Advances in the Physiology of Transvascular Exchange and A New Look At Rational Fluid Prescription.

The Starling principle is a model that explains the transvascular distribution of fluids essentially governed by hydrostatic and oncotic forces, which dynamically allow vascular refilling according to the characteristics of the blood vessel. However, careful analysis of fluid physiology has shown that the principle, while correct, is not complete. The revised Starling principle (Michel-Weinbaum model) provides relevant information on fluid kinetics. Special emphasis has been placed on the endothelial glycocalyx, whose subendothelial area allows a restricted oncotic pressure that limits the reabsorption of fluid from the interstitial space, so that transvascular refilling occurs mainly from the lymphatic vessels. The close correlation between pathological states of the endothelium (eg: sepsis, acute inflammation, or chronic kidney disease) and the prescription of fluids forces the physician to understand the dynamics of fluids in the organism; this will allow rational fluid prescriptions. A theory that integrates the physiology of exchange and transvascular refilling is the "microconstant model", whose variables include dynamic mechanisms that can explain edematous states, management of acute resuscitation, and type of fluids for common clinical conditions. The clinical-physiological integration of the concepts will be the hinges that allow a rational and dynamic prescription of fluids.

Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.

Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and radiotherapy and further adjuvant chemotherapy if necessary. Despite this regimen, prognosis remains grim. Immunotherapy has shown promising success in a variety of solid tumor types, but efficacy in glioblastoma is yet to be demonstrated. Barriers to the success of immunotherapy in glioblastoma include: a heterogeneous tumor cell population, a highly immunosuppressive microenvironment, and the blood-brain barrier, to name a few. Several immunotherapeutic approaches are actively being investigated and developed to overcome these limitations. In this review, we present different classes of immunotherapy targeting glioblastoma, their most recent results, and potential future directions.

Mechanism of Action and Efficacy of Immunosupressors in Lupus Nephritis.

Approximately 70% of the patients with systemic lupus erythematosus will have clinical evidence of kidney damage during their evolution. Patients with impaired renal function at onset and those with recurrent flares have a poor prognosis. Understanding the mechanism of action of immunosuppressants is essential for proper prescription. Steroids inhibit the DNA sequence that promotes the release of inflammatory cytokines. Phosphoramide mustard, metabolite of cyclophosphamide, cross-link with the DNA, causing the aggregation of an alkyl group, causing cell death. Mycophenolate inhibits inosine monophosphate dehydrogenase, prevents de novo synthesis of guanine, inducing cell arrest in S phase. Azathioprine blocks the synthesis of purines and induces apoptosis. Calcineurin inhibitors prevent the dephosphorylation of NFAT and reduce the production of interleukin 2. Antimalarials alter the enzymatic release of lysosomes by increasing intravesicular pH. The mechanism of action of rituximab is related to complement-dependent cytotoxicity and the elimination of anti-CD20-labeled B cells. Progress in the knowledge and management of low doses of steroids may change the current paradigm and reduce the frequency of related adverse events. Mycophenolate seems to be a better choice than cyclophosphamide for induction, it is also preferred over azathioprine as a maintenance immunosuppressive agent, although azathioprine is preferred in women with a desire for conception, those pregnant, or with low resources. For treatment-resistant cases, tacrolimus, rituximab or belimumab may be effective. Ongoing clinical trials with new drugs offer promising results.

Saccharomyces boulardii modulates oxidative stress and renin angiotensin system attenuating diabetes-induced liver injury in mice.

Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.

Coral reef restoration efforts in Latin American countries and territories.

Coral reefs worldwide are degrading due to climate change, overfishing, pollution, coastal development, coral bleaching, and diseases. In areas where the natural recovery of an ecosystem is negligible or protection through management interventions insufficient, active restoration becomes critical. The Reef Futures symposium in 2018 brought together over 400 reef restoration experts, businesses, and civil organizations, and galvanized them to save coral reefs through restoration or identify alternative solutions. The symposium highlighted that solutions and discoveries from long-term and ongoing coral reef restoration projects in Spanish-speaking countries in the Caribbean and Eastern Tropical Pacific were not well known internationally. Therefore, a meeting of scientists and practitioners working in these locations was held to compile the data on the extent of coral reef restoration efforts, advances and challenges. Here, we present unpublished data from 12 coral reef restoration case studies from five Latin American countries, describe their motivations and techniques used, and provide estimates on total annual project cost per unit area of reef intervened, spatial extent as well as project duration. We found that most projects used direct transplantation, the coral gardening method, micro-fragmentation or larval propagation, and aimed to optimize or scale-up restoration approaches (51%) or provide alternative, sustainable livelihood opportunities (15%) followed by promoting coral reef conservation stewardship and re-establishing a self-sustaining, functioning reef ecosystems (both 13%). Reasons for restoring coral reefs were mainly biotic and experimental (both 42%), followed by idealistic and pragmatic motivations (both 8%). The median annual total cost from all projects was $93,000 USD (range: $10,000 USD-$331,802 USD) (2018 dollars) and intervened a median spatial area of 1 ha (range: 0.06 ha-8.39 ha). The median project duration was 3 years; however, projects have lasted up to 17 years. Project feasibility was high with a median of 0.7 (range: 0.5-0.8). This study closes the knowledge gap between academia and practitioners and overcomes the language barrier by providing the first comprehensive compilation of data from ongoing coral reef restoration efforts in Latin America.

Evaluation of the masticatory muscle function, physiological sleep variables, and salivary parameters after electromechanical therapeutic approaches in adult patients with Down syndrome: a randomized controlled clinical trial.

BACKGROUND: There are many comorbidities associated with Down syndrome (DS), including obstructive sleep apnea (OSA) and masticatory muscle alteration. Muscular hypotonia, in particular, of the masticatory and oropharyngeal muscles is one of the main characteristics of individuals with DS, resulting in impairments of speech, swallowing, and mastication in these individuals. In addition, total or partial obstruction of the airways during sleep can occur due to pharyngeal hypotonia, leading to snoring and to OSA. This progressive respiratory disorder is associated with a high risk of morbidity and mortality in individuals with DS. The aim of this research is to assess the therapeutic effects of surface neuromuscular electrical stimulation (NMES), the mastication apparatus (MA), and a mandibular advancement oral appliance (OAm) with an embedded thermosensitive microchip on the functions of masticatory muscles (bilateral masseter and temporal muscles), physiological sleep variables, and salivary parameters in adult patients with DS. METHODS: The patients with DS will be randomly selected and divided into three groups (DS-NMES, DS-MA, and DS-OAm) with a minimum of 10 patients in each group. A thermosensitive microchip will be embedded in the OAm to record its compliance. The therapeutic effects on masticatory muscle function will be investigated through electromyography, a caliper, and a force-transducer device; the sleep variables, in turn, will be evaluated by means of polysomnography. The physicochemical and microbiological properties of the saliva will also be analyzed, including the salivary flow, viscosity, buffer capacity, cortisol levels (susceptibility to psychological and/or physical stress), and Pseudomonas aeruginosa levels (risk of aspiration pneumonia) in these patients. The methods determined for this study will be carried out prior to and after 2 months of the recommended therapies. DISCUSSION: The primary outcomes would be the improvement and/or reestablishment of the function of masticatory muscles and the physiological sleep variables in this target public since individuals with DS commonly present generalized muscular hypotonia and dysfunction of the oropharyngeal musculature. As a secondary outcome indicator, the impact of the applied therapies (NMES, MA, and OAm) on the salivary microbiological and physicochemical properties in DS individuals will also be assessed. Furthermore, the compliance of OAm usage will be measured through a thermosensitive microchip. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos, RBR-3qp5np . Registered on 20 February 2018.

Promising vaccines for treating glioblastoma.

INTRODUCTION: Conventional therapies for glioblastoma  (GBM) typically fail to provide lasting antitumor benefits, owing to their inability to specifically eliminate all malignant cells. Cancer vaccines are currently being evaluated as a means to direct the adaptive immune system to target residual GBM cells that remain following standard-of-care treatment. AREAS COVERED: In this review, we provide an overview of the more noteworthy cancer vaccines that are under investigation for the treatment of GBM, as well as potential future directions that may enhance GBM-vaccine effectiveness. EXPERT OPINION: To date, no cancer vaccines have been proven effective against GBM; however, only a few have reached phase III clinical testing. Clinical immunological monitoring data suggest that GBM vaccines are capable of stimulating immune responses reactive to GBM antigens, but whether these responses have an appreciable antitumor effect on GBM is still uncertain. Nevertheless, there have been several promising outcomes in early phase clinical trials, which lend encouragement to this area of study. Further studies with GBM vaccines are, therefore, warranted.

Infrared laser photobiomodulation (lambda 830 nm) on bone tissue around dental implants: a Raman spectroscopy and scanning electronic microscopy study in rabbits.

OBJECTIVE: The aim of this study was to assess, through Raman spectroscopy, the incorporation of calcium hydroxyapatite (CHA; approximately 960 cm(1)), and scanning electron microscopy (SEM), the bone quality on the healing bone around dental implants after laser photobiomodulation (lambda830 nm). BACKGROUND DATA: Laser photobiomodulation has been successfully used to improve bone quality around dental implants, allowing early wearing of prostheses. METHODS: Fourteen rabbits received a titanium implant on the tibia; eight of them were irradiated with lambda830 nm laser (seven sessions at 48-h intervals, 21.5 J/cm(2) per point, 10 mW, phi approximately 0.0028 cm(2), 86 J per session), and six acted as control. The animals were sacrificed 15, 30, and 45 days after surgery. Specimens were routinely prepared for Raman spectroscopy and SEM. Eight readings were taken on the bone around the implant. RESULTS: The results showed significant differences on the concentration of CHA on irradiated and control specimens at both 30 and 45 days after surgery (p < 0.001). CONCLUSION: It is concluded that infrared laser photobiomodulation does improve bone healing, and this may be safely assessed by Raman spectroscopy or SEM.