Metabolism of niclosamide in sediment and water systems.
A series of experiments analyzed the kinetics and mechanisms of [(14)C]niclosamide degradation. The aerobic aquatic metabolism of [(14)C]niclosamide was studied in nonsterile river water/sediment mixtures. Test systems, maintained under aerobic conditions, were treated with niclosamide and incubated in the dark at 25.0 +/- 1.0 degrees C for 30 days. Half-lives of 4.9 and 5.4 days were calculated for the chlorosalicylic acid- and chloronitroaniline-labeled test systems, respectively. From 0 to 21 days after treatment (DAT), the only metabolism product observed in either test system was aminoniclosamide. At the final sampling interval, five peaks were resolved from the chlorosalicylic acid label, and three peaks were resolved from the chloronitroaniline label test substance. By 30 DAT, sediment-bound residues represented approximately 70% of the observed radioactivity. For the anaerobic aquatic metabolism of [(14)C]niclosamide, test systems were incubated under anaerobic conditions for 365 days. Half-lives of 0.65 day for the chlorosalicylic acid label and 2.79 days for the chloronitroaniline label were calculated. From 0 to 3 DAT, niclosamide was first transformed into aminoniclosamide. Aminoniclosamide is readily formed, as it was observed in the chlorosalicylic acid label 0 DAT sampling. Several minor metabolites were observed in the water and sediment extracts. None of these metabolites were formed to a significant amount until the parent niclosamide dissipated below the detection limit. Two of the byproducts from these metabolism studies are polar unknowns eluting at 3 and 5 min by HPLC, similar to the unknowns observed in aqueous photolysis studies.


Calcium-activated cation channel in rat portal vein myocytes.
A rapid transient rise in the free cytosolic Ca2+ concentration is one of the earliest events in smooth muscle cell activation and is involved in the opening of several classes of Ca2(+)-sensitive ion channels such as K+ channels and Cl- channels. In portal vein smooth muscle cells, in addition to the Ca(2+)-dependent Cl-current, single-channel activities were recorded in response to external application of 10 mM caffeine, in the absence of EGTA in the pipette solution. The conductance of this novel type of channel was around 200 pS for membrane potentials ranging between -100 to +60 mV. The single-channel activities were also induced by external application of noradrenaline (10(-5) M) or acetylcholine (10(-5) M), by Ca2+ entry through voltage-dependent Ca(2+)-channels, and by intracellular application of ryanodine (10(-5) M). The caffeine-activated single-channel currents disappeared when 10 mM EGTA were added to the pipette solution or after replacement of external Ca2+ with Ba2+. These results show that these channels are Ca(2+)-dependent. Alteration of the Cl- equilibrium potential did not produce any change in the reversal potential of the caffeine-activated single-channel current, indicating that it was not carried by Cl- ions. The value of the reversal potential was about + 10 mV, irrespective of the CsCl-, KCl- or NaCl-containing solutions used to fill the pipette. Caffeine activated single-channel currents when cells were bathed in 90 mM Ba2+ plus 1 mM Ca(2+)- or 91 mM Ca(2+)-containing solutions, showing that divalent cations permeate the channels.(ABSTRACT TRUNCATED AT 250 WORDS)


Nonuniform muscle hypertrophy: its relation to muscle activation in training session.
Muscle hypertrophy in response to resistance training has been reported to occur nonuniformly along the length of the muscle. The purpose of the present study was to examine whether the regional difference in muscle hypertrophy induced by a training intervention corresponds to the regional difference in muscle activation in the training session. Twelve young men participated in a training intervention program for the elbow extensors with a multijoint resistance exercise for 12 wk (3 d · wk(-1)). Before and after the intervention, cross-sectional areas of the triceps brachii along its length were measured with magnetic resonance images. A series of transverse relaxation time (T2)-weighted magnetic resonance images was recorded before and immediately after the first session of training intervention. The T2 was calculated for each pixel within the triceps brachii. In the images recorded after the session, the number of pixels with a T2 greater than the threshold (mean + 1 SD of T2 before the session) was expressed as the ratio to the whole number of pixels within the muscle and used as an index of muscle activation (percent activated area). The percent activated area of the triceps brachii in the first session was significantly higher in the middle regions than that in the most proximal region. Similarly, the relative change in cross-sectional area induced by the training intervention was also significantly greater in the middle regions than the most proximal region. The results suggest that nonuniform muscle hypertrophy after training intervention is due to the region-specific muscle activation during the training session.


Adaptive Prescribed-Time Control of Time-Delay Nonlinear Systems via a Double Time-Varying Gain Approach.
This article studies the global prescribed-time stabilization problem for a class of time-delay nonlinear systems with uncertain parameters. First, we design two time-varying gains with special properties, in which one is introduced into virtual controllers to achieve prescribed-time convergence and the other one is used to construct the Lyapunov-Krasovskii (L-K) functional and Lyapunov function to handle the nonlinear time-delay term and unknown parameters, respectively. Then, by utilizing double time-varying gains and the scaling-free backstepping design approach, a dynamic state feedback controller is constructed, which guarantees that all state variables reach zero within a prescribed time, and the prescribed time can be specified in advance. Then, based on new functionals and regular differential inequality, we figure out the explicit expression for the upper bound of all variables, which plays an important role in proving the boundedness of all system variables. Final, a simulation example is given to demonstrate the effectiveness of the proposed method.


Prevention of deep venous thrombosis in vascular surgical procedures by LMW-heparin.
The risk of Deep Venous Thrombosis (DVT) in the immediate postoperative period varies from 0.8 to 96% of cases depending on major or minor operations and on age of patients. We have employed 8,000 I.U. AXa/daily of LMW-Heparin injected subcutaneously from one day preoperatively and prolonged for 8 days after surgical procedures in 40 patients operated upon by an aorto-femoral bypass in 25 cases, a femoro-popliteal below the knee in 8 and an extra-anatomical bypass in 7. The onset of DVP in the lower limbs was investigated by clinical examination, venous Doppler pressure evaluation, waveform analysis and echotomography and the 125I-Fibrinogen uptake test. There was no intraoperative increased bleeding and the preclotting of the prosthetic grafts was inaffected. A DVT was detected during the second postoperative day, by means of the 125I-Fibrinogen test in the calf of only one patient (1/40-2.5%), submitted to an aorto-bifemoral bypass, in whom the clinical pattern and ultrasound investigations were negative. The single daily subcutaneous administration has never caused side effects in the site of injection and it seems a real improvement in the heparin treatment. These results emphasize the advantage of the use of LMW-Heparins in patients submitted to arterial surgical reconstructions of the lower limbs for the prevention of the DVT.


Diagnostic criteria for sporadic Creutzfeldt-Jakob disease.
Making a clinical diagnosis of sporadic Creutzfeldt-Jakob disease relies on the evaluation of rapidly progressive dementia, ataxia, myoclonus, changes on the electroencephalogram, and other neurological signs. A definite diagnosis, however, is confined to cases that have been evaluated neuropathologically or by equivalent diagnostic techniques. This places a high priority on the establishment of reliable neuropathologic methods for the investigation and diagnosis of Creutzfeldt-Jakob disease. To evaluate existing morphological and laboratory diagnostic techniques to reach a consensus on the definition of "definite Creutzfeldt-Jakob disease." The existing morphological techniques, particularly immunohistochemistry, used in 4 laboratories--Germany, Great Britain, Japan, and the United States--are evaluated, and various laboratory diagnostic techniques are discussed. Immunohistochemistry with antibodies against the prion protein combined with special tissue pretreatment regimens gives reliable diagnostic results and, for its applicability to formalin-fixed and paraffin-embedded tissue, is superior to other techniques that may be more sensitive but require fresh, unfixed brain tissue. Our experience suggests the following regimen for the diagnosis of suspected Creutzfeldt-Jakob disease: light microscopy of various brain regions, which in typical cases may lead to definite diagnosis. Immunohistochemistry with antibodies against the prion protein is preferable in all suspected cases of Creutzfeldt-Jakob disease and is mandatory whenever a routine histological workup does not yield definite results. Additional special techniques can be applied if required.


Factors determining development of researchers within a research network on cancer diagnosis in primary care (CanTest): an interview study.
Developing connections with other researchers in a network, learning informally through these connections and using them to reach goals, is expected to increase research capacity and strengthen performance. So far, this has not been empirically demonstrated. We assessed what and how network collaboration adds to development of researchers. Exploratory qualitative study using semistructured online interviews, analysed by inductive and deductive methods. For the deductive analysis, an existing value creation framework to study informal learning in networks was used and adjusted to our context. The CanTest Collaborative-an international team of primary care cancer researchers working on early detection and diagnosis of cancer. Sixteen primary care cancer researchers. Connections with other researchers in an international network created diverse value cycles, where most outcomes were in the potential value cycle, acquiring knowledge, skills, social capital, resources and ideas. Not all potential value will be applied but many interviewees described realised as well as transformational value. In our context, the transformational value from the framework appeared to be related to other perspectives on the research process. Advancement of the network depends on opportunities, timing, role models and connections between different perspectives. Focus on the factors that are relevant for network advancement will support researchers in early detection and diagnosis of cancer research patients who participate in an international network and bring sustainable change in this domain. When, subsequently, researchers in the CanTest network bring about more realised and transformational learning outcomes, this will contribute to capacity development.


Genetic polymorphism among Cryptosporidium parvum isolates: evidence of two distinct human transmission cycles.
We report the results of molecular analysis of 39 isolates of Cryptosporidium parvum from human and bovine sources in nine human outbreaks and from bovine sources from a wide geographic distribution. All 39 isolates could be divided into either of two genotypes, on the basis of genetic polymorphism observed at the thrombospondin-related adhesion protein (TRAP-C2) locus. Genotype 1 was observed only in isolates from humans. Genotype 2, however, was seen in calf isolates and in isolates from a subset of human patients who reported direct exposure to infected cattle or consumed items thought to be contaminated with cattle faces. Furthermore, experimental infection studies showed that genotype 2 isolates were infective to mice or calves under routine laboratory conditions, whereas genotype 1 isolates were not. These results support the occurrence of two distinct transmission cycles of C. parvum in humans.


Connexin: a potential novel target for protecting the central nervous system?
Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer's disease, Parkinson's disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.


Genetic thrombophilia in patients with VTE in eastern Mediterranean located tertiary care center; is it time to change the algorithm for thrombophilia work up decision making?
Genetic thrombophilia work up performance is subject to debate because of the utility of the information it provides regarding prognosis of recurrence of venous thromboembolism (VTE) and guidance of duration of therapy with anticoagulation. Certain algorithms have been locally developed to guide decision making process to increase the yield of thrombophilia work up. These algorithms are not based on locally derived data. Data from the Eastern Mediterranean area (Lebanon) have shown high prevalence of thrombophilia mutations. Therefore the aim of this study was to describe the experience of a tertiary care center in thrombophilia work up among patients diagnosed with VTE. A retrospective chart analysis of the cases diagnosed with pulmonary embolism or deep venous thrombosis with radiological confirmation. A total of 133 patients' charts were reviewed, 27 patients had thrombophilia work up performed, 56% had heterozygous MTHFR mutation, 44% were heterozygous for the Factor V Leiden mutation and 3.2% were found to have Factor II heterozygous mutations, and a total of 33.3% of patients had more than one genetic mutation. The common causes of provoked VTE were 59.53% malignancy, 22.64% post surgery, 12.98% bed ridden patients, and 4.85% oral contraceptive pills. Only 14% of patients with a malignancy who presented with VTE where receiving prophylactic heparin. Doubly heterozygous prothrombotic genetic mutations are commonly present among Eastern Mediterranean patients with VTE. A prospective study to determine the predictive (negative and positive) power of the currently followed algorithm for genetic thrombophilia work up remains of significant importance. Stressing the favorable role of VTE prophylaxis among patients suffering from malignancies remains a target for raising awareness among oncologists.


Acute otitis media guidelines in selected developed and developing countries: uniformity and diversity.
Acute otitis media (AOM) is a common childhood disease, with an enormous economic and healthcare-related burden. Guidelines and consensus papers for AOM diagnosis and management were published in many countries. Our objective was to study the differences and similarities between these protocols in developing and developed countries. The keywords: 'acute otitis media' AND 'children' AND ['treatment' or 'management'] AND ['guideline' or 'consensus'] were used in various electronic databases between 1 January 1989 through 31 December 2015. Overall, 99 sources from 62 countries were retrieved: 53 from 22 developed countries, and 46 from 40 developing countries. Representative guidelines from America (the USA, Argentina), Europe (Italy, Moldova), Africa (South Africa, Tanzania, Ethiopia), Asia (Japan, Afghanistan, Sri Lanka),and Oceania (South Australia, Fiji) were compared. Paediatric societies publish guidelines in most developed countries; in developing countries, the Ministry of Health usually initiates guideline formulation. Most guidelines use the same diagnostic criteria and offer watchful waiting in mild-moderate scenarios. Amoxicillin is the suggested first-line antibiotic, whereas options for second-line and third-line therapies vary. Duration of therapy varies and is usually age dependent: 5-7 days for children <2 years and 10 days for children >2 years in developed countries, while duration and age groups vary greatly in developing countries. Reduction of AOM risk factors is encouraged in developed countries, but rarely in developing countries. Guidelines for AOM from developing and developed countries are similar in many aspects, with variation in specific recommendations, due to local epidemiology and healthcare accessibility. Formulation of regional guidelines may help reduce AOM burden.


Test-potentiated learning of motor sequences.
We investigated effects of retrieving body movements from memory on subsequent re-encoding of these movements (i.e., test-potentiated learning). In Experiment 1, participants first learned to perform 12 sequential finger movements as responses to letter stimuli. Eight of these movements then had to be recalled in response to their stimuli (initial test). Subsequently, learning trials were repeated for four of the previously to-be-retrieved movements as well as the previously not-to-be-retrieved movements. Restudy benefited from prior retrieval. In a final test, again requiring motoric recall in response to letter stimuli, performance was better for restudied items that were previously cued for retrieval as compared to items that had been restudied without prior retrieval. However, no such indirect testing benefit occurred when initial and final testing formats were incongruent, that is, when participants had to recall the stimuli in response to movements as cues at the final test. In Experiment 2, we replicated the finding of test-potentiated learning with a different design, manipulating initial-testing status between participants.


Magnetotransport Anomaly in Room-Temperature Ferrimagnetic NiCo2 O4 Thin Films.
The inverse spinel ferrimagnetic NiCo2 O4 presents a unique model system for studying the competing effects of crystalline fields, magnetic exchange, and various types of chemical and lattice disorder on the electronic and magnetic states. Here, magnetotransport anomalies in high-quality epitaxial NiCo2 O4 thin films resulting from the complex energy landscape are reported. A strong out-of-plane magnetic anisotropy, linear magnetoresistance, and robust anomalous Hall effect above 300 K are observed in 5-30 unit cell NiCo2 O4 films. The anomalous Hall resistance exhibits a nonmonotonic temperature dependence that peaks around room temperature, and reverses its sign at low temperature in films thinner than 20 unit cells. The scaling relation between the anomalous Hall conductivity and longitudinal conductivity reveals the intricate interplay between the spin-dependent impurity scattering, band intrinsic Berry phase effect, and electron correlation. This study provides important insights into the functional design of NiCo2 O4 for developing spinel-based spintronic applications.


Effects of Dual-Task Training on Gait Parameters in Elderly Patients with Mild Dementia.
This study aimed to investigate the effectiveness of dual-task training (DTT) compared to single-task training (STT), on gait parameters in elderly patients with mild dementia (MD). Twenty-four elderly patients with MD were randomly assigned to the DTT (n = 13) or the STT group (n = 11). The DTT group performed a specific cognitive-motor DTT, while the STT group received only motor task training. Both training sessions lasted 8 weeks, with a frequency of 3 days per week, and the cognitive functions and gait parameters were measured. A statistically significant interaction effect was found between the two groups in stride length, stride velocity, cadence, step length, swing phase, stance phase, and double support phase (p < 0.05). After 8 weeks, the DTT group showed significant improvement in spatiotemporal parameters, except for the kinematic parameters (p < 0.05). In the between-group analysis, the DTT group showed more improvement than the STT group in stride velocity, step length, swing phase, stance phase, and double support (p < 0.05). These findings suggest that improvements in spatiotemporal gait parameters after DTT are reported in patients with MD. Our results can guide therapists to include dual tasks in their gait rehabilitation programs for the treatment of mild dementia.


Calculated Terahertz Spectra of Glycine Oligopeptide Solutions Confined in Carbon Nanotubes.
To reduce the intense terahertz (THz) wave absorption of water and increase the signal-to-noise ratio, the THz spectroscopy detection of biomolecules usually operates using the nanofluidic channel technologies in practice. The effects of confinement due to the existence of nanofluidic channels on the conformation and dynamics of biomolecules are well known. However, studies of confinement effects on the THz spectra of biomolecules are still not clear. In this work, extensive all-atom molecular dynamics simulations are performed to investigate the THz spectra of the glycine oligopeptide solutions in free and confined environments. THz spectra of the oligopeptide solutions confined in carbon nanotubes (CNTs) with different radii are calculated and compared. Results indicate that with the increase of the degree of confinement (the reverse of the radius of CNT), the THz absorption coefficient decreases monotonically. By analyzing the diffusion coefficient and dielectric relaxation dynamics, the hydrogen bond life, and the vibration density of the state of the water molecules in free solution and in CNTs, we conclude that the confinement effects on the THz spectra of biomolecule solutions are mainly to slow down the dynamics of water molecules and hence to reduce the THz absorption of the whole solution in confined environments.


Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer.
Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay. No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P < .001). IDM-2101 was well tolerated, and evidence of efficacy was suggested.


Diagnostic potential of combined transthoracic echocardiography and x-ray computed tomography in suspected aortic dissection.
Transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) are considered optimal diagnostic methods in the setting of suspected aortic dissection. However, although less sensitive as single modalities, transthoracic echocardiography (TTE) and contrast-enhanced computed tomography (x-ray CT) are more widely available and less costly. This study was undertaken to compare the diagnostic performance and reliability of the combined use of TTE and x-ray CT with TEE and/or MRI findings in the setting of suspected aortic dissection. The diagnostic power of combined TTE and x-ray CT was compared with both single use of TTE and x-ray CT and with TEE and/or MRI in a series of 168 consecutive patients with suspected aortic dissection (AD). Of these, 28 women and 58 men (mean age 53 +/- 16 years) underwent TTE and x-ray CT prior to TEE (n = 52) and/or MRI (n = 69). Diagnostic results of combined TTE/x-ray CT were retrospectively but independently reevaluated in blinded fashion; diagnostic findings were validated by angiography (n = 63), surgery (n = 52), or autopsy (n = 7). Type A dissection was found in 29 patients (34%), type B dissection in 10 (12%), whereas aortic dissection was excluded in 47 (55%). With 95%, the sensitivity of TTE and x-ray CT was significantly enhanced when used in a combined access compared with 67 and 79%, respectively, when used as single methods (95%; p < 0.05). Sensitivity and specificity (95 and 91%, respectively) of combined TTE/x-ray CT evaluation were not different from TEE and/or MRI (100 and 96%, respectively; NS). Thrombus formation, side-branch involvement, aortic regurgitation, pericardial effusion or mediastinal hematoma were also detected with similar sensitivities and specificities both by combined TTE/x-ray CT and TEE and/or MRI. This first controlled study comparing the combined information of TTE and x-ray CT with TEE and/or MRI revealed a similar diagnostic potential of both diagnostic strategies in the setting of suspected aortic dissection. Thus, in an environment with access to color Doppler TTE and x-ray CT only, the information from both tests should be combined to decide on diagnostic management of these patients.


[Principles of antimicrobial therapy regimens for patients treated in intensive care units].
The current literature review is devoted to infectious complications occurred in intensive care unit. The classification of the complications, the pecularity of microbial spectrum and microbe sensitivity to antibiotics are discussed in the article. Esspecially, special attention is paid to antibiotic resistance. Antimicrobial drugs of choice and principles of antimicrobial regimen prescription are presented in the article in detail.


Morphogenesis and molecular considerations on congenital cardiac septal defects.
The primary unseptated heart tube undergoes extensive remodeling including septation at the atrial, atrioventricular, ventricular, and ventriculo-arterial level. Alignment and fusion of the septal components is required to ensure full septation of the heart. Deficiencies lead to septal defects at various levels. Addition of myocardium and mesenchymal tissues from the second heart field (SHF) to the primary heart tube, as well as a population of neural crest cells, provides the necessary cellular players. Surprisingly, the study of the molecular background of these defects does not show a great diversity of responsible transcription factors and downstream gene pathways. Epigenetic modulation and mutations high up in several transcription factor pathways (e.g. NODAL and GATA4) may lead to defects at all levels. Disturbance of modulating pathways, involving primarily the SHF-derived cell populations and the genes expressed therein, results at the arterial pole (e.g. TBX1) in a spectrum of ventricular septal defects located at the level of the outflow tract. At the venous pole (e.g. TBX5), it can explain a variety of atrial septal defects. The various defects can occur as isolated anomalies or within families. In this review developmental, morphological, genetic, as well as epigenetic aspects of septal defects are discussed.


Guam ALS/parkinsonism-dementia: a long-latency neurotoxic disorder caused by "slow toxin(s)" in food?
Parkinsonism (P) with progressive dementia (D) of the Alzheimer type is recognized as a clinical variant of a form of amyotrophic lateral sclerosis (ALS) that has occurred in high incidence among the Chamorro people of the islands of Guam and Rota in the Marianas chain of Micronesia. The declining annual incidence, upward shifting of the age of onset, narrowing of the sex ratio, and occurrence of the disease among non-Chamorros, point to a disappearing environmental causation peculiar to the traditional culture of these islands. Evidence is presented in support of the proposal that heavy use of certain toxic plants, notably cycads, a traditional source of food and medicine for the Chamorro people, plays an important etiological role. Clinical and epidemiological approaches are offered to test for a relationship between ALS/P-D and long-latency plant toxicity.


Life cycle approach to child and adolescent health.
Young people are our human capital for the future, therefore child and adolescent health has attracted considerable political and professional attention in recent years. Health is indivisible, requires holistic approach throughout the individual's life. Healthy outcome at one point in the life cycle, provides a positive determinant for health elsewhere in the cycle. Health and development of the 0-19 age group links intimately, at both ends of the range, with reproductive health. Health during childhood is in part determined by the health of the mother, and affected also by factors such as the nutrition of adolescent girls and the avoidance of early pregnancy. These factors, in turn, are influenced by healthy growth and development in childhood. The paper presents main environmental and socio-cultural challenges for each of the stages of child and adolescent life. Main challenge described are: unsafe abortion, malnutrition, anaemia, malformations, and infections during pregnancy; low birth weight, asphyxia, hypothermia, infection, failure to initiate early and full breastfeeding in the neonatal period; poor nutrition, growth and development, frequent illnesses, injury, abuse and neglect in the early childhood; poor nutrition, growth and development, injury, abuse, neglect, and helminth infections in the early school age; poor nutrition, poor development, chronic conditions, mental disorders, injury, drug abuse, and violence in the adolescence. Both, prevention of ill health and care for illnesses are important at all times but the balance between them shifts over time during the childhood and adolescence. Main actions needed to meet the child and adolescent needs are presented as well.


Oxidative stress and early mortality in acute ischemic stroke: A prospective cohort study.
Malondialdehyde (MDA) is an oxidative stress biomarker, which represents a unifying mechanism of brain injury that occurs throughout the ischemic stroke cascade. The current study aimed to examine whether or not acute ischemic stroke (AIS) patients who had elevated serum MDA levels at admission had an increased risk of mortality and a worse functional outcome three months later. An observational, prospective cohort study that enrolled 90 patients with AIS. The patients were examined in the first 24 hours and then followed up for three months to assess mortality, short-term neurological functional outcome, and neurological disability by the Modified Rankin Scale (MRS). The mean of serum MDA level among AIS patients was 6.3 ± 3.7 nmol/ml. Non-survivor cases were associated with statistically significantly higher serum MDA levels compared to survivors (9.7 ± 4.3 vs. 5.3 ± 2.8, p < 0.001), respectively. Patients with severe stroke, according to NIHSS score, were associated with significantly (p < 0.05) higher MDA levels compared to moderate and mild cases (7.4 ± 4.3 vs. 5.4 ± 2.6 vs. 3.3 ± .6). At a cutoff point of ≥ 6.7 nmol/ml, the area under the curve (AUC) for serum MDA levels as a predictor of mortality was 0.8 (0.69-0.91; p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value were 77%, 80%, 89.5%, and 48.5%, respectively. Multivariate regression demonstrated that MDA level was a significant independent predictor of mortality among patients with AIS (OR = 1.29, 95% CI: 1.01 to 1.65; p = 0.041). MDA serum level was significantly higher in non-survivors than in survivors patients, so MDA could be used as a predictor for early mortality and short-term outcome of cases with AIS.


Tensile bond strength of ceramic orthodontic brackets bonded to porcelain surfaces.
The aim of this study was to compare various surface treatment methods to define the procedure that produces adequate bond strength between ceramic brackets and porcelain. The specimens used in this study, 60 porcelain tabs, were produced by duplication of the labial surface of a maxillary first premolar. The 6 different preparation procedures tested were: (1) sandblasting with 50 microm aluminum oxide in a sandblasting device, (2) application of silane to the porcelain and the bracket base, (3) sandblasting followed by application of silane, (4) acid etching with 9.6% hydrofluoric acid, (5) acid etching with 9.6% hydrofluoric acid followed by application of silane, and (6) sandblasting followed by application of 4-Meta adhesive. The ceramic brackets were bonded with no-mix orthodontic bonding material. A bonding force testing machine was used to determine tensile bond strengths at a crosshead speed of 0.5 mm per second. The results of the study showed that porcelain surface preparation with acid etching followed by silane application resulted in a statistically significant higher tensile bond strength (P < .05). Sandblasting the porcelain surface before silane treatment provided similar bond strengths, but sandblasting or acid etching alone were less effective. Silane application was recommended to bond a ceramic bracket to the porcelain surface to achieve bond strengths that are clinically acceptable.


The role of prostaglandins in androgenetic alopecia.
Though androgenetic alopecia (AGA) is one of the most common diseases affecting both sexes and all races, its pathogenesis is not completely clarified. The aim of this study was to investigate the role of the four major prostaglandins (PGs) (PGE2 , PGD2 , PGF2α , and PI2 or prostacyclin) in the pathogenesis of AGA in males and females. Human scalp biopsies were obtained from 30 adults (17 males and 13 females) suffering from AGA and from 30 healthy adults (18 males and 12 females). In each subject, two skin biopsies were performed, one from the frontal bald area and another one from the occipital area with normal hair growth. In the healthy group, biopsies were taken from both areas too. In each sample, all four PGs were measured. In the patient group, PGD2 and prostacyclin or PGI2 levels were increased in bald compared to haired scalp. On the contrary, measurements of PGE2 and PGF2α showed that they were diminished in bald areas compared to haired areas. PG levels in healthy samples were comparable to the haired areas. These results support that there is a fine balance between these four proteins in scalp hair follicles, and its maintenance may be crucial for hair growth. Furthermore, their receptors could be potential targets for treatment of AGA.


Medicare program; national coverage decisions--HCFA. General notice.
This notice lists those current Medicare national coverage decisions which have been issued in the Medicare Coverage Issues Manual (HCFA Pub. 6). These national coverage decisions are also widely distributed through the U.S. Government Printing Office, the National Technical Information Service, and private publishers such as the Commerce Clearing House. From time to time, some of the individual decisions have been published in the Federal Register. In this Federal Register notice, HCFA is publishing a compilation of these national coverage decisions. We will publish subsequent national coverage decisions in the Federal Register on a quarterly basis.


Percutaneous core biopsy of the breast: correlates of anxiety.
The authors performed this study to investigate the level of patient anxiety immediately preceding breast biopsy and examined potential clinical and demographic correlates of anxiety. The authors evaluated 102 women who were referred to a radiology breast clinic to undergo breast biopsy. The women were assessed with a self-report of demographic and medical items and the State Trait Anxiety Inventory (STAI) immediately before their biopsy. The STAI also was administered at 1 and 5 days after biopsy. The participants' mean state anxiety T score as measured with the State Trait Anxiety Inventory was 71.1 (standard deviation, 7.2). Multiple regression analysis was performed to determine the correlates of state anxiety. The variables that showed the strongest correlation with state anxiety were trait anxiety, being concerned about the results of biopsy, education (less education was associated with more anxiety), age (an older age was associated with more anxiety), and number of relatives with breast cancer. Given the expected overlap (r = 0.55) between state and trait anxiety, a second regression analysis was performed that controlled for trait anxiety. The results of this analysis also identified age, being concerned about the results of the biopsy. and number of relatives with breast cancer as relevant correlates of state anxiety. Overall, the results give some indication of the characteristics of women likely to be most anxious before biopsy. Future research should assess the effectiveness of different strategies for addressing situational anxiety.


Urethrocutaneous fistula: a rare presentation of penile tuberculosis.
A man in his 50s presented with two urethrocutaneous fistulae with intermittent dribbling of urine from the opening of fistula on the surface of glans penis. A skin biopsy from indurated margin of fistula was suggestive of fibrosing granulomatous reaction. Anti-tubercular therapy was given with a diagnosis of penile tuberculosis and there was 50% improvement within two months of treatment.


Holmium Laser Lithotripsy in the New Stone Age: Dust or Bust?
Modern day holmium laser systems for ureteroscopy (URS) provide users with a range of settings, namely pulse energy (PE), pulse frequency (Fr), and pulse width (PW). These variables allow the surgeon to choose different combinations that have specific effects on stone fragmentation during URS lithotripsy. Contact laser lithotripsy can be performed using fragmentation or dusting settings. Fragmentation employs settings of low Fr and high PE to break stones that are then extracted with retrieval devices. Dusting is the utilization of high Fr and low PE settings to break stones into submillimeter fragments for spontaneous passage without the need for basket retrieval. Use of the long PW mode during lithotripsy can reduce stone retropulsion and is increasingly available in new generation lasers. During non-contact laser lithotripsy, stone fragments are rapidly pulverized in a calyx in laser bursts that result in stones breaking into fine fragments. In this review, we discuss the effect of different holmium laser settings on stone fragmentation, and the clinical implications in a very much evolving field.


Moderate-high intensity exercise training after myocardial infarction: effect on left ventricular remodeling.
Regular exercise increases exercise capacity and physical fitness, but questions remain about the effects of exercise on left ventricle (LV) remodeling after myocardial infarction. This study investigated the effects of moderate to high intensity exercise training on LV remodeling after a first myocardial infarction. An exercise group of 68 patients in cardiac rehabilitation after a first myocardial infarction had an initial echocardiogram and exercise stress test. Thirty patients completed the 12 weeks of training and had echocardiograms suitable for quantitative analysis. Follow-up echocardiograms and exercise tests were performed. A carefully matched control group of 30 patients with echocardiograms at fixed intervals after myocardial infarction and no formal exercise training were also studied. LV size was expressed as the endocardial surface area-to-body surface area (ESAi), whereas infarct size was characterized by the percent abnormal wall motion (%AWM) by echocardiography using an endocardial surface area mapping technique. Indices of LV shape (sphericity) were also assessed. In the exercise group, no significant changes were seen in ESAi (57.95 +/- 13.1 vs 57.80 +/- 12.04 cm2/m2) or in %AWM (19.33 +/- 15.27 vs 20.11 +/- 15.95) from the initial to the final echo. The indices of sphericity were also unchanged. None of these parameters changed in the control group. Within each group was found heterogeneity in LV remodeling. Multivariate regression analysis revealed initial ESAi and initial %AWM to predict change in ESAi over time. In this study of patients with predominately small infarcts, exercise training did not adversely affect LV remodeling after myocardial infarction. Remodeling is heterogeneous and appears related to infarct and LV size.


Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments.
The temporal pattern of exposure to glucocorticoids has been reported to be a critical factor in determining the outcome of glucocorticoid actions at the brain. In this work, the effects of different regimes of subcutaneous corticosterone administration (acute-single injection-vs. chronic-daily injection for 21 days) on the expression of the neural cell adhesion molecule (NCAM) were evaluated in different rat brain regions (CA1-CA4, dentate gyrus, frontal cortex, striatum, and hypothalamus). The treatments were selected according to previous studies in which we showed biphasic effects of corticosterone on memory formation, with acute corticosterone effects being facilitating and chronic effects being deleterious. In addition, the chronic treatment was shown by others to result in structural alterations at the hippocampus. NCAM was evaluated given its cell-cell recognition and adhesion properties, and the involvement on synaptic stabilisation subserving long-term memory formation. The results showed a biphasic modulation of NCAM levels at the frontal cortex, with acute corticosterone resulting in enhanced NCAM levels at 8 h and 24 h posttraining, and the chronic treatment decreasing its expression. None of the other brain areas examined showed significant changes in NCAM expression with corticosterone treatments, except for the hypothalamus that showed reduced NCAM levels after the chronic corticosterone regime. These results support the view that NCAM regulation at the frontal cortex might be a mechanism by which corticosterone treatments influence memory formation. They also highlight the hypothalamus as a brain area particularly sensitive to NCAM regulation by prolonged exposure to elevated glucocorticoids.


How Prediction Based on Sequence Detection in the Cerebellum Led to the Origins of Stone Tools, Language, and Culture and, Thereby, to the Rise of Homo sapiens.
This article extends Leiner et al.'s watershed position that cerebellar mechanisms played prominent roles in the evolution of the manipulation and refinement of ideas and language. First it is shown how cerebellar mechanism of sequence-detection may lead to the foundational learning of a predictive working memory in the infant. Second, it is argued how this same cerebellar mechanism may have led to the adaptive selection toward the progressively predictive phonological loop in the evolution of working memory of pre-humans. Within these contexts, cerebellar sequence detection is then applied to an analysis of leading anthropologists Stout and Hecht's cerebral cortex-based explanation of the evolution of culture and language through the repetitious rigors of stone-tool knapping. It is argued that Stout and Hecht's focus on the roles of areas of the brain's cerebral cortex is seriously lacking, because it can be readily shown that cerebellar sequence detection importantly (perhaps predominantly) provides more fundamental explanations for the origins of culture and language. It is shown that the cerebellum does this in the following ways: (1) through prediction-enhancing silent speech in working memory, (2) through prediction in observational learning, and (3) through prediction leading to accuracy in stone-tool knapping. It is concluded, in agreement with Leiner et al. that the more recently proposed mechanism of cerebellar sequence-detection has played a prominent role in the evolution of culture, language, and stone-tool technology, the earmarks of Homo sapiens. It is further concluded that through these same mechanisms the cerebellum continues to play a prominent role in the relentless advancement of culture.


[Liver morphology and clinical aspects of a case of cholesterol ester storage disease].
Liver specimen morphology and clinical course of a case of cholesterol ester storage disease are presented. In a 16-year-old boy on the first biopsy a massive storage of neutral fats was found light microscopically and of cholesterol ester micropolariscopically. Advanced portal field fibrosis and severe reactive hepatitis indicate the danger of progression up to metaplasia. Typical membrane-surrounded lipid inclusions were found electron microscopically in hepatic cells, stellate cells and also in bile duct epithelium.


An econometric analysis of inter-fuel substitution in energy sector of Pakistan.
Hydroelectricity is playing a significant role in lowering CO2 emissions as it contributes a desirable platform to fulfill the growing energy demand while releasing fewer GHGs in comparison to other fossil fuels. Utilizing the trans-log production model, this study is an endeavor to investigate the potential inter-fuel substitution by estimating the substitution elasticity between pairs of coal, natural gas, petroleum, and hydroelectricity to suggest policy for Pakistan to achieve higher economic growth, environmental sustainability, and increased energy access by its citizens. Over the period 1980-2013, the ridge regression was approved to estimate the model's parameters. The findings show that the output elasticity of hydroelectricity is the highest and all the factor inputs are substitutes; whereas, the elasticity of substitution between coal vs. natural gas is the highest, thus suggesting an increased focus on the coal extraction to switch from the alternative usage of gas. Moreover, encouragement of energy subsidy programs, coupled with taxes and infrastructural developments, can be adapted to redirect technology towards hydroelectricity. Hence, the result that hydroelectricity is substituted for all fuels submit that Pakistan has the potential to switch from petroleum to cleaner energy; therefore, reducing the adverse environmental implications and to retain the ability to fuel its energy sector.


Disruption of cytoskeleton by methylmercury in cultured CHO cells.
The effect of methylmercury (MM) on three main cytoskeletal components [i.e. microtubules (MT), microfilaments (MF) and intermediate filaments (IF)] and on specific biochemical parameters (i.e. glutathione transferase (GST), glutathione reductase (RED), glutathione peroxidase (GSH-Px), glyoxalase 1 (GLY 1) and total -SH groups (TSH) of the cytosolic fraction) was studied in cultured Chinese hamster ovary (CHO) cells. The experiments were conducted with increasing doses of MM (i.e. 1, 4 and 8 mum), using an exposure time of 16 hr; and with a fixed dose of MM (2 mum), using increasing exposure periods (i.e. 0-24 hr). The morphological changes observed by immunofluorescence seemed to indicate that MF were damaged as much as (if not more than) MT after 16 hr of exposure to 4 mum-MM. At a concentration of 1 mum, MM only affected MF. The time-course experiments revealed that IF as well as MF and MT were severely disorganized after 3 and 6 hr of incubation in the presence of 2 mum-MM. However, an obvious reorganization was observed after 24 hr of exposure. In experiments using increasing MM doses, changes in the enzymatic activities were less noticeable than those observed in the morphology; only a modest decrease in TSH and RED activities (<30%) was recorded at the highest dose of MM used (i.e. 8 mum). In contrast, increasing the time of exposure to MM induced changes in both the cytoskeletal structures and the biochemical parameters: the lowest RED activity and TSH were observed after 3-6 hr exposure; control values were obtained after an exposure period of 24 hr. Ultrastructural observations on cells treated with increasing doses of MM showed changes in plasmamembrane profile, cytoskeleton organization and mitochondrion structure. The results confirm that MM causes non-specific damage to CHO cells and suggest that a functional interaction may exist between GSH-dependent enzymes and cytoskeletal structures.


Supramolecular n/p-heterojunction photosystems with oriented multicolored antiparallel redox gradients (OMARG-SHJs).
Directional electron and hole transport is essential in photosynthesis. Applied to molecular optoelectronics such as organic solar cells, these lessons from nature call for oriented supramolecular n/p-heterojunctions (SHJs) that contain various chromophores and antiparallel redox gradients (OMARGs). In this tutorial review, we summarize recent progress made toward the construction of OMARG-SHJs. This conceptually innovative twist added to a timely topic should appeal to the synthetic organic, supramolecular, biological, physical, analytical and materials chemist as well as to the expert in energy and environmental sciences.


Properties of adenotin reconstituted into phospholipid vesicles.
Adenotin is a low affinity adenosine binding protein that has amino terminal homology with mammalian and avian stress proteins. Human placental adenotin was solubilized and reconstituted into phospholipid vesicles with an overall yield of 30%. The properties of adenotin in vesicles were similar to the native membranes as follows: association has a Kobs of 0.61 +/- 0.03 minute-1; equilibrium is reached in approximately 15 minutes; and the first order dissociation constant is 5.0 +/- 0.3 minute-1. Displacement analysis reveals an agonist potency order and Ki values as follows: N-ethylcarboxamidoadenosine, 0.35 microM; 2-chloroadenosine, 1.5 microM; R-phenylisopropyladenosine, greater than 1000 microM. The addition of 100 microM 5'-guanylylimidodiphosphate did not decrease binding of 5'-N-ethylcarboxamidoadenosine (NECA) at 37 degrees C or 4 degrees C but did decrease the IC50 for PC12 and JAR cell membrane agonist binding from 9.9 to 3.3 microM and increase the binding to 150-211% of the control value at 37 degrees C. The latter studies at 37 degrees C showed high variability. Using binding sites reconstituted into vesicles and gel filtration chromatography and agonist related guanine nucleotide release, the authors investigated whether these changes were related to an interaction between adenotin and a guanine nucleotide regulatory protein. No evidence for such an interaction was found. These data suggest that adenotin retains its binding properties when reconstituted into phospholipid vesicles. The function of this low affinity adenosine binding site remains to be discovered. However, the reconstitution of adenotin into phospholipid vesicles provides a method to study its function.


Effect of calcitonin gene-related peptide receptor antagonism on the systemic blood pressure responses to mechanistically diverse vasomodulators in conscious rats.
The effects of calcitonin gene-related peptide (CGRP) receptor antagonism with CGRP 8-37 on blood pressure changes evoked by the intravenous administration of the vasoactive modulators angiotensin II, phenylephrine, adenosine, nitroglycerine, and sodium nitroprusside were assessed in conscious rats. The effects of sumatriptan and dihydroergotamine on the blood pressure responses evoked by these vasomodulators also were assessed. The intravenous test dose of CGRP 8-37 was validated through block of depressor responses to intravenous CGRP in conscious rats, whereas the intravenous test doses of sumatriptan and dihydroergotamine were validated by reductions in carotid blood flow in anesthetized rats. CGRP 8-37 had no significant effects on blood pressure dose-response profiles and individual dose blood pressure responses to any of the vasomodulators tested. In contrast, sumatriptan altered the blood pressure dose-response profiles to angiotensin II and sodium nitroprusside (P < 0.03) and dihydroergotamine altered the blood pressure dose-response profile to sodium nitroprusside (P < 0.02) and tended to alter that of phenylephrine (P = 0.06). Both sumatriptan and dihydroergotamine displayed frequent alterations of individual dose blood pressure responses to all vasomodulators. These findings are consistent with concerns for sumatriptan and dihydroergotamine to alter systemic hemodynamics, whereas CGRP receptor antagonism did not display the same hemodynamic liability.


Differences in radiation sensitivity of recovery of spermatogenesis between rat strains.
Previous studies with Lewis/Brown-Norway (BN) F1 hybrid rats indicated that spermatogenesis was much more sensitive to ionizing radiation than in the widely studied outbred Sprague Dawley stock, suggesting that there were genetically based differences; however, the relative sensitivities of various inbred strains had not been established. As a first step to defining the genes responsible for these differences, we compared the sensitivities of seven rat strains to radiation damage of spermatogenesis. Recovery of spermatogenesis was examined 10 weeks after 5-Gy irradiation of seven strains (BN, Lewis, Long-Evans, Wistar Kyoto, spontaneously hypertensive [SHR], Fischer 344, and Sprague Dawley). The percentages of tubules containing differentiated cells and testicular sperm counts showed that BN and Lewis were most sensitive to radiation (< 2% of tubules recovered, < 2 × 10(5) late spermatids per testis), Long-Evans, Wistar Kyoto, Fischer, and SHR were more resistant, and Sprague Dawley was the most resistant (98% of tubules recovered, 2 × 10(7) late spermatids per testis). Although increases in intratesticular testosterone levels and interstitial fluid volume after irradiation had been suggested as factors inhibiting recovery of spermatogenesis, neither appeared to correlate with the radiation sensitivity of spermatogenesis in these strains. In all strains, the atrophic tubules without differentiated germ cells nevertheless showed the presence of type A spermatogonia, indicating that their differentiation was blocked. Thus, we conclude that the differences in radiation sensitivity of recovery of spermatogenesis between rat strains of different genetic backgrounds can be accounted for by differences in the extent of the radiation-induced block of spermatogonial differentiation.


A neurocomputational model of classical conditioning phenomena: a putative role for the hippocampal region in associative learning.
Some existing models of hippocampal function simulate performance in classical conditioning tasks using the error backpropagation algorithm to guide learning (Gluck, M.A., and Myers, C.E., (1993). Hippocampal mediation of stimulus representation: a computational theory. Hippocampus, 3(4), 491-516.). This algorithm is not biologically plausible because it requires information to be passed backward through layers of nodes and assumes that the environment provides information to the brain about what correct outputs should be. Here, we show that the same information-processing function proposed for the hippocampal region in the Gluck and Myers (1993) model can also be implemented in a network without using the backpropagation algorithm. Instead, our newer instantiation of the theory uses only (a) Hebbian learning methods which match more closely with synaptic and associative learning mechanisms ascribed to the hippocampal region and (b) a more plausible representation of input stimuli. We demonstrate here that this new more biologically plausible model is able to simulate various behavioral effects, including latent inhibition, acquired equivalence, sensory preconditioning, negative patterning, and context shift effects. In addition, the newer model is able to address some new phenomena including the effect of the number of training trials on blocking and overshadowing.


Neuroimmune mechanisms in Parkinson's disease.
The potential role of immune mechanisms in the pathogenesis of Parkinson's disease is still a matter of controversy. Both peripheral and central immunological disturbances have been reported. It is possible that this altered function of the immune system is responsible for autodestruction of neurons in Parkinson's disease and other neurodegenerative disorders. In this case possible neuroprotective therapeutic strategies could be developed. However, further investigations are necessary to elucidate the conditions of normal or pathologic interaction between the brain and the immune system.


A new fluorescence method for the continuous determination of surface lipid oxidation in lipoproteins and plasma.
We report on a new method for the determination of lipid oxidation in lipoproteins and plasma. The biological lipid system is preloaded with a fluorescent analog of phosphatidylcholine containing diphenylhexatriene (DPH) propionic acid covalently linked to the sn-2 position. When externally added, the respective phospholipid label (DPHPC) localizes to the surface monolayer of a lipoprotein. Under oxidative conditions (e.g. in the presence of Cu2+ ions) the fluorophore undergoes decomposition, resulting in a continuous decrease of fluorescence intensity which reflects the oxidation of a chemically defined phospholipid molecule with well defined localization. When incorporated into LDL particles, the kinetics of the decrease in DPHPC fluorescence intensity upon exposure to Cu2+ us very similar to that of conjugated diene accumulation. Furthermore, our assay can be applied to follow the oxidation of lipids in diluted serum and may also be developed into a suitable test system for clinical studies of susceptibility of plasma lipids to oxidation.


Eclampsia in Sweden.
Assess the actual rate of eclampsia in Sweden, describe the clinical picture of the disease and the maternal and perinatal outcomes. Analysis of data regarding incidence of eclampsia registered in the Swedish Medical Birth Register 1991-1992. The records of all the cases with the diagnosis of eclampsia in Sweden during 1991-1992 were retrospectively evaluated regarding maternal and fetal outcomes. The incidence of eclampsia after case review was 3.3/10,000 births. There was no maternal mortality. Severe maternal complications occurred in 30%. Recurrent fits were reported in 41%. Antenatal eclampsia was usually either not preceded by symptoms or signs of preeclampsia or by just a very short period of prodromal symptoms. Among intrapartum and postnatal cases of eclampsia, preeclampsia or high blood pressure was more frequently noted when convulsions occurred. Perinatal mortality rate was 4/80 (4.7%). Of the infants, 13% were small for gestational age. Compared with earlier studies, the incidence of eclampsia has increased significantly. It is questionable whether the incidence of eclampsia could be reduced by earlier diagnosis and treatment of preeclampsia. The risk of severe complications and recurrent fits was substantial, which underlines the importance of adequate treatment of eclampsia.


Decree-Law No. 482/88, 26 December 1988.
This Decree-Law adopts measures aimed at resolving land use matters that remained following the implementation of the Portuguese land reform policy under Law No. 2014 of 27 May 1946. The two principal measures introduced by the Decree-Law are 1) the lifting of legal impediments to the use of land acquired by the Colonization Agency under the 1946 statutes, but not redistributed under that policy and 2) the granting of full property rights to settlers who have paid and/or do not default on future payments of annuities owed pursuant to land distribution plans under the land reform policy.


The labour ward analgesic service at King Edward VIII Hospital, Durban.
The provision of analgesic services to the labour ward at King Edward VIII Hospital was studied during a 1-week period. Of 249 patients, 113 (45%) received no analgesia whatsoever. Intramuscular pethidine was the commonest form of analgesia and was used in 97 patients (39%). Thirty-six patients (14%) received epidural analgesia and only 4 inhalational analgesia using nitrous oxide and oxygen (Entonox). A significant proportion of patients who received pethidine were given the drug between 1 and 3 hours before delivery, increasing the potential for opiate-related neonatal depression. Of the patients given opiate analgesia, 22 (23%) proceeded to caesarean section and could have been at increased risk of aspiration of gastric contents owing to delayed gastric emptying caused by the opiate. One hundred and eleven mothers (76%) who had an obstetric indication for epidural analgesia were denied it because of lack of medical staffing.


Ertapenem and Faropenem against Mycobacterium tuberculosis: in vitro testing and comparison by macro and microdilution.
Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB). The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution. 19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC. MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition. 18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates. 10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL). Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status. The lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation. No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging. This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use.


HLA class I polymorphism in a Moroccan population from Casablanca.
We have studied the distribution of HLA-A and -B alleles and haplotypes by sequence-specific primer amplification in a sample of 100 unrelated healthy individuals belonging to both Berber and Arabic-speaking groups from the region of Casablanca in Morocco. Among the 17 HLA-A and 23 HLA-B alleles observed, the most frequent were HLA-A2 (21%), -A1 (11%), -A3 (10%), -B44 (11.4%), -B50 (9.9%), -B5(8.5%) and -B35 (6.5%). Six two-locus haplotypes were observed with a frequency above 5%: A2-B50 (9.6%), A23-B44 (7.4%), A2-B15 (6.4%), A68-B39 (5.3%), A1-B51 (5.3%) and A68-B44 (4.3%). Our data confirm that, on the basis of genetic distances, the majority of present-day North Africans from Morocco are closely related to Berbers and also to Iberians. They cluster apart from Middle-Eastern Mediterranean populations, and show greater genetic distances to Eastern and other Mediterranean populations. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations.


Desmoplastic infantile ganglioglioma: a report of 2 cases and a review of the literature.
Desmoplastic infantile gangliogliomas (DIG) are rare intracranial tumors that typically occur in infants and involve the cerebral cortex and the leptomeninges. They are usually very large in size and partially cystic. Total resection, if possible, is the treatment of choice, without the need for further adjuvant therapy. We report 2 cases of DIG. In both cases, computed tomography and magnetic resonance imaging revealed supratentorial mixed cystic and solid tumors, which presented as large cystic components with intense contrast enhancement of a mural nodule. The tumors were completely removed by surgery. The histological diagnosis was DIG. On follow-up examinations no tumor recurrence was noted.


Serial assessment of left ventricular function after myocardial infarction.
Left ventricular (LV) function is an important predictor of morbidity and mortality after myocardial infarction (MI). Changes in LV function have been examined during the early and late phases after MI, but serial measurements of LV function during the subacute period have not been performed. To assess sequential changes in LV function during the subacute period after MI, we used quantitative two-dimensional echocardiography to examine 22 patients over a 1-year period. Twenty-one of the 22 patients had a Q-wave MI. Eleven had an anterior MI and 10 had an inferior MI; their peak creatine phosphokinase (CPK) was 1213 mIU/ml +/- 14. Three weeks after acute MI, LV ejection fraction (LVEF) had increased from 45% to 52%. Seven of 19 patients showed an LVEF < 43% at baseline. In five of these patients, LVEF improved, but in two patients, LVEF was still < 43% in week 3. There was a significant enlargement of LV end-diastolic volume (LVEDV) (94 ml to 112 ml, p < 0.05) across the four observations but no change in LV end-systolic volume (LVESV; 54 ml to 56 ml, p = n.s.). When two groups (G1 [depressed], LVEF < or = 43%; G2 [preserved], LVEF > 43%) were compared, the group with depressed LVEF demonstrated a higher probability of improvement in LVEF (34% to 47%, p < 0.001) and stroke volume (38 ml to 65 ml, p < 0.01).


Diagnosis, staging and treatment of hepatocellular carcinoma.
Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.


Phase II study of sunitinib in men with advanced prostate cancer.
This study explored the efficacy and tolerability of sunitinib, an inhibitor of tyrosine kinase receptors, in men with castration-resistant prostate cancer (CRPC). Men with no prior chemotherapy (group A) and men with docetaxel (Taxotere)-resistant prostate cancer (group B) were treated with sunitinib. The primary end point was confirmed 50% prostate-specific antigen (PSA) decline. Secondary end points included objective response rate and safety. Serum-soluble biomarkers were measured. Seventeen men were enrolled in each group. One confirmed PSA response was observed in each group, and an additional eight men and seven men had stable PSA at week 12 in groups A and B, respectively. Improvements in imaging were observed in the absence of post-treatment PSA declines. Common adverse effects included fatigue, nausea, diarrhea, myelosuppression and transaminase elevation. Significant changes following sunitinib treatment were observed in serum-soluble biomarkers including soluble vascular endothelial growth factor receptor-2, platelet-derived growth factor aa, placental growth factor and leptin. Sunitinib monotherapy resulted in few confirmed 50% post-treatment declines in PSA in men with CRPC. Serum markers of angiogenesis confirmed on-target effects of sunitinib. Assessments of radiographic disease status were often discordant with changes in PSA, indicating that alternate end points are important in future trials.


The Bonebridge semi-implantable bone conduction hearing device: experience in an Asian patient.
For over three decades, bone conduction hearing aids have been changing the lives of patients with impaired hearing. The size, appearance and fitting discomfort of early generations of bone conduction hearing aids made them unpopular. The advent of bone-anchored hearing aids in the 1970s offered patients improved sound quality and fitting comfort, due to the application of osseointegration. However, the issue of post-operative peri-abutment pin tract wound infection persisted. The Bonebridge system incorporates the first active bone conduction device, and aims to resolve peri-abutment issues. Implantation of this system in an Asian patient is presented.


Giant pandas discriminate individual differences in conspecific scent.
The functions and mechanisms of chemical communication are well established for many species of small mammal amenable to investigation, but systematic research is virtually absent for large, rare species. The present study marks the first systematic investigation of chemical communication in the endangered giant panda, Ailuropoda melanoleuca. Using a habituation-discrimination paradigm, we sought to determine whether giant pandas can discriminate between scents from different individuals on the basis of chemical cues afforded by female urine and male anogenital gland secretions. Pandas habituated to successive presentations of scent stimuli from a single individual, as evidenced by diminished responsiveness across five habituation trials. In the discrimination test for male anogenital gland secretions, subjects of both sexes investigated a new individual's scent significantly more than a familiar scent to which they were previously habituated. Neither sex significantly discriminated novel from habituated female urine, although a strong tendency to differentiate the stimuli was evident. We also found that the sex of the subject affected patterns of response. Females showed a significant preference for male anogenital gland secretions, whereas males investigated both types of scent stimuli equally. In general, male subjects were more responsive than females to conspecific scent, especially female urine. This study provides clear evidence that giant pandas distinguish individual odours emanating from male anogenital secretions, and implies that these odours contain individually distinctive chemical signatures. These results have implications that can be applied to the conservation and management of this species. Copyright 1999 The Association for the Study of Animal Behaviour.


GLUT1, GLUT3 Expression and 18FDG-PET/CT in Human Malignant Melanoma: What Relationship Exists? New Insights and Perspectives.
Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8-3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone.


Hot spot formation in focused-ion-beam-fabricated YBa2Cu3O7-x nanobridges with high critical current densities.
We report on the fabrication and evaluation of nanoscale YBa2Cu3O7-x (YBCO) constrictions using focused-ion-beam techniques for potential application as YBCO bolometers. A gold protective layer was found to be critical for supressing contamination from gallium ions in order to obtain high critical current densities. Further processing using a radio-frequency plasma to remove the gold protective layer has also been studied and was found to be effective in minimizing sample damage resulting from overheating. Current-voltage measurement indicate that the nanobridges go through the transition from superconducting to normal state with different dissipation mechanism including flux creep and hot spot formation.


Veno-Venous Extracorporeal Membrane Oxygenation in COVID-19-Where Are We Now?
The recent development in extracorporeal life support (ECLS) has created new therapeutic opportunities for critically ill patients. An interest in extracorporeal membrane oxygenation (ECMO), the pinnacle of ECLS techniques, has recently increased, as for the last decade, we have observed improvements in the survival of patients suffering from severe acute respiratory distress syndrome (ARDS) while on ECMO. Although there is a paucity of conclusive data from clinical research regarding extracorporeal oxygenation in COVID-19 patients, the pathophysiology of the disease makes veno-venous ECMO a promising option.


Gold-catalyzed oxidative cyclization of 4-allenyl-1-ynes with 8-methylquinoline oxide.
Gold-catalyzed oxidative cyclizations of 4-allenyl-1-ynes with 8-methylquinoline oxide are described; diverse products are produced depending on the allenyl substituents. This reaction comprises initial formation of α-oxo gold carbenes that are attacked by allene to form allyl cation intermediates.


Renal function in the long term after pediatric liver transplantation: is there a need for protocol kidney biopsies?
With improving survival rates following solid organ transplantation, assessment of its success has broadened with a focus on long-term outcomes, including nongraft-related medical outcomes and family and patient perceptions of quality of life. Posttransplant renal dysfunction contributes to long-term morbidity and mortality following pediatric liver transplantation. In this review, we provide an overview of our understanding and approach to managing posttransplant renal dysfunction and highlight the existing gaps in knowledge in this area. The literature regarding renal dysfunction following liver transplant primarily focuses on the experience in the adult population. Studies on children are limited by small numbers and varying definitions of outcomes. Thus, lessons in the current literature must be closely examined before they can be extrapolated and applied to children. The current literature validates that posttransplant renal dysfunction is a frequent and important outcome for adults and children. Although the characteristics of children at high risk are less clear, calcineurin inhibitor minimization is considered a viable strategy for preserving renal function. The risk-benefit ratio of kidney biopsy in children and the possibility of renal preservation via immunosuppression withdrawal are intriguing concepts that remain to be defined.


Comment on "The silicate-mediated formose reaction: bottom-up synthesis of sugar silicates".
Lambert et al. (Reports, 19 February 2010, p. 984) reported that silicate ions catalyze the formation and stabilization of four- and six-carbon sugars from simple sugars, suggesting a possible prebiotic pathway for the synthesis of biologically important sugars. Here, we show that silicate has minimal impact in these respects, especially when compared to borate minerals.


Long-term age-dependent behavioral changes following a single episode of fetal N-methyl-D-Aspartate (NMDA) receptor blockade.
Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine during the perinatal period can produce a variety of behavioral and neuroanatomical changes. Our laboratory has reported reliable changes in learning and memory following a single dose of ketamine administered late in gestation. However, the nature of the drug-induced changes depends on the point during embryonic development when ketamine is administered. Embryonic day 18 (E18) rat fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal circulation) and taught a conditioned taste aversion (CTA) learn and remember the CTA, whereas E19 fetuses do not. The current study sought to determine if long-term behavioral effects could be detected in animals that received ketamine or a saline control injection on either E18 or E19. Rat behavior was evaluated on two different measures: spontaneous locomotion and water maze learning. Measurements were collected during 2 periods: Juvenile test period [pre-pubertal locomotor test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult test period [post-pubertal locomotor test: P60; post-pubertal water maze test: P81]. Water maze performance of ketamine-treated rats was similar to that of controls when tested on P18. Likewise, the age of the animal at the time of ketamine/saline treatment did not influence learning of the maze. However, the young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine exposure - especially during the initial re-training trial. On the first trial of the young adult test, rats treated with ketamine on E18 reached the hidden platform faster than any other group - including rats treated with ketamine on E19. Swim speeds of experimental and control rats were not significantly different. Spontaneous horizontal locomotion measured during juvenile testing indicated that ketamine-treated rats were less active than controls. However, later in development, rats treated with ketamine on E18 were more active than rats that received the drug on E19. These data suggest that both the day in fetal development when ketamine is administered and the timing of post-natal behavioral testing interact to influence behavioral outcomes. The data also indicate that the paradoxical age-dependent effects of early ketamine treatment on learning, previously described in fetuses and neonates, may also be detected later in young adult rats.


Comparative profiling of genes and miRNAs expressed in the newborn, young adult, and aged human epididymides.
To understand roles of transcriptional factors and miRNAs in regulating gene expression in the epididymis from postnatal development through aging, systematic profiling of genes and miRNAs expressed in the newborn, young adult, and aged human epididymides was performed by cDNA array and miRNA array analysis, respectively. The newborn human epididymis expressed the fewest mRNAs but the largest number of miRNAs, whereas the adult and aged epididymides expressed the most mRNAs but the fewest miRNAs, a negative correlation between mRNAs and miRNA during aging. By integrative analysis, a set of miRNA targets were predicted based on the miRNA and cDNA arrays. In the newborn epididymis, 127 miRNAs were exclusively or preferentially expressed but only 3 and 2 miRNAs showed an age-enriched expression pattern in the adult and aged epididymides, respectively. This study provides a basic database as well as new insights and foundations for further studies on the complex regulation of gene expression in the epididymis.


Clinical and Functional Outcomes of Gastrocnemius Recession for Chronic Achilles Tendinopathy.
Although gastrocnemius recession has been proposed and used in the treatment of chronic noninsertional Achilles tendinopathy, only weak evidence exists to support this operative indication. The purpose of our study was to assess the clinical and functional outcomes of patients treated with gastrocnemius recession at 2 institutions for this problem. Thirty-four patients were identified through our medical records and asked to participate in this study. Thirty patients (35 legs) responded to the invitation. Sixteen patients were eligible for clinical follow-up, and 14 patients responded by letter or telephone interview. Two patients did not want to participate, and 2 patients could not be reached. Data were collected by a satisfaction questionnaire, the Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire, a visual analog scale (VAS) for pain, a functional test battery, and a clinical examination. A subgroup with preoperative data (n = 8) showed an increase in the mean VISA-A score from 39.5 to 91.9. The mean overall VISA-A score (n = 30) was 91.4 at follow-up. The mean VAS for pain score when walking decreased from 7.5 before surgery to 0.8 after surgery. Twenty-eight of 30 patients reported that they were satisfied with their results after surgery. Functional testing showed no difference in gastrocnemius-soleus function between the operated and nonoperated leg (n = 10). The findings support the promising results from other studies regarding gastrocnemius recession as an effective and safe way of treating chronic Achilles tendinopathy. The patients recovered both in terms of pain and function. Level IV, retrospective case series.


Palliative care in Japan: a review focusing on care delivery system.
Providing palliative care in Japan is one of the most important health issues. Understanding palliative care delivery systems of other countries is useful when developing and modifying palliative care systems worldwide. This review summarizes the current status of palliative care in Japan, focusing on the structure and process development. Palliative care units and hospital palliative care consultation teams are the two main specialized palliative care services in Japan. The number of palliative care units is 215 (involved in 8.4% of all cancer deaths), and there are approximately 500 hospital palliative care teams. Conversely, specialized home care services are one of the most undeveloped areas in Japan. However, the government has been trying to develop more efficient home care services through modifying laws, healthcare systems, and multiple educational and cooperative projects. The numbers of palliative care specialists are increasing across all disciplines: cancer pain nurses (1365), palliative care nurses (1100), palliative care physicians (646), and palliative care pharmacists (238). Postgraduate education for physicians is performed via the special nationwide efforts of the Palliative care Emphasis program on symptom management and Assessment for Continuous medical Education (PEACE) project - a 2-day program adopting a trainer-trainee strategy. Over 30,000 physicians have participated in the PEACE program. A total of 1298 and 544 physicians have completed a trainer course for palliative medicine and psycho-oncology, respectively. Multiple structure and process evaluation, bereaved family surveys in palliative care units, and patient and family evaluation in the regional palliative care program indicate many improvements. Palliative care in Japan has progressed rapidly, and the Cancer Control Act has played a very important role in developing palliative medicine. Challenges include developing a structure for palliative care in the community or regional palliative care programs, establishing a method to measure and improve the quality of palliative care at a national level, developing evidence-based medicine and policy making, and palliative care for the noncancerous population.


Online monitoring of chemical reactions by polarization-induced electrospray ionization.
Polarization-induced electrospray ionization (PI-ESI) is a simple technique for instant generation of gas-phase ions directly from a microliter-sized droplet for mass spectrometric analysis. A sample droplet was placed over a dielectric substrate and in proximity (2-3 mm) to the inlet of a mass spectrometer. Owing to the polarization effect induced by the high electric field provided by the mass spectrometer, the droplet was polarized and the electrospray was generated from the apex of the droplet. The polarization-induced electrospray could last for tens of seconds, which was sufficiently long to monitor fast reactions occurring within few seconds. Thus, we demonstrated the feasibility of using the droplet-based PI-ESI MS for the online monitoring of fast reactions by simply mixing two droplets (5-10 μL) containing reactants on a dielectric substrate placed in front of a mass spectrometer applied with a high voltage (-4500 V). Schiff base reactions and oxidation reactions that can generate intermediates/products within a few seconds were selected as the model reactions. The ionic reaction species generated from intermediates and products can be simultaneously monitored by PI-ESI MS in real time. We also used this approach to selectively detect acetone from a urine sample, in which acetone was derivatized in situ. In addition, the possibility of using this approach for quantitative analysis of acetone from urine samples was examined.


A Comparison of the Separate and Concurrent Calibration Methods for the Full-Information Bifactor model.
When calibrating items using multidimensional item response theory (MIRT) models, item response theory (IRT) calibration programs typically set the probability density of latent variables to a multivariate standard normal distribution to handle three types of indeterminacies: (a) the location of the origin, (b) the unit of measurement along each coordinate axis, and (c) the orientation of the coordinate axes. However, by doing so, item parameter estimates obtained from two independent calibration runs on nonequivalent groups are on two different coordinate systems. To handle this issue and place all the item parameter estimates on a common coordinate system, a process called linking is necessary. Although various linking methods have been introduced and studied for the full MIRT model, little research has been conducted on linking methods for the bifactor model. Thus, the purpose of this study was to provide detailed descriptions of two separate calibration methods and the concurrent calibration method for the bifactor model and to compare the three linking methods through simulation. In general, the concurrent calibration method provided more accurate linking results than the two separate calibration methods, demonstrating better recovery of the item parameters, item characteristic surfaces, and expected score distribution.


Stimulation of human periodontal ligament fibroblast collagenase production by a gingival epithelial cell-derived factor.
To examine whether cell-to-cell interactions between human gingival epithelial cells (HGE) and periodontal ligament fibroblasts (PLF) or gingival fibroblasts (GF) take place in the periodontium, the effects on collagenase production by PLF and GF were analyzed after adding several concentrations of HGE-conditioned medium (HGE-CM) to PLF or GF culture. Collagenase production by both cell populations was stimulated by adding HGE-CM, which stimulated collagenase production by PLF to a greater extent than that by GF. The HGE-derived stimulatory factor had a molecular mass of approximately 20 kDa, and its stimulant effect was inhibited markedly in the presence of an anti-human interleukin-1 alpha (IL-1 alpha) neutralizing antibody, indicating that the factor was identical to, or antigenically cross-reactive with, IL-1 alpha. These results suggest that epithelial apical migration in the periodontium may occur after interstitial resident cells have released tissue-degrading enzymes, such as collagenase, and damaged the extracellular matrix, once a sufficient amount of IL-1 alpha-like factor for stimulating the production of proteolytic enzyme has been released by HGE in periodontal lesions.


Stroke risk factor knowledge in university students.
Cerebrovascular disease is the third leading cause of mortality in this country and is a leading cause of disability. To develop successful prevention programs to decrease the incidence of stroke, individuals should adopt cerebrovascular-healthy behaviors during youth, rather than in middle or old age, when risks for stroke are highest. The authors assessed the knowledge of stroke risk factors in university students presenting to a student health neurology clinic over a 14-month period. Half of the 98 students surveyed thought stress, a very weak risk factor, was a causative factor in the development of stroke. Only one third named hypertension or smoking as a risk factor. No significant gender, ethnic, or age differences were observed in student identification of stroke risk factors. These data indicate that university students have an incomplete understanding of the characteristics that are risk factors for stroke. This knowledge deficit is likely to have a negative influence on students' health behaviors.


Characterization of fecal vancomycin-resistant enterococci with acquired and intrinsic resistance mechanisms in wild animals, Spain.
The objectives were to evaluate the presence of vancomycin-resistant enterococci with acquired (VRE-a) and intrinsic (VRE-i) resistance mechanisms in fecal samples from different wild animals, and analyze their phenotypes and genotypes of antimicrobial resistance. A total of 348 cloacal/rectal samples from red-legged partridges (127), white storks (81), red kites (59), and wild boars (81) (June 2014/February 2015) were inoculated in Slanetz-Bartley agar supplemented with vancomycin (4 μg/mL). We investigated the susceptibility to 12 antimicrobials and the presence of 19 antimicrobial resistance and five virulence genes. In addition, we performed multilocus sequence typing, detection of IS16 and studied Tn1546 structure. One VRE-a isolate was identified in one wild boar. This isolate was identified as Enterococcus faecium, harbored vanA gene included into Tn1546 (truncated with IS1542/IS1216), and belonged to the new ST993. This isolate contained the erm(A), erm(B), tet(M), dfrG, and dfrK genes. Neither element IS16 nor the studied virulence genes were detected. Ninety-six VRE-i isolates were identified (89 Enterococcus gallinarum and seven Enterococcus casseliflavus), with the following prevalence: red kites (71.2 %), white storks (46.9 %), red-legged partridges (7.9 %), and wild boars (4.9 %). Most E. gallinarum isolates showed resistance to tetracycline (66.3 %) and/or erythromycin (46.1 %). High-level resistance to aminoglycosides was present among our VRE-i isolates: kanamycin (22.9 %), streptomycin (11.5 %), and gentamicin (9.4 %). In general, VRE-i isolates of red kites showed higher rates of resistance for non-glycopeptide agents than those of other animal species. The dissemination of acquired resistance mechanisms in natural environments could have implications in the global spread of resistance with public health implications.


[Cytomegalovirus rhombencephalomyelitis in an immunocompetent subject].
We report the clinical and MRI findings of a 31-year-old healthy immuno-competent patient who presented following 48 hours of diffuse headache with progressive and severe rhombencephalomyelitis signs. Cerebral and medullar MRI confirmed the central nervous system improvement. Serology showed relation with cytomegalovirus infection. Spontaneous improvement was observed and favoured by ganciclovir administration.


Abdominal symptoms as initial manifestation of COVID-19: a case series.
The COVID-19 became a pandemic in early 2020. It was found, at first, that the main manifestations of this new virus occur through respiratory and constitutional symptoms. Therefore, chest tomography was elected as the best imaging test to assess the extent of pulmonary involvement and as a good prognostic predictor for the disease. However, as new studies were produced, the gastrointestinal involvement of COVID-19 becomes more evident, with reports from patients who manifested mainly or only gastrointestinal symptoms in the course of the disease. Thus, in some cases, the initial investigation is carried out at the emergency department with an abdominal computed tomography. We report a case series of ten patients who came to the emergency department of our institution with a chief gastrointestinal complaint, and were initially submitted to an abdominal computed tomography as the first investigation. Although most of the patients did not have significant changes in the abdominal images, most reported patients had pulmonary findings visualized at the lung bases, which were later designated as typical COVID-19 pulmonary findings on chest computed tomography. Only one patient had atypical COVID-19 lung changes on chest computed tomography. All patients had a positive real-time polymerase chain reaction for COVID-19. It is imperative to alert radiologists, especially abdominal radiologists, with the possibility of COVID-19 isolated gastrointestinal symptoms. Besides, it must become a habit to radiologists to assess the pulmonary basis on abdominal scans, a site commonly affected by the new coronavirus.


DNA curvature and phosphate neutralization: an important aspect of specific protein binding.
A theoretical study is presented of the influence of salt bridges between protein cationic side chains and DNA phosphates on DNA conformation and flexibility. Two DNA sequences are studied containing respectively the HNF3 and CAP binding sites. The effect of salt bridges is modelled by the neutralisation of net phosphate charges for the groups involved in such interactions in the complex. Energy optimised conformations are obtained by molecular mechanics calculations using the JUMNA program. Base sequence dependence is studied by moving the phosphate neutralisation pattern along the sequence, while normal mode analysis is used to evaluate DNA flexibility. The results show that phosphate neutralisation has a strong influence on DNA conformation. For the HNF3 binding sequence, the free oligomer is bent in direction very different from that observed in the protein complex. Phosphate neutralisation changes this direction by 45 degrees to within only 4 degrees of the direction in the complex, without changing the bending angle. For the CAP binding sequence, the free oligomer is already intrinsically curved in the direction favoured by the protein, but phosphate neutralisation increases the bending angle. For both oligomers studied these effects are strongly sequence dependent. It is also shown that oligomer flexibility cannot be explained by a simple superposition of the properties of successive dinucleotide steps. Important long range coupling effects are observed. However, for both sequence studied, phosphate neutralisation however leads to a reduction in oligomer flexibility.