Pacemakers in aggregation fields of Dictyostelium discoideum: does a single cell suffice?

In this paper we address the following question: can a single cell of the cellular slime mold Dictyostelium discoideum serve as a pacemaker for the aggregation phase? Whether or not this is possible is determined by the relative importance of cyclic AMP production due to self-stimulation as compared to diffusion of cyclic AMP away from the cell and extracellular degradation. We determine the conditions under which a single cell on an infinite place can emit periodic signals of cyclic AMP using a model developed previously for signal relay and adaptation in Dictyostelium. Elsewhere it has been shown that this model provides an accurate representation of the stimulus-response behavior of Dictyostelium for a variety of experimental conditions.     

Pain and suffering in invertebrates?

All animals face hazards that cause tissue damage and most have nociceptive reflex responses that protect them from such damage. However, some taxa have also evolved the capacity for pain experience, presumably to enhance long-term protection through behavior modification based on memory of the unpleasant nature of pain. In this article I review various criteria that might distinguish nociception from pain. Because nociceptors are so taxonomically widespread, simply demonstrating their presence is not sufficient. Furthermore, investigation of the central nervous system provides limited clues about the potential to experience pain. Opioids and other analgesics might indicate a central modulation of responses but often peripheral effects could explain the analgesia; thus reduction of responses by analgesics and opioids does not allow clear discrimination between nociception and pain. Physiological changes in response to noxious stimuli or the threat of a noxious stimulus might prove useful but, to date, application to invertebrates is limited. Behavior of the organism provides the greatest insights. Rapid avoidance learning and prolonged memory indicate central processing rather than simple reflex and are consistent with the experience of pain. Complex, prolonged grooming or rubbing may demonstrate an awareness of the specific site of stimulus application. Tradeoffs with other motivational systems indicate central processing, and an ability to use complex information suggests sufficient cognitive ability for the animal to have a fitness benefit from a pain experience. Available data are consistent with the idea of pain in some invertebrates and go beyond the idea of just nociception but are not definitive. In the absence of conclusive data, more humane care for invertebrates is suggested.     

Schistosomiasis in Brazil: Does social development suffice?

Up to 15 years ago, when asked to identify the major public health problems of Brazil, there would be no hesitation in naming infant diarrhoea, Chagas disease and Schistosoma mansoni. While most field workers have now eliminated schistosomiasis from the list, now certainly headed by malaria, in academic and bureaucratic circles the old priorities are still maintained.     

Artificial womb technology and clinical translation: Innovative treatment or medical research?

In 2017 and 2019, two research teams claimed ‘proof of principle’ for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research–treatment distinction, pervasive in regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a ‘beneficial treatment’. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico-legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed.     

Quackery versus professionalism? Characters,places and media of medical knowledge in eighteenth-century Hungary

This essay discusses the question of health in the Kingdom of Hungary during the Age of Enlightenment. It explores the relationships and tensions between central theories of medical police and the local expectations of government administrators, as well as those between academic or official knowledge and implicit or alternative knowledge about health. The reigns of Maria Theresia and Joseph II marked the moment at which particular kinds of folk and practical knowledge about healing became visible and above all legible. This is to be seen in the enormous rise in book production, which in itself represented an 'approved knowledge' that found legitimation in new academic and bureaucratic institutions, such as the reformed medical faculty of the University of Vienna, the newly-founded medical faculty at Tyrnau, the establishment of a health department within the Hungarian Statthalterei, as well as in the emission of royal legislation supporting the agendas of the new enlightened science of 'medical police'.     

Developmental neurobiology and clinical disorders: lost in translation?

Advances in defining mechanisms of cortical development have been paralleled in recent years by an intense interest in translating these findings into greater insight of both childhood- and adult-onset cognitive and mental health disorders of developmental etiology. Successful integration of basic and clinical findings have been applied to monogenic disorders. The greater challenge lies in studying cortical development in the context of gene x environment interactions, which underlie the pathogenesis of the most common neurodevelopmental disorders. This can occur through an improved delineation of pathophysiological characteristics unique to specific complex disorders and the application of this information to the refinement of the most relevant model systems.     

Subjective and psychopathological response in patients under different antipsychotic treatments: are there differences in real clinical practice?

The aim of this study is to investigate whether subjective well-being in patients under treatment with typical (ATPs) and atypical antipsychotic (ATPsA) compounds can be compared with the improvement of psychopathological state and to verify if both variables correlate to adherence to treatment. We assessed 106 consecutive patients receiving ATPs or ATPsA in the University Psychiatric Ward of L?Aquila, according to DSM-IV diagnosis of Schizophrenia and Bipolar Disorder. Psychopathological state was assessed by Brief Psychiatric Rating Scale-4.0 version (BPRS), adherence to treatment and subjective well-being was assessed by Drug Attitude Inventory (DAI-10) and Subjective Well-being under Neuroleptics (SWN), respectively. BPRS and DAI-10 were administered on admission (T0) and at the end of recovery (T1). The subjects enrolled in this study were divided into 2 groups according to ATP prescribed. We observed an improvement of BPRS and SWN total scores in each group, and increasing scores in DAI-10, from admission to discharge, both in total samples and in each group. There were statistical differences between the patients receiving ATPs and those receving ATPsA regardindg the SWN total score and its different dimensions. This study emphasizes that patients receiving ATPsA show better subjective response compared with patients undergoing ATP treatment, although the adherence to pharmacotherapy and clinical improvement do not differ between the groups.     

Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

Aims

Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation.

Methods and results

This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12–0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities.

Conclusion

In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician’s awareness of NT-proBNP concentrations.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-013-0503-y) contains supplementary material, which is available to authorized users.     

Pain and distress: what really matters?

Federal regulations mandate the minimization of both pain and distress in laboratory animals. That no clear definition exists for 'distress' complicates its recognition, quantification, and alleviation. The author argues that IACUCs and investigators should shift their focus from pain to distress, and that in doing so both problems will be better dealt with. She discusses criteria for defining 'significant' distress, and offers suggestions for the conduct of studies to determine levels of distress.     

Diversity in the Monogenea and Digenea: does lifestyle matter?

If the cestodes are excluded, then the parasitic platyhelminths of fishes divide neatly into the external and monoxenous Monogenea and the internal and heteroxenous Digenea. Both groups have apparently had long associations of coevolution, host switching and adaptation with fishes and have become highly successful in their respective habitats. Current estimates of species richness for the two groups suggest that they may be remarkably similar. Here we consider the nature of the diversity of the Monogenea and Digenea of fishes in terms of richness of species and higher taxa to determine what processes may be responsible for observed differences. The Monogenea includes at least two super-genera (Dactylogyrus and Gyrodactylus) each of which has hundreds of species; no comparable genera are found in the Digenea. Possible reasons for this difference include the higher host specificity of monogeneans and their shorter generation time. If allowance is made for the vagaries of taxonomic 'lumping' and 'splitting', then there are probably comparable numbers of families of monogeneans and digeneans in fishes. However, the nature of the families differ profoundly. Richness in higher taxa (families) in the Digenea is explicable in terms of processes that appear to have been unimportant in the Monogenea. Readily identifiable sources of diversity in the Digenea are: recolonisation of fishes by taxa that arose in association with tetrapods; adoption of new sites within hosts; adoption of new diets and feeding mechanisms; adaptations relating to the exploitation of ecologically similar groups of fishes and second intermediate hosts; and adaptations relating to the exploitation of phylogenetic lineages of molluscs. In contrast, most higher- level monogenean diversity (other than that associated with the subclasses) relates principally to morphological specialisation for attachment by the haptor.     

Apoptosis: why and how does it occur in biology?

The literature on apoptosis has grown tremendously in recent years, and the mechanisms that are involved in this programmed cell death pathway have been enlightened. It is now known that apoptosis takes place starting from early development to adult stage for the homeostasis of multicellular organisms, during disease development and in response to different stimuli in many different systems. In this review, we attempted to summarize the current knowledge on the circumstances and the mechanisms that lead to induction of apoptosis, while going over the molecular details of the modulator and mediators of apoptosis as well as drawing the lines between programmed and non-programmed cell death pathways. The review will particularly focus on Bcl-2 family proteins, the role of different caspases in the process of apoptosis, and their inhibitors as well as the importance of apoptosis during different disease states. Understanding the molecular mechanisms involved in apoptosis better will make a big impact on human diseases, particularly cancer, and its management in the clinics.     

Patients with left bundle branch block pattern and high cardiac risk myocardial SPECT: does the current management suffice?

Introduction

Myocardial perfusion SPECT (MPS) is frequently used for cardiovascular risk stratification. The significance of MPS in patients with abnormal electrical ventricular activation is often questionable. This review assesses the value of MPS for risk stratification of patients with intrinsic left bundle branch block or that due to right ventricular apical pacing.

Methods

We reviewed the literature by a search of the MEDLINE database (January 1980 to September 2010). The terms prognosis or prognostic value were combined with SPECT and LBBB or pacing or pacemakers. MPS was categorised as low and high risk according to the original definitions.

Results

We identified 11 studies suitable for review. A low-risk MPS is associated with a low risk of cardiac events whereas high-risk MPS carries a 4.8-fold increased risk, 95% CI [3.2 – 7.2] (p < 0.0001). Despite secondary prevention and an improved medical and interventional care, these figures have hardly changed over time.

Conclusion and clinical implications

A low-risk MPS permits a policy of watchful waiting whereas a high-risk MPS requires further analysis and treatment. The persistent high cardiac death and acute myocardial infarction rate after a high-risk MPS suggest that the current management of these patients does not suffice and needs reconsideration.     

Backtranslating clinical knowledge for use in cheminformatics—What is the potential?

'From bench to bedside' is seeing a very strong focus in current Drug Discovery. However, often overlooked are the advantages that turn out if data is used 'from bedside to bench', the fact one can also make beneficial use of clinical information in early Drug Discovery. By leveraging the wealth of clinical data carried by each marketed drug, down to the level of a single person, one can gain a deep insight that can be leveraged in conjunction with chemical structure information and therefore within all kinds of cheminformatics analyses. This supports the design of drugs that better fit the requirements of a well-defined subpopulation. Within this contribution I am going to focus on the realm of cheminformatics applications and how this data can thereby used to better impact the decisions of medicinal chemists.     

Newly registered elderly patients: who are they and why such delay in the transfer of their medical records?

The time taken to transfer the records of elderly patients registering with a new general practice was investigated. Thirty five (5%) of a total of 671 patients aged 75 and over were entered as new patients on to the age-sex register of an urban group practice during one year. Twenty nine had moved into the area and six had changed their general practitioner for personal and other reasons. An average of 141 (range 71-296) days elapsed before dispatch of their medical records to the new practice. During this period an average of 3·5 (range 0-15) consultations with a general practitioner were recorded, indicating the need of such patients for medical care. The long delays were caused by the processing of medical records at the central register and the transfer of records between family practitioner committees and general practitioners. Delays were most apparent in the time taken for general practitioners to dispatch the necessary documents to the family practitioner committees, and these should be minimised.The use of a summary card written and updated by the general practitioner and retained by the patient would facilitate continuing care should patients change to a new practice. Meanwhile, assessment of elderly patients after registration with a new practice by a member of the primary health care team may identify problems before the records have been transferred and may help the resettlement of these high risk elderly patients.     

Parasitism and survival in a damselfly: does host sex matter?

We present experimental data on the survivorship of damselflies infested by parasitic water mites from a population in field cages. In addition, we show correlative laboratory data under simulated severe weather conditions. In the manipulative experiment, parasitized females' individual condition, which was measured as weight at emergence, was an important determinant of survival under field conditions. In contrast, such a relationship did not occur in males and unparasitized females. It was found in the laboratory experiment that water mites as well as weight at emergence both contributed significantly to the reduced survivorship of male and female damselflies. It was concluded that the impact of parasitism depends on environmental conditions and that host sexes differ in their responses to parasitism. This is discussed in the light of immunocompetence in invertebrates.     

Serum heat shock protein 70 and oxidized LDL in patients with type 2 diabetes: does sex matter?

Several studies suggest that the response to various stressors differs between the sexes. We aimed to study serum HSP70 and levels of oxidized-LDL (ox-LDL) as markers of oxidative stress in men and women with type 2 diabetes. We quantified serum HSP70 and levels of ox-LDL in three cohorts; patients with newly diagnosed diabetes, patients with long-standing diabetes and normal controls. The cohort of patients with newly diagnosed diabetes was followed up for 3 months under glucose-lowering therapy with metformin. Our findings showed that serum HSP70 level was increased in women with long-standing diabetes in comparison with men. HSP70 did not decrease after glucose lowering therapy in women with newly diagnosed diabetes, but it did decrease in men. There was no significant difference on ox-LDL between men and women in any of the studied cohorts. It decreased significantly in the cohort of patients with newly diagnosed diabetes after treatment, regardless of sex. There was no significant correlation between HSP70 and ox-LDL in any of the studied cohorts except among normal women. We suggest that diabetes induces an immune response and impairs cellular defense mechanisms against oxidative stress more commonly in women with type 2 diabetes than in men.