Background: Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. Objective: To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. Design: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propy\x=req-\ leneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy.
Vaccines represent the single most cost-efficient and equitable way to combat and eradicate infectious diseases. While traditional licensed vaccines consist of either inactivated/attenuated versions of the entire pathogen or subunits of it, most novel experimental vaccines against emerging infectious diseases employ nucleic acids to produce the antigen of interest directly in vivo. These include DNA plasmid vaccines, mRNA vaccines, and recombinant viral vectors. The advantages of using nucleic acid vaccines include their ability to induce durable immune responses, high vaccine stability, and ease of large-scale manufacturing. In this review, we present an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discuss the advantages and limitations of the different viral vector platforms.
NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target NaV1.6 channels. Such a molecule provides a precision-medicine approach to target SCN8A-related epilepsy syndromes (SCN8A-RES), where gain-of-function (GoF) mutations lead to excess NaV1.6 sodium current, or other indications where NaV1.6 mediated hyper-excitability contributes to disease (Gardella & Moller, 2019; Johannesen et al., 2019; Veeramah et al., 2012). NBI-921352 is a potent inhibitor of NaV1.6 (IC50 0.051 µM), with exquisite selectivity over other sodium channel isoforms (selectivity ratios of 756X for NaV1.1, 134X for NaV1.2, 276X for NaV1.7, and >583X for NaV1.3, NaV1.4, and NaV1.5). NBI-921352 is a state-dependent inhibitor, preferentially inhibiting inactivated channels. The state dependence leads to potent stabilization of inactivation, inhibiting NaV1.6 currents, including resurgent and persistent NaV1.6 currents, while sparing the closed/rested channels. The isoform-selective profile of NBI-921352 led to a robust inhibition of action-potential firing in glutamatergic excitatory pyramidal neurons, while sparing fast-spiking inhibitory interneurons, where NaV1.1 predominates. Oral administration of NBI-921352 prevented electrically induced seizures in a Scn8a GoF mouse, as well as in wild-type mouse and rat seizure models. NBI-921352 was effective in preventing seizures at lower brain and plasma concentrations than commonly prescribed sodium channel inhibitor anti-seizure medicines (ASMs) carbamazepine, phenytoin, and lacosamide. NBI-921352 was well tolerated at higher multiples of the effective plasma and brain concentrations than those ASMs. NBI-921352 is entering phase II proof-of-concept trials for the treatment of SCN8A-developmental epileptic encephalopathy (SCN8A-DEE) and adult focal-onset seizures.
Background
The AmpliVue™ Trichomonas Assay (Quidel) is a new FDA cleared rapid test for qualitative detection of Trichomonas vaginalis (TV) DNA in female vaginal specimens. The assay is based on BioHelix’s Helicase-Dependent Amplification (HDA) isothermal technology in conjunction with a disposable lateral-flow detection device, with a total turn-around time of approximately 45 minutes.
Objective
The objective of this study was to compare the performance of this new assay to wet preparation and culture, as well as to another FDA cleared nucleic acid amplification assay.
Methods
Four clinician collected vaginal swabs were obtained from women attending STD, family planning, and OB/GYN clinics and tested by AmpliVue™ Trichomonas Assay and comparator tests: saline microscopy, TV culture (InPouch™), and Aptima® TV (ATV). AmpliVue™ Trichomonas Assay results were compared to a composite positive comparator (CPC) as determined by the results from culture and/or wet mount microscopic examination. At least one of either the wet preparation or culture reference test results was required to be positive to establish CPC.
Results
A total of 992 patients, 342 symptomatic and 650 asymptomatic patients, were included in the study. Results for AmpliVue for all women combined compared to saline microscopy and culture as a composite positive comparator yielded a sensitivity of 100%. Specificity for all women was 98.2%. Overall percent agreement versus Aptima® TV was 97.8%. Sensitivity for AmpliVue compared to Aptima® was 90.7% %, while specificity was 98.9%.
Conclusions
The rapid AmpliVue™ Trichomonas Assay performed as well as microscopy and culture, and had comparable sensitivity and specificity to another NAAT for the detection of TV. This study provided evidence of new diagnostic options and indicated very good performance of amplified testing for detection of TV in symptomatic and asymptomatic women.
Objective:Food insecurity, or self-reports of inadequate food access due to limited financial resources, remains prevalent among people living with HIV (PLHIV). We examined the impact of food insecurity on combination antiretroviral therapy (cART) adherence within an integrated care programme that provides services to PLHIV, including two meals per day.Design:Adjusted OR (aOR) were estimated by generalized estimating equations, quantifying the relationship between food insecurity (exposure) and cART adherence (outcome) with multivariable logistic regression.Setting:We drew on survey data collected between February 2014 and March 2016 from the Dr. Peter Centre Study based in Vancouver, Canada.Participants:The study included 116 PLHIV at baseline, with ninety-nine participants completing a 12-month follow-up interview. The median (quartile 1–quartile 3) age was 46 (39–52) years at baseline and 87 % (n 101) were biologically male at birth.Results:At baseline, 74 % (n 86) of participants were food insecure (≥2 affirmative responses on Health Canada’s Household Food Security Survey Module) and 67 % (n 78) were adherent to cART ≥95 % of the time. In the adjusted regression analysis, food insecurity was associated with suboptimal cART adherence (aOR = 0·47, 95 % CI 0·24, 0·93).Conclusions:While food provision may reduce some health-related harms, there remains a relationship between this prevalent experience and suboptimal cART adherence in this integrated care programme. Future studies that elucidate strategies to mitigate food insecurity and its effects on cART adherence among PLHIV in this setting and in other similar environments are necessary.
SurePath specimens from women referred to colposcopy were treated with Aptima Transfer Solution (ATS) before testing in Aptima HPV (AHPV) and Aptima HPV 16, 18/45 (AHPV-GT) assays. Untreated SurePath specimens were tested with the cobas HPV test. PreservCyt specimens were assessed for cytology and tested with AHPV. High-grade cervical intraepithelial neoplasia lesions served as the reference standard. Excellent agreement (95.5%; k=0.91) was observed for ATS-treated SurePath specimens between Tigris and Panther systems and between the PreservCyt and ATS-treated SurePath specimens (91.1%, k=0.81) with the AHPV assay on Tigris. Agreement between the AHPV and cobas assays with SurePath specimens was substantial (89.9%, k=0.80). AHPV sensitivity for CIN2+(n=147) was 91.2% for SurePath and PreservCyt. Cobas HPV sensitivity was 93.9% for SurePath specimens. AHPV testing of SurePath specimens was more specific (59.4%) than cobas (54.7%) (p<0.001). Detection and genotyping showed similar absolute and relative risks. ATS-treated SurePath specimens tested with AHPV and AHPV-GT assays showed similar performance with greater specificity than cobas HPV on SurePath specimens. Similar overall results were seen using a CIN3 disease endpoint.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.