[Nocturnal fears in children and their relation to epilepsy].
As many as 41 children aged 3 to 14 years with nocturnal fears were examined. As shown by observations, the majority of nocturnal fears are of mixed nature, i.e. they have both epileptic and neurotic characteristics at a time. None of the symptoms analyzed may be regarded as absolute to prove the epileptic genesis of nocturnal fears. Clinico-electroencephalographic correlations revealed a direct relationship between the number of the clinical symptoms providing evidence in favour of epilepsy and changes on the EEG.


Interprofessional pre-qualification clinical education: a systematic review.
A search was made of relevant databases and the reference lists of key textbooks and reviews. Of 420 potentially relevant articles, 25 were included in the review. Medicine, nursing, physiotherapy, occupational therapy and social work were the professions most often included. Aims and activities of interprofessional clinical education (IPCE) programs were varied, and there was inconsistency in outcome evaluation approach and tools. The models of IPCE described in the literature are diverse. The major barriers to IPCE were logistical, and the careful planning and negotiation required to overcome these barriers was time consuming. Detailed planning, stakeholder enthusiasm and commitment appear to be essential to the success of IPCE. The literature provides guiding principles for establishing a program; however, there is limited evidence to support a particular approach.


Cone Density Is Correlated to Outer Segment Length and Retinal Thickness in the Human Foveola.
Assessment of the relationship between in vivo foveolar cone density, cone outer segment length (OSL), and foveal retinal thickness (RT). Foveolar cone density maps covering the central ±300 µm of the retina were derived from adaptive optics scanning laser ophthalmoscopy images. The corresponding maps of foveal cone OSL and RT were derived from high-resolution optical coherence tomography volume scans. Alignment of the two-dimensional maps containing OSL and RT with the cone density map was achieved by placing the location of maximum OSL on the cone density centroid (CDC). Across 10 participants (27 ± 9 years; 6 female), cone density at the CDC was found to be between 147,038 and 215,681 cones/mm². The maximum OSL and minimum RT were found to lie between 31 and 40, and 193 and 226 µm, respectively. A significant correlation was observed between cone density at the CDC and maximum OSL (P = 0.001), as well as the minimal RT (P < 0.05). Across all participants, the best fit for the relationship between normalized cone density and normalized OSL within the central 300 µm was given by a quadratic function. Using optical coherence tomography-derived measurements of OSL enables to estimate CDC cone density and two-dimensional foveal cone density maps for example in patient eyes unsuitable for adaptive optics imaging. Furthermore, the observation of a fixed relationship between the normalized OSL and cone density points to a conserved mechanism shaping the foveal pit.


Hydroxyl-Directed Regio- and Diastereoselective Allylic Sulfone Reductions with [Sm(H2O)n]I2.
Allylic 1,2- and 1,3-hydroxy phenyl sulfones undergo regioselective and diastereoselective desulfonylation with double bond migration upon treatment with [Sm(H2O)n]I2. Selectivity in these reactions is thought to arise from the formation of a chelated organosamarium intermediate followed by intramolecular protonation by samarium-bound water, which is supported by observed diastereoselectivity and stereospecificity trends along with deuterium labeling experiments. The reaction was then featured in the synthesis of the phenolic fragment of the thailandamide natural products.


Determinants of the relative reduction potentials of type-1 copper sites in proteins.
The relative Cu(2+)/Cu(+) reduction potentials of six type-1 copper sites (cucumber stellacyanin, P. aeruginosa azurin, poplar plastocyanin, C. cinereus laccase, T. ferrooxidans rusticyanin, and human ceruloplasmin), which lie in a reduction potential range from 260 mV to over 1000 mV, have been studied by quantum mechanical calculations. The range and relative orderings of the reduction potentials are reproduced very well compared to experimental values. The study suggests that the main structural determinants of the relative reduction potentials of the blue copper sites are located within 6 A of the Cu atoms. Further analysis suggests that the reduction potential differences of type-1 copper sites are caused by axial ligand interactions, hydrogen bonding to the S(Cys), and protein constraint on the inner sphere ligand orientations. The low reduction potential of cucumber stellacyanin is due mainly to a glutamine ligand at the axial position, rather than a methionine or a hydrophobic residue as in the other proteins. A stronger interaction with a backbone carbonyl group is a prime contributor to the lower reduction potential of P. aeruginosa azurin as compared to poplar plastocyanin, whereas the reverse is true for C. cinereus laccase and T. ferrooxidans rusticyanin. The lack of an axial methonine ligand also contributes significantly to the increased reduction potentials of C. cinereus laccase and human ceruloplasmin. However, in the case of C. cinereus laccase, this increase is attenuated by the presence of only one amide NH hydrogen bond to the S(Cys) rather than two in the other proteins. In human ceruloplasmin the reduction potential is further increased by the structural distortion of the equatorial ligand orientation.


Investigating the impact of metal ions and 3D printed droplet microfluidics chip geometry on the luminol‑potassium periodate chemiluminescence system for estimating total phenolic content in olive oil.
The impact of the chip design and the mixing mechanisms using six different 3D printed microfluidic chips were investigated. The study was conducted using novel 3D printed droplet based microfluidics. A multi-mixing approach was utilized to enhance the CL signal of the CL system under investigation. The approach is based on droplet formation, droplet mixing and droplets merging in the 3D printed microfluidic chip. A 154% higher CL signal intensity was obtained using this approach compared to the CL signal obtained using the serpentine chip commonly used for improving the mixing inside droplet microfluidics. This chip was exploited to study the role of three metal ions: Co2+, Mn2+ and Fe2+ on catalyzing the luminol‑potassium periodate chemiluminescence (CL) reaction with selected phenolic compounds in basic media was carefully investigated. Furthermore, the luminol‑potassium periodate-metal ions system was optimized for all metal ions using gallic acid as the reference standard. Despite the popularity of luminol systems in estimating antioxidant activity or total phenolic content (TPC), the results of this study revealed the necessity of careful and vigilant attention when applying it to complex matrices. The only metal ion that showed quenching behavior with all 20 of the tested phenolic compounds was Fe2+, while Co2+and Mn2+ showed both quenching and enhancement in the CL signal. The luminol‑potassium periodate-Fe2+ system was applied to estimate TPC in olive oil extracts.


Nearly complete survival of an entangled biphoton through bound states in continuum in disordered photonic lattices.
Bound states in the continuum (BICs) of periodic lattices have been the recent focus in a variety of photonic nanostructures. Motivated by the recent results about the photons evolving in BIC structures, we investigate the quantum decay of entangled biphotons through disordered photonic lattices. We report that the persistence of bound states in disordered photonic lattices leads to an interplay between the BIC and disorder-induced Anderson localized states. We reveal a novel effect resulting from such an interplay: a nearly complete quantum survival for the entangled biphoton respecting the antisymmetric exchange symmetry. This is in contrast to the complete vanishment in a periodic photonic lattice.


Immunohistochemical and ultrastructural study of mixed small cell/large cell carcinoma of the lung. Expression of Sialyl LeX-i antigens and scarcity of neuroendocrine characteristics.
The authors examined the immunohistochemical and ultrastructural characteristics of mixed small cell/large cell carcinoma (mixed subtype) of the lung which has been newly categorized as anaplastic small cell lung carcinoma. The 34 cases of small cell lung carcinoma examined consisted of 18 cases of pure small cell carcinoma (pure subtype), 12 cases of the mixed subtype and 4 cases of combined small cell carcinoma. Immunohistochemically, the number of immunoreactive tumor cells for chromogranin A was smaller (P less than 0.05) and that for creatine kinase BB was relatively larger in the mixed subtype. Sialyl LeX-i antigen (SLX), one of the SSEA-1 related carbohydrate antigens, was expressed specifically in the mixed subtype. Ultrastructurally, tumor cells in the mixed subtype had smaller amounts of neurosecretory granules and larger amounts of desmosomes than those in the pure subtype (P less than 0.05, P less than 0.005, respectively). These results suggest that the mixed subtype may show more epithelial than neuroendocrine differentiation and that SLX may be a specific marker for the mixed subtype to be used in pretherapeutic diagnosis.


Implications of hepatitis C virus infection for behavioral symptoms and activities of daily living.
Hepatitis C virus (HCV) is neurovirulent and has been shown to be associated with neuropsychological (NP) deficits in a subset of infected individuals. Despite these previous findings, little work has been done to examine neurobehavioral symptoms associated with HCV infection. We examined 34 HCV seropositive (HCV+) individuals and 35 healthy comparison participants (HCV-) with the self-rating form of the Frontal Systems Behavior Scale (FrSBe). Results showed that at the group level, only the FrSBe apathy subscale mean was clinically elevated (T score >65) among HCV+ persons; executive dysfunction, disinhibition, and total subscale means were not clinically elevated. At the individual level, a significantly higher proportion of HCV+ individuals than of HCV- individuals reported clinically elevated FrSBe T scores . Moreover, HCV+ individuals were nearly 3 times as likely to report clinically elevated FrSBe T scores of apathy, executive dysfunction, and disinhibition as compared to HCV- participants. A multiple regression that included substance use disorders, neuropsychological impairment, and age indicated that HCV status was an independent predictor of self-reported FrSBe total T scores. Across all participants, small, yet significant, correlations were found between elevated self-reported FrsBe T scores and dependence in activities of daily living. These results show that a subset of HCV-infected individuals report clinically elevated behavioral symptoms. Clinical implications for the assessment and management of elevated behavioral symptoms in HCV are discussed.


Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII.
Neurite extension and branching are important neuronal plasticity mechanisms that can lead to the addition of synaptic contacts in developing neurons and changes in the number of synapses in mature neurons. Here we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates movement, extension, and branching of filopodia and fine dendrites as well as the number of synapses in hippocampal neurons. Only CaMKIIbeta, which peaks in expression early in development, but not CaMKIIalpha, has this morphogenic activity. A small insert in CaMKIIbeta, which is absent in CaMKIIalpha, confers regulated F-actin localization to the enzyme and enables selective upregulation of dendritic motility. These results show that the two main neuronal CaMKII isoforms have markedly different roles in neuronal plasticity, with CaMKIIalpha regulating synaptic strength and CaMKIIbeta controlling the dendritic morphology and number of synapses.


Current concepts in the surgical management of glioma patients.
The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical subspecialisation in the management of patients with glioma.


Oxidative Stress as a Primary Risk Factor for Brain Damage in Preterm Newborns.
The risk of oxidative stress is high in preterm newborns. Room air exposure of an organism primed to develop in a hypoxic environment, lacking antioxidant defenses, and subjected to hyperoxia, hypoxia, and ischemia challenges the newborn with oxidative stress production. Free radicals can be generated by a multitude of other mechanisms, such as glutamate excitotoxicity, excess free iron, inflammation, and immune reactions. Free radical-induced damage caused by oxidative stress appears to be the major candidate for the pathogenesis of most of the complications of prematurity, brain being especially at risk, with short to long-term consequences. We review the role of free radical oxidative damage to the newborn brain and propose a mechanism of oxidative injury, taking into consideration the particular maturation-dependent vulnerability of the oligodendrocyte precursors. Prompted by our observation of an increase in plasma Adenosine concentrations significantly associated with brain white matter lesions in some premature infants, we discuss a possible bioenergetics hypothesis, correlated to the oxidative challenge of the premature infant. We aim at explaining both the oxidative stress generation and the mechanism promoting the myelination disturbances. Being white matter abnormalities among the most common lesions of prematurity, the use of Adenosine as a biomarker of brain damage appears promising in order to design neuroprotective strategies.


The effect of adherens junction components on keratinocyte adhesion in vitro: potential implications for sealing the skin-implant interface of intraosseous transcutaneous amputation prostheses.
Amputation places a significant burden on healthcare systems worldwide as patients suffer life-long complications associated with the stump-socket interface. Skin penetrating, osseointegrated implants like intraosseous transcutaneous amputation prostheses, could overcome this, however, they rely on the formation and maintenance of an infection-free seal at the skin-implant interface. Epithelial cell migration around transcutaneous implants creates downgrowth, which leads to infection and implant failure. Epithelial cells form cell-cell attachments via adherens junctions and desmosomes that prevent cell migration via contact inhibition. If epithelial cells formed cell-cell attachments with an implant surface, it could facilitate stronger cell attachment and prevent downgrowth. In adherens junctions, E-cadherin is essential in homotypic cell attachment. In this study, we have demonstrated that cell-cell adherens junctions can be formed on substrates adsorbed with E-cadherin. We have assessed the effects of two E-cadherin peptides and determined an optimal concentration for increasing cell attachment via adherens junctions. We have demonstrated that adsorption of 15 μg/mL of the full extracellular domain of E-cadherin to titanium alloy significantly increases metabolic activity, cell area, and attachment of murine keratinocytes in vitro, with a fourfold increase in attachment via adherens junctions at 24, 48, and 72 h.


Interfacial recombination kinetics in aged perovskite solar cells measured using transient photovoltage techniques.
The reduction of interfacial charge recombination kinetics in perovskite solar cells is key to increase device photovoltaic efficiencies. Thus, it is necessary to fully understand which are the major carrier losses and, thereafter, how they can be minimized. Transient Photovoltage (TPV) has been widely used to study carrier recombination in solar cells under operando conditions. Interestingly, a novel negative transient deflection appears in perovskite solar cells when carrying out TPV measurements and it has been related to the ionic accumulation at the perovskite interfaces, which is a process that requires great attention to fully understand how perovskite solar cells work. Herein, we moved one step further and continuously monitored the evolution of the negative trace with the aging of the perovskite solar cell. Importantly, we demonstrated that the negative signal changes with aging of the solar cells and such a change can be directly related to the enhancement of the open circuit voltage and fill factor of the devices and thus the solar cell efficiency. We postulate that this increase in efficiency is due to better/faster ion redistribution within the perovskite material.


[Reflections and feelings from a team of volunteers from the Ministry of Health and the Chilean Medical Association, after the recent earthquake].
The experience of a group of 9 doctors and 6 nurses, most of them younger than 30 years of age, whom were part of the several volunteer groups directed towards the most damaged earthquake regions, is described. The team had to overcome a number of intense personal emotions related with the magnitude of the destruction, especially in the "adobe"-constructed houses and villages, in order to provide useful medical support. Moving out of the hospital setting, reaching out to the community in schools and emergency posts proved to be important in rural communities. An appropriate coordination of the volunteer groups, with the simultaneous action of municipal and state health authorities, together with well-guided leadership, was critical for an effective response in the larger city of Talcahuano /Hualpén. Within the second week of the aftermath, acute respiratory and intestinal infections were the most common medical complaints together with intense -in many cases severe- emotional distress associated mostly with fear to after shakes ("replicas"), tsunami, and social unrest. The severe earthquake that struck Chile has left many lessons for the future that will need to be analyzed seriously and with the conviction that effective and timely prevention of catastrophic aftermath consequences, although costly, must be a key element of the country's development plan. More importantly, the hundreds if not thousands of volunteers from a variety of health related professions that were moved by the scenes of suffering, and whom responded to individual or group initiatives, allow to foresee that the nation has the moral stamina required to overcome the tragedy and become a better society.


Purifying Deep Boltzmann Machines for Thermal Quantum States.
We develop two cutting-edge approaches to construct deep neural networks representing the purified finite-temperature states of quantum many-body systems. Both methods commonly aim to represent the Gibbs state by a highly expressive neural-network wave function, exemplifying the idea of purification. The first method is an entirely deterministic approach to generate deep Boltzmann machines representing the purified Gibbs state exactly. This strongly assures the remarkable flexibility of the ansatz which can fully exploit the quantum-to-classical mapping. The second method employs stochastic sampling to optimize the network parameters such that the imaginary time evolution is well approximated within the expressibility of neural networks. Numerical demonstrations for transverse-field Ising models and Heisenberg models show that our methods are powerful enough to investigate the finite-temperature properties of strongly correlated quantum many-body systems, even when the problematic effect of frustration is present.


[Preparation of uniform-sized chitosan microspheres and application as carriers for protein drugs].
Chitosan microsphere has been wildly researched in controlled release of protein and peptide drug because of its excellent mucoadhesive and permeation enhancing effect across the biological surfaces. The control of the size and size distribution of microspheres is necessary in order to improve reproducibility, bioavailability, and repeatable release behavior. In this work, uniform-sized chitosan microspheres containing insulin were prepared by a novel membrane emulsification technique combined with glutaraldehyde crosslinking method. In order to prepare uniform-sized chitosn microspheres, it is necessary to modify hydrophilic membrane into hydrophobicity. It is found that there exists a linear relationship between the size of chitosan microspheres and pore size of the membrane used, so it is easy to control the size of microspheres by using membranes with different pore size. In this study, the effect of different amount of crosslinker and crosslinking time on microspheres' morphology, encapsulation efficiency (EE) and release profile of drug in vitro were investigated. It is shown that the morphology of microspheres is more smooth and spherical, and the release rate is slower with the increase of amount of glutaraldehyde and prolongation of crosslinking time. When the molar ratio of amino group of chitosan to aldehyde group of glutaraldehyde is 1:0.7, and crosslinking time is 1 h, the highest EE was obtained (about 65%). Date obtained suggest that chitosan microspheres prepared by this new method would be a promising system for controlled release of protein drugs.


Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions.
Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labeled with energetic 1-particle emitters such as 32p, 89Sr, 153Sm, and 186Re, in addition to the low-energy electron emitter 117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic , particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone. New S values (mean absorbed dose per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic 1 particles (32p, 89Sr, 153Sm, 186Re, and 177Lu) and radionuclides that emit low-energy electrons or beta particles (169Er, 117mSn, and 33p) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow alpha equal to 10 and 100 were used. When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and alpha was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide 32p were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for 89Sr, 186Re, 153Sm, 177Lu, 169Er, 117mSn, and 33P, respectively. In contrast, when the radiopharmaceutical is assumed to be uniformly distributed in the bone volume, the RAF values for these 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectively. These results suggest that low-energy electron emitters such as 117mSn and 33P are more likely to deliver a therapeutic dose to the bone while sparing the bone marrow than are energetic beta emitters such as 32p and 89Sr. Therefore, radiochemicals tagged with low-energy electron or beta emitters are the radiopharmaceuticals of choice for treatment of painful metastatic disease in bone.


Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats.
Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model. Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains. Our data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.


The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis.
To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (p<0.05) between 6 hours and 24 hours, 6 hours and 18 hours through visual observation. However, the inflammation happened 6 hours after infusion, the loss of venous endothelial cells demonstrated differences among four groups through histopathological evaluation (p<0.05). There were significant differences (p<0.05) after 4 days among the intervention groups through visual observation, the effects of Xianchen group (five times a day) were better than Xianchen group (tid) (p<0.01). The treatment of edema demonstrated differences among groups through histopathological evaluation (p<0.05), Xianchen (five times a day) better relieved the degree of edema (p<0.05). The study showed that inflammatory reaction of phlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.


The oculocerebrorenal syndrome of Lowe: an update.
The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, intellectual disability, and proximal renal tubular dysfunction. Whereas the ocular manifestations and severe muscular hypotonia are the typical first diagnostic clues apparent at birth, the manifestations of incomplete renal Fanconi syndrome are often recognized only later in life. Other characteristic features are progressive severe growth retardation and behavioral problems, with tantrums. Many patients develop a debilitating arthropathy. Treatment is symptomatic, and the life span rarely exceeds 40 years. The causative oculocerebrorenal syndrome of Lowe gene (OCRL) encodes the inositol polyphosphate 5-phosphatase OCRL-1. OCRL variants have not only been found in classic Lowe syndrome, but also in patients with a predominantly renal phenotype classified as Dent disease type 2 (Dent-2). Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for the loss of enzyme function. Extensive research has demonstrated that OCRL-1 is involved in multiple intracellular processes involving endocytic trafficking and actin skeleton dynamics. This explains the multi-organ manifestations of the disease. Still, the mechanisms underlying the wide phenotypic spectrum are poorly understood, and we are far from a causative therapy. In this review, we provide an update on clinical and molecular genetic findings in Lowe syndrome and the cellular and physiological functions of OCRL-1.


The Burden of Autosomal Recessive Congenital Ichthyoses on Patients and their Families: An Italian Multicentre Study.
Autosomal recessive congenital ichthyoses (ARCI) are characterized by generalized skin scaling, hyperkeratosis, erythroderma, and disabling features affecting the skin (palmoplantar keratoderma, fissures, pain, itch), eyes, ears, and joints. Disease severity and chronicity, patient disfigurement, and time and costs required for care impose a major burden on quality of life. This multicentre cross-sectional study investigated the impact of ARCI on quality of life of patients and families, using the Dermatology Life Quality Index (DLQI), the Children DLQI (CDLQI) and Family Burden of Ichthyosis (FBI) questionnaires. Disease severity was assessed by a dermatologist. A total of 94 patients were recruited, of whom 52 (55.3%) children. Mean age was 20.1 (median 13.5) years. The mean CDLQI/DLQI score was 7.8, and 21 patients scored >10, indicating a major impairment in quality of life: symptoms, feelings and treatment problems were the most affected domains of quality of life. FBI showed a major repercussion on psychological factors and work. The results of this study highlight the impact of ARCI on specific aspects of patient and family life, underlining the need for psychological support.


Risk of birth defects associated with maternal pregestational diabetes.
Maternal diabetes preceding pregnancy may increase the risk of birth defects in the offspring, but not all studies confirm this association, which has shown considerable variation over time, and the effect of having type 1 versus type 2 diabetes is unclear. We conducted a population-based cohort study in the Northern Italy Emilia-Romagna region linking administrative databases with a Birth Defects Registry. From hospital discharge records we identified all diabetic pregnancies during 1997-2010, and a population of non-diabetic parturients matched for age, residence, year and delivery hospital. We collected available information on education, smoking and drug prescriptions, from which we inferred the type of diabetes. We found 62 malformed infants out of 2,269 births among diabetic women, and 162 out of 10,648 births among non-diabetic women. The age-standardized prevalence ratio (PR) of malformation associated with maternal pregestational diabetes was 1.79 (95 % confidence interval 1.34-2.39), a value that varied little by age. Type of diabetes strongly influenced the PR, with higher values related to type 2 diabetic women. Most major subgroups of anomalies had PRs above 1, including cardiovascular, genitourinary, musculoskeletal, and chromosomal abnormalities. There was an unusually high PR for the rare defect 'extra-ribs', but it was based on only two cases. This study indicates that maternal pregestational type 2 diabetes is associated with a higher prevalence of specific birth defects in offspring, whereas for type 1 diabetic mothers, particularly in recent years, the association was unremarkable.


Experience of treatment of lung cancer patients using paclitaxel and carboplatin.
Nineteen patients with stage III & IV nonsmall cell lung cancer were treated with a regimen containing paclitaxel and carboplatin at Dharmais National Cancer Center Hospital and Pertamina Central General Hospital, Jakarta, Indonesia. There were 14 males and 5 females, the histologic diagnosis being adenocarcinoma in 13 patients, squamous carcinoma in 5 patients and adenosquamous carcinoma in 1 patient. Fourteen patients were in stage IV, 4 had stage IIIB, and one had stage IIIA disease. The regimen contained paclitaxel 135-200 mg/m2, combined with carboplatin 300 mg/m2 or AUC 6 mg/ml.min, given every 3 weeks. Those who underwent at least 3 cycles of chemotherapy were followed up until death. Objective improvement (PR) was seen in 12 patients or 63%; 2 had stable disease (11%) and 5 had progressive disease (26%). Two patients are still alive at 17.5 months and 19 months after starting chemotherapy. The one-year survival rate was 58%, and median survival time was 14 months.


Factor VII and fibrinogen levels examined by age, sex, and other atherosclerotic risk factors in a Japanese population. The Jichi Medical School Cohort Study.
Factor VII coagulant activity (FVIIc) and fibrinogen (Fbg) levels have been investigated as cardiovascular risk factors. We studied these two factors with stratification for age, sex and blood pressure, and the relation with other atherosclerotic risk factors in a Japanese general population. The subjects were 3,139 Japanese (1,315 males and 1,824 females) aged 30 to 89 in 1992 and 1993. A linear increase with age was observed in the levels of Fbg in both men and women, but no differences were observed between men and women in each age group. A linear increase with age was also seen in the levels of FVIIc in women, but the levels of FVIIc in men were significantly higher for the age group 40-49 years than for any other age group. The levels of FVIIc in women were significantly higher than in men at age > or = 60 years. As concerning the effect of alcohol intake status, Fbg had a tendency to decrease with alcohol intake. Fbg and FVIIc levels were associated with an increase in smoking status in men, but no association was seen in women in either Fbg or FVIIc. FVIIc was positively correlated with age, body mass index, total cholesterol, triglycerides and fasting insulin level. Fbg was positively correlated with age, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL-cholesterol and triglycerides in women, but Fbg had few positive correlations with risk factors in men. A comparison with previous Western studies showed that the Fbg levels of our Japanese population were lower than those of the Caucasians studied, but the present FVIIc levels were nearly the same level or slightly higher than theirs. The association of Fbg and FVIIc and with other cardiovascular risk factors in Japanese was similar to those observed in Caucasians.


Biological cells as templates for hollow microcapsules.
Microcapsules in the micrometer size range with walls of nanometer thickness are of both scientific and technological interest, since they can be employed as micro- and nano-containers. Liposomes represent one example, yet their general use is hampered due to limited stability and a low permeability for polar molecules. Microcapsules formed from polyelectrolytes offer some improvement, since they are permeable to small polar molecules and resistant to chemical and physical influences. Both types of closed films are, however, limited by their spherical shape which precludes producing capsules with anisotropic properties. Biological cells possess a wide variety of shapes and sizes, and, thus, using them as templates would allow the production of capsules with a wide range of morphologies. In the present study, human red blood cells (RBC) as well as Escherichia coli bacteria were used; these cells were fixed by glutardialdehyde prior to layer-by-layer (LbL) adsorption of polyelectrolytes. The growth of the layers was verified by electrophoresis and flow cytometry, with morphology investigated by atomic force and electron microscopy; the dissolution process of the biological template was followed by confocal laser scanning microscopy. The resulting microcapsules are exact copies of the biological template, exhibit elastic properties, and have permeabilities which can be controlled by experimental parameters; this method for microcapsule fabrication, thus, offers an important new approach for this area of biotechnology.


Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite.
While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non-stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non-working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1)) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non-stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.


K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1.
Cyclooxygenase (COX) 2 expression is regulated via the Ras signaling pathway, and induction of mutated Ras rapidly increases COX-2 levels in intestinal epithelial cells. Protein kinase B (Akt/PKB) is an important effector of Ras signaling and a critical component of Ras-mediated transformation. Here we investigate the role of Akt/PKB in K-Ras-mediated induction of COX-2. Rat intestinal epithelial cells (IEC-6) were transfected with an inducible K-RasVal12 cDNA (IEC-iK-Ras cells). Addition of 5 mM isopropyl-1-thio-beta-D-galactopyranoside induced the expression of K-RasVal12, followed by increased activity of extracellular signal-regulated kinase and Akt/PKB. COX-2 levels were dramatically increased after induction of K-RasVal12. Inhibition of MAPK/ERK kinase activity by PD 98059 completely blocked the K-Ras-mediated induction of COX-2, whereas inhibition of PI3K/Akt/PKB activity with LY 294002 or by expressing a dominant negative Akt (Akt-K179M) partially blocked the induction of COX-2 by K-Ras. Transient transfection of cells with phosphatidylinositol 3-kinase and Akt expression vectors revealed that PI3/Akt/PKB activity predominantly regulates the stability of COX-2 mRNA. Thus, Akt/PKB activity is involved in K-Ras-induced expression of COX-2 and stabilization of COX-2 mRNA largely depends on the activation of Akt/PKB.


When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies.
The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.


Exact solutions of kinetic equations in an autocatalytic growth model.
Kinetic equations are introduced for the transition-metal nanocluster nucleation and growth mechanism, as proposed by Watzky and Finke [J. Am. Chem. Soc. 119, 10382 (1997)]. Equations of this type take the form of Smoluchowski coagulation equations supplemented with the terms responsible for the chemical reactions. In the absence of coagulation, we find complete analytical solutions of the model equations for the autocatalytic rate constant both proportional to the cluster mass, and the mass-independent one. In the former case, ξ(k)=s(k)(ξ(1))[proportionality]ξ(1)(k)/k was obtained, while in the latter, the functional form of s(k)(ξ(1)) is more complicated. In both cases, ξ(1)(t)=h(μ)(M(μ)(t)) is a function of the moments of the mass distribution. Both functions, s(k)(ξ(1)) and h(μ)(M(μ)), depend on the assumed mechanism of autocatalytic growth and monomer production, and not on other chemical reactions present in a system.


Does Raising the Early Retirement Age Increase Employment of Older Workers?
Two pension reforms in Austria increased the early retirement age (ERA) from 60 to 62 for men and from 55 to 58.25 for women. We find that raising the ERA increased employment by 9.75 percentage points among affected men and by 11 percentage points among affected women. The reforms had large spillover effects on the unemployment insurance program but negligible effects on disability insurance claims. Specifically, unemployment increased by 12.5 percentage points among men and by 11.8 percentage points among women. The employment response was largest among high-wage and healthy workers, while low-wage and less healthy workers either continued to retire early via disability benefits or bridged the gap to the ERA via unemployment benefits. Taking spillover effects and additional tax revenues into account, we find that for a typical birth-year cohort a one year increase in the ERA resulted in a reduction of net government expenditures of 107 million euros for men and of 122 million euros for women.


Ruminative Tendency Relates to Ventral Striatum Functionality: Evidence From Task and Resting-State fMRI.
Ruminative responding involves repetitive and passive thinking about one's negative affect. This tendency interferes with initiation of goal-directed rewarding strategies, which could alleviate depressive states. Such reward-directed response selection has been shown to be mediated by ventral striatum/nucleus accumbens (VS/NAcc) function. However, to date, no study has examined whether trait rumination relates to VS/NAcc functionality. Here, we tested whether rumination moderates VS/NAcc function both in response to reward and during a ruminative state. Trait rumination was considered dimensionally using Rumination Response Scale (RRS) scores. Our sample (N = 80) consisted of individuals from a community sample and from patients diagnosed with major depressive disorder, providing a broad range of RRS scores. Participants underwent fMRI to assess two modes of VS/NAcc functionality: 1) in response to reward, and 2) during resting-state, as a proxy for ruminative state. We then tested for associations between RRS scores and VS/NAcc functional profiles, statistically controlling for overall depressive symptom severity. RRS scores correlated positively with VS/NAcc response to reward. Furthermore, we noted that higher RRS scores were associated with increased ruminative-dependent resting-state functional connectivity of the VS/NAcc with the left orbitofrontal cortex. These findings suggest that ruminative tendencies manifest in VS/NAcc reward- and rumination-related functions, providing support for a theoretical-clinical perspective of rumination as a habitual impairment in selection of rewarding, adaptive coping strategies.


Clusters of Antibiotic Resistance Genes Enriched Together Stay Together in Swine Agriculture.
Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk. Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. As governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.


Host factors in the susceptibility of mice to tumour initiating and promoting agents.
It has been known for a long time that skin tumours can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation stage) followed by repetitive treatment with a noncarcinogenic promoter (promotion stage). In mouse skin, the initiation stage requires only a single application of either a direct-acting carcinogen or a procarcinogen and is essentially an irreversible step, which, as data suggest, probably involves a somatic cell mutation. The promotion stage in mouse skin can be accomplished by a wide variety of weak or noncarcinogenic agents and is initially reversible, later becoming irreversible. Current information suggests that skin tumour promoters are not mutagenic but bring about a number of important epigenetic changes, such as epidermal hyperplasia and an increase in levels of polyamines, prostaglandins and dark basal keratinocytes as well as other embryonic conditions. Recently, tumour promotion in mouse skin was shown to consist of at least two stages, each of which can be accomplished by either a known promoter or a weak or nonpromoting agent. Some of the important characteristics of the first stage of promotion are: (1) only one application of a first-stage promoter, such as phorbol ester tumour promoters, calcium ionophore A23187, hydrogen peroxide and wounding, is needed; (2) it is partially irreversible; (3) increases in dark basal keratinocytes and prostaglandins are important; and (4) it can be inhibited by anti-inflammatory steroids and protease inhibitors. The second stage of promotion is initially reversible but later becomes irreversible. Polyamines and epidermal cell proliferation are important events in the second stage of promotion. A number of weak or nonpromoting agents, such as mezerein, are effective second-stage promoters, which can be counteracted by retinoic acid, anti-inflammatory steroids and polyamine synthesis inhibitors. Although skin tumour promotion has been studied extensively in mice, not all strains and stocks of mice are susceptible to phorbol ester tumour promoters. In this regard, C57Bl/6 mice appear to be fairly resistant to these tumour promoters. Not all species are equally susceptible to phorbol ester tumour promotion (mouse greater than rat greater than hamster, and the miniature swine is fairly resistant). It is not presently known if other experimental systems of carcinogenesis or the induction of human cancer go through a series of stages similar to that in the mouse skin.


Displacement of Xenopus transcription factor IIIA from a 5S rRNA gene by a transcribing RNA polymerase.
In the absence of other components of the RNA polymerase III transcription machinery, transcription factor IIIA (TFIIIA) can be displaced from both strands of its DNA-binding site (the internal control region) on the somatic-type 5S rRNA gene of Xenopus borealis during transcription elongation by bacteriophage T7 RNA polymerase, regardless of which DNA strand is transcribed. Furthermore, substantial displacement is observed after the template has been transcribed only once. Since the complete 5S rRNA transcription complex has previously been shown to remain stably bound to the gene during repeated rounds of transcription by either RNA polymerase III or bacteriophage SP6 RNA polymerase, these results indicate that a factor(s) in addition to TFIIIA is required to create a complex that will remain stably associated with the template during transcription. Thus, transcription complex stability during passage of RNA polymerase cannot be explained solely on the basis of the DNA-binding properties of TFIIIA.


Contemporary management of subclavian and axillary artery injuries-A Western Trauma Association multicenter review.
Subclavian and axillary artery injuries are uncommon. In addition to many open vascular repairs, endovascular techniques are used for definitive repair or vascular control of these anatomically challenging injuries. The aim of this study was to determine the relative roles of endovascular and open techniques in the management of subclavian and axillary artery injuries comparing hospital outcomes, and long-term limb viability. A multicenter, retrospective review of patients with subclavian or axillary artery injuries from January 1, 2004, to December 31, 2014, was completed at 11 participating Western Trauma Association institutions. Statistical analysis included χ, t-tests, and Cochran-Armitage trend tests. A p value less than 0.05 was significant. Two hundred twenty-three patients were included; mean age was 36 years, 84% were men. An increase in computed tomography angiography and decrease in conventional angiography was observed over time (p = 0.018). There were 120 subclavian and 119 axillary artery injuries. Procedure type was associated with injury grade (p < 0.001). Open operations were performed in 135 (61%) patients, including 93% of greater than 50% circumference lacerations and 83% of vessel transections. Endovascular repairs were performed in 38 (17%) patients; most frequently for pseudoaneurysms. Fourteen (6%) patients underwent a hybrid procedure. Use of endovascular versus open procedures did not increase over the duration of the study (p = 0.248). In-hospital mortality rate was 10%. Graft or stent thrombosis occurred in 7% and graft or stent infection occurred in 3% of patients. Mean follow-up was 1.6 ± 2.4 years (n = 150). Limb salvage was achieved in 216 (97%) patients. The management of subclavian and axillary artery injuries still requires a wide variety of open exposures and procedures, especially for the control of active hemorrhage from more than 50% vessel lacerations and transections. Endovascular repairs were used most often for pseudoaneurysms. Low early complication rates and limb salvage rates of 97% were observed after open and endovascular repairs. Prognostic/epidemiologic, level IV.


Quantification of bioluminescence from the surface to the deep sea demonstrates its predominance as an ecological trait.
The capability of animals to emit light, called bioluminescence, is considered to be a major factor in ecological interactions. Because it occurs across diverse taxa, measurements of bioluminescence can be powerful to detect and quantify organisms in the ocean. In this study, 17 years of video observations were recorded by remotely operated vehicles during surveys off the California Coast, from the surface down to 3,900 m depth. More than 350,000 observations are classified for their bioluminescence capability based on literature descriptions. The organisms represented 553 phylogenetic concepts (species, genera or families, at the most precise taxonomic level defined from the images), distributed within 13 broader taxonomic categories. The importance of bioluminescent marine taxa is highlighted in the water column, as we showed that 76% of the observed individuals have bioluminescence capability. More than 97% of Cnidarians were bioluminescent, and 9 of the 13 taxonomic categories were found to be bioluminescent dominant. The percentage of bioluminescent animals is remarkably uniform over depth. Moreover, the proportion of bioluminescent and non-bioluminescent animals within taxonomic groups changes with depth for Ctenophora, Scyphozoa, Chaetognatha, and Crustacea. Given these results, bioluminescence has to be considered an important ecological trait from the surface to the deep-sea.


Mechanisms of antidepressant resistance.
Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.


Simple renal cysts and circadian blood pressure: are they related to each other in patients with hypertension?
Previous studies have shown that the presence of simple renal cysts was related to hypertension. However, the relationship between simple renal cysts and circadian blood pressure was not studied before. Our study population comprised of newly diagnosed patients with essential hypertension. Medical history, physical examination and office blood pressure measurements, laboratory analysis, ambulatory blood pressure measurements, renal ultrasonography, and 24-h urine specimens were collected. In total, the study included 190 patients (male/female ratio 77/113; mean age 50.3 ± 11.3). Overall, 127 (66.8%) patients were dippers and 92 (48.4%) had at least one simple renal cyst. Thirty-five patients had solitary cysts and 57 patients had multiple cysts. Cysts were bilateral in 47 of patients. Most of ambulatory blood pressure recordings were higher in patients with at least one simple cyst when compared to patients without cysts. In multivariate logistic regression analysis, serum uric acid (P: 0.047, OR: 1.287, CI: 1.011-1.658), lower creatinine clearance (P: 0.001, OR: 1.030, CI: 1.012-1.049), presence of diabetes (P: 0.029, OR: 2.451, CI: 1.094-5.491), and presence of at least one cyst in each kidney (P: 0.002, OR: 3.087, CI: 1.533-6.212) were found to be independently related to nocturnal non-dipping. In conclusion, the presence of simple renal cysts is related to higher ambulatory BP and is associated with non-dipping phenomenon in patients with essential hypertension.


Lung function studies before and after a work shift.
The lung function of 23 underground coal workers and eight surface workers at a Scottish colliery was measured immediately before and after a work shift. Changes in lung function were assessed in relation to the measured respirable dust exposure and the time of day in which the shift was worked. Large, and statistically significant, decrements of lung function during the shift were found in night-shift workers compared with workers on other shifts. Measurements derived from the forced expiratory manoeuvre, particularly FEV1, Vmax50, and Vmax25, after three vital capacity breaths of an 80% He/20% O2 mixture, showed large reductions in night-shift men, smaller reductions in afternoon-shift men, and small increases or decreases in morning-shift underground and surface workers. Within-shift changes for other tests, such as closing volume, N2 index, and volume of isoflow, did not differ significantly between shifts. No significant relationship was found between dust exposure and functional changes during a shift for any test. Lung function changes in a control group of 25 female workers not exposed to dust (hospital nurses) did not show the same large variations between day and night shifts. Examination of a further control group of 16 office workers did not show any difference in diurnal changes between smokers and non-smokers. It is concluded that these coal miners, even on permanent shift patterns, had widely different changes in their lung function cycle depending on which shift they were working. These changes did not appear to be related to dust exposure or cigarette smoking and were not consistent with other biological adaptations known to result from regular night-shift working.


The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.
Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting in the accumulation of multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)-deficient fibers in skeletal muscle secondary to a disorder of mtDNA maintenance. Patients typically present with isolated extraocular muscle involvement, with little apparent evidence of the clinical heterogeneity documented in other mtDNA maintenance disorders, in particular POLG-related disease. We reviewed the clinical, histochemical, and molecular genetics analysis of 33 unreported patients from 26 families together with all previous cases described in the literature to define the clinical phenotype associated with PEO1 mutations. Ptosis and ophthalmoparesis were almost universal clinical features among this cohort, with 52% (17/33) reporting fatigue and 33% (11/33) having mild proximal myopathy. Features consistent with CNS involvement were rarely described; however, in 24% (8/33) of the patients, cardiac abnormalities were reported. Mitochondrial histochemical changes observed in muscle showed remarkable variability, as did the secondary mtDNA deletions, which in some patients were only detected by PCR-based assays and not Southern blotting. Moreover, we report 7 novel PEO1 variants. Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of adPEO may well be underestimated. Direct sequencing of the PEO1 gene should be considered in adPEO patients prior to muscle biopsy.


Sex differences in ventricular arrhythmia: epidemiology, pathophysiology and catheter ablation.
Evidence on sex differences in the pathophysiology and interventional treatment of ventricular arrhythmia in ischemic (ICM) or non-ischemic cardiomyopathies (NICM) is limited. However, women have different etiologies and types of structural heart disease due to sex differences in genetics, proteomics and sex hormones. These differences may influence ventricular electrophysiological parameters and may require different treatment strategies. Considering that women were consistently under-represented in all randomized-controlled trials on VT ablation, the applicability of the study results to female patients is not known. In this article, we review the current knowledge and gaps in evidence about sex differences in the epidemiology, pathophysiology and catheter ablation in patients with ventricular arrhythmias.


Genome-wide association analyses reveal polygenic genomic architecture underlying divergent shell morphology in Spanish Littorina saxatilis ecotypes.
Gene flow between diverging populations experiencing dissimilar ecological conditions can theoretically constrain adaptive evolution. To minimize the effect of gene flow, alleles underlying traits essential for local adaptation are predicted to be located in linked genome regions with reduced recombination. Local reduction in gene flow caused by selection is expected to produce elevated divergence in these regions. The highly divergent crab-adapted and wave-adapted ecotypes of the marine snail Littorina saxatilis present a model system to test these predictions. We used genome-wide association (GWA) analysis of geometric morphometric shell traits associated with microgeographic divergence between the two L. saxatilis ecotypes within three separate sampling sites. A total of 477 snails that had individual geometric morphometric data and individual genotypes at 4,066 single nucleotide polymorphisms (SNPs) were analyzed using GWA methods that corrected for population structure among the three sites. This approach allowed dissection of the genomic architecture of shell shape divergence between ecotypes across a wide geographic range, spanning two glacial lineages. GWA revealed 216 quantitative trait loci (QTL) with shell size or shape differences between ecotypes, with most loci explaining a small proportion of phenotypic variation. We found that QTL were evenly distributed across 17 linkage groups, and exhibited elevated interchromosomal linkage, suggesting a genome-wide response to divergent selection on shell shape between the two ecotypes. Shell shape trait-associated loci showed partial overlap with previously identified outlier loci under divergent selection between the two ecotypes, supporting the hypothesis of diversifying selection on these genomic regions. These results suggest that divergence in shell shape between the crab-adapted and wave-adapted ecotypes is produced predominantly by a polygenic genomic architecture with positive linkage disequilibrium among loci of small effect.


Infection of Small-Bore Tunneled Central Venous Catheters.
OBJECTIVE. The purpose of this study is to evaluate the association of common clinical variables with small-bore tunneled central venous catheter (CVC) infection. MATERIALS AND METHODS. Retrospective data were collected from all small-bore (6-French) tunneled CVCs placed by the interventional radiology service between 2012 and 2015. Only patients who had a documented reason for tunneled CVC removal were included in the analysis to capture all events. Transfemoral, transhepatic, and translumbar placements were excluded to reduce cohort heterogeneity. Multiple clinical variables were collected from a review of the medical record. The t test and Fisher exact test were used for two-group comparisons for continuous variables and categoric variables, respectively. Logistic regression analyses were further used to identify variables that were associated with catheter infection. RESULTS. One hundred eighty-two patients (105 women [57.7%] and 77 men [42.3%]) with a mean (± SD) age of 49.7 ± 16 years were included. Thirty-two catheters (17.6%) were removed because of infection. Noninfected lines were removed at a mean of 39 (SD, 57.3) days, whereas infected lines were removed at a mean of 95.9 (SD, 113.4) days after placement (p < 0.001). There was a statistically significant difference in the number of tunneled CVCs removed for infection when the indication for tunneled CVC placement was the administration of IV antibiotics (p = 0.04). By multivariate analysis, only time to removal (p = 0.002; odds ratio, 0.992; 95% CI, 0.986-0.998) and a history of tunneled CVC (p = 0.01; odds ratio, 0.306; 95% CI, 0.121-0.772) were associated with catheter removal for infection. CONCLUSION. Time to catheter removal and history of tunneled CVC were associated with an increased risk of tunneled CVC removal because of infection.


Problems and approaches in the surveillance and control of sexually transmitted agents associated with pelvic inflammatory disease in Africa.
The problems in surveillance of sexually transmitted disease (STD) in Africa are numerous and are based mainly on socioeconomic barriers. Policies for controlling STD are either inadequate or nonexistent in many African countries. Gonococci are becoming increasingly insusceptible to penicillin and other drugs because of widespread use of inadequate therapy. Gonorrhea is recognized as the major pathogen of pelvic inflammatory disease in Africa. The magnitude of the PID problem is so great that current efforts are directed at case treatment rather than surveillance and control. The formation of the African Union Against Venereal Diseases and Treponematoses is an important step, and its suggestions and resolutions form a sound basis for improved STD control in Africa.


Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering.
Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.


Epigenomic annotation-based interpretation of genomic data: from enrichment analysis to machine learning.
One of the goals of functional genomics is to understand the regulatory implications of experimentally obtained genomic regions of interest (ROIs). Most sequencing technologies now generate ROIs distributed across the whole genome. The interpretation of these genome-wide ROIs represents a challenge as the majority of them lie outside of functionally well-defined protein coding regions. Recent efforts by the members of the International Human Epigenome Consortium have generated volumes of functional/regulatory data (reference epigenomic datasets), effectively annotating the genome with epigenomic properties. Consequently, a wide variety of computational tools has been developed utilizing these epigenomic datasets for the interpretation of genomic data. The purpose of this review is to provide a structured overview of practical solutions for the interpretation of ROIs with the help of epigenomic data. Starting with epigenomic enrichment analysis, we discuss leading tools and machine learning methods utilizing epigenomic and 3D genome structure data. The hierarchy of tools and methods reviewed here presents a practical guide for the interpretation of genome-wide ROIs within an epigenomic context. email@example.com. Supplementary data are available at Bioinformatics online.


Neural derivation of human dental pulp stem cells via neurosphere technique.
Human dental pulp stem cells (hDPSCs) are multipotent stem cells providing an autologous noninvasive cell source. The study evaluates the neurogenic potential of hDPSCs using neural growth factor inducers and neurosphere technique. The hDPSCs were differentiated into neurons using neural induction medium containing retinoic acid (RA). Neuroprogenitor cells were evaluated for nestin and NF68 using immunocytochemistry. The mature neuron markers, MAP‑2 and β-tubulin, were investigated at the end stage of induction phase. The neuroprogenitor differentiation was confirmed by immunostaining for nestin and NF68 markers. The differentiated neurons were positive for specific neuron markers, namely for MAP‑2 and β-tubulin. The results indicated that the neural differentiation medium and neurosphere technique improve the generation of neuroprogenitor cells as well as mature neurons via exhibiting specific neural markers, namely nestin, NF68, MAP‑2 and β-tubulin. Our findings highlight the differentiation capacity of hDPSCs via neurosphere technique in the presence of neural inducers for mesenchymal stem cells. It is suggested that the neural differentiation potential of hDPSCs can be exploited as a source of stem cells for therapy of neurodegenerative diseases (Fig. 5, Ref. 20).


Collective response to perturbations in a data-driven fish school model.
Fish schools are able to display a rich variety of collective states and behavioural responses when they are confronted by threats. However, a school's response to perturbations may be different depending on the nature of its collective state. Here we use a previously developed data-driven fish school model to investigate how the school responds to perturbations depending on its different collective states, we measure its susceptibility to such perturbations, and exploit its relation with the intrinsic fluctuations in the school. In particular, we study how a single or a small number of perturbing individuals whose attraction and alignment parameters are different from those of the main population affect the long-term behaviour of a school. We find that the responsiveness of the school to the perturbations is maximum near the transition region between milling and schooling states where the school exhibits multistability and regularly shifts between these two states. It is also in this region that the susceptibility, and hence the fluctuations, of the polarization order parameter is maximal. We also find that a significant school's response to a perturbation only happens below a certain threshold of the noise to social interactions ratio.


The health of aging lesbian, gay and bisexual adults in California.
Research on the health of lesbian, gay and bisexual (LGB) adults generally overlooks the chronic conditions that are the most common health concerns of older adults. This brief presents unique population-level data on aging LGB adults (ages 50-70) documenting that they have higher rates of several serious chronic physical and mental health conditions compared to similar heterosexual adults. Although access to care appears similar for aging LGB and heterosexual adults, aging LGB adults generally have higher levels of mental health services use and lesbian/bisexual women report greater delays in getting needed care. These data indicate a need for general health care and aging services to develop programs targeted to the specific needs of aging LGB adults, and for LGB-specific programs to increase attention to the chronic conditions that are common among all older adults.


Cardiac myoglobin deficit has evolved repeatedly in teleost fishes.
Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in aerobic striated muscles. It functions principally in oxygen delivery and provides muscle with its characteristic red colour. Members of the Antarctic icefish family (Channichthyidae) are widely thought to be extraordinary for lacking cardiac Mb expression, a fact that has been attributed to their low metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb deficit, associated with pale heart colour, has evolved repeatedly during teleost evolution. This trait affects both gill- and air-breathing species from temperate to tropical habitats across a full range of salinities. Cardiac Mb deficit results from total pseudogenization in three-spined stickleback and is associated with a massive reduction in mRNA level in two species that evidently retain functional Mb. The results suggest that near or complete absence of Mb-assisted oxygen delivery to heart muscle is a common facet of teleost biodiversity, even affecting lineages with notable oxygen demands. We suggest that Mb deficit may affect how different teleost species deal with increased tissue oxygen demands arising under climate change.


Nerve growth factor receptors on chick embryo sympathetic ganglion cells: binding characteristics and development.
NGF is essential for the development and maintenance of sympathetic and certain sensory neurons. The NGF receptors on the surface of sympathetic ganglion cells from chick embryos were characterized; they consist of high-affinity receptors with a dissociation constant of about 10(-11) M, and low-affinity receptors with a dissociation constant of about 10(-9) M. There are more than 10 times as many low-affinity as high-affinity receptors per cell. The heterogeneity of NGF binding is not due to negatively cooperative interactions among the receptors. The high- and low-affinity components of NGF binding defined at steady state correspond to slowly and rapidly dissociating components of bound NGF seen in kinetic experiments. In addition, a very slowly dissociating component of bound NGF was observed; this component was a small fraction of binding at low concentrations of NGF but increased to 20-60% of bound NGF at the highest NGF concentrations examined. This very slowly dissociating component of bound NGF accounts for several peculiarities in the binding data not accounted for by steady-state binding of NGF to its high- and low-affinity receptors. Developmental studies showed that both high- and low-affinity NGF receptors were present on chick embryo sympathetic ganglion cells from 6.5 to 20 d in ovo. No significant differences in the numbers or affinities of the receptors were seen with cells from ganglia at 9, 11, or 15 d of development. Cultured non-neuronal cells from sympathetic ganglia had only low-affinity NGF receptors.


Meeting the Mental Health Needs of College Students with a Background in Foster Care.
Many colleges and universities are creating campus-based programs to support students with a background in foster care. When considering the histories of trauma experienced by these young people, meeting mental health needs is an important part of a portfolio of services. ASuPIRE is a strengths-based, trauma-informed counseling program that was designed to respond to the unique needs of college students who aged-out and/or experienced foster care at any point across their development. This program can stand alone or can be used to supplement campus-based support programs. This approach, including its theoretical framework and related interventions, will be described. A case study is also provided to illustrate the model for other post-secondary institutions interested in adopting this approach.


[Local use of cytostatic drugs following removal of glioblastomas].
Local application of Methotrexate after removal of glioblastomas enables a high chemotherapeutic concentration to be achieved in the wall of the surgical cavity without appreciable side effects on sensitive structures of the body. This procedure, followed by intravenous chemotherapy may prevent local recurrence, on the assumption that glioblastoma recurrences originate in the operation site. Five groups (269 patients) subjected to different strategies of postoperative therapy were compared in terms of average survival time. The group given local chemotherapy following total or subtotal removal of the tumour, then intravenous chemotherapy after 8 days, followed by radiotherapy, demonstrated an average survival time of 75 weeks. In this group the number of living patients at the time of investigation was particularly high, namely 56. The longest survival time was 355 weeks, and this patient was symptomless. There were no side effects or complications of local cytostatic therapy with 50 mg Methotrexate.


Inflammatory markers and heart rate variability in women with coronary heart disease.
Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive protein (CRP). Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay. Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study. Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.


Pathobionts in Inflammatory Bowel Disease: Origins, Underlying Mechanisms, and Implications for Clinical Care.
The gut microbiota plays a significant role in the pathogenesis of both forms of inflammatory bowel disease (IBD), namely, Crohn's disease (CD) and ulcerative colitis (UC). Although evidence suggests dysbiosis and loss of beneficial microbial species can exacerbate IBD, many new studies have identified microbes with pathogenic qualities, termed "pathobionts," within the intestines of patients with IBD. The concept of pathobionts initiating or driving the chronicity of IBD has largely focused on the putative aggravating role that adherent invasive Escherichia coli may play in CD. However, recent studies have identified additional bacterial and fungal pathobionts in patients with CD and UC. This review will highlight the characteristics of these pathobionts and their implications for IBD treatment. Beyond exploring the origins of pathobionts, we discuss those associated with specific clinical features and the potential mechanisms involved, such as creeping fat (Clostridium innocuum) and impaired wound healing (Debaryomyces hansenii) in patients with CD as well as the increased fecal proteolytic activity (Bacteroides vulgatus) seen as a biomarker for UC severity. Finally, we examine the potential impact of pathobionts on current IBD therapies, and several new approaches to target pathobionts currently in the early stages of development. Despite recognizing that pathobionts likely contribute to the pathogenesis of IBD, more work is needed to define their modes of action. Determining whether causal relationships exist between pathobionts and specific disease characteristics could pave the way for improved care for patients, particularly for those not responding to current IBD therapies.


The value of history and goals of care with code status; even in an emergency setting.
This is a case report involving an elderly Jehovah's Witness woman with a history of chronic anaemia who suffers cardiac arrest and is resuscitated. This case illustrates, even in an emergency setting, (1) the value of obtaining relevant history, (2) addressing code status within the framework of achievable goals of care and (3) the need to revise both history and goals of care, as more information becomes available. We also propose aspects of this discussion that would benefit from future research.


Re-Classifying Hypertension in the Venezuelan EVESCAM Database Using 2017 AHA/ACC Criteria: High Prevalence, Poor Control, and Urgent Call for Action.
In 2017 the American Heart Association (AHA)/American College of Cardiology (ACC) changed the criteria to define hypertension (HTN). To re-analyze Venezuelan data to update HTN prevalence rates and estimate the number of adults with uncontrolled blood pressure (BP) using AHA/ACC criteria. The EVESCAM was a national population-based, cross-sectional, randomized cluster sampling study, which assessed 3,420 adults from July 2014 to January 2017, with a response rate of 77.3%. The mean of two BP measurements was obtained using a standard oscillometric device protocol. HTN was defined using both 2017 AHA/ACC guideline (BP ≥ 130/80 mmHg) and JNC7 (BP ≥ 140/90 mmHg) criteria. The crude prevalence of HTN using 2017 AHA/ACC guideline criteria was 60.4%, 13% higher than with the JNC7 criteria. The age-standardized prevalence was 55.4% in men and 49.0% in women (p < 0.001), 17.5% and 12.7% higher, respectively, compared with the JNC7 criteria. In subjects without self-reported HTN, the age-standardized prevalence of HTN was 43.4% in men and 32.3% in women, of whom, 22.9% and 19.2% were between 130-139/80-89 mmHg, respectively. In those with self-reported HTN, the prevalence of uncontrolled BP (≥130/80 mmHg) on antihypertensive medication was 66.8% in men and 65.8% in women. The total estimated number of subjects with HTN in Venezuela increased to 11 million, and only about 1.8 million are controlled. Using the new 2017 AHA/ACC guideline, the prevalence of HTN in Venezuela is approximately half of the adult population and associated with relatively poor BP control.


IRANIAN SCIENCE: Iranian Women Hear the Call of Science.
Despite institutions such as separate reading rooms for each sex, women are a growing presence at Iran's universities, making up nearly 60% of incoming classes, almost double their share in 1978. But as in many other countries, some female academics in Iran point to a glass ceiling that keeps their representation among university professors low.


Suppression by 1,3-butanediol of the ethanol withdrawal syndrome in rats.
1,3-Butanediol was tested for its ability to suppress an ethanol with drawal syndrome. Male Sprague-Dawley rats were rendered physically dependent on ethanol by intragastric administration of ethanol at a dosage of 9 to 15 grams per kilogram per day over a 4-day period. A nonintoxicating oral dose of 1,3-butanediol at 4 grams per kilogram administered after elimination of ethanol from the blood was effective against the tremulous and conbulsive components of the ethanol withdrawal syndrome in all animals for 1 to 5 hours. This period coincided with the time of maximum severity of the withdrawal syndrome, as seen in the control animals.


Worth it or not? Analysis of survival benefit from primary tumor resection and individualized prediction of overall survival for lung cancer patients with bone metastasis.
The clinical management of lung cancer (LC) patients with bone metastasis (BM) is still a significant challenge. This study aimed to explore the role of primary tumor resection (PTR) on survival outcome of LC patients with BM and to develop two web-based nomograms for predicting the overall survival (OS) of LC patients with BM who received PTR and those who did not. We enrolled LC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Propensity score matching (PSM) was then conducted to balance the baseline characteristics of covariates between patients in surgery and non-surgery groups. Next, Kaplan-Meier analysis with log-rank test was performed to evaluate the survival benefit of PTR before and after PSM methods and to explore the impact of surgical resection extent on the prognosis of LC patients with BM and clinical outcomes in patients with different metastatic patterns. Cox proportional hazard regression analysis was then applied to determine the independent prognostic factors for OS of patients receiving PTR and did not receiving PTR, respectively. Subsequently, we constructed two individualized nomograms for predicting the 12-, 18- and 24-months OS. Finally, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were generated to evaluate discrimination, accuracy and clinical utility of the nomograms. A total of 7747 eligible patients were included in this analysis. The survival analysis revealed that PTR was closely associated with better survival outcome among LC patients with BM(P < 0.05), while the survival benefit of PTR was suboptimal in patients presented with multiple metastases(P > 0.05). Besides, lobectomy shows best survival benefit. Two nomograms were then constructed based on independent prognostic factors of patients in the surgery group and the non-surgery group. The ROC curves showed good discrimination of the two nomograms, with the area under curve (AUC) of each time point being higher than 0.7 in both the training set and testing set. The calibration curves also demonstrated satisfactory consistency between actual survival and nomogram-predicted OS of both nomograms. The DCA showed high benefit of nomogram in a clinical context. Moreover, the study population was stratified into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.05). This study showed that surgical resection of the primary site strategy can prolong survival of LC patients with BM to some extent, depending on different sites of metastasis and highly selected patients. Furthermore, the web-based nomograms showed significant accuracy in predicting OS for patients with or without surgery, which may provide valuable insights for patients' counseling and individualized decision-making for clinicians.


Areola-sparing mastectomy with immediate breast reconstruction.
Skin-sparing mastectomy with immediate breast reconstruction is a proved option for patients with early-stage breast cancer requiring mastectomy. Based on the authors' recent pathologic analysis of mastectomy specimens showing less than 1% malignant involvement of the areola, they have begun to perform areola-sparing mastectomies (ASMs) on a select group of patients. They report their results from an ongoing study of ASM at their institution. During a 20-month period, 17 ASMs with immediate reconstruction were performed on 12 patients. Mastectomy was performed for breast cancer prophylaxis (n = 10), ductal carcinoma in situ (n = 4), and less than 2 cm of peripheral infiltrating carcinoma (n = 3). The most frequent incision performed was intraareola (n = 13). Thirteen patients were reconstructed with tissue expanders and 4 with pedicled transverse rectus abdominis musculocutaneous flaps. There was 1 postoperative complication, which consisted of a localized wound infection. Overall the authors found that ASM with immediate reconstruction provides excellent aesthetic results with infrequent complications.


Potassium adsorption in soil cultivated with sugarcane.
Vinasse is a byproduct of the process of distillation of sugarcane juice for the manufacture of sugar and alcohol. Because it is rich in nutrients, mainly potassium (K), is used as fertilizer and applied via fertigation, without concerning for the fate of this compound in the soil. Thus, the objective of the study was to evaluate the interactions of the potassium ion (K+), applied via vinasse in a soil representative of the sugarcane zone of the State of Pernambuco using adsorption isotherms. The methodology was based on physical, chemical and soil mineralogical characterization, as well as equilibrium batch tests, where the experimental curves were fitted by Langmuir and Freundlich isotherm models. The results allowed to infer that the Freundlich model showed better fit of the curve in both forms: linear and non-linear (direct fit); the non-linear model was selected due to the values of coefficient of determination (R²). The interaction between potassium and soil occurred mainly with organic matter and the presence of soil kaolinite, because they showed negative ions on the external surface, thereby promoting potassium adsorption. Soil potassium adsorption capacity was higher for the first layer (0-20 cm) and decreased along the depth profile.


Pupil-linked arousal correlates with neural activity prior to sensorimotor decisions.
Sensorimotor decisions require the brain to process external information and combine it with relevant knowledge prior to actions. In this study, we explore the neural predictors of motor actions in a novel, realistic driving task designed to study decisions while driving. We show that steering behavior can be predicted from oscillatory power in the visual cortex, dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). Through a spatiospectral assessment of functional connectivity during the premotor period, we identified the organization of visual cortex regions of interest into a distinct scene-processing network. Additionally, we identified a motor action selection network characterized by coherence between the ACC and DLPFC. Power during the premotor periods (specific to the theta and beta bands) correlates with pupil-linked arousal and saccade duration. We interpret our findings in the context of network-level correlations with saccade-related behavior and show that the DLPFC is a key node in arousal circuitry and in sensorimotor decisions.


Second Neoplasms in Children Following a Treatment for Acute Leukemia and/or Lymphoma: 29 Years of Experience in a Single Institution in Argentina.
Childhood acute leukemias (AL) and lymphomas achieve good survival rates. However, second neoplasms (SN) are a devastating event. From August 1987 to December 2016, 34 of 3321 (1%) patients with diagnosis of AL or lymphoma developed SN. SN were AL (n=16), CNS tumors (n=5), endocrinal tumors (n=3), lymphomas (n=2), schwannoma (n=2) assorted sarcomas (n=4), retinal melanoma (n=1), and Vanek tumor (n=1). Median latency was 51 (range, 10 to 110) months for hematological malignancies and 119 (range, 25 to 236) months for solid tumors (P=0.001). A total of 33 patients with SN were treated taking into account cumulative doses of anthracyclines and radiotherapy. Twenty-three (67.6%) patients achieved complete remission (CR), 5 died early during therapy and 5 were refractory or partial responders. Six patients presented relapses of the SN and 1 died in CR. Seventeen patients remain alive in CR, with a median follow-up of 110 (range, 4 to 276) months. (1) The latency period was significantly longer for patients developing solid tumors than for those developing AL. (2) AL was the most frequent SN. (3) Our results strongly encourage giving standard therapy to SN, considering cumulative doses of previous treatment, since similar probabilities of surviving as "de novo" counterparts can be achieved.


Condemnation of Statutory Rape Based on Respondent Race, Perpetrator Race, and Victim Race.
Race impacts perceptions of crimes, perpetrators, and victims. Although statutory rape generally receives little empirical or media attention, it has important implications for victims and offenders across the United States and appears to be enforced in a haphazard way. This study used a between-subjects experimental survey design at two universities (n = 1,370) to assess the impact of respondent race, perpetrator race, and victim race on attitudes toward statutory rape. Results of a repeated measures analysis of variance indicated that respondents viewed both White victims and their perpetrators as bad, blameworthy, deserving of punishment, harmed, and likely to commit crime in the future, judgments suggesting that the respondents take this sexual activity seriously. In contrast, analyses revealed that respondents were significantly less concerned about Black victims than White victims. Consistent with the liberation hypothesis, these differences in attitudes may contribute to the law being enforced inconsistently, providing differential access to justice based on a variable that is not legally relevant.


Chimerism status is a useful predictor of relapse after allogeneic stem cell transplantation for acute leukemia.
The role of hematopoietic chimerism after allogeneic stem cell transplantation (SCT) for acute leukemia remains controversial. We studied the relationship between hematopoietic chimerism and several prognostic variables on the outcome of SCT in patients with acute leukemia. Chimerism was determined by a semiquantitative method, based on polymerase chain reaction (PCR) amplification of variable number tandem repeat (VNTR) minisatellites, in 133 consecutive patients who underwent allogeneic SCT for acute leukemia (68 myeloid, 58 lymphoid and 7 biphenotypic), all receiving a myeloablative conditioning regimen. The median follow-up for the surviving patients was 44.8 months (range: 12.0-129.0). Recipient hematopoiesis (mixed chimerism, MC) was detected in 40 cases (30.1%). Two types of patients could be distinguished in this MC group: 29 with increasing MC and 9 with decreasing MC. The remaining 93 cases maintained complete donor chimerism (CC) over the whole follow-up period. Patients with increasing MC showed a significantly higher (p<0.001) rate of relapse (93.1%) and death (89.7%) in comparison to both those with CC (26.9% relapse, 44.1% dead) or decreasing MC (11.1% relapse, 44.4% dead). The detection of increasing MC preceded relapse by a median of 74 days (range: 5-434) and was significantly related with the absence of chronic graft-versus-host disease. Univariate and multivariate analysis confirmed that chimerism was the most significant variable involved in relapse, leukemia-free survival and overall survival after SCT. These results demonstrate that sequential determination of chimerism allows the prediction of relapse and death after SCT for acute leukemia. The interval between detection of increasing MC and relapse may permit timely implementation of therapeutic measures.