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Journal: Diseases (Basel, Switzerland)


The microbiome gut brain (MGB) axis consists of bidirectional routes of communication between the gut and the brain. It has emerged as a potential therapeutic target for multiple medical specialties including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder and irritable bowel syndrome. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced a clinically measurable symptom improvement in patients with depressive disorder. To date, some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach.


The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3-4 years of age. Furthermore, it is understood that the microbiome promotes cues that instruct the neonate’s mucosal tissues and skin in the language of molecular and cellular biology. Post birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged co-establishing the intestinal microbiome with a developing immune system. Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via shifts in the intestinal microbiome phyla. A plausible appreciation is that dysregulated pro-inflammatory signals from intestinal resident macrophages could breach the loop by providing adverse mood signals via vagus nerve afferents to the brain. In this commentary, we further suggest that the intestinal resident macrophages act as an upstream traffic controller of translocated microbes and metabolites in order to maintain local neuro-endocrine-immunological equilibrium. When macrophages are overwhelmed through intestinal microbiome and intestinal epithelial cell dysbiosis, pro-inflammatory signals are sustained, which may then lead to mood disorders. The administration of probiotics as an adjunctive medicine co-administered with antidepressant medications in improving depressed mood may have biological and clinical standing.

Concepts: Immune system, Medicine, Bacteria, Metabolism, Immunology, Epithelium, Skin, Bipolar disorder


The diaphragm is the primary muscle of respiration, and its weakness can lead to respiratory failure. Diaphragmatic palsy can be caused by various causes. Injury to the phrenic nerve during thoracic surgeries is the most common cause for diaphragmatic palsy. Depending on the cause, the symptoms of diaphragmatic palsies vary from completely asymptomatic to disabling dyspnea requiring mechanical ventilation. On pulmonary function tests, there will be a decrease in the maximum respiratory muscle power. Spirometry shows reduced lung functions and a significant drop of lung function in supine position is typical of diaphragmatic palsy. Diaphragmatic movements with respiration can be directly visualized by fluoroscopic examination. Currently, this test is being replaced by bedside thoracic ultrasound examination, looking at the diaphragmic excursion with deep breathing or sniffing. This test is found to be equally efficient, and without risks of ionizing radiation of fluoroscope. Treatment of diaphragmatic palsy depends on the cause. Surgical approach of repair of diaphragm or nonsurgical approach of noninvasive ventilation has been tried with good success. Overall prognosis of diaphragmatic palsy is good, except when it is related to neuromuscular degeneration conditions.

Concepts: Pulmonology, Lung, Respiratory physiology, Symptoms, Respiratory system, Thoracic diaphragm, Respiration, Phrenic nerve


Chronic pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), NIH category III is difficult to treat without understanding its cause. The main symptom of chronic prostatitis is pain. In this study, we would like to explain the origin of pain in men with CP/CPPS and its therapy. Forty-five patients with CP/CPPS have received thermobalancing therapy (TT) enabled by Dr Allen’s therapeutic device (DATD) for six months as mono-therapy. The control group comprised 45 men with CP/CPPS did not receive TT. Before and after six months the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores, prostatic volume (PV) by ultrasound measurement and uroflowmetry (Qmax) were compared between the groups. Baseline characteristics have shown no difference. After TT, significant improvements in pain score (p < 0.001), quality of life index (QoL) (p < 0.001), decrease of PV (p < 0.001), and increase Qmax (p < 0.001) were determined. There were not noteworthy changes in the control group. Chronic pain due to CP/CPPS happens as a consequence and challenges at the capillary level, namely pathological capillary activity. In response to initial triggers-such as inflammation, cold, psychological and other factors-constriction and spontaneous expansion of capillaries follows, creating a continuous secondary trigger-i.e., the micro-focus of hypothermia-which in turn provokes expansion of capillaries. The additional tissue due to vascular changes into the prostate increases pressure on nociceptors causing pain. TT relieves chronic pelvic pain by eliminating the lasting focus of hypothermia in the affected prostate tissue.

Concepts: Syndromes, Pain, Nociception, Prostate, Myofascial pain syndrome, Interstitial cystitis, Chronic prostatitis/chronic pelvic pain syndrome, Chronic pain syndromes


Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

Concepts: Protein, Nutrition, Fatty acids, Obesity, Saturated fat, Non-alcoholic fatty liver disease, Fatty liver, Unsaturated fat


Alzheimer’s disease is a neurodegenerative sickness, where the speed of personal disease progression differs prominently due to genetic and environmental factors such as life style. Alzheimer’s disease is described by the construction of neuronal plaques and neurofibrillary tangles composed of phosphorylated tau protein. Mitochondrial dysfunction may be a noticeable feature of Alzheimer’s disease and increased production of reactive oxygen species has long been described. Superoxide dismutases (SODs) protect from excess reactive oxygen species to form less reactive hydrogen peroxide. It is suggested that SODs can play a protective role in neurodegeneration. In addition, PI3K/AKT pathway has been shown to play a critical role on the neuroprotection and inhibiting apoptosis via the enhancing expression of the SODs. This pathway appears to be crucial in Alzheimer’s disease because it is related to the tau protein hyper-phosphorylation. Dietary supplementation of several ordinary compounds may provide a novel therapeutic approach to brain disorders by modulating the function of the PI3K/AKT pathway. Understanding these systems may offer a better efficacy of new therapeutic approaches. In this review, we summarize recent progresses on the involvement of the SODs and PI3K/AKT pathway in neuroprotective signaling against Alzheimer’s disease.

Concepts: Alzheimer's disease, Oxygen, Mitochondrion, Oxidative phosphorylation, Reactive oxygen species, Neurology, Hydrogen peroxide, Peroxide


Wine has been popular worldwide for many centuries and currently remains an important component of our diet. Scientific interest in wine and its health effects has grown considerably since the 1990s with the emergence of the “French Paradox” concept, correlating moderate wine consumption, a characteristic of the Mediterranean diet, and low incidence of coronary heart diseases. Since then, the positive effects on health, health promotion, disease prevention, and disease prognosis of moderate wine consumption, in particular red wine, have been attributed to its polyphenolic compounds such as resveratrol, quercetin, and other flavonoids acting as antioxidants. Several epidemiological, in vivo and in vitro, studies have reported that moderate red wine or red wine polyphenolic extract consumption may be active in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, degenerative pathologies, and cancer. The aim of this review is to summarize the current findings about the effects of red wine polyphenols on cancer and to discuss how the polyphenolic composition of red wine may influence its chemopreventive properties.


Neurodegenerative diseases (NDs) have a profound impact on human health worldwide and their incidence is predicted to increase as the population ages. ND severely limits the quality of life and leads to early death. Aside from treatments that may reduce symptoms, NDs are almost completely without means of therapeutic intervention. The genetic and biochemical basis of many NDs is beginning to emerge although most have complex etiologies for which common themes remain poorly resolved. Largely relying on progress in vector design, gene therapy is gaining increasing support as a strategy for genetic treatment of diseases. Here we describe recent developments in the engineering of highly defective herpes simplex virus (HSV) vectors suitable for transfer and long-term expression of large and/or multiple therapeutic genes in brain neurons in the complete absence of viral gene expression. These advanced vector platforms are safe, non-inflammatory, and persist in the nerve cell nucleus for life. In the near term, it is likely that HSV can be used to treat certain NDs that have a well-defined genetic cause. As further information on disease etiology becomes available, these vectors may take on an expanded role in ND therapies, including gene editing and repair.


Moderate wine consumption is a characteristic of the Mediterranean diet. Studies around the world have shown a beneficial effect of moderate alcohol intake, especially wine, on health. This review aims to critically summarise the most recent studies that investigate the beneficial effects of moderate wine intake on human health.


Previous studies suggest that pulses may have the potential to protect against cancer development by inhibiting pathways that result in the development of cancer. These pathways include those that result in inflammation, DNA damage, cell proliferation, and metastasis. Other studies have demonstrated extracts from pulses have the capacity to induce apoptosis specifically in cancer cells. Compounds reported to be responsible for these activities have included phenolic compounds, proteins and short chain fatty acids. The majority of the studies have been undertaken using in vitro cell culture models, however, there are a small number of in vivo studies that support the hypothesis that pulse consumption may inhibit cancer development. This review highlights the potential benefit of a diet rich in pulse bioactive compounds by exploring the anti-cancer properties of its polyphenols, proteins and short chain fatty acids.