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Tick-Borne Encephalitis Virus Infection Alters the Sialome of Ticks During the Earliest Stages of Feeding.

Ticks are hematophagous arthropods that transmit a number of pathogens while feeding. Among these is tick-borne encephalitis virus (TBEV), a flavivirus transmitted by ticks in the temperate zone of Europe. The infection results in febrile illness progressing to encephalitis and meningitis with a possibility of fatality or long-term neurological sequelae. The composition of tick saliva plays an essential role in the initial virus transmission during tick feeding. Ticks secrete a diverse range of salivary proteins to modulate the host response, such as lipocalins to control the itch and inflammatory response, and both proteases and protease inhibitors to prevent blood coagulation. Here, the effect of viral infection of adult females of was studied with the goal of determining how the virus alters the tick sialome to modulate host tissue response at the site of infection. Uninfected ticks or those infected with TBEV were fed on mice and removed and dissected one- and 3-h post-attachment. RNA from the salivary glands of these ticks, as well as from unfed ticks, was extracted and subjected to next-generation sequencing to determine the expression of key secreted proteins at each timepoint. Genes showing statistically significant up- or down-regulation between infected and control ticks were selected and compared to published literature to ascertain their function. From this, the effect of tick viral infection on the modulation of the tick-host interface was determined. Infected ticks were found to differentially express a number of uncategorized genes, proteases, Kunitz-type serine protease inhibitors, cytotoxins, and lipocalins at different timepoints. These virus-induced changes to the tick sialome may play a significant role in facilitating virus transmission during the early stages of tick feeding.

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[Migraine burden and clinical inertia: what can we do?]

To study the compliance of neurologists and headache specialists to chronic headache and chronic migraine (CM) diagnosis and treatment guidelines.

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A Patient with Complex Gout with an Autoinflammatory Syndrome and a Sternoclavicular Joint Arthritis as Presenting Symptoms.

A 50-year-old man presented to the emergency department with widespread pain, especially at the chest level, fever, and night sweats. Physical examinations revealed a swelling with localized pain in the left sternoclavicular joint. Laboratory tests showed a CPR of 134 mg/l and an ESR of 70 mm/h. The patient's anamnesis is, for a chronic gouty arthritis, poorly controlled type 2 diabetes and a lumbosacral radicular syndrome. Home therapy includes metformin, sitagliptin, gliclazide, naproxen with partial benefit on pain, and febuxostat. Differential diagnoses of sternoclavicular swelling include infection, crystal or psoriatic arthropathy, tumor pathology, SAPHO syndrome, and osteoarthritis. An ultrasound scan performed at the thoracic level showed the presence of effusion in the sternoclavicular joint. A thoracoabdominal CT scan, performed in doubt of neoplasias, shows no masses but osteostructural nonspecific alterations of the sternoclavicular joint. We performed a dual energy CT (DECT) which reports a gouty arthropathy at the sternoclavicular joints (in the literature, only three similar cases are proved). Because of the poor therapeutic effects using febuxostat and systemic corticosteroids, the patient was treated with anakinra, an interleukin 1 receptor antagonist, which led, 6 months after the event, to a total remission.

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Singapore SPICE: Sedation Practices in Intensive Care Evaluation in Singapore – a prospective cohort study of the public healthcare system.

A study was conducted to describe the sedation practices of Singapore intensive care units (ICUs) in terms of drug use, sedation depth and the incidence of delirium in both early (< 48 hours) and late (> 48 hours) periods of ICU admission.

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A tool to improve functional outcome assessment of a multimodal program for patients with chronic low back pain: A study on walk tests (at comfortable and fast speed).

Tools for functional assessment of chronic low back pain (LBP) are lacking.

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Severe Colitis Caused by Hepatic Arterial Infusion Chemotherapy with Cisplatin for Hepatocellular Carcinoma.

A 78-year-old man with chronic hepatitis C underwent hepatectomy for hepatocellular carcinoma (HCC) 11 years prior to presentation. He was diagnosed with multiple intrahepatic recurrences of HCC with portal vein invasion and received hepatic arterial infusion chemotherapy (HAIC) with cisplatin. He developed abdominal pain, diarrhea, and blood-stained stool following treatment. Computed tomography revealed significant bowel wall thickening throughout the colon. Colonoscopy revealed reddish edematous mucosa with a reduced vascular pattern without ischemic changes. Conservative treatment with total parenteral nutrition improved his condition and his imaging findings. This is the first report of severe colitis following HAIC with cisplatin.

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β-blockers: their new life from hypertension to cancer and migraine.

The pharmacological class of β-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect that may span far beyond the cardiovascular system. Although all these compounds share the pharmacological blockade of the adrenergic receptors, each of them is characterized by specific pharmacological properties, including selectivity of action depending on the adrenergic receptors subtypes, intrinsic sympathomimetic activity (ISA), lipid solubility, pharmacokinetic profile, and also other ancillary properties that impact their clinical effect. Their use in the treatment of hypertension has been extensively debated and at the moment a class indication is not present. However, in specific niche of patients, such as in those young individuals in which hypertension is mainly driven by a sympathetic hyperactivation, strong evidence pose β-Blockers as a highly reasonable first-line treatment. Lipophilic β-blockers, specifically propranolol and metoprolol, can cross the Blood Brain Barrier and have a Class A indication for the prophylactic treatment of migraine attacks. Moreover, since β-adrenergic receptors affect the proliferative process of both cancer and immune cells, their blockade has been associated with metastasis reduction in several epithelial and solid organ tumors posing β-Blockers as a new attractive, inexpensive and relatively safe therapeutic strategy in patients with several types of cancer. However, further dedicated prospective, randomized, placebo-controlled studies are needed to determine the real efficacy of these compounds.

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Ultrasound-guided rectus sheath block: an anatomic study in dog cadavers.

To describe the ultrasound-guided rectus sheath block technique and the anatomical spread of two volumes of methylene blue injection in dog cadavers.

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Low-tidal-volume prevent ventilation induced inflammation in a mouse model of sepsis.

Pulmonary inflammation, increased vascular permeability, and pulmonary edema, occur in response to primary pulmonary infections like pneumonia but are also evident in endotoxemia or sepsis. Mechanical ventilation augments pre-existing lung injury and inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that low-tidal-volume prevent ventilation induced lung injury in sepsis.

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Neurotoxicity of antibodies in cancer therapy: A review.

The objective of this manuscript is to identify the neurological side effect profile associated with different classes of antibodies used in cancer pharmacotherapy and to estimate the frequency in which these neurotoxicity occurs. A systematic review of the literature was conducted using OVID MEDLINE and EMBASE databases for articles written between January of 2010 till August of 2018. The spectrum of neurotoxicity was searched using expanded terminology, medical subject headings, truncation, spelling variations and database specific controlled vocabulary. 2134 citations were retrieved that were narrowed down to 151 when SORT 1 or SORT 2 critical appraisal tool was applied to articles with human subjects. Meta-analysis using random effect model was done to estimate the prevalence of neurological symptoms per class of antibody described in SORT1 and SORT2 articles. It was found that the most common neurotoxicity per antibody class are as follows; Bi-specific T-cell engagers was headache 38% [35-40%; I 0%]; anti-CD20, neuropathy, 16% [7-24%, I 65%]; anti-CD30, neuropathy 57% [46-68%, I 72%]; anti-CD52, neuropathy 5-15%; anti-CTL4, headache 12% [7-16%, I 49%]; anti-EGFR, headache 25% [11-38%, I 92%]; anti-Her2, neuropathy 33% [18-49%, I 98%]; anti-PD1 and PDL1, headache 3% [2-5%, I 85%]; and anti-VEGF, headache 25% [16-35%, I 73%]. Therefore, all classes of antibodies used in cancer pharmacotherapy have associated neurotoxicity with a wide spectrum of effects afflicting the nervous system as a whole. The specific side effects and the frequency at which they occur differ per class of antibody. Broader and more severe symptoms were noted to effect patients with preexisting brain lesions.

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