits a large and extraordinarily prolonged response, with a unique shape among known photoreceptors. Notably, like rods, these cells are capable of signalling single-photon absorption. A flash causing a few hundred isomerized melanopsin molecules in a retina is sufficient for reaching threshold for the pupillary light reflex.


Elevated red blood cell distribution width predicts mortality in acute exacerbation of COPD.
Red blood cell distribution width (RDW) has been shown to predict clinical outcomes in many diseases. To our knowledge, the prognostic significance of RDW in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has not been reported so far. The aim of the present study is to investigate the relation of RDW to in-hospital mortality in patients with AECOPD. We retrospectively reviewed hospital records of inpatients with AECOPD in two referral teaching hospitals in two provinces of east Azerbaijan and west Azerbaijan, Iran. Associations between RDW and in-hospital death were analyzed with using correlation, logistic regression analysis, and receiver operating characteristic (ROC) curves is SPSS software. We studied 330 patients, of whom 75 (22.7%) did not survive to hospital discharge. In univariate analysis higher RDW-SD values were associated with increased hospital mortality (30.2% vs. 15.8% p=0.002 odds ratio 2.31). Using the first quartile of RDW as reference, odds ratio (OR) mortality among patients in the highest RDW quartile was 5.34 (95%CI, 2.70-12.57;9=0.001). In multivariate analysis RDW-SD remained an independent risk factor for mortality after correction for age, thrombocytopenia, leukocyte count, mean corpuscular volume, anemia. In receiver-operating curve analysis the AUC for RDW was 0.663, which was more than that of hemoglobin, platelets. RDW on admission day proves to be a useful indicator to predict in-hospital death in AECOPD.


Assessment of osteoporosis in patients with type 2 diabetes mellitus: A study from the central region of Saudi Arabia.
To understand the impact of diabetes on bone mineral density and whether it increases the likelihood of osteoporosis. This study was performed on 327 Saudis (aged >40 years) who were screened for osteoporosis and diabetes mellitus (DM). The levels of osteoporosis were determined by an estimation of Bone mineral density (BMD) using a DEXA scan examination. The data on BMD from diabetic subjects were compared with healthy nondiabetic controls. Out of 327 enrolled subjects, 38 (11.6%) were found to be osteoporotic, whereas 138 (42.2%) had DM. The data showed that the number of patients with osteoporosis in the DM group was 14 (36.8%), significantly lower than in nondiabetic patients, 21 (55.2%) (p=0.0015). Notably, the data showed no significant difference in the mean BMD of the femur in patients with DM (0.926 g/cm2) and non-diabetes (0.936 g/cm2) (p=0.280; T-score p=0.4746). The mean BMD levels in the spine of the DM study group (1.049 g/cm2) were significantly higher when compared with nondiabetic healthy controls (0.990 g/cm2) (p=0.0031). Patients with diabetes had higher lumbar BMD than nondiabetics, although femoral BMD was similar. Patients with diabetes have a lower osteoporosis risk than nondiabetics.


Patient aggression in a general hospital setting: do nurses perceive it to be a problem?
Aggressive incidents in the general hospital setting have been recognised as problematic for health care workers. Despite an awareness of the problem by nursing staff, there is little known about these incidents. A survey was therefore conducted in a metropolitan tertiary hospital to determine the prevalence and extent of patient aggression in order to direct future management strategies. A survey tool elicited information about the aggressor, factors leading to the incident, the nature of the incident, how it was managed and the outcome. Sixty-eight incidents of aggression were reported over a five-month period; all were reported by nursing staff. The majority of incidents occurred after hours when staff resources were limited. Frequent actions taken by staff to manage aggressive patients were chemical and physical restraint. Nurses identified that many of the incidents were unavoidable despite the aggression management training they had received. This paper outlines strategies taken by the hospital to address the issues identified in the survey.


Mesenchymal Stromal Cells Enhance Vascularization and Epithelialization within 7 Days after Gingival Augmentation with Collagen Matrices in Rabbits.
Soft gingival tissue deficiency remains a severe problem leading to postoperative recession, peri-implantitis, and bone resorption. The use of collagen matrices does not always lead to complete rebuilding of the gingiva volume. The application of mesenchymal stromal cells (MSCs) simultaneously with collagen materials represents a promising approach for the restoration of soft gingival tissues. However, short-term effects of MSCs-enriched collagen grafts after gingival augmentation have not yet been studied properly. Mucograft and Mucoderm matrices were implanted in rabbits (n = 12) simultaneously with the intraoperative injection of rabbit bone marrow-derived mesenchymal stromal cells (BM-MSCs) or without cells. Collagen matrices were implanted under the flap or by the surface technique without intentional primary closure. The samples were harvested seven days after implantation, histological staining with hematoxylin and eosin, and immunohistochemical staining for VEGF, IGF1, and TGF were performed. The use of Mucoderm led to better augmentation outcomes on day 7 compared with Mucograft (p < 0.0001). Gingival augmentation in combination with the local administration of BM-MSCs led to better regeneration of the soft gingival tissues independently of the type of implanted collagen matrices (p < 0.0001). Furthermore, injection of BM-MSCs significantly enhanced gingival vascularization and epithelization with a clear positive correlation between vascular growth and epithelial response. Administration of BM-MSCs in combination with various collagen materials may potentially improve gingiva regeneration.


γ-Tocotrienol Suppression of the Warburg Effect Is Mediated by AMPK Activation in Human Breast Cancer Cells.
Cancer cell metabolism is characterized by aerobic glycolysis or the "Warburg effect". Enhanced Akt signaling is associated with activation of various downstream enzymes involved in the glycolytic process, whereas activation of 5'-AMP-activated kinase (AMPK) acts to terminate energy expending mechanisms and decrease glycolytic enzyme expression. Studies were conducted to determine if the anticancer effects of γ-tocotrienol, are mediated through a suppression in aerobic glycolysis. Results show that treatment with 0-7 μM γ-tocotrienol throughout a 4-day culture period resulted in a dose-responsive increase in AMPK activation, and corresponding decrease in Akt activity in human MCF-7 and MDA-MB-231 breast cancer cells. γ-Tocotrienol treatment was also found to induce a dose-responsive decrease in phosphorylated-Fox03 (inactivated), a transcription factor that acts to inhibit in the levels of glycolytic enzyme, and this decrease was associated with a reduction in glycolytic enzyme levels and activity, as well as glucose consumption in these cells. PCR microarray analysis shows that γ-tocotrienol treatment decreases the expression of genes associate with metabolic signaling and glycolysis in MCF-7 and MDA-MB-231 breast cancer cells. In summary, these findings demonstrate that the anticancer effects of γ-tocotrienol are mediated, at least in part, by a suppression in the Warburg effect.


A comparison of probing and radiographic methods for detection of periodontal disease progression.
Over the last decade new technology has increasingly been applied to periodontal probing and radiography to result in diagnostic methods with greater resolution, repeatability, and accuracy. The goal of this paper is to discuss these methods with special emphasis on data published within the past year. Moreover, this paper summarizes the state of our current understanding of the usefulness of these methods in patient care and research.