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Treatment as usual has historically been used as control arms for randomized controlled trials (RCTs), but utilizing wellness interventions as active comparison conditions can advance the evidence base of such interventions while increasing access to health promotion content. We use the results from the CONNECT 2 RCT's wellness intervention control arm as a case example of active comparison conditions that can control for dosage or attentional effects in future research. We summarized existing studies on wellness control HIV RCT interventions, introduced CONNECT 2, and discussed recruitment, randomization, and the intervention. Overall, Wellness Promotion participants were more likely to engage in physical activity, eat healthier, and do more vigorous exercise when compared with HIV Risk Reduction. CONNECT 2 Wellness intervention results solidify why wellness interventions can play an important role in treatment guidelines. Developing and implementing this model can be a more ethical, equitable, and holistic approach among underserved communities.

To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED).Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data. Nephrology group outcomes were analyzed by two-way ANOVA and Kruskal-Wallis and chi-square tests.There were 98 encounters in the historical cohort and 143 encounters in the fast track dialysis cohort. FTD had significantly lowered median ED LOS (4.05 h, vs 5.3 h, p 0.001), median hospital LOS (12.8 h vs 27 h, p 0.001), time to hemodialysis (4.78 h vs 7.29 h, p 0.001), and median hospital charges ($26,040 vs $30,747, p 0.016). The FTD cohort had increased 30 day ED return for each encounter compared to the historical cohort (1.85 visits vs 0.73 visits, p 0.001), however no significant increase in 1 year ED visits (6.52 visits vs 5.80, p = 0.4589) or 1 year readmissions (5.89 readmissions vs 4.81 readmissions, p = 0.3584). Most nephrology groups had significantly lower time to hemodialysis order placement and time to start hemodialysis.A multidisciplinary approach with key stakeholders using a standard pathway can lead to improved efficiency in throughput, reduced charges, and hospital resource utilization for patients needing urgent or routine hemodialysis. A study with a dedicated geographic observation unit for protocolized short stay patients including conditions ranging from low risk chest pain to transient ischemic events that incorporates FTD patients under this protocol should be considered.

Ravenna, the former grand capital of the late Roman and early Byzantine Empires and a popular modern UNESCO World Heritage site, is a city rarely included in major historical surveys of Italy during the Grand Tour. An exploration of period sources may reveal why: it was, for many centuries between the Middle Ages and the nineteenth century, a rundown parish town that was incredibly difficult to reach by conventional transportation. This article collates and deconstructs a number of Grand Tour sources in order to gain an understanding of Ravenna in the eighteenth century, and, further, an understanding of the contemporary attitudes towards post-Classical monuments and artwork. This exploration allows us to ask broader questions about Ravenna’s place on the Grand Tour. As a city with very little to offer in the way of Classical monuments, it slightly complicates our idea of classical reception on the Grand Tour and shows us how travellers navigated a place replete with late antique basilicas and Byzantine mosaics instead of marble sculptures and tombs.

The intrinsically disordered N-terminal region of the E7 protein from high-risk human papillomavirus (HPV) strains is responsible for oncogenic transformation of host cells through its interaction with a number of cellular factors, including the TAZ2 domain of the transcriptional coactivator CREB-binding protein. Using a variety of spectroscopic and biochemical tools, we find that despite its nanomolar affinity, the HPV16 E7 complex with TAZ2 is disordered and highly dynamic. The disordered domain of HPV16 E7 protein does not adopt a single conformation on the surface of TAZ2 but engages promiscuously with its target through multiple interactions involving two conserved motifs, termed CR1 and CR2, that occupy an extensive binding surface on TAZ2. The fuzzy nature of the complex is a reflection of the promiscuous binding repertoire of viral proteins, which must efficiently dysregulate host cell processes by binding to a variety of host factors in the cellular environment.

Drug resistant epilepsy affects ∼30% of people with epilepsy and is associated with epilepsy syndromes with frequent and multiple types of seizures, lesions or cytoarchitectural abnormalities, increased risk of mortality and comorbidities such as cognitive impairment and sleep disorders. A limitation of current preclinical models is that spontaneous seizures with comorbidities take time to induce and test, thus making them low-throughput. Kcna1-null mice exhibit all the characteristics of drug resistant epilepsy with spontaneous seizures and comorbidities occurring naturally; thus, we aimed to determine whether they also demonstrate pharmacoresistanct seizures and the impact of medications on their sleep disorder comorbidity. In this exploratory study, Kcna1-null mice were treated with one of four conventional antiseizure medications, carbamazepine, levetiracetam, phenytoin, and phenobarbital using a moderate throughput protocol (vehicle for 2 days followed by 2 days of treatment with high therapeutic doses selected based on published data in the 6 Hz model of pharmacoresistant seizures). Spontaneous recurrent seizures and vigilance states were recorded with video-EEG/EMG. Carbamazepine, levetiracetam and phenytoin had partial efficacy (67%, 75% and 33% were seizure free, respectively), whereas phenobarbital was fully efficacious and conferred seizure freedom to all mice. Thus, seizures of Kcna1-null mice appear to be resistant to three of the drugs tested. Levetiracetam failed to affect sleep architecture, carbamazepine and phenytoin had moderate effects, and phenobarbital, as predicted, restored sleep architecture. Data suggest Kcna1-null mice may be a moderate throughput model of drug resistant epilepsy useful in determining mechanisms of pharmacoresistance and testing novel therapeutic strategies.

Background Babesiosis is an important cause of thrombocytopenia and hemolytic anemia in dogs. Babesia vulpes, reported in European dogs and North American foxes, rarely has been reported in domestic North American dogs. Newly optimized polymerase chain reaction (PCR) primers facilitate more sensitive amplification of B. vulpes DNA. Objectives To determine the prevalence of Babesia sp. infections in dogs being tested for Babesia infection, and to describe co-infections and clinicopathologic abnormalities in B. vulpes positive dogs. Animals Dog blood or tissue samples (n = 9367) submitted to a diagnostic laboratory between June 2015 and June 2018 were tested using an optimized Babesia PCR assay. Methods Comprehensive canine vector-borne disease diagnostic testing was performed on convenience samples. Results Babesia sp. DNA was amplified from 269/9367 (2.9%) North American dogs. Babesia sp. infections included B. gibsoni monoinfection (157; 1.7%), B. vulpes monoinfection (19; 0.20%), and B. gibsoni and B. vulpes coinfection (29; 0.31%). Forty-three of the 48 total B. vulpes-infected dogs were American Pit Bull Terrier-type breeds, of which 36 historically were involved with dog fights. Coinfections with Mycoplasma, Dirofilaria immitis, or Wolbachia and coexposures to Bartonella, Ehrlichia, and Rickettsia spp. were documented in B. vulpes-infected dogs. Clinicopathologic data in B. vulpes-infected dogs both with and without coinfections included anemia, thrombocytopenia, hyperglobulinemia, hypoalbuminemia, and proteinuria. Conclusions and clinical importance Babesia vulpes infection in domestic North American dogs is commonly found in conjunction with other coinfections, including B. gibsoni and hemotropic Mycoplasma. Similar to B. gibsoni, dog-to-dog transmission of B. vulpes may be a frequent mode of transmission.

A 6-year-old male neutered domestic longhair cat presented to our Neurology Service for changing anisocoria and progressive gait abnormalities. The cat was rescued at about 5 months of age and had ...

Aim: Case presentation of the effects of 3D-printed models on the maternal bonding of two fetuses with facial clefts. Method: In one case the Maternal Antenatal Attachment Scale was used to score maternal bonding before and after viewing of 3D-printed images. In the other case, the effect of the 3D-printed image was witnessed anecdotally. Both 3D prints were created using polylactic acid on an Ultramaker 2+ printer. Result: In both cases maternal bonding appeared to be improved. Increased global bonding and quality of attachment was quantifiably measured in the second case. Conclusion: 3D-printed models can be a useful addition to patient education and can positively impact maternal–fetal bonding. Further study is required to evaluate how 3D printing can affect maternal bonding in a larger setting.

Mycoplasma spp. are known from several chelonian and other reptilian species. We determined if turtles obtained by the Turtle Rescue Team at North Carolina State University are carriers of hemotropic Mycoplasma or Bartonella spp. Spleen samples were collected at necropsy during May through July, 2014 from 53 turtles of seven species. All turtles were dead or were euthanized upon arrival due to severe traumatic injuries, or they died shortly after beginning treatment. We used PCR amplification for both bacterial genera; Bartonella spp. DNA was not amplified. Based upon sequencing of the 16S rRNA subunit, one eastern box turtle (Terrapene carolina carolina) and one yellow-bellied slider (Trachemys scripta scripta) were infected with Mycoplasma spp. that have genetic similarities to strains that infect other animals.

Prostatic leiomyosarcoma is an aggressive malignancy with a high risk of metastasis and a poor prognosis that poses unique diagnostic and treatment challenges.

A 28-year-old female polar bear (Ursus maritimus) housed in a zoo in Upstate New York presented with acute inappetence and lethargy. The bear's condition rapidly deteriorated, and because laboratory testing indicated severe hepatic and renal disease, the bear was humanely euthanized. Examination of a blood smear from a sample collected just prior to euthanasia revealed the presence of intra-erythrocytic inclusions, which were identified as Babesia sp. by PCR. Although it is unclear if babesiosis contributed to this bear's clinical signs, this is the first report of Babesia sp. infection in this species. Zoological institutions exhibiting polar bears and located in tick-endemic areas, as well as managers of wild populations, should be aware of this species' susceptibility to babesiosis.

Background Babesiosis is a protozoal, tick transmitted disease found worldwide in humans, wildlife and domesticated animals. Commonly used approaches to diagnose babesiosis include microscopic examination of peripheral blood smears, detection of circulating antibodies and PCR. To screen and differentiate canine Babesia infections many PCR assays amplify the 18S rRNA gene. These sequences contain hypervariable regions flanked by highly conserved regions allowing for amplification of a broad-range of Babesia spp. However, differences in the 18S rRNA gene sequence of distantly related clades can make it difficult to design assays that will amplify all Babesia species while excluding the amplification of other eukaryotes. By targeting Babesia mitochondrial genome (mtDNA), we designed a novel three primer qPCR with greater sensitivity and broader screening capabilities to diagnose and differentiate Babesia spp. Methods Using 13 Babesia mtDNA sequences, a region spanning two large subunit rRNA gene fragments (lsu5-lsu4) was aligned to design three primers for use in a qPCR assay (LSU qPCR) capable of amplifying a wide range of Babesia spp. Plasmid clones were generated and used as standards to determine efficiency, linear dynamic range and analytical sensitivity. Animals naturally infected with vector-borne pathogens were tested retrospectively and prospectively to determine relative clinical sensitivity and specificity by comparing the LSU qPCR to an established 18S rDNA qPCR. Results The LSU qPCR efficiencies ranged between 92 and 100% with the limit of detection at five copies/reaction. The assay did not amplify mammalian host or other vector-borne pathogen gDNA except Cytauxzoon felis (a feline protozoal pathogen). The LSU qPCR assay amplified 12 different Babesia. sp. and C. felis from 31/31 (100%) archived samples, whereas the 18S qPCR amplified only 26/31 (83.9%). By prospective analysis, 19/394 diagnostic accessions (4.8%) were LSU qPCR positive, compared to 11/394 (2.8%) 18S rDNA qPCR positive. Conclusions We have developed a more sensitive qPCR assay with a more expansive range of Babesia spp. detection by targeting a highly conserved region of mtDNA, when compared to an established 18S qPCR.

Objectives Routine food insecurity screening is recommended in diabetes care to inform more tailored interventions that better support diabetes self-management among food-insecure patients. This pilot study explored the acceptability and feasibility of a food insecurity screening initiative within a diabetes care setting in Toronto. Methods A systematic literature review informed the development of a food insecurity screening initiative to help health-care providers tailor diabetes management plans and better support food-insecure patients with type 2 diabetes. Interviews with 10 patients and a focus group with 15 care providers elicited feedback on the relevance and acceptance of the food insecurity screening questions and a care algorithm. Subsequently, 5 care providers at 4 sites implemented the screening initiative over 2 weeks, screening 33 patients. After implementation, 7 patients and 5 care providers were interviewed to assess the acceptability and feasibility of the screening initiative. Results Our findings demonstrate that patients are willing to share their experiences of food insecurity, despite the sensitivity of this topic. Screening elicited information about how patients cope with food insecurity and how this affects their ability to self-manage diabetes. Care providers found this information helpful in directing their care and support for patients. Conclusions Using a standardized, respectful method of assessing food insecurity can better equip health-care providers to support food-insecure patients with diabetes self-management. Further evaluation of this initiative is needed to determine how food insecurity screening can affect patients' self-management and related health outcomes.

3- and 4-methoxyphencyclidine (3-MeO-PCP, 4-MeO-PCP), structural analogs of phencyclidine (PCP), were among the first legal PCP alternatives to show up on the novel psychoactive substances (NPS) market in Europe in the 2000s. Their structural similarities to PCP and ketamine likely contribute to their demonstrated dissociative anesthetic effects. Limited information exists in the literature about toxic and lethal concentrations of these drugs in biological samples. This case report presents the first two death cases in Washington State in which 3-MeO-PCP was identified. Alkaline drug screen analysis by gas chromatography-mass spectrometry (GC-MS) revealed a peak with a retention time similar to PCP and base peak of m/z 230. Certified reference materials for 3-and 4-MeO-PCP were obtained and the isomers were able to be distinguished based on different retention times and mass spectra. A quantitative GC-MS method was developed and validated for casework, utilizing a dynamic range of 10-1,000 ng/mL and a limit of detection of 1 ng/mL. Postmortem (peripheral/central) blood samples were analyzed using this method and the resulting concentrations were 0.63 and 3.2 mg/L of 3-MeO-PCP. Methamphetamine (0.11 mg/L) was additionally detected in the blood of one of the decedents; while the second decedent was additionally positive for ethanol (0.047 g/100 mL), bupropion (1.8 mg/L), delorazepam, paroxetine and mitragynine. The results presented in this case report are higher than previously reported concentrations in fatal cases, but the presence of polysubstance abuse is consistent with previously reported NPS intoxications. Both of these individuals were in drug rehabilitation facilities prior to their deaths; however, users continue to be drawn to 3-MeO-PCP due to its dissociative effects and its accessibility on the internet.

Interpersonal dysfunction and weight/shape-based self-worth have been implicated as key constructs for eating disorders, although the relationship between these two concepts is under-researched. This study investigated the moderating role of weight/shape-based self-worth in terms of the impact of interpersonal rejection on attentional bias regarding thin-ideal and non-thin images. Participants were 94 females without an eating disorder, who were exposed to either interpersonal rejection or acceptance (using the Cyberball paradigm), and subsequently assessed in terms of their attentional biases regarding thin-ideal and non-thin images. Results revealed that weight/shape-based self-worth moderated the relationship between interpersonal rejection/acceptance and attentional biases for thin-ideal (but not non-thin) images. Specifically, participants with a greater tendency to base their self-worth on weight/shape demonstrated reduced avoidance of thin-ideal images when rejected relative to those who were accepted. The findings support the role of interpersonal rejection in eliciting attentional disturbances among those with higher body weight/shape-based self-worth.

Monokines (i.e., interleukin [IL]-12, -18, and -15) induce natural killer (NK) cells to produce interferon-gamma (IFN-gamma), which is a critical factor for immune surveillance of cancer and monocyte clearance of infection. We show that SET, which is a potent inhibitor of protein phosphatase type 2A (PP2A) activity, is highly expressed in human CD56bright NK cells, which produce more IFN-gamma than CD56dim NK cells. SET was up-regulated upon monokine stimulation of primary human NK cells. Furthermore, ectopic overexpression of SET significantly enhanced IFN-gamma gene expression in monokine-stimulated NK cells. In contrast, RNAi-mediated suppression of SET expression renders NK cells inefficient in producing high levels of IFN-gamma in response to monokine costimulation. Mechanistically, suppression of PP2A activity by SET is important for IFN-gamma gene expression in NK cells. In fact, treatment of primary human NK cells with the PP2A activator 1,9-dideoxy-forskolin, as well as administration of the drug to C57BL/6 mice, significantly reduced NK-dependent IFN-gamma production in response to monokine treatment. Further, SET knockdown or pharmacologic activation of PP2A diminished extracellular signal-regulated kinase 1/2, p65RelA, signal transducer and activator of transduction 4 (STAT4), and STAT5 activity in monokine-stimulated NK cells, potentially contributing to the reduction in IFN-gamma gene expression. Thus, SET expression is essential for suppressing PP2A phosphatase activity that would otherwise limit NK cell antitumoral and/or antiinflammatory functions by impairing NK cell production of IFN-gamma.

Background With the exception of Bartonella spp. or Cytauxzoon felis, feline vector-borne pathogens (FVBP) have been less frequently studied in North America and are generally under-appreciated as a clinical entity in cats, as compared to dogs or people. This study investigated selected FVBP seroreactivity and PCR prevalence in cats using archived samples. Methods Feline blood samples submitted to the Vector Borne Diseases Diagnostic Laboratory (VBDDL) at North Carolina State University College of Veterinary Medicine (NCSU-CVM) between 2008 and 2013 were tested using serological assays and PCR. An experimental SNAP® Multi-Analyte Assay (SNAP® M-A) (IDEXX Laboratories, Inc. Westbrook, Maine, USA) was used to screen all sera for antibodies to Anaplasma and Ehrlichia genus peptides and A.phagocytophilum, A.platys, B.burgdorferi, E.canis, E.chaffeensis, and E.ewingii species-specific peptides. PCR assays were used to amplify Anaplasma or Ehrlichia DNA from extracted ethylenediaminetetraacetic acid (EDTA)-anti-coagulated blood samples. Amplicons were sequenced to identify species. Results Overall, 7.8 % (56/715) of cats were FVBP seroreactive and 3.2 % (13/406) contained Anaplasma or Ehrlichia DNA. Serologically, B.burgdorferi (5.5 %) was the most prevalent FVBP followed by A.phagocytophilum (1.8 %). Ehrlichia spp. antibodies were found in 0.14 % (12/715) of cats with species-specific seroreactivity to E.canis (n = 5), E.ewingii (n = 2) and E.chaffeensis (n = 1). Of seropositive cats, 16 % (9/56) were exposed to more than one FVBP, all of which were exposed to B.burgdorferi and either A.phagocytophilum (n = 7) or E.ewingii (n = 2). Based upon PCR and DNA sequencing, 4, 3, 3, 2, and 1 cat were infected with A.phagocytophilum, A.platys, E. ewingii, E. chaffeensis and E.canis, respectively. Conclusions Cats are exposed to and can be infected with vector-borne pathogens that commonly infect dogs and humans. To our knowledge, this study provides the first evidence for E.chaffeensis and E.ewingii infection in naturally-exposed cats in North America. Results from this study support the need for regional, serological and molecular FVBP prevalence studies, the need to further optimize serodiagnostic and PCR testing for cats, and the need for prospective studies to better characterize clinicopathological disease manifestations in cats infected with FVBP.

OBJECTIVE To establish normative parameters of the spleen by ultrasonography in tall athletes. DESIGN Prospective cohort observational study. SETTING University of Buffalo, Erie County Community College, University of Texas at Tyler, and Austin College. PARTICIPANTS Sixty-six athletes enrolled and finished the study. Height requirements were at least 6 feet 2 inches for men and at least 5 feet 7 inches in women. INTERVENTIONS Measurement of spleen size in tall athletes. MAIN OUTCOME MEASURES Ultrasound measurements of spleen size in tall athletes were compared with "normal-sized" controls from the literature. Mean, SD, and variance determined the sample distribution, and a one sample t test compared measurements in tall athletes with historical measurements in the average height population. Statistical significance was defined as P < 0.05. RESULTS Mean height was 192.26 cm (SD, ± 6.52) for men and 176.54 cm (SD, ± 5.19) for women. Mean splenic measurements for all subjects were 12.19 cm (SD, ± 1.45) for spleen length, 8.88 cm (SD, ± 0.96) for spleen width, and 5.55 cm (SD, ± 0.76) for spleen thickness. The study mean for spleen length was 12.192 cm (95% confidence interval, 11.835-12.549) and population mean was 8.94 cm (2 tailed t test, P < 0.01). In this population of tall athletes, normal spleen size was significantly larger than the normal spleen size of an average individual. CONCLUSIONS In the clinical arena, it can be difficult to know when the tall athletes with splenomegaly from infectious mononucleosis can safely return to contact sports. Previously, there has not been a sufficient "norm" for this population, but this study helps to establish baseline values.

Background With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. Objective This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. Methods At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. Results Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 μg/g for Alternaria alternata , 2.06 μg/g for Can f 1, 1.43 μg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 μg/g for Der p 1, 0.10 μg/g for Der f 1, and 0.01 μg/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata , Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. Conclusions In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens.

When mucoid (alginate-producing) Pseudomonas aeruginosa FRD1 is grown under low oxygen conditions in liquid culture (static), non-mucoid variants appear and eventually predominate. This conversion is not readily observed in aerobic, shaken cultures or static cultures containing the alternative electron acceptor nitrate. In this study, it is shown that the non-mucoid variants that arise under static growth conditions are almost exclusively algT mutants. It has been shown that AlgT not only positively regulates alginate biosynthesis, but also directly or indirectly negatively regulates flagellum synthesis. Indeed, during static growth, conversion to the non-mucoid phenotype is accompanied by the acquisition of flagellum-mediated motility. Surprisingly, by using a reporter gene fusion with the fliC promoter (pfliC::xylE), it was found that fliC expression begins within hours of static growth and is reversible after returning the culture to shaking conditions. The ability of the strain to produce alginate seems to be irrelevant to this phenomenon, as an AlgT(+) deltaalgD strain showed identical results. Thus, it is suggested that the first effect of static growth is to induce motility as an adaptive measure in the presence of wild-type algT. This may afford P. aeruginosa the ability to swim towards areas of higher oxygen concentrations. Subsequent to this, algT mutations are likely to secure the motile phenotype.

TGF-β can be a potent suppressor of lymphocyte effector cell functions and can mediate these effects via distinct molecular pathways. The role of TGF-β in regulating CD16-mediated NK cell IFN-γ production and antibody-dependent cellular cytotoxicity (ADCC) is unclear, as are the signaling pathways that may be utilized. Treatment of primary human NK cells with TGF-β inhibited IFN-γ production induced by CD16 activation with or without IL-12 or IL-2, and it did so without affecting the phosphorylation/activation of MAP kinases ERK and p38, as well as STAT4. TGF-β treatment induced SMAD3 phosphorylation, and ectopic overexpression of SMAD3 resulted in a significant decrease in IFN-γ gene expression following CD16 activation with or without IL-12 or IL-2. Likewise, NK cells obtained from smad3−/− mice produced more IFN-γ in response to CD16 activation plus IL-12 when compared with NK cells obtained from wild-type mice. Coactivation of human NK cells via CD16 and IL-12 induced expression of T-BET, the positive regulator of IFN-γ, and T-BET was suppressed by TGF-β and by SMAD3 overexpression. An extended treatment of primary NK cells with TGF-β was required to inhibit ADCC, and it did so by inhibiting granzyme A and granzyme B expression. This effect was accentuated in cells overexpressing SMAD3. Collectively, our results indicate that TGF-β inhibits CD16-mediated human NK cell IFN-γ production and ADCC, and these effects are mediated via SMAD3.