Neurology, technology, and the diagnostic imperative

Advancements in diagnostic technologies have revolutionized the field of neurology. The use of these tools in the course of neurological evaluations is driven by a strong version of the diagnostic imperative, with the goal of precisely identifying the locus and extent of disease processes. Because of the discrepancy between the sophistication of these technologies and the availability of therapeutic interventions, there is active debate regarding the appropriate use of these tools when the diagnosis is clear, or when no change is made to the therapeutic management. A narrow view of management that is bounded by the availability of pharmacological or surgical interventions results in a more rigid dichotomy between the needs of doctors and patients. A broader view that relaxes the constraint between diagnostic procedures and interventions is more in keeping with the observation that many acts are performed for the benefit of doctors and patients alike. An historical and ethical analysis of the diagnostic imperative, with attention to the rise of innovative medical technologies and current concepts of therapeutic intervention, can help clarify the principles of medical paternalism and beneficence that guide current models of decision making in the neurological sciences.     

Attachment,Mothering and Mental Illness: Mother–Infant Therapy in an Institutional Context

This paper is an ethnographic exploration of how attachment theory underpins therapeutic practices in an Australian institutional context where mothers of infants have been diagnosed and are undergoing treatment for mental illness. We argue that attachment theory in this particular context rests on a series of principles or assumptions: that attachment theory is universally applicable; that attachment is dyadic and gendered; that there is an attachment template formed which can be transferred across generations and shapes future social interactions; that there is understood to be a mental health risk to the infant when attachment is characterised as problematic; and that this risk can be mitigated through the therapeutic practices advocated by the institution. Through an in-depth case study, this paper demonstrates how these assumptions cohere in practice and are used to assess mothering as deficient, to choose therapeutic options, to shape women’s behaviour, and to formulate decisions about child placement.     

Polymicrobial challenges to Koch's postulates: Ecological lessons from the bacterial vaginosis and cystic fibrosis microbiomes

Koch's postulates have shaped our understanding of infectious diseases; however, one of the tangential consequences of them has been the emergence of a predominantly monomicrobial perspective concerning disease aetiology. This orthodoxy has been undermined by the growing recognition that some important infectious diseases have a polymicrobial aetiology. A significant new development in our understanding of polymicrobial infections is the recognition that they represent functional ecosystems and that to understand such systems and the outcome and impact of therapeutic interventions requires an understanding of how these communities arise and develop. Therefore, it is timely to explore what we can learn from other fields. In particular, ecological theory may inform our understanding of how polymicrobial communities assemble their structure and their dynamics over time. Such work may also offer insights into how such communities move from stable to unstable states, as well as the role of invasive pathogens in the progression of the disease. Ecological theory offers a theoretical framework around which testable hypotheses can be developed to clarify the polymicrobial nature and dynamics of such infections in the face of environmental change and therapeutic interventions.     

Dyskinesia in Parkinson's disease: mechanisms and current non‐pharmacological interventions

Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarizes the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including dopamine‐cAMP‐regulated neuronal phosphoprotein, extracellular signal‐regulated kinase, mammalian target of rapamycin, mitogen and stress‐activated kinase‐1 and Histone H3 are summarized, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity and animal behavioral results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non‐pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease‐associated motor symptoms, especially the development of dyskinesia.

     

Advantages and limitations of Internet‐based interventions for common mental disorders

Several Internet interventions have been developed and tested for common mental disorders, and the evidence to date shows that these treatments often result in similar outcomes as in face‐to‐face psychotherapy and that they are cost‐effective. In this paper, we first review the pros and cons of how participants in Internet treatment trials have been recruited. We then comment on the assessment procedures often involved in Internet interventions and conclude that, while online questionnaires yield robust results, diagnoses cannot be determined without any contact with the patient. We then review the role of the therapist and conclude that, although treatments including guidance seem to lead to better outcomes than unguided treatments, this guidance can be mainly practical and supportive rather than explicitly therapeutic in orientation. Then we briefly describe the advantages and disadvantages of treatments for mood and anxiety disorders and comment on ways to handle comorbidity often associated with these disorders. Finally we discuss challenges when disseminating Internet interventions. In conclusion, there is now a large body of evidence suggesting that Internet interventions work. Several research questions remain open, including how Internet interventions can be blended with traditional forms of care.     

Autism Crises: Music Therapeutic Practice & Research at the Social Care Centre Tloskov,Czech Republic. A Short Report

CSS Tloskov is a social pediatric care center and a leading institution in the Czech Republic. Sixty-five percent of its clients are diagnosed with autism spectrum disorder (ASD) and receive usually music therapy as a main constituent of individually designed pedagogical and therapeutic programs. In contrast to numerous music therapeutic concepts that are based on musical improvisation, the Tloskov model advocates a complex approach involving favorite songs, instrumental improvisation, and body-oriented modalities such as muscle relaxation and breathing techniques.

Clinical analyses allow us to distinguish typical psychiatric exacerbations in our ASD-clients. These “autistic crises” comprise an “onset phase,” a “gradation phase,” a “culmination phase,” and a “subsiding phase,” which can be partly controlled by music therapeutic interventions. On the basis of Grounded Theory we used qualitative methods to examine system compatibility between clinical data and the 4-phase autism crisis theory and to generate hypotheses about mechanisms of successful music therapy.

Outcomes involve five main principles: identification and avoidance of specific stimuli and cues that trigger autism crises; direct musical “sedation”; acquisition of music-behavioral skills to “auto-regulate” pathological developments; and a sort of music therapeutic emotional re-balancing and consolidation of an inner equilibrium. The “right moment” of intervention and adjustment of musical experiences within a narrow range of the client’s aesthetic-emotional intensity tolerance are critical to therapeutic outcomes. Possible music therapeutic contra-indications have to be taken into consideration.     

Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites

Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction - that host immune responses have differential effects on the mating ability of males and females - have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be 'evolution-proof' than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications.     

The vacuolar ATPase in bone cells: a potential therapeutic target in osteoporosis

The vacuolar ATPase (V-ATPase) is a multisubunit enzyme that couples ATP hydrolysis to proton pumping across membranes. Recently, there is increasing evidence that V-ATPase may contribute to the pathogenesis of bone resorption disorders due to it is predominantly expressed in osteoclasts also function in bone resorption making it a good candidate in a therapeutic target for osteoporosis. Osteoclasts are capable of generating an acidic microenvironment necessary for bone resorption by utilizing V-ATPases to pump protons into the resorption lacuna. In addition, it has been shown that therapeutic interventions have been proposed that specifically target inhibition of the osteoclast proton pump. Modulation of osteoclastic V-ATPase activity has been considered to be a suitable therapy for the treatment of osteoporosis. All theses findings suggest that V-ATPase have important biological effects in bone resorption that might be a promising therapeutic target for osteoporosis. In this review, we will briefly discuss the biological features of osteoporosis and summarize recent advances on the role of V-ATPase in the pathogenesis and treatment of osteoporosis.     

Membrane computing: brief introduction, recent results and applications

The internal organization and functioning of living cells, as well as their cooperation in tissues and higher order structures, can be a rich source of inspiration for computer science, not fully exploited at the present date. Membrane computing is an answer to this challenge, well developed at the theoretical (mathematical and computability theory) level, already having several applications (via usual computers), but without having yet a bio-lab implementation. After briefly discussing some general issues related to natural computing, this paper provides an informal introduction to membrane computing, focused on the main ideas, the main classes of results and of applications. Then, three recent achievements, of three different types, are briefly presented, with emphasis on the usefulness of membrane computing as a framework for devising models of interest for biological and medical research.     

The number needed to treat: a clinically useful nomogram in its proper context.

The number needed to treat is a meaningful way of expressing the benefit of an active treatment over a control. It can be used either for summarising the results of a therapeutic trial or for medical decision making about an individual patient, but its use at the bedside has been impeded by the need for time consuming calculations. A nomogram has therefore been devised that will greatly simplify the calculations. Since calculations are now easy, the number needed to treat can be used to access the value of several interventions, although it does have its limitations. In particular it should not be used when it is not known whether the relative risk reduction associated with an intervention is constant for all levels of risk, or for periods of time longer than that studied in the original trials.     

Restoring the patient's voice: the case of Gilda Radner.

In the past few years, the medical case report has been studied as a document that evidences the way the patient and, by extension, the experiential and subjective aspects of an illness tend to be marginalized in contemporary medical theory and practice. First-person narratives about illness, our popular "pathographies," may in part represent our attempt as a culture to respond to this problem of "the vanishing patient." A rich source of information about patient experience, pathographies can be useful to us in locating specific issues in the medical enterprise that need understanding and perhaps require correction. Gilda Radner's It's Always Something demonstrates how two important issues--both neglected in the conventional medical history--powerfully affect the medical enterprise: the hopes, expectations, and wishes of the experiencing patient, and the perceived attitudes and demeanor of the patient's physicians. The restoration of patient and physician to the "history" is important not only because it reminds us of the personal dimension of the medical enterprise, but also because it alerts us to problems of attitude and action that bear directly on diagnosis, course of treatment, and the therapeutic transaction.     

Effects of polymer molecular weight on the size, activity, and stability of PEG-functionalized trypsin

Polymer conjugation increases an enzyme's circulation time and stability for use as a therapeutic agent, but this attachment indubitably affects its properties. Covalent attachment of multiple polyethylene glycol chains with sizes of either 2, 5, 10, or 20 kDa increases the molecular weight and hydrodynamic radius of the model enzyme trypsin. The sizes of these polymer-enzyme conjugates are increased to be within the recommended limits for PDEPT applications. The T(d) increases from 49 to 60 °C to expand the enzyme's workable range of conditions. This functionalization with PEG polymers of varying lengths maintains trypsin's enzymatic activity. Conjugate activities are 79-120% that of native trypsin at room temperature and 221-432% that of trypsin at 37 °C.     

Tu Youyou winning the Nobel Prize: Ethical research on the value and safety of traditional Chinese medicine

In 2015, the Chinese pharmacologist, Tu Youyou, was awarded the Nobel Prize for Physiology or Medicine for the discovery of artemisinin. Traditional Chinese medicine (TCM) was the source of inspiration for Tu's discovery and provides an opportunity for the world to know more about TCM as a source of medical knowledge and practice. In this article, the value of TCM is evaluated from an ethical perspective. The characteristics of ‘jian, bian, yan, lian’ are explored in the way they promote accessibility and economic efficiency for TCM. The article also examines how the increased use and prevalence of TCM reflects the scientific, cultural, and ethical values of TCM and their increasing attraction in meeting major challenges to medicine and health systems currently and in the future. The article discusses safety issues within TCM, which is a controversial area, and also comments on some shortcomings and challenges which pose difficulties for more widespread and greater uptake of TCM-derived clinical or therapeutic interventions. The article concludes that TCM is generally safe if it is used according to TCM theory and where such applications are cognizant of the strengths and weaknesses of TCM. TCM has important bioethical values which may inform potential measures for meeting challenges facing global health care systems and the article argues that it can have an increasing role in improving human health.     

Laser‐induced capillary leakage for blood biomarker detection and vaccine delivery via the skin

Circulation system is the center for coordination and communication of all organs in our body. Examination of any change in its analytes or delivery of therapeutic drugs into the system consists of important medical practice in today's medicine. Two recent studies prove that brief illumination of skin with a low powered laser, at wavelengths preferentially absorbed by hemoglobin, increases the amount of circulating biomarkers in the epidermis and upper dermis by more than 1,000‐fold. When probe‐coated microneedle arrays are applied into laser‐treated skin, plasma blood biomarkers can be reliably, accurately, and sufficiently quantified in 15～30 min assays, with a maximal detection in one hr in a manner independent of penetration depth or a molecular mass of the biomarker. Moreover, the laser treatment permits a high efficient delivery of radiation‐attenuated malarial sporozoites (RAS) into the circulation, leading to robust immunity against malaria infections, whereas similar immunization at sham‐treated skin elicits poor immune responses. Thus this technology can potentially instruct designs of small, portable devices for onsite, in mobile clinics, or at home for point‐of‐care diagnosis and drug/vaccine delivery via the skin.

Laser‐induced capillary leakage ( a ) to induce extravasation of circualing molecules only ( b ) or facilitate entry of attenuated malaria sporozoites into the capillary ( c ). Skin illumination with a laser preferably absorbed by hemoglobin causes dilation of the capillary beneath the skin. The extravasated molecules can be sufficiently measured in the skin or guide sporozoites to enter the vessel.     

Towards the use of bioresorbable fibers in time‐domain diffuse optics

In the last years bioresorbable materials are gaining increasing interest for building implantable optical components for medical devices. In this work we show the fabrication of bioresorbable optical fibers designed for diffuse optics applications, featuring large core diameter (up to 200 μm) and numerical aperture (0.17) to maximize the collection efficiency of diffused light. We demonstrate the suitability of bioresorbable fibers for time‐domain diffuse optical spectroscopy firstly checking the intrinsic performances of the setup by acquiring the instrument response function. We then validate on phantoms the use of bioresorbable fibers by applying the MEDPHOT protocol to assess the performance of the system in measuring optical properties (namely, absorption and scattering coefficients) of homogeneous media. Further, we show an ex‐vivo validation on a chicken breast by measuring the absorption and scattering spectra in the 500–1100 nm range using interstitially inserted bioresorbable fibers. This work represents a step toward a new way to look inside the body using optical fibers that can be implanted in patients. These fibers could be useful either for diagnostic (e. g. for monitoring the evolution after surgical interventions) or treatment (e. g. photodynamic therapy) purposes. Picture : Microscopy image of the 100 μm core bioresorbable fiber.

     

Reflections in art

When artists depict a mirror in a painting, it necessarily lacks the most obvious property of a mirror: as we move around the painting of the mirror, the reflections we see in it do not change. And yet representations of mirrors and other reflecting surfaces can be quite convincing in paintings. Here, we will examine the rules of reflection, the many ways that painters can break those rules without losing the impression of reflection and the rules that cannot be broken. The rules that govern the perception of reflection are a small subset of the physical rules of reflection.     

Time-Limited,Structured Youth Mentoring and Adolescent Problem Behaviors

Four theoretical perspectives about why father involvement could have positive consequences for child development are briefly reviewed: attachment theory, social capital theory, Bronfenbrenner's ecological theory, and "essential father" theory. Strengths and weaknesses of each perspective are discussed, and the prospects for an integrated ecological-parental capital theory of paternal influence on child development are considered.     

Mass-Produced,Assembly-Line Abortion—A Prime Example of Unethical,Unscientific Medicine

The incidence of psychologic sequelae associated with abortion cannot be established scientifically, and so continues to be disputed. Since there are no truly scientific criteria on which to make a prediction as to the psychologic outcome, it seems only proper that elective abortion be labeled “experimental,” rather than “therapeutic.”This uncertainty as to therapeutic benefit is compounded by the fact that adequate studies and information about physical sequelae are also lacking. Furthermore, preliminary statistics from the Population Council indicate that the morbidity rate of abortion performed even under proper medical auspices is unacceptably high.Viewed in this light and in relation to our own ethical code, the current practice of performing innumerable, mechanized, elective abortions can only be considered unethical. If it is argued that abortion can be ethically validated merely by surrounding it with the same controls used in other experimental procedures, then the medical profession should insist on such controls forthwith.     

Cryopreservation of isolated human hepatocytes for transplantation: State of the art

Hepatocytes isolated from unused donor livers are being used for transplantation in patients with acute liver failure and liver-based metabolic defects. As large numbers of hepatocytes can be prepared from a single liver and hepatocytes need to be available for emergency and repeated treatment of patients it is essential to be able to cryopreserve and store cells with good thawed cell function. This review considers the current status of cryopreservation of human hepatocytes discussing the different stages involved in the process. These include pre-treatment of cells, freezing solution, cryoprotectants and freezing and thawing protocols. There are detrimental effects of cryopreservation on hepatocyte structure and metabolic function, including cell attachment, which is important to the engraftment of transplanted cells in the liver. Cryopreserved human hepatocytes have been successfully used in clinical transplantation, with evidence of replacement of missing function. Further optimisation of hepatocyte cryopreservation protocols is important for their use in hepatocyte transplantation.     

Development of Combined Vaccines: Manufacturers' Viewpoint

Abstract. Rapid and exciting research breakthroughs in the fields of immunology and molecular biology in recent years have greatly enhanced the potential for developing new vaccines or improving existing ones. The resulting rising number of diseases that can be prevented by vaccination, coupled with the growing trend of preferring cost-effective preventive medical interventions over expensive therapeutic modalities, has increased the complexity of administering to all those who need them, the many different vaccines that will soon be available. Hence attention in the field of vaccinology is now focusing on the development of combined vaccines that, in a few inoculations, can elicit protection against as many diseases as possible. Some of the recent achievements, future objectives and difficulties of vaccine manufacturers in the development of combined vaccines are surveyed.