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PD-1 Blockade in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with -wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized monoclonal antibody against the programmed death-1 (PD-1) receptor.

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Far Lateral Approach for in-situ Occlusion of Craniospinal Cervicomedullary AVM Presenting with Subarachnoid Hemorrhage.

A 49 y.o. female presented with sudden onset headache and meningismus. CT scan revealed a posterior fossa subarachnoid hemorrhage extending from the foramen magnum to the ambient cistern. Angiography showed a pial extramedullary arteriovenous malformation (AVM) at the lateral ventral surface of the cervicomedullary junction with primary supply from the left posterior inferior cerebellar artery (PICA), and dominant drainage into the anterior median perimedullary vein. Embolization of the AVM was considered high-risk as feeding arteries originated from the proximal lateral medullary segment of the left PICA. A far lateral approach with suboccipital craniotomy and C1-C2 laminectomy was performed. PICA was disconnected from the AVM, and multiple small feeders interrupted with bipolar cautery and aneurysm clips to achieve an in-situ occlusion of the pial AVM. Intraoperative indocyanine green video-angiography was used to define the AVM and critical en passant vessels prior to disconnection, and to demonstrate no residual early venous filling after the in-situ occlusion. Postoperative angiography demonstrated no residual arteriovenous shunting or nidiform vessels, with preservation of patency of the left PICA. The patient had an uneventful postoperative course and was discharged with no significant neurological deficits.

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Global REACH 2018: The Effect of an Expiratory Resistance Mask with Dead Space on Sleep and Acute Mountain Sickness During Acute Exposure to Hypobaric Hypoxia.

We hypothesized that an expiratory resistance and dead space (ER/DS) mask, a version of which was previously shown to partially alleviate sleep-disordered breathing and headache severity during acute normobaric hypoxia (Patrician et al.), would exhibit similar results in conditions of hypobaric hypoxia. In a randomized, single-blinded, sham-controlled, and sex-matched design, 31 healthy lowlanders rapidly (6-8 hours) ascended from sea level to 4300 m (Cerro de Pasco, Peru) and slept with either an ER/DS mask ( = 15) or sham mask ( = 16). Sleep was assessed (via WatchPAT) and questionnaires collected before sleep and upon waking the morning after. There was no difference in apnea-hypopnea index (AHI) between the ER/DS (77 ± 20 events/h) or sham mask (84 ± 27 events/h;  = 0.57). In addition, there was no alleviation of headache scores, improvement in sleep quality, or acute mountain sickness symptom severity. Both the sham and ER/DS masks were poorly tolerated (∼50% subject noncompliance in both groups). These findings highlight the importance and necessity of field-testing and demonstrate that more testing is needed before ER/DS devices, such as these, can be recommended for prophylactic benefits at high altitude.

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Efficacy of Adjunctive Infliximab vs. Placebo in the Treatment of Anhedonia in Bipolar I/II Depression.

We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 48 subjects completed the study (infliximab: n=21, placebo: n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.

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Alcohol Use Disorder and the Persistence/Recurrence of Major Depression.

This study aims to determine the role of alcohol use disorder and other potential risk factors on persistence/recurrence of major depression in a Canadian population sample.

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Non-invasive assessment of endothelial function in patients with spontaneous coronary artery dissection: A case-control study.

The physiopathology underlying spontaneous coronary artery dissection remains largely unknown. Endothelial dysfunction is an early feature of many vascular disorders. We sought to determine the endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) in patients with SCAD and compare it to that of non-SCAD patients with similar cardiovascular risk profile.

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Adverse effect of delayed pushing on postpartum blood loss in nulliparous women with epidural analgesia.

To test for an association between blood loss and time until pushing (TUP) after full cervical dilation in nulliparous women with epidural analgesia.

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Casticin ameliorates scopolamine-induced cognitive dysfunction in mice.

The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia.

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Aqueous surface gels as low friction interfaces to mitigate implant-associated inflammation.

Aqueous surface gels are fragile yet resilient biopolymer-based networks capable of sustaining extremely low friction coefficients despite tribologically-challenging environments. These superficial networks are ubiquitous in natural sliding interfaces and protect mechanosensitive cells from excessive contact pressures and frictional shear stresses from cell-fluid, cell-cell, or cell-solid interactions. Understanding these complex lubrication mechanisms may aid in the development of materials-based strategies for increasing biocompatibility in medical devices and implants. Equally as important is characterizing the interplay between soft and passive yet mobile implant materials and cellular reactions in response to direct contact and frictional shear stresses. Physically interrogating living biological systems without rupturing them in the process is nontrivial. To this end, custom biotribometers have been designed to precisely modulate contact pressures against living human telomerase-immortalized corneal epithelial (hTCEpi) cell layers using soft polyacrylamide membrane probes. Reverse-transcription quantitative polymerase chain-reaction (RT-qPCR) indicated that increased duration and, to a much greater extent, the magnitude of frictional shear stress lead to increased production of pro-inflammatory (IL-1β, IL-6, MMP9) and pro-apoptotic (DDIT3, FAS) genes, which in clinical studies are linked to pathological pain. The hierarchical structure often found in biological systems has also been investigated through the fabrication of high-water content (polyacrylamide) hydrogels through free-radical polymerization inhibition. Nanoindentation experiments and friction coefficient measurements indicate that these "gradient surface gels" reduce contact pressures and frictional shear stresses at the surface of the material while still maintaining stiffness within the bulk. Reducing frictional shear stresses through informed materials and surface design may concomitantly increase lubricity and quiet the immune response, and thus provide bio-inspired routes to improve patient outcomes and quality of life.

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PREVALENCE AND OUTCOME OF LASSA FEVER AMONG HOSPITALIZED PATIENTS IN EBONYI STATE, NIGERIA, 2018 – 2019.

Lassa fever (LF) is a viral hemorrhagic illness endemic in West Africa. Annually, about 300,000 – 500,000 people are being infected, with about 5,000 deaths. Symptoms of LF include high grade fever, headache, malaise, abdominal pain, vomiting, diarrhea, or sore throat. Terminal features may include bleeding from all orifices (mouth, nose, ear, anus and vagina), facial and neck oedema or pleural effusion. People of all ages, gender, and occupations were included in this study. A total of 440 patients' samples and Bio data were used for this study. The samples were analyzed for Lassa fever virus RNA using Real Time Reverse Transcriptase Polymerase Chain Reaction. The data obtained were analyzed using SPSS 20.0 and version 7 of Epi-Info statistical software. Analysis of these samples showed LASV prevalence of 25.7 %. Chi-square analysis (p 0.05) showed that LASV infection does not depend on age, gender, or occupation. Our research re-emphasized the fact that LASV is a serious cause of fatality in humans. Our data showed that among 327 negative patients, 19 died. On the contrary, 113 LASV confirmed positive cases had 42 deaths. This result is highly significant. More so, Lassa fever disease outcome was compared across gender. There was no significant difference between the two genders. Death or recovery from LF infection does not depend on sex. However, recovery from LF significantly depend on age of the patient. Fatal outcome is significantly higher among adults/elderly. We aim to raise awareness to the recurrence of LASV in Ebonyi State and urgent need for other medical interventions, including other therapeutic measures, and possible vaccine production, considering the impact of this virus.

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