Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Primary malignant epithelioid hemangioendothelioma of the pleura: A review and report of a novel case

Epithelioid hemangioendothelioma is considered an uncommon tumor originating from vascular tissues. Although this disease is an extremely rare malignant cancer, its pleural subtype is even less common. We discuss a 68‐year‐old man with isolated pleural epithelioid hemangioendothelioma, along with a literature review of all similar cases.     

Immobilization effect of Ruta graveolens L. on human sperm: a new hope for male contraception

AIM OF THE STUDY: Contraceptive plants which were introduced by folk in traditional remedies are investigated worldwide. In this study, the contraceptive effects of Ruta graveolens L., which has been mentioned for male contraceptive in Iranian traditional folk medicine, was experimented on human sperm. MATERIALS AND METHODS: Different doses of lyophilized aqueous extract of Ruta graveolens L. were added to an amount of fresh semen, containing 10(6) cells in a 1:1 volumic ratio. Motility and viability of cells, DNA status, mitochondrial activity and sperm revival tests were carried out. RESULTS: The sperm immobilization effects of the extract appeared immediately in a does-dependent manner and 100% of the sperms became immotile at a concentration of 100mg/ml but other parameters were intact. After washing the sperms, motility was returned in 30.8+/-3.2% of the sperms, besides coiled tails in 38.6+/-5.5% of the treated cells, in comparison to 12.5+/-2.0% of the control group (p=0.001). The part of the extract, responsible for immobilization of the sperms was stable upon boiling. CONCLUSIONS: As the cells were alive and immotile, probably some ionic currents are blocked by a thermostable component of the plant which can be promising as a new male channel blocker contraceptive.     

Down syndrome due to partial trisomy 21q

A patient is reported with a typical Down syndrome phenotype, caused by patrial trisomy of chromosome 21. Based on the present case and data from the literature, it is suggested that the Down phenotype is due to the trisomy of the distal portion of the band (q22) of chromosome 21.     

Platelet-rich fibrin (PRF) gel modified by a carbodiimide crosslinker for tissue regeneration

Platelet-rich fibrin (PRF) as a rich source of effective growth factors has been used as a scaffold in tissue regeneration. It is known that PRF exhibits rapid degradability against enzymes, which should be decreased using crosslinking agents to reduce the release rate of growth factors and increase the effectiveness of tissue regeneration. In this study, a carbodiimide crosslinker with different concentrations (0.01%, 0.05%, 1%, and 2%) was used to modify and improve the properties of PRF gel. The crosslinked gels were evaluated with analyses such as SEM, swelling, degradability, mechanical strength, release test, cytotoxicity, and cell adhesion. The results showed that with increasing crosslinker concentration, the morphology of the fiber structure changes drastically, the swelling rate decreases from 300% (control) to 160% for the crosslinked gel, the degradation time for the control sample increases from 8 days to more than two weeks for the crosslinked gel, and the Young''s modulus increases from 0.15 MPa (control) to 0.61 MPa for the crosslinked samples. Growth factors also showed lower release with increasing crosslinking ratio. Cytotoxicity assays demonstrated that by increasing the crosslinker concentration to 1% w/v, no cytotoxicity was observed. Cellular studies with DAPI staining showed that the cells penetrated well into the gels and were well distributed, especially in gels with lower crosslinker concentrations. In addition, the modified PRF gel can be used as a scaffold for tissue regeneration.

1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) as a crosslinker can improve the physical and mechanical properties of PRF gel by forming covalent bonds.     

Prospective analysis of a surgical algorithm to achieve ventilator weaning in cervical tetraplegia

Objectives: Chronic ventilator dependency in cervical tetraplegia is associated with substantial morbidity. When non-invasive weaning methods have failed the primary surgical treatment is diaphragm pacing. Phrenic nerve integrity and diaphragm motor units are requirements for effective pacing but may need to be restored for successful weaning. A surgical algorithm that includes: 1. Diaphragm pacing, 2. Phrenic nerve reconstruction, and 3. Diaphragm muscle replacement, may provide the capability of reducing or reversing ventilator dependency in virtually all cervical tetraplegics.Design: Prospective case series.Setting: A university-based hospital from 2015 to 2019.Participants: Ten patients with ventilator-dependent cervical tetraplegia.Interventions: I. Pacemaker alone, II. Pacemaker + phrenic nerve reconstruction, or III. Pacemaker + diaphragm muscle replacement.Outcome measures: Time from surgery to observed reduction in ventilator requirements (↓VR), ventilatory needs as of most recent follow-up [no change (NC), partial weaning (PW, 1–12 h/day), or complete weaning (CW, >12 h/day)], and complications.Results: Both patients in Group I achieved CW at 6-month follow-up. Two patients in Group II achieved CW, and in another two patients PW was achieved, at 1.5–2-year follow-up. The remaining two patients are NC at 6 and 8-month follow-up, respectively. In group III, both patients achieved PW at 2-year follow-up. Complications included mucous plugging (n = 1) and pacemaker malfunction requiring revision (n = 3).Conclusion: Although more investigation is necessary, phrenic nerve reconstruction or diaphragm muscle replacement performed (when indicated) with pacemaker implantation may allow virtually all ventilator-dependent cervical tetraplegics to partially or completely wean.     

Constrictive pericarditis in systemic lupus erythematosus. demonstration of immunoglobulins in the pericardium

A 17-year-old male with systemic lupus erythematosus presented with clinical signs of severe constrictive pericarditis that was confirmed by cardiac catheterization. At surgery, a fibrous pericardium was removed, followed by complete relief of symptoms. Immunopathology of the pericardial tissue revealed deposition of IgG, IgM, and C3. A review of the literature produced only three similar cases. Although rare, constrictive pericarditis, a potentially life threatening complication, may occur in systemic lupus erythematosus presumably with an immunological basis.     

Revolutionary Impact of Nanodrug Delivery on Neuroscience

Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders.