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PubMed2006

What can we learn about ecology and evolution from the fossil record?

The increased application of abundance data embedded within a more detailed and precise environmental context is enabling paleontologists to explore more rigorously the dynamics and underlying processes of ecological and evolutionary change in deep time. Several recent findings are of special theoretical interest. Community membership is commonly more stable and persistent than expected by chance, even in the face of the extreme environmental changes of the Ice Ages, and major evolutionary novelties commonly lie dormant for tens of millions of years before the ecological explosions of the clades that possess them. As we discuss here, questions such as these cannot be adequately addressed without the use of the fossil record.

Animals↗
PubMed1999

Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients.

There is a renewal of interest in surgical approaches including lesions and deep brain stimulation directed at motor subcorticofrontal loops. Bilateral lesioning presents a far greater risk of adverse effects, especially cognitive impairment. Furthermore, the main advantages of the stimulation procedure over lesioning are adaptability and reversibility of effects. The aim of this study was to assess the influence of bilateral stimulation of the subthalamic nucleus or internal globus pallidus on memory and executive functions in Parkinson's disease. Sixty-two patients were assessed before and after 3 to 6 months of chronic bilateral stimulation of the subthalamic nucleus (n = 49) or internal globus pallidus (n = 13). The neuropsychological tests used were the Mattis Dementia Rating Scale, the Grober and Buschke Verbal Learning Test, the Wisconsin Card Sorting Test, category and literal fluency, graphic and motor series, the Stroop Test, and the Trail Making Test. Mood was evaluated by the Beck Depression Inventory. Only 4 of 25 cognitive variables were affected by deep brain stimulation. Under stimulation, performance improved for Parts A and B of the Trail Making Test, but there was a deterioration in literal and total lexical fluency. There was also a mild but significant improvement in mood. It may therefore be concluded that stimulation of the subthalamic nucleus or internal globus pallidus does not change the overall cognitive performance in Parkinson's disease and does not greatly affect the functioning of subcorticofrontal loops involved in cognition in humans. This relative absence of cognitive impairment in bilateral deep brain stimulation is likely because of the accurate positioning of the electrodes, allowing the effects of stimulation to be confined to sensorimotor circuits.

Electric Stimulation↗
PubMed2006

Training of A3-A3 side-to-side anastomosis in a deep corridor using a box with 6.5-cm depth: technical note.

BACKGROUND: Cerebral revascularization in the deep surgical field is technically challenging. Especially, side-to-side anastomosis like A3-A3 could be technically more difficult compared with end-to-side anastomosis. To improve surgeon's dexterity and maneuverability in the deep surgical field, the authors developed an easily accessible and well-simulating training system using prosthetic tubes and a box. METHODS: Two prosthetic tubes (silicon tube, 1.2 mm in diameter) are mounted in parallel on the bottom of 6.5-cm-deep emptied 'tissue paper box.' The orifice of the box is restricted to 2 x 2 cm to simulate a deep and narrow surgical corridor. Using bayonet-shaped micro needle holder and forceps, the side-to-side anastomosis of the tubes is performed with 10-0 nylon under operative microscope. RESULTS: Prosthetic tubes well simulated real A3-A3 anastomosis. From the standpoint of technical difficulty, this training system needed slightly higher level of dexterity compared with real A3-A3 anastomosis because of narrower and deeper surgical corridor, and the wall of prosthetic tube was slightly thicker and more inflexible. After this training, the surgical technique in real A3-A3 anastomosis was improved. CONCLUSIONS: This training system worked well to ease the transition from anastomosis in shallow surgical field to deep and narrow surgical field. The prosthetic tube we used approximates real A3 relatively well, and the ease in setting up this system enabled repeated practice, which resulted in steep learning curve of the technique.

Aged↗
PubMed1998

The progress of the Polio Eradication Initiative: what prospects for eradicating measles?

Although various attempts have been made to eradicate infectious diseases, only smallpox has been eradicated to date. Polio is targeted for eradication in 2000 and already planning has begun for the eradication of measles. However, before we commit to a measles eradication effort, we must examine the lessons to be learned from polio eradication. Of particular importance is the debate over whether resources should be invested in 'horizontal' or 'vertical' programmes. The outcome of these debates will have a very deep and lasting impact on global health development in years to come. Collaboration between targeted programmes and the primary health care sector through polio and measles eradication efforts will help bring about the necessary balance between goal-oriented programmes, which are subject to quality control and can be evaluated by measurable outcomes, and broader efforts to build up sustainable health infrastructure.

Communicable Disease Control↗
PubMed1996

Localization of ATP-gated ion channels in cerebellum using P2x2R subunit-specific antisera.

The distribution of the P2x2 purinoceptor subunit protein, which forms ATP-gated ion channels by homo- and hetero-multimeric assembly, was examined in the adult rat and guinea-pig cerebellum using two novel antisera generated against separate 18 amino acid sequences located in the predicted extracellular domain of this subunit. These antisera, the first available for labelling the P2x2R subunit protein, were validated by selective labelling of a fusion protein containing the target amino acid sequences, and in cerebellum, by peptide specific block of immunoreactivity and by comparison with the distribution of P2x2R mRNA. P2x2R-like immunoreactivity was seen in Purkinje cells, specifically the soma and dendrites, neurons in the granular and molecular layers and deep cerebellar nuclei. The identification of P2x2R-like immunoreactivity within the cerebellar neural circuitry is consistent with a role for extracellular ATP acting as a fast neurotransmitter in motor learning and coordination of movement. Additionally, labelling of neuroglia and fibre tracts supports a diverse role for extracellular ATP in CNS homeostasis.

Adenosine Triphosphate↗
PubMed2004

Entropy and information in neural spike trains: progress on the sampling problem.

The major problem in information theoretic analysis of neural responses and other biological data is the reliable estimation of entropy-like quantities from small samples. We apply a recently introduced Bayesian entropy estimator to synthetic data inspired by experiments, and to real experimental spike trains. The estimator performs admirably even very deep in the undersampled regime, where other techniques fail. This opens new possibilities for the information theoretic analysis of experiments, and may be of general interest as an example of learning from limited data.

Journal Article↗
PubMed2006

Fifteen years ago laser was supposed to open arteries, now it is supposed to close veins: what is the reality behind the tool?

Laser first emerged as a technology for use in the vascular arena nearly 20 years ago. The ability of laser to evaporate atherosclerotic plaque was extensively studied; however, the goal of creation of an adequate channel without arterial wall perforation proved to be elusive, and the technique fell into disfavor. More than a decade later, interest in lasers was sparked again with its application to endovenous thermal ablation of axial superficial venous reflux. The mechanism of action of endovenous laser therapy involves thermal damage of the vein wall, resulting in destruction of the intima and collagen denaturation of the media with eventual fibrotic occlusion of the vein. Apart from the obvious attraction of a minimally invasive procedure to ablate superficial venous reflux with its attendant benefits, another advantage of laser ablation includes a potentially decreased incidence of neovascularization in the groin secondary to preservation of superficial venous drainage of the abdominal wall. Early success in terms of ablation of the refluxing saphenous vein has been reported as 90% to 95%. Minor complications are reported in 3% to 10% of patients and include bruising around the puncture site, transient paresthesias, superficial phlebitis, and skin burns or pigmentation. The more serious complications of deep venous thrombosis or extension of thrombus into the femoral vein have been variously reported in 0% to 2.3% of limbs treated. Pulmonary embolism is extremely rare. There is a learning curve, with a decrease in the incidence of all complications with experience. The importance of detailed preoperative and intraoperative duplex ultrasound examination cannot be overemphasized. The identification of all refluxing venous segments and their ablation is the key to optimizing the rate of successful ablation to 97% at 1 year and minimizing recurrence of varicose veins. With encouraging early and mid-term results with endovenous laser therapy, future developments in this field must mandate standardization of technical aspects, follow-up imaging, and reporting.

Humans↗
PubMed1979

Actions not words.

The deep-rooted respect of the value of each individual in Sweden is shown in its community-based care of the mentally handicapped. Author looks at the lessons Britain can learn in this field.

Education of Persons with Intellectual Disabilitie↗
PubMed2004

Hypercapnia: what is the limit in paediatric patients? A case of near-fatal asthma successfully treated by multipharmacological approach.

We describe a case of prolonged severe hypercapnia with respiratory acidosis occurring during an episode of near-fatal asthma in an 8-year-old boy, followed by complete recovery. After admission to the intensive care unit, despite treatment with maximal conventional bronchodilatative therapy, the clinical picture deteriorated with evident signs of respiratory muscle fatigue. The child was sedated, intubated and mechanically ventilated. Magnesium sulphate, ketamine and sevoflurane were gradually introduced together with deep sedation, curarization and continuous bronchodilatative therapy. Ten hours after admission, arterial pCO2 reached 39 kPa (293 mmHg), pH was 6.77 and pO2 8.6 kPa (65 mmHg). Chest radiograph showed severe neck subcutaneous emphysema, with signs of mediastinal emphysema. No episode of haemodynamic instability was seen despite severe prolonged hypercapnia lasting more than 14 h. Oxygenation was maintained and successful recovery followed without neurological or cardiovascular sequelae. This case shows the cardiovascular and neurological tolerance of a prolonged period of supercarbia in a paediatric patient. The most important lesson to be learned is the extreme importance of maintaining adequate tissue perfusion and oxygenation during an asthma attack. The second lesson is that when conventional bronchodilators fail, the intensivist may resort to the use of drugs such as ketamine, magnesium sulphate and inhalation anaesthesia. In this context deep sedation and curarization are important not only to improve oxygenation, but also to reduce cerebral metabolic requirements.

Acidosis, Respiratory↗
PubMed2005

Firing activities of identified posterior interpositus nucleus neurons during associative learning in behaving cats.

On the basis of stimulation and permanent or transient lesions of putatively involved structures, and using transgenic mice with defective functional circuits, it has been proposed that cerebellar cortex and/or nuclei could be the sites where classically conditioned nictitating membrane/eyelid responses are acquired and stored. Here, we review recent information regarding the electrical activities of deep cerebellar nuclei neurons recorded during the performance of reflex and acquired eyeblinks. In particular, the rostral pole of the dorsolateral region of the posterior interpositus nucleus contains neurons significantly related to reflexively evoked and classically conditioned eyelid responses. Thus, type A interpositus neurons increase their discharge rate during eyelid movements, modulating it depending upon eyelid motorics. In contrast, type B neurons decrease their firing, even to a stop, during the same eyelid responses. However, as these changes in firing start after the onset of eyelid conditioned responses (CRs), and because they do not seem to encode eyelid position and velocity during the CR, the interpositus nucleus cannot be conclusively considered the site where eyelid learned responses are generated and stored. Additional microstimulation and pharmacological blockage of the recorded sites support the suggestion that posterior interpositus neurons contribute to the enhancement of CRs. Moreover, interpositus neurons probably contribute to the proper damping of newly acquired eyelid responses. The contributing role of other neuronal centers and circuits related to the eyelid motor system are also discussed.

Action Potentials↗
PubMedDate not supplied

Safety of modern oral contraception: the options for women: lessons to be learned.

The relatively short history of hormonal contraception has been marked by a series of 'pill scares', all of which--after creating panic among users--were proven to be unfounded in terms of public health impact. The latest pill scare, provoked by regulatory action in the United Kingdom and the Federal Republic of Germany in response to the publication of a series of articles indicating a doubling of risk of deep venous thrombosis in users of oral contraceptives containing third-generation progestins, seems finally settled: both the British and the German Drug Regulatory Authorities have now reverted their verdict. The damage unfortunately stays: hundreds of thousands of women have been compelled to abandon the pill of their choice, often deciding to drop contraception altogether, thereby exposing themselves to unwanted pregnancy and--in a number of cases--to pregnancy termination. This latest episode should be turned into something positive: we need to learn that, in the case of drugs in widespread use, before restrictive action is taken--and except for very rare and specific instances--the scientific community must carry out an exhaustive debate on the reality and importance of the observed effects. Although the public should, in each instance, be properly informed, it is only after this process has been completed that restrictive action should be taken. It is hoped that, after this last episode, all concerned have learned this simple principle and will accept being guided by it from now on.

Contraceptives, Oral↗
PubMed1983

A proposed neuropathological basis for learning disabilities in children born prematurely.

This study aimed at providing understanding of the etiology and mechanisms responsible for the learning and behavioral disabilities in the increasing numbers of survivors of neonatal intensive care units who develop MBD/LD-type (minimal brain dysfunction, learning disabilities) complications. The brains of 16 premature infants who died within the first month of life were studied by microscopic examination. Significant neuropathological findings in gray-matter and white-matter were found in many areas, including both superficial cortical and deep basal brain structures. These lesions are postulated to be precursors to later LD and MBD syndromes in infants who survive, such that similar lesions of varying severity correlate with varying degrees of brain dysfunction. Premature infants who survive are known from other studies to be high-risk candidates for LD- and MBD- type developmental disabilities.

Brain↗
PubMed2026

Fine-grained structural classification of biosynthetic gene cluster-encoded products.

MOTIVATION: Biosynthetic gene clusters (BGCs) are responsible the biosynthesis of many natural products, including a multitude of effective therapeutics and their precursors. Advances in genomic data collection as well as computational techniques have made it possible to identify BGCs at scale. However, accurately determining the types of BGC-encoded products from genomic content remains elusive. RESULTS: Here, we introduce BGC annotation tool (BGCat), a machine learning method for fine-grained structural classification of BGC-encoded products, leveraging the NPClassifier natural product nomenclature. Our method leverages a pre-trained protein language model for creating meaningful gene representations and a deep neural network for class label prediction. We show the method outperforms state-of-the-art approaches in coarse-grained product classification and is effective for detailed classification. We implement a clustering-based augmentation strategy for BGC-product relationships, addressing a crucial gap in the available datasets. We then introduce the concept of product class profiles of gene cluster families (GCFs), associating each GCF with a probabilistic distribution of product types and offering a new perspective on GCF functions. Lastly, we use BGCat to provide new product class labels for over 100k BGCs in antiSMASH DB that presently have minimal information about their products. AVAILABILITY AND IMPLEMENTATION: The source code and trained model weights are freely available at https://github.com/HassounLab/BGCat.

Multigene Family↗
PubMed2003

[The antagonistic action of Gastrodia elata combined with E-gelatin on lead-induced down regulation of c-fos expression in rat brain].

OBJECTIVE: To observe the effect of lead on the expression of c-fos mRNA in hippocampus and cerebellum and the ability of learning and memory in rat, and to observe the antagonistic action of Gastrodia elata and E-gelatin on the effect mentioned above. METHODS: Rats were exposed to lead acetate (0.2 g x kg(-1) x d(-1) and 0.1 g x kg(-1) x d(-1)). The single and combined administration of Gastrodia elata (4 g x kg(-1) x d(-1)) and E-gelatin (1 g x kg(-1) x d(-1)) were conducted at the same time. Blood lead concentration in rats were measured. The ability of learning and memory by Y-maze test were examined. The expression of c-fos mRNA in hippocampus and cerebellum during Y-maze test were observed by in situ hybridization (ISH). RESULTS: (1) Blood lead concentrations were significantly increased in both high and low doses of lead-exposed rats (P < 0.01). But there were no differences among high dose groups or low dose groups (P > 0.05). (2) In Y-maze test, the number of electric stroke during learning in lead-exposed group was significantly increased (P < 0.01) while that in Gastrodia elata and E-gelatin groups was significantly decreased (P < 0.05), and that in combined use group was more significantly decreased (P < 0.01). (3) There were much more deep-colored c-fos positive cells in CA3 area of hippocampus in low dose of Pb-exposed with Gastrodia elata + E-gelatin group. These cells were also found in high Pb with combined use or single use group, but which were not so densely distributed as the former. And they were hardly found in high and low doses of Pb alone groups. The changes of expression of c-fos cells in cerebellam were similar to those in hippocampus. CONCLUSION: The down regulation of c-fos expression may be one of the molecular mechanism of lead-induced impairment of learning and memory. Gastrodia elata and E-gelatin may antagonize the effect of lead on c-fos expression, and combined use of both drugs may potentiate the antagonism.

Animals↗
PubMed1999

Occupational physicians' education and training across European Union countries.

The framework directive on improvements in the safety and health of workers is being implemented into the national legislation of European Union countries, and occupational physicians are requested to play a key role in undertaking preventive measures. Since there is no common specific requirement for the training and education of these health professionals, this report aims to provide a comparative picture of the educational process across European Union training bodies. Each curriculum provides theoretical knowledge and practical experience, but deep differences exist among different countries. Core knowledge is mainly based on the traditional disciplines (such as occupational hygiene, occupational toxicology, ergonomics, epidemiology and biostatistics, relevant legislation, and preventive medicine). General learning objectives should include assessment of the workplace environment, communication and education, legislation, occupational diseases, and relationships between health and work. Core experience, often based on task-based learning, emphasizes the need for assessment of a range of working environments; for surveillance, including the biological monitoring, of workers at risk; for assessment of disability, impairment, and fitness for work; for the clinical ability to recognize occupational diseases; for the formulation of differential diagnosis; and for management of workers developing disease in the course of their employment. New curricular elements (such as management, economics, quality assurance, and marketing) are being introduced in some institutions with the aim of stressing the renewed role of the occupational physician in meeting society and employers' needs. The need to educate and train a professional figure whose competence should allow the delivery of high-quality occupational health services across European Union countries compels the harmonization of the formative process of occupational physicians.

Curriculum↗
PubMed2001

Clinical and magnetic resonance imaging regression of progressive multifocal leukoencephalopathy in an AIDS patient after intensive antiretroviral therapy.

A 36-year-old homosexual man with 6 months of visual symptoms and headaches had right homonymous hemianopia, mild new learning impairment, and alexia with agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported consistent with left occipital infarction. Subsequent MRI demonstrated abnormal demyelination in subcortical white matter and deep parieto-occipital white matter bilaterally, but primarily left. Human immunodeficiency virus testing and cerebrospinal fluid polymerase chain reaction for JC virus DNA were both positive, consistent with progressive multifocal leukoencephalopathy (PML) with AIDS. His clinical status steadily deteriorated, and MRI white matter abnormalities worsened despite high-dose antiretroviral therapy. After the antiretroviral regimen was intensified by the addition of a protease inhibitor, rapid clinical and radiographic improvement occurred with subsequent MRI studies revealing only residual left parieto-occipital encephalomalacia. PML in AIDS patients has been associated with a nearly uniformly poor prognosis until recent reports of improved outcomes after highly active antiretroviral therapy. This patient with PML and AIDS similarly showed a robust clinical and MRI response to intensive antiretroviral combination therapy, which has been maintained for more than 3 years.

AIDS-Related Opportunistic Infections↗
PubMed2004

Using a reflective diary to develop bracketing skills during a phenomenological investigation.

In this article, I have attempted to show how a reflective diary can be an effective tool for developing bracketing skills. A framework is necessary to guide reflective thought and encourage deep and critical thinking. My framework was influenced by the work of Schön (1987) and Johns (1984), and related to the concepts of reflecting 'on' and 'in' action, and identified specific learning that had taken place. Bracketing is an important part of the Husserlian approach to descriptive phenomenology. It is a continuous process that can be used in a number of ways. Within my study I used bracketing 'pre', 'in', and 'on' actions. In addition to using bracketing to facilitate the clear emergence of the phenomenon under investigation, it can also be used to help review the methodology of a study. Examples have been given within the article to highlight different situations where bracketing took place.

Attitude of Health Personnel↗