Topographic laparoscopy for buffaloes in the quadruped position.

This study aimed to describe the anatomical topography of the abdominal cavity of buffaloes in the quadruped position to establish the best endosurgical access and vantage points and identify possible limitations. Laparoscopies were performed on 10 healthy female buffaloes obtained from the Universidade Federal Rural da Amazônia to explore possible access points to the abdomen. Techniques for assessing and possibly observing certain organs and structures through the left and right flanks of 10 animals have been described. In five animals, access was created through the right side of the last intercostal space to allow more cranial access to the abdominal cavity. Despite the presence of the rumen, access through the left flank allowed the visualization of the structures of the gastrointestinal tract and the genitourinary system. With access through the right flank, however, imaging was hampered by the presence of the greater omentum and its deep and superficial walls, which prevented the progression of the endoscope. Access through the last right intercostal space allowed the visualization of the cranial structures of the abdominal cavity, such as the caudate process, right lobe of the liver, right kidney, and pancreas. Laparoscopic access through the left flank and the last intercostal space in healthy buffaloes in the quadruped position is feasible, and it is promising for the exploration, diagnosis, and treatment of various disorders in buffaloes.

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control.

Chikungunya fever is a mosquito-borne viral illness characterized by a sudden onset of fever associated with joint pains. It was first described in the 1950s during a Chikungunya virus (CHIKV) outbreak in southern Tanzania and has since (re-) emerged and spread to several other geographical areas, reaching large populations and causing massive epidemics. In recent years, CHIKV has gained considerable attention due to its quick spread to the Caribbean and then in the Americas, with many cases reported between 2014 and 2017. CHIKV has further garnered attention due to the clinical diagnostic difficulties when Zika (ZIKV) and dengue (DENV) viruses are simultaneously present. In this review, topical CHIKV-related issues, such as epidemiology and transmission, are examined. The different manifestations of infection (acute, chronic and atypical) are described and a particular focus is placed upon the diagnostic handling in the case of ZIKV and DENV co-circulating. Natural and synthetic compounds under evaluation for treatment of chikungunya disease, including drugs already licensed for other purposes, are also discussed. Finally, previous and current vaccine strategies, as well as the control of the CHIKV transmission through an integrated vector management, are reviewed in some detail.

Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

Emerging and re-emerging viral infections transmitted by insect vectors (arthopode-borne viruses, arbovirus) are a serious threat to global public health. Among them, yellow fever (YFV), dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses are particularly important in tropical and subtropical regions. Although vector control is one of the most used prophylactic measures against arboviruses, it often faces obstacles, such as vector diversity, uncontrolled urbanization and increasing resistance to insecticides. In this context, vaccines may be the best control strategy for arboviral diseases. Here, we provide a general overview about licensed vaccines and the most advanced vaccine candidates against YFV, DENV, CHIKV and ZIKV. In particular, we highlight vaccine difficulties, the current status of the most advanced strategies and discuss how the molecular characteristics of each virus can influence the choice of the different vaccine formulations.

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

ABSTRACT Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years—many of which are based on single centers and small cohorts, with a low level of evidence—many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications.

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years-many of which are based on single centers and small cohorts, with a low level of evidence-many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

Functional Independence following Endovascular Treatment for Basilar Artery Occlusion despite Extensive Bilateral Pontine Infarcts on Diffusion-Weighted Imaging: Refuting a Self-Fulfilling Prophecy.

BACKGROUND AND PURPOSE: Extensive brainstem diffusion-weighted imaging (DWI) hyperintensity has been associated with poor outcomes. We aim at documenting a series of patients with extensive DWI pontine lesions who achieved independence following endovascular therapy and aggressive medical therapy in the setting of posterior circulation basilar artery occlusion (BAO). METHODS: This is a retrospective endovascular database review of a single-operator experience over a 9-year period for patients with (1) complete BAO, (2) extensive bilateral pontine DWI changes and (3) 90-day modified Rankin scale 0-2. RESULTS: Three out of a total of 40 patients met the inclusion criteria. Case 1 was an 18-year-old male with National Institutes of Health Stroke Scale (NIHSS) 32 on admission, treated 25 h after symptom onset. Case 2 was a 56-year-old male with NIHSS 19, treated 10 h after onset. Case 3 was a 73-year-old male with NIHSS 29, treated 6 h after onset. Full endovascular reperfusion was achieved in all 3 patients. A literature review identified 9 additional cases of extensive pontine DWI changes and good outcome. These patients were young (32 ± 22 years), mostly males (69%), presented with a relatively low posterior circulation Acute Stroke Prognosis Early CT Score (6 ± 1), were treated relatively late from last known normal (13 ± 10 h) and were mostly (84%) treated with endovascular intervention. CONCLUSION: Extensive bilateral pontine DWI lesions among patients with BAO are not an unequivocal indicator of poor prognosis. We advise strong caution when considering these findings in the treatment decision algorithm.

Intestinal epithelial restitution after TcdB challenge and recovery from Clostridium difficile infection in mice with alanyl-glutamine treatment.

BACKGROUND: Clostridium difficile is an anaerobic bacterium that causes antibiotic-associated diarrhea. It produces toxin A and toxin B (TcdB), which cause injury to the gut epithelium. Glutamine is a fundamental fuel for enterocytes, maintaining intestinal mucosal health. Alanyl-glutamine (AQ) is a highly soluble dipeptide derivative of glutamine. We studied whether administration of AQ ameliorates the effects of TcdB in the intestinal cells and improves the outcome of C. difficile infection in mice. METHODS: WST-1 proliferation and cell-wounding-migration assays were assessed in IEC-6 cells exposed to TcdB, with or without AQ. Apoptosis and necrosis were assessed using Annexin V and flow cytometry. C57BL/6 mice were infected with VPI 10463 and treated with either vancomycin, AQ, or vancomycin with AQ. Intestinal tissues were collected for histopathologic analysis, apoptosis staining, and determination of myeloperoxidase activity. RESULTS: AQ increased proliferation in intestinal cells exposed to TcdB, improved migration at 24 and 48 hours, and reduced apoptosis in intestinal cells challenged with TcdB. Infected mice treated with vancomycin and AQ had better survival and histopathologic findings than mice treated with vancomycin alone. CONCLUSIONS: AQ may reduce intestinal mucosal injury in C. difficile-infected mice by partially reversing the effects of TcdB on enterocyte proliferation, migration, and apoptosis, thereby improving survival from C. difficile infection.

A proteomic insight into the effects of the immunomodulatory hydroxynaphthoquinone lapachol on activated macrophages.

We report the effect of an immunomodulatory and anti-mycobacterial naphthoquinone, lapachol, on the bi-dimensional patterns of protein expression of toll-like receptor 2 (TLR2)-agonised and IFN-γ-treated THP-1 macrophages. This non-hypothesis driven proteomic analysis intends to shed light on the cellular functions lapachol may be affecting. Proteins of both cytosol and membrane fractions were analysed. After quantification of the protein spots, the protein levels corresponding to macrophages activated in the absence or presence of lapachol were compared. A number of proteins were identified, the levels of which were appreciably and significantly increased or decreased as a result of the action of lapachol on the activated macrophages: cofilin-1, fascin, plastin-2, glucose-6-P-dehydrogenase, adenylyl cyclase-associated protein 1, pyruvate kinase, sentrin-specific protease 6, cathepsin B, cathepsin D, cytosolic aminopeptidase, proteasome ß type-4 protease, tryptophan-tRNA ligase, DnaJ homolog and protein disulphide isomerase. Altogether, the comparative analysis performed indicates that lapachol could be hypothetically causing an impairment of cell migration and/or phagocytic capacity, an increase in NADPH availability, a decrease in pyruvate concentration, protection from proteosomal protein degradation, a decrease in lysosomal protein degradation, an impairment of cytosolic peptide generation, and an interference with NOS2 activation and grp78 function. The present proteomic results suggest issues that should be experimentally addressed ex- and in-vivo, to establish more accurately the potential of lapachol as an anti-infective drug. This study also constitutes a model for the pre-in-vivo evaluation of drug actions.

The hydroxy-naphthoquinone lapachol arrests mycobacterial growth and immunomodulates host macrophages.

The present study reports the anti-mycobacterial activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol) as well as its influence on macrophage functions. Lapachol (L) did not induce apoptosis/necrosis of THP-1 macrophages at ≤32 µg/mL. Mycobacterium avium liquid growth was arrested by ≥32 µg/mL and intra-macrophage proliferation by ≥16 µg/mL lapachol. The main immuno-modulatory effects of lapachol observed were an up-regulation of interferon-γ-receptor 1 (IFN-γR1) and major histocompatibility complex class II (MHCII) surface expression, and a marked inhibition of IL-10 secretion. Lapachol did not affect resting, IFN-γ- or toll-like receptor 2 (TLR2)-induced levels of oxygen and nitrogen metabolism key proteins nor the TLR2-mediated secretion of TNF-α, nor induced either oxidative or endoplasmic reticulum (ER) stress. Lapachol inhibited the surface expression of the co-stimulatory molecule CD86 but not that of CD80 and CD83. The results obtained indicate that the substituted naphthoquinone lapachol exhibits an anti-mycobacterial activity that is more efficient intra- than extra-cellularly, and exerts immuno-modulatory effects some of which may enhance the capacity of the host cell to control mycobacterial growth. The immune-modulatory action of lapachol could contribute to its more efficient intra-macrophage anti-mycobacterial activity.