SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Journal of clinical medicine

143

Current strategies for preventing the transmission of mitochondrial disease to offspring include techniques known as mitochondrial replacement and mitochondrial gene editing. This technology has already been applied in humans on several occasions, and the first baby with donor mitochondria has already been born. However, these techniques raise several ethical concerns, among which is the fact that they entail genetic modification of the germline, as well as presenting safety problems in relation to a possible mismatch between the nuclear and mitochondrial DNA, maternal mitochondrial DNA carryover, and the “reversion” phenomenon. In this essay, we discuss these questions, highlighting the advantages of some techniques over others from an ethical point of view, and we conclude that none of these are ready to be safely applied in humans.

Concepts: Ethics, Gene, Bacteria, Mitochondrial disease, Cell, Mitochondrion, Mitochondrial DNA, DNA

26

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting.

Concepts: Symptom, Novel, Fatigue, Therapy, Virus, Bacteria, Infection, Medicine

25

By the sixth decade of life, nearly one quarter of the population has substantial muscle atrophy, or sarcopenia. Despite the creation of a standardized definition of sarcopenia by the European Working Group on Sarcopenia in Older People, variability may exist in the diagnostic criteria utilized for clinical sarcopenia research. The primary objectives of this review were to characterize diagnostic criteria used for measurement of sarcopenia in original studies, and to describe associations between sarcopenia and important clinical outcomes. We performed a literature review of the term “sarcopenia” in PubMed. Inclusion criteria were English language, original data, a clear and specific definition for diagnosing sarcopenia, and the analysis of sarcopenia’s effect on a clinical outcome. A total of 283 studies met inclusion criteria. More than half of the included sarcopenia investigations were level IV studies (54.1%), while 43.1% provided level II evidence. Under one third (27.6%) of studies examined sarcopenia with regard to surgical outcomes. In terms of diagnostic criteria for sarcopenia, 264 (93.3%) studies used measures of skeletal muscle mass, with dual energy X-ray absorptiometry (DEXA) being the most common modality (43.6%). Sarcopenia was found to be a consistent predictor of chronic disease progression, all-cause mortality, poorer functional outcomes, and postoperative complications. In conclusion, there is substantial evidence that sarcopenia impacts both medical and surgical outcomes. However, current research has utilized heterogeneous diagnostic criteria for sarcopenia. Further efforts to standardize the modalities used to diagnose sarcopenia in clinical research and practice will help strengthen our ability to study this important phenomenon.

Concepts: Clinical research, Atrophy, Sarcopenia, Medicine, Diagnosis, Muscle atrophy, Osteoporosis, Muscle

20

(1) Objective: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) Methods: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) Results: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: -11.3, -2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: -2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) Conclusion: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications.

Concepts: Serotonin, Fluoxetine, Venlafaxine, Bupropion, Antidepressants, Sertraline, Selective serotonin reuptake inhibitor, Antidepressant

18

There is a growing interest in the use of augmented reality (AR) to assist children and adults with autism spectrum disorders (ASD); however, little investigation has been conducted into the safety of AR devices, such as smartglasses. The objective of this report was to assess the safety and potential negative effects of the Empowered Brain system, a novel AR smartglasses-based social communication aid for people with ASD. The version of the Empowered Brain in this report utilized Google Glass (Google, Mountain View, CA, USA) as its hardware platform. A sequential series of 18 children and adults, aged 4.4 to 21.5 years (mean 12.2 years), with clinically diagnosed ASD of varying severity used the system. Users and caregivers were interviewed about the perceived negative effects and design concerns. Most users were able to wear and use the Empowered Brain (n = 16/18, 89%), with most of them reporting no negative effects (n = 14/16, 87.5%). Caregivers observed no negative effects in users (n = 16/16, 100%). Most users (77.8%) and caregivers (88.9%) had no design concerns. This report found no major negative effects in using an AR smartglasses-based social communication aid across a wide age and severity range of people with ASD. Further research is needed to explore longer-term effects of using AR smartglasses in this population.

15

A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.

Concepts: Schizophrenia, Abnormal psychology, Mental disorder, Eicosapentaenoic acid, Attention-deficit hyperactivity disorder, Borderline personality disorder, Omega-3 fatty acid, Fatty acid

12

Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gut microbiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.

Concepts: Human, Autoimmunity, Systemic autoimmune diseases, Bacteria, Gut flora, Immune system, Rheumatology, Rheumatoid arthritis

10

Sperm cryopreservation has been utilized routinely for over 40 years to preserve fertility in men undergoing cancer therapy and allow conception for infertile couples. This article provides a concise and up-to-date review of the literature and covers the latest advances in sperm cryopreservation and its array of clinical indications. Over recent years, the scope of clinical indications used for sperm cryopreservation has expanded widely. Consequently, more patient groups are eligible for sperm freezing, requiring specialist resources and higher running costs. Although sperm cryopreservation prior to cancer therapy is readily available in many countries, referral rates by oncology specialists and levels of patient engagement with cryopreservation services are both reported as low. Furthermore, sperm banking continues to raise ethical issues such whether sperm donation should be anonymous and whether sperm can be utilized posthumously by the surviving partner without consent from the patient. This review focuses on the technological advances and ethical controversies in sperm cryopreservation, and how better understanding of these issues could lead to improved access to fertility preserving treatment for patients.

Concepts: Sperm, Technology, Patience, Ethics, Philosophy, Spermatozoon, Patient, Fertility

8

Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters.

Concepts: Electron transport chain, Hydrogen peroxide, Mitochondrion, Oxidative stress, Antioxidant, Metabolism, Reactive oxygen species, Oxidative phosphorylation

7

Background: Despite known health benefits of spiritual care and high patient interest in discussing spirituality with their physicians, the frequency of spiritual discussions in the medical consultation is low. We investigated spiritual conversations for doctors caring for patients with advanced cancer; why these conversations so difficult; and what the underlying challenges are for discussing spirituality with patients; Methods: Participants were contacted through the Australian and New Zealand Society of Palliative Medicine and the Medical Oncology Group of Australia, including physicians from two secular countries. Semi-structured interviews were taped and transcribed verbatim. The text was analyzed using thematic analysis; Results: Thematic saturation was reached after 23 participants had been interviewed. The following themes were identified: (1) confusing spirituality with religion; (2) peer pressure; (3) personal spirituality; (4) institutional factors; (5) historical factors; Conclusion: This study explored the underlying attitudes contributing to the reluctance doctors have to discuss spirituality in the medical consultation. Underlying confusion regarding the differences between religion and spirituality, and the current suspicion with which religion is regarded in medicine needs to be addressed if discussion of spirituality in the medical consultation is to become routine. Historical opposition to a biopsychosocial-spiritual model of the human being is problematic.

Concepts: Specialty, Debate, Palliative care, Cancer, Spirituality, Medicine, Physician, Oncology