536 research outputs found

    Diagnosis and management of adrenal incidentalomas

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    PURPOSE: The incidental discovery of adrenal masses has become a common clinical problem. We address current trends in clinical, endocrine, radiological and scintigraphic evaluation, and strategies for management of adrenal masses. A diagnostic and therapeutic algorithm is suggested. MATERIALS AND METHODS: A comprehensive review of the literature was performed using MEDLINE, bibliographies of select articles, current issues of peer reviewed general medicine, endocrinology, diagnostic imaging and surgical journals, and meeting abstracts of recent international congresses. RESULTS: Most adrenal incidentalomas are benign and nonhypersecreting but all should be evaluated to exclude from diagnosis hypersecretory syndromes or malignancy. In all cases hormonal screening for pheochromocytoma, hyperaldosteronism and subclinical hypercortisolism should be performed. Attenuation values on computerized tomography, chemical shift magnetic resonance imaging and scintigraphy reveal the nature of the mass in most cases. Fine needle aspiration biopsy should be reserved for cases suspected of extra-adrenal malignancy. CONCLUSIONS: A multidisciplinary approach, including hormonal screening, radiological evaluation and scintigraphy, is required to identify and remove adrenal masses with endocrine and oncological morbidity. Long-term morphofunctional followup is suggested for nonoperated cases

    Ongoing and emerging arbovirus threats in Europe

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    During the last decades, arboviruses that are endemic in Europe have expanded their geographic range and caused an increasing number of human outbreaks. These viruses include West Nile virus, which is expanding its area of circulation in central and southern Europe; Usutu virus, with increasing evidence of a role in human disease; tick-borne encephalitis virus, which is being detected in northern areas and at higher altitudes as a consequence of climate warming; Crimean-Congo hemorrhagic fever virus, which is endemic in Eastern Europe and the Middle East, but has been recently detected in Spain; other viruses, such as California encephalitis virus antigenic group, which circulate in northern and central Europe but whose relevance for human disease in largely unknown. In addition, the rise in global travel and trade has posed Europe to an increased risk of introduction and expansion of exotic arthropod vectors and autochthonous transmission of arboviruses, like dengue and chikungunya viruses, following new introductions from endemic areas. Implementation of integrated arbovirus surveillance programs has been crucial to adopt proper control measures. The identification of emerging outbreaks is however challenging and requires a high degree of awareness and laboratory capacity, especially for the most neglected but potentially threatening pathogens

    Current views on Zika virus vaccine development

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    Zika virus (ZIKV) is a mosquito-borne flavivirus, which was identified in 1947 in the Zika Forest of Uganda. The virus has emerged in the recent years and caused large human outbreaks in the Pacific area (Yap Island in 2007; French Polynesia in 2013 to 2014) and in the Americas (since late 2014). As of 8 June 2017, according to the Pan American Health Organization/World Health Organization, 48 countries in South America, Central America, and Caribbean reported ZIKV outbreaks, with a total of 212,545 confirmed cases of infection and 565,749 suspected cases. In addition, in 2016, Florida and Texas (USA) observed 225 autochthonous cases of ZIKV infection. The incidence was estimated as about 200 cases/100,000 population in countries like Brazil, Colombia, and Venezuela, where large and intense epidemic waves were registered during the first half of 2016. Although ZIKV transmission has significantly decreased in the region during the second half of 2016, most of the countries are still reporting cases of infection. Outsides the Americas, areas of ongoing intense transmission include countries in Asia (Singapore, Thailand, Vietnam, Malaysia, and the Philippines), Africa (Angola), and the South Pacific region (American Samoa)

    Recent developments in vaccines and biological therapies against Japanese encephalitis virus

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    Japanese encephalitis is the most common vaccine-preventable encephalitis in the Asia-Pacific region. Areas covered: We provide an overview on Japanese encephalitis virus and associated disease, review the results of studies on the immunogenicity and efficacy of the licensed vaccines, and describe the new vaccines that are under development. We also discuss data on candidate anti-Japanese encephalitis drugs that have shown promising results in experimental models. Expert opinion: The global burden of the Japanese encephalitis and associated mortality is still high, thus emphasizing the need to achieve the highest vaccination coverage in endemic areas. Clinical trials exhaustively demonstrated the safety and efficacy of current Japanese encephalitis vaccines. In addition, several new vaccine candidates, characterized by high immunogenicity and broad cross-protection, have been developed and evaluated in experimental models, warranting further clinical testing. No licensed anti-Japanese encephalitis drugs are available, notwithstanding intense research efforts. Some candidate antiviral agents that inhibit viral entry and replication have been identified, including compounds with broad-spectrum antiviral activity. Further research is needed to refine candidate compounds into drugs suitable for clinical evaluation, characterized by low toxicity, ability to penetrate the blood-brain barrier, activity during the late phase of infection, and high genetic barrier to resistance

    Zika virus infection in semen: Effect on human reproduction

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    Unique among vector-borne flaviviruses, Zika virus can infect testis and male genital tract, can persist in semen for months after symptoms onset, and be sexually transmitted. In The Lancet Infectious Diseases, Guillaume Joguet and colleagues report alterations of sperm and testicular function in men with Zika virus infection, with potential effect on human reproduction. In this prospective longitudinal study, the authors detected viral RNA in the semen of 11 of 15 tested men, including five with persistent seminal shedding after viral clearance in blood. Notably, they were able to isolate infectious virus from motile spermatozoa obtained using semen separation methods that are generally used in assisted reproductive procedures. Semen alterations were observed, including a decreased sperm count and a concurrent increment of multiple sperm anomalies, especially in patients with Zika virus RNA-positive seminal specimens, while recovery was observed at day 120 post infection. In addition, inhibin β concentrations decreased after infection, suggesting an impairment of Sertoli cells, which are key components of the blood–testis barrier, produce immunoregulatory factors, and provide support to sperm cells during spermatogenesis. These findings suggest a direct effect of viral infection on the testis or epididymis with impairment of sperm development, in agreement with findings in animal models

    West Nile Virus Infections in (European) Birds

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    West Nile virus (WNV), a member of the Flaviviridae family is an important emerging pathogen transmitted by mosquitoes of the Culex sp . wild-and (peri) domesticated birds act as the natural hosts of WNV. Birds are not only susceptible to WNV, but also participate in maintaining the transmission cycle

    West Nile virus and kidney disease

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    West Nile virus (WNV), the causative agent of West Nile fever and West Nile neuroinvasive disease in humans, has become endemic in many countries in all continents. Concerns on long-term mobility from WNV have arisen from recent studies that reported chronic kidney disease in patients who recovered from WNV infection, supported by data from animal models that showed prolonged excretion of the virus with urine. The purpose of this review is to summarize and discuss the results of studies in the literature that investigated WNV infection of the kidney in humans and in animal models and WNV excretion with urine, the potential damage to the kidney caused by WNV infection, the risk of WNV disease in kidney transplant recipients, the significance of detecting WNV in urine and its use in the diagnosis of WNV infection, and kidney involvement by other mosquito-borne flaviviruses

    Genome editing technologies to fight infectious diseases

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    Genome editing by programmable nucleases represents a promising tool that could be exploited to develop new therapeutic strategies to fight infectious diseases. These nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) and homing endonucleases, are molecular scissors that can be targeted at predetermined loci in order to modify the genome sequence of an organism. Areas covered: By perturbing genomic DNA at predetermined loci, programmable nucleases can be used as antiviral and antimicrobial treatment. This approach includes targeting of essential viral genes or viral sequences able, once mutated, to inhibit viral replication; repurposing of CRISPR-Cas9 system for lethal self-targeting of bacteria; targeting antibiotic-resistance and virulence genes in bacteria, fungi, and parasites; engineering arthropod vectors to prevent vector-borne infections. Expert commentary: While progress has been done in demonstrating the feasibility of using genome editing as antimicrobial strategy, there are still many hurdles to overcome, such as the risk of off-target mutations, the raising of escape mutants, and the inefficiency of delivery methods, before translating results from preclinical studies into clinical applications

    KDM2B in papillomavirus-related cancer

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    Human papillomaviruses (HPVs) are small viruses with a circular double-stranded DNA genome that specifically infect mucosal and cutaneous stratified squamous epithelia. HPV life cycle is tightly linked to the differentiation program of host epithelial cells. The virus infects proliferating cells of the basal layer of epithelia, probably targeting cells with stemness features, and exploits host replication machinery for viral DNA synthesis. As infected cells differentiate while moving up in the epithelium, viral proteins are synthesized allowing assembly of viral particles and their release with exfoliated epithelial cells. Most HPV infections are cleared within two years; however, in some cases, infection may persist, especially with the so-called high-risk HPV types, which are drivers for malignant transformation. High-risk HPVs, especially HPV16 and HPV18, are the causative agents of virtually all cases of cervical cancer and of a proportion of other ano-genital malignancies and head and neck squamous cell carcinomas
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