Diseases, Volume 6, Issue 3 (September 2018) – 31 articles

The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited. Full article

The rapidly expanding field of bioactive lipids is exemplified by the many sphingolipids, which are structurally and functionally diverse molecules with significant physiologic functions. These sphingolipids are main constituents of cellular membranes and have been found associated with plasma lipoproteins, and their concentrations are altered in several metabolic disorders such as atherosclerosis, obesity, and diabetes. Understanding the mechanisms that regulate their biosynthesis and secretion may provide novel information that might be amenable to therapeutic targeting in the treatment of these diseases. Several sphingolipid synthesis genes have been targeted as potential therapeutics for atherosclerosis. In recent years, significant progress has been made in studying the role of microRNAs (miRNAs) in lipid metabolism. However, little effort has been made to investigate their role in sphingolipid metabolism. Sphingolipid biosynthetic pathways involve various enzymes that lead to the formation of several key molecules implicated in atherosclerosis, and the identification of miRNAs that regulate these enzymes could help us to understand these complex pathways better and may prove beneficial in alleviating atherosclerosis. Full article

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect blood volume changes in the microvascular bed of tissue. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features, such as the amplitude and the pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study, innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least five minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude variability and PAT variability were then quantified in the time-domain using two simple statistical measures and in the frequency-domain bilaterally using magnitude squared coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (interquartile range 0.0217–0.0744) vs. PAD 0.0160 (0.0080–0.0338) (p < 0.0001)) and significantly increased PAT variability (healthy control 0.0063 (0.0052–0.0086) vs. PAD 0.0093 (0.0078–0.0144) (p < 0.0001)) was demonstrated for the toe site in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups. Full article

Our aim is to review the efficacy of various herbs and supplements as a possible therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver disease (NAFLD). We performed a systematic review of medical literature using the PubMed Database by searching the chemical names of many common herbs and supplements with “AND (NAFLD or NASH)”. Studies and medical literature that discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many studies have claimed that the use of various herbs and supplements may improve disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver function tests were noted. Amelioration or reduction of lobular inflammation, hepatic steatosis, and fibrosis were also noted. However, well-designed studies demonstrating improved clinical outcomes are lacking. Furthermore, experts remain concerned about the lack of regulation of herbs/supplements and the need for further research on potential adverse effects and herb–drug interactions. In conclusion, preliminary data on several herbs have demonstrated promising antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties that may help curtail the progression of NAFLD/NASH. Clinical trials testing the safety and efficacy must be completed before widespread use can be recommended. Full article

Periapical actinomycosis is a relatively rare form of cervicofacial actinomycosis, which typically involves the periapical region with subsequent potential spread to the jaw bones. We hereby present two cases of periapical actinomycosis. Both patients presented with jaw pain and “holes” in their gum and lacked the characteristic clinical features commonly seen in cervicofacial actinomycosis such as jaw mass, draining ulcers, sinuses and fistulae. The first patient was an immunocompetent host with chronic stable medical conditions but with a rather bad dentition requiring multiple recent teeth extractions. The second patient was edentulous, had refractory multiple myeloma, was on low-dose chronic steroids and pomalidomide therapy and therefore relatively immunocompromised. Both cases of actinomycosis were diagnosed by jaw bone histopathology, which showed characteristic sulfur granules and embedded Actinomyces-like organisms. The two patients had excellent clinical response to six months of penicillin therapy without any need for surgical intervention. The cases remind clinicians of including actinomycosis in the differential diagnosis of periapical lesions and illustrates the possibility of achieving cure with non-surgical treatment. Full article

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. Full article

Despite epidemiological findings of improvements in cardiovascular risk factors with a light-to-moderate intake of alcohol, many misconceptions remain regarding alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Argentine physicians and to establish their sources of knowledge. An online national survey was distributed through the Argentine Federation of Cardiology (FAC) to cardiologists, internal medicine specialists, general and other subspecialty physicians in Argentina. The survey was completed by 745 physicians, of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate alcohol intake to be beneficial for cardiovascular health, 36% believed only wine offered such benefits, 24% viewed any intake to be harmful, and 5% had other opinions. More than half (57%) self-reported their knowledge came from academic sources. Regarding knowledge of drinking guidelines, only 41% of physicians were aware of the concept of “standard drink”. Physicians were generally not comfortable converting standard drinks into other metric units, however men tended to be more comfortable than women (p = 0.052). Physicians were not satisfied with their knowledge of drinking guidelines (3.01 ± 2.73, on a 0–10 scale). Physicians were generally comfortable in counselling patients regarding safe limits of consumption (6.22 ± 3.20, on a 0–10 scale). Argentine physicians were not satisfied with their knowledge of alcohol consumption guidelines or their understanding of the reported metrics. Only one-third of study participants viewed moderate alcohol intake as beneficial for cardiovascular health. This study shows the necessity to optimize the sources of knowledge. Full article

Extra virgin olive oil (EVOO) and red wine (RW) are two basic elements that form part of the so-called Mediterranean diet. Both stand out because of their high phenolic compound content and their potential related health benefits. The present study is focused on the metabolic disposition of resveratrol (RESV), tyrosol (TYR), and hydroxytyrosol (HT) following the consumption of EVOO, RW, and a combination of both. In this study, 12 healthy volunteers consumed a single dose of 25 mL of EVOO, 150 mL of RW, and a combination of both in a crossover randomized clinical trial. Urinary recovery of RESV, TYR, and HT was analysed in urine samples collected over a 6-h period following the intake of each treatment. Higher HT levels were observed following EVOO compared to RW (3788 ± 1751 nmols and 2308 ± 847 nmols respectively). After the combination of EVOO and RW, the recovery of TYR and HT metabolites increased statistically compared to their separate consumption (4925 ± 1751 nmols of TYR and 6286 ± 3198 nmols of HT). EVOO triggered an increase in glucuronide conjugates, while RW intake raised sulfate metabolites. Marginal effects were observed in RESV increased bioavailability after the combination of RW with the fat matrix provided by EVOO. Full article

Cryptococcal meningitis is a life-threatening condition caused by a fungal pathogen, Cryptococcus neoformans, that can infect both immunosuppressed and immunocompetent hosts. It is an important cause of morbidity and mortality in severely immunodeficient patients. However, in an immunocompetent patient it represents a diagnostic challenge, mainly because it is extremely rare, but also because of its nonspecific clinical manifestation. Neurovascular involvement in cryptococcal meningitis is rare and not well known and only few reports have described this association. We describe a cryptococcal meningitis in an immunocompetent patient associated with central nervous system vasculitis. Full article

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. Full article

Introduction: 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. Methods: The PubMed database was comprehensively searched to identify trials published from 2013 to 2018 that investigated the association between moderate wine consumption and health. Results: The most recent studies confirm the valuable role of moderate wine consumption, especially red wine, in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, cognitive decline, depression, and cancer. In the meantime, recent studies also highlight the beneficial role of red wine against oxidative stress and in favour of desirable gut bacteria. The beneficial role of red wine has been attributed to its phytochemical compounds, as highlighted by clinical trials, where the effect of red wine has been compared to white wine, non-alcoholic wine, other alcoholic drinks, and water. Conclusions: Moderate wine intake, at 1–2 glasses per day as part of the Mediterranean diet, has been positively associated with human health promotion, disease prevention, and disease prognosis. Full article

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. Full article

There has been a progressive rise in the incidence of blood stream infections (BSI) caused by multidrug-resistant Gram-negative organisms (MDR GN), which cause increased morbidity and mortality. For this reason, recent studies have focused on risk factors of acquisition of carbapenemase-producing Enterobacteriaceae and extended-spectrum beta-lactamase producers. However, there is limited data on risk factors for BSI caused by AmpC-producing Enterobacteriaceae (AmpC EC), especially in low prevalence settings such as Australia. This study was performed to identify risk factors for acquisition of AmpC E. coli, using a retrospective matched case control design over a 3-year period. Patients with BSI caused by AmpC E. coli were matched with controls (third generation cephalosporin susceptible E. coli) by age and site of infection (n = 21). There was no significant difference in age, sex, clinical outcome, time to onset of BSI, recent antibiotic use (last 3 months), comorbidities (type 2 diabetes mellitus, renal failure) intensive care unit admission, underlying hematological condition, immunosuppressant use, APACHE II score, or any recent urological procedures (within last 3 months) between the two groups. On univariate analysis, the AmpC E. coli group were more likely to have had a surgical procedure in hospital and lived in a residential aged care facility. On multivariate logistic regression analysis, a recent surgical procedure was associated with the onset of AmpC E. coli BSI (Odd’s Ratio (OR) 4.78, p = 0.034). We concluded that in a relatively low prevalence setting such as Australia, AmpC E. coli BSI is potentially associated with surgery performed in hospital due to previous antibiotic exposure and longer hospitalization. Full article

Cryptococcosis is a fungal infection that is typically associated with acquired immunodeficiency syndrome (AIDS). The advent of highly active antiretroviral therapy has decreased the frequency of this infection, but has led to the emergence of atypical cases of immune reconstitution inflammatory syndrome (IRIS). Here, we describe the case of a 40-year-old man who was diagnosed with HIV infection and cryptococcal meningitis. He was successfully treated with antifungals and then started antiretroviral therapy. The patient returned to the hospital 15 months later complaining of fever, pain, and neck swelling. A computed tomography (CT) scan revealed a conglomerate of necrotic lymph nodes in the supraclavicular region. He underwent biopsy and histology showed granulomatous inflammation with fungal elements, consistent with Cryptococcus. He tested positive for serum cryptococcal antigen. The patient was treated with liposomal amphotericin and flucytosine. After induction therapy, he was re-started on fluconazole. The final fungal cultures were negative. We attributed our patient’s clinical presentation to “paradoxical” IRIS, which was associated with his previously treated cryptococcosis. Near resolution of the supraclavicular mass was noted at the 3-month follow-up. Full article

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and for providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat, has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular and comprehensive follow up are necessary. Full article

Prompt and accurate diagnosis of Nocardia skin infections is important in immunocompromised hosts, especially transplant patients. The sporotrichoid form, which is otherwise known as the lymphocutaneous form of Nocardia skin involvement, can mimic other conditions, including those caused by fungi, mycobacteria, spirochetes, parasites and other bacteria. Delayed or inaccurate diagnosis and treatment of Nocardia skin infections in transplant patients could lead to dissemination of disease and other poor outcomes. Nocardia brasiliensis is a rare cause of lymphocutaneous nocardiosis in solid organ transplant patients with only two other cases reported to our knowledge. This case describes a middle-aged man, who presented 16 years post kidney transplant. He developed a sporotrichoid lesion on his upper extremity one week after gardening. Ultrasound showed a 35-cm abscess tract on his forearm, which was subsequently drained. Nocardia brasiliensis was isolated from pus culture and he was treated successfully with amoxicillin/clavulanate for 6 months. A review of the relevant literature is included. Full article

In the prevention of neurodegeneration associated with aging and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neuronal differentiation is of interest. In this context, neurotrophic factors are a family of peptides capable of promoting the growth, survival, and/or differentiation of both developing and immature neurons. In contrast to these peptidyl compounds, polyphenols are not degraded in the intestinal tract and are able to cross the blood–brain barrier. Consequently, they could potentially be used as therapeutic agents in neurodegenerative pathologies associated with neuronal loss, thus requiring the stimulation of neurogenesis. We therefore studied the ability to induce neuronal differentiation of two major polyphenols present in the Mediterranean diet: resveratrol (RSV), a major compound found in grapes and red wine, and apigenin (API), present in parsley, rosemary, olive oil, and honey. The effects of these compounds (RSV and API: 6.25–50 µM) were studied on murine neuro-2a (N2a) cells after 48 h of treatment without or with 10% fetal bovine serum (FBS). Retinoic acid (RA: 6.25–50 µM) was used as positive control. Neuronal differentiation was morphologically evaluated through the presence of dendrites and axons. Cell growth was determined by cell counting and cell viability by staining with fluorescein diacetate (FDA). Neuronal differentiation was more efficient in the absence of serum than with 10% FBS or 10% delipidized FBS. At concentrations inducing neuronal differentiation, no or slight cytotoxicity was observed with RSV and API, whereas RA was cytotoxic. Without FBS, RSV and API, as well as RA, trigger the neuronal differentiation of N2a cells via signaling pathways simultaneously involving protein kinase A (PKA)/phospholipase C (PLC)/protein kinase C (PKC) and MEK/ERK. With 10% FBS, RSV and RA induce neuronal differentiation via PLC/PKC and PKA/PLC/PKC, respectively. With 10% FBS, PKA and PLC/PKC as well as MEK/ERK signaling pathways were not activated in API-induced neuronal differentiation. In addition, the differentiating effects of RSV and API were not inhibited by cyclo[DLeu⁵] OP, an antagonist of octadecaneuropeptide (ODN) which is a neurotrophic factor. Moreover, RSV and API do not stimulate the expression of the diazepam-binding inhibitor (DBI), the precursor of ODN. Thus, RSV and API are able to induce neuronal differentiation, ODN and its receptor are not involved in this process, and the activation of the (PLC/PKC) signaling pathway is required, except with apigenin in the presence of 10% FBS. These data show that RSV and API are able to induce neuronal differentiation and therefore mimic neurotrophin activity. Thus, RSV and API could be of interest in regenerative medicine to favor neurogenesis. Full article

Feeding and nutrition follow the growth trajectory of the course of life. The profound physiological changes that human body experiences during ageing affect separate aspects of food intake, from tastant perception to satiety. Concurrent morbidities, such as neurodegeneration, as seen in dementia, and metabolic syndrome, may further shape nutritional behaviours, status and adequacy. In an effort to fill the gap between the exhausting basic research and the actual needs of professionals caring for the exponentially expanding ageing population, the current review addresses major factors relevant to appetite and eating disturbances. Does age alter the perception of food modalities? Is food generally still perceived as alluring and delicious with age? Is there an interplay between ageing, cognitive decline, and malnutrition? What tools can we adopt for proper and timely monitoring? Finally, what anatomical and pathophysiological evidence exists to support a hypothesis of central regulation of metabolic perturbations in normal and accelerated cognitive impairment, and how can we benefit from it in health practice? Full article

The aim of this study was to investigate urinary tract infections among patients with Bladder Outlet Obstruction (BOO) at the Korle Bu Teaching Hospital (KBTH) in Accra, Ghana, including the prevalence, risk factors, aetiological agents and their antibiogram. Urine specimens were collected from 188 male patients presenting with BOO and cultured for bacteria. The bacterial isolates were identified using standard microbiological methods and tested against a spectrum of antimicrobial agents using the Kirby Bauer method. Demographic information and the clinical history of study participants were also recorded. The prevalence of urinary tract infection among the BOO patients was 76.6% and the main risk factor identified was catheterization (p < 0.0001). A wide range of bacterial organisms was isolated from urine specimens and they were predominantly, Enterobacteriaceae; Escherichia coli was the most frequent cause of bacteriuria (33.3%), followed by Klebsiella (17.3%). Bacterial isolates were most resistant to Augmentin (97.8%) followed by tetracycline (85.8%), nalidixic acid (82.8%) and ciprofloxacin (75%) while 93.6% were multi-drug resistant. The highest susceptibility was observed with amikacin, which had a resistance prevalence of 4.4% resistance. These findings have important implications in the treatment of urinary tract infections among the BOO patients in Ghana. Full article

Lassa fever virus (LFV) belongs to the Arenaviridae family and can cause acute hemorrhagic fever in humans. The LFV Z protein plays a central role in virion assembly and egress, such that independent expression of LFV Z leads to the production of virus-like particles (VLPs) that mimic egress of infectious virus. LFV Z contains both PTAP and PPPY L-domain motifs that are known to recruit host proteins that are important for mediating efficient virus egress and spread. The viral PPPY motif is known to interact with specific host WW-domain bearing proteins. Here we identified host WW-domain bearing protein BCL2 Associated Athanogene 3 (BAG3) as a LFV Z PPPY interactor using our proline-rich reading array of WW-domain containing mammalian proteins. BAG3 is a stress-induced molecular co-chaperone that functions to regulate cellular protein homeostasis and cell survival via Chaperone-Assisted Selective Autophagy (CASA). Similar to our previously published findings for the VP40 proteins of Ebola and Marburg viruses, our results using VLP budding assays, BAG3 knockout cells, and confocal microscopy indicate that BAG3 is a WW-domain interactor that negatively regulates egress of LFV Z VLPs, rather than promoting VLP release. Our results suggest that CASA and specifically BAG3 may represent a novel host defense mechanism, whereby BAG3 may dampen egress of several hemorrhagic fever viruses by interacting and interfering with the budding function of viral PPxY-containing matrix proteins. Full article

The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia. Full article

In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000–2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000–2013) versus current (2014–2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation. Full article

Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension and cardiovascular disease (CVD). Therefore, the aim of this study was to analyse the remained potential of grape by-products from important Rhône Valley red wine cultivars: Grenache, Syrah, Carignan, Mourvèdre and Alicante. For that, six different extracts from grape pomaces, selected by their antioxidant activity, were studied in vivo during six weeks with spontaneously hypertensive rats (SHR). Extracts used in SHR1, SHR2 and SHR6 groups presented a « rebound effect » on systolic blood pressure, whereas the other extracts do not change it significantly. The bioavailability of Grenache (GRE1) (EA70) seed pomace extract (SHR1 group), Mouvendre (MOU) (EA70) skin pomace extract (SHR5 group) and Alicante (ALI) (EA70) skin pomace extract (SHR6 group) was studied by High Performance Liquid Chromatography with Photodiode Array detector and Electrospray Ionization Mass Spectrometer (HPLC-PDA-ESI-MSⁿ) in urine, plasma and tissues to search differences on the metabolism of the different extracts intake. Full article

Natural infection with dengue virus (DENV) induces an increase in the production of cytokines that play an important role in disease pathogenesis. Despite numerous scientific studies, there are still no commercially available disease-specific therapeutics. Previous evidence shows that inhibiting histone deacetylase enzymes (HDACs) regulates the immune response in several inflammatory disease models. The aim of the current study was to evaluate the effect of HDAC inhibition in the production of inflammatory cytokines in human monocyte-derived macrophages infected with DENV serotype 2 (DENV-2). To this end, human monocyte-derived macrophages (MDMs) were treated with valproic acid (VPA) before or after infection and the inflammatory cytokine concentration was quantified by flow cytometry. We found that infected MDMs secreted IL-8, IL-1b, IL-6, TNF-alpha, and IL-10, but not IL-12. Strikingly, treatment of infected cells with VPA had a differential and concentration-dependent effect on the production of specific cytokines without eliciting significant changes in cell viability. Using the highest concentration of VPA, a significant reduction in the production of all cytokines was observed. These results suggest that HDAC inhibition during DENV-2 infection could exert an important regulatory effect in the production of inflammatory cytokines, representing a significant advance in the design of novel therapeutic dengue treatments. Full article

The aim of this study was to assess the role of Action Observation (AO) to improve balance, gait, reduce falls, and to investigate the changes in P300 pattern. Five cognitively intact People with Parkinson’s disease (PwP) were enrolled in this prospective, quasi-experimental study to undergo a rehabilitation program of AO for gait and balance recovery of 60 min, three times a week for four weeks. The statistical analysis showed significant improvements for Unified Parkinson’s Disease Rating Scale (UPDRS) motor section III p = 0.0082, Short form 12-items Healthy Survey (SF-12) Mental Composite Score (MCS) p = 0.0007, Freezing of gait Questionnaire (FOG-Q) p = 0.0030, The 39-items Parkinson’s Disease Questionnaire (PDQ-39) p = 0.100, and for P300ld p = 0.0077. In conclusion, AO reveals to be a safe and feasible paradigm of rehabilitative exercise in cognitively preserved PwP. Full article

Although the development of effective viral vectors put gene therapy on the road to commercialization, nonviral vectors show promise for practical use because of their relative safety and lower cost. A significant barrier to the use of nonviral vectors, however, is that they have not yet proven effective. This apparent lack of interest can be attributed to the problem of the low gene transfer efficiency associated with nonviral vectors. The efficiency of gene transfer via nonviral vectors has been reported to be 1/10th to 1/1000th that of viral vectors. Despite the fact that new gene transfer methods and nonviral vectors have been developed, no significant improvements in gene transfer efficiency have been achieved. Nevertheless, some notable progress has been made. In this review, we discuss studies that report good results using nonviral vectors in vivo in animal models, with a particular focus on studies aimed at in vivo gene therapy to treat cancer, as this disease has attracted the interest of researchers developing nonviral vectors. We describe the conditions in which nonviral vectors work more efficiently for gene therapy and discuss how the goals might differ for nonviral versus viral vector development and use. Full article

Recent evidence has suggested that the gut microbiome is involved in human health and diseases, such as inflammatory bowel disease, liver cirrhosis, rheumatoid arthritis, and type 2 diabetes. Cardiovascular diseases, which are associated with high morbidity and mortality across the world, are no exception. Increasing evidence has suggested a strong relationship between the gut microbiome and the progression of cardiovascular diseases. We first reported such a relationship with coronary artery disease two years ago. Next-generation sequencing techniques, together with bioinformatics technology, constantly and dramatically expand our knowledge of the complex human gut bacterial ecosystem and reveal the exact role of this bacterial ecosystem in cardiovascular diseases via the functional analysis of the gut microbiome. Such knowledge may pave the way for the development of further diagnostics and therapeutics for prevention and management of cardiovascular diseases. The aim of the current review is to highlight the relationship between the gut microbiome and their metabolites, and the development of cardiovascular diseases by fostering an understanding of recent studies. Full article

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α-galactosidase that leads to a systemic accumulation of globotriaosylceramide. Handheld in vivo reflectance confocal microscopy (HH-RCM) is a useful modern technique in diagnosis and follow-ups of many skin diseases. This noninvasive device provides high-resolution and high-contrast real-time images to study both the skin and the ocular surface structures that can help clinicians to confirm the diagnosis of FD. HH-RCM could be helpful even for the follow-ups of these patients, enabling us to monitor the effect of enzyme replacement therapy on corneal cells and keratinocytes. Full article

Neurocysticercosis is a parasitosis caused by the larval stage of the pork tapeworm Taenia solium. The diagnosis is challenging as morphology on neuroimaging can be inconclusive and serology is frequently negative. We describe the case of a 24-year old Hispanic man who presented with seizures and loss of consciousness. Magnetic resonance imaging (MRI) showed a cystic mass in right frontal lobe. Work-up that included body computed tomography (CT) scan and Western blot serology for Echinococcus and cysticercosis was unrevealing. He underwent craniotomy with resection of the mass. Histopathology showed fragments of Taenia solium. He was treated with albendazole for 14 days. No further seizures were noted at 6-month follow-up. Full article