Traumatic brain injury heterogeneity affects cell death and autophagy.

Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. Impact variability influences the origin, spread, and classification of molecular dysfunction which limits strategies for comprehensive clinical intervention. Indeed, there are currently no clinically approved therapeutics for treating the secondary consequences associated with TBI. Thus, examining pathophysiological changes from heterogeneous impacts is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Here we utilized TBI models that varied in both injury mechanism and severity including severe traditional controlled cortical impact (CCI), modified mild CCI (MTBI), and multiple severities of closed-head diffuse TBI (DTBI), and assessed pathophysiological changes. Severe CCI induced cortical lesions and necrosis, while both MTBI and DTBI lacked lesions or significant necrotic damage. Autophagy was activated in the ipsilateral cortex following CCI, but acutely impaired in the ipsilateral hippocampus. Additionally, autophagy was activated in the cortex following DTBI, and autophagic impairment was observed in either the cortex or hippocampus following impact from each DTBI severity. Thus, we provide evidence that autophagy is a therapeutic target for both mild and severe TBI. However, dramatic increases in necrosis following CCI may negatively impact the clinical translatability of therapeutics designed to treat acute dysfunction in TBI. Overall, these results provide evidence that injury sequalae affiliated with TBI heterogeneity is linked through autophagy activation and/or impaired autophagic flux. Thus, therapeutic strategies designed to intervene in autophagy may alleviate pathophysiological consequences, in addition to the cognitive and behavioral deficits observed in TBI.

Examining gender differences in adolescent exposure to food and beverage marketing through go-along interviews.

This study explores how adolescents engage with unhealthy food and beverage marketing in online settings, from a gender perspective. Employing an online ethnography approach and using go-along interviews, we explored the experiences of adolescent boys and girls aged 13-17 as they navigated their online experiences with digital food and beverage marketing. Notable themes emerged, including the identification of predatory actions by food companies, the role of protective factors such as family, and the influence of social media influencers in shaping adolescent dietary preferences. Importantly, this research unearthed gender disparities in the participants' responses. Girls, in particular, exhibited a heightened awareness of the protective role played by their families, emphasized the influence of color in marketing strategies, recognized the significance of gender in marketing, and reported exposure to alcohol advertisements-findings that boys less frequently echoed. The study underscores the importance of adolescence as a critical phase in development, during which food companies target these impressionable individuals, driven by their independence and potential for brand loyalty. Moreover, it highlights the potential avenue of gender-specific marketing, offering valuable insights into the gendered dimensions of adolescents' food marketing experiences. By examining the interplay between digital food marketing and gender, this research addresses a critical gap in the literature, shedding light on how gender influences adolescents' perceptions, responses, and behaviors in the context of food marketing strategies. These findings have the potential to inform adolescents of the marketing techniques that target them and guide policymakers in developing and implementing evidence-based regulations aimed at safeguarding adolescents from exposure to unhealthy food marketing.

A novel neurotropic microsporidium from the swamp guppy Micropoecilia picta from Grenada, West Indies.

A novel microsporidium was observed in wild swamp guppies Micropoecilia picta from Levera Pond within Levera National Park Grenada, West Indies. Initial observations indicated similarity with Pseudoloma neurophilia, an important pathogen in zebrafish Danio rerio. P. neurophilia exhibit broad host specifity, including members of the family Poecillidae, and both parasites infect the central nervous system. However, spore morphology and molecular phylogeny based on rDNA showed that the swamp guppy microsporidium (SGM) is distinct from P. neurophilia and related microsporidia (Microsporidium cerebralis and M. luceopercae). Spores of the SGM were smaller than others in the clade (3.6 µm long). Differences were also noted in histology; the SGM formed large aggregates of spores within neural tissues along with a high incidence of numerous smaller aggregates and single spores within the surface tissue along the ventricular spaces that extended submeninx, whereas P. neurophilia and M. cerebralis infect deep into the neuropile and cause associated lesions. Analysis of small subunit ribosomal DNA sequences showed that the SGM was <93% similar to these related microsporidia. Nevertheless, one of 2 commonly used PCR tests for P. neurophilia cross reacted with tissues infected with SGM. These data suggest that there could be other related microsporidia capable of infecting zebrafish and other laboratory fishes that are not being detected by these highly specific assays. Consequently, exclusive use of these PCR tests may not accurately diagnose other related microsporidia infecting animals in laboratory and ornamental fish facilities.

Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Rupture of the gastrocnemius muscle at its distal musculotendinous junction: conservative treatment and outcomes in 11 dogs.

CASE HISTORY: Medical records from three veterinary referral centres and a university veterinary teaching hospital in Australia and the USA were reviewed to identify dogs with a diagnosis of distal gastrocnemius musculotendinous junction rupture (DGMJR) that were treated without surgery between 2007 and 2020. CLINICAL AND IMAGING FINDINGS: All dogs (n = 11) presented with unilateral, pelvic limb lameness and bruising, swelling or pain on palpation at the distal musculotendinous junction. The diagnosis was confirmed with ultrasound or MRI in six dogs; radiographs were used to excluded stifle and tarsus pathology in four dogs; and five dogs were diagnosed on physical examination findings. TREATMENT AND OUTCOME: All dogs were managed conservatively, either with complete confinement alone (n = 10; median 9 weeks), external coaptation alone (n = 1), or a combination of both (n = 4). Sporting dogs (n = 7) were completely confined (median 22 weeks) for longer periods than companion dogs (n = 3; median 5 weeks).A good to excellent outcome was achieved for all cases in this cohort. The seven sporting dogs achieved an excellent outcome; returning to their previous level of sport, with complete resolution of lameness and recovery of a normal tibiotarsal stance. The four companion dogs achieved a good outcome; returning to their previous level of activity but with persistently increased tibiotarsal standing angle compared to the contralateral limb. CLINICAL RELEVANCE: Conservative treatment represents a viable treatment option for dogs with a rupture of the gastrocnemius muscle at its distal musculotendinous junction.

Testing the automaticity features of the affect misattribution procedure: The roles of awareness and intentionality.

The affect misattribution procedure (AMP) is a measure of implicit evaluations, designed to index the automatic retrieval of evaluative knowledge. The AMP effect consists in participants evaluating neutral target stimuli positively when preceded by positive primes and negatively when preceded by negative primes. After multiple prior tests of intentionality, Hughes et al. (Behav Res Methods 55(4):1558-1586, 2023) examined the role of awareness in the AMP and found that AMP effects were larger when participants indicated that their response was influenced by the prime than when they did not. Here we report seven experiments (six preregistered; N = 2350) in which we vary the methodological features of the AMP to better understand this awareness effect. In Experiments 1-4, we establish variability in the magnitude of the awareness effect in response to variations in the AMP procedure. By introducing further modifications to the AMP procedure, Experiments 5-7 suggest an alternative explanation of the awareness effect, namely that awareness can be the outcome, rather than the cause, of evaluative congruency between primes and responses: Awareness effects emerged even when awareness could not have contributed to AMP effects, including when participants judged influence awareness for third parties or primes were presented post hoc. Finally, increasing the evaluative strength of the primes increased participants' tendency to misattribute AMP effects to the influence of target stimuli. Together, the present findings suggest that AMP effects can create awareness effects rather than vice versa and support the AMP's construct validity as a measure of unintentional evaluations of which participants are also potentially unaware.

Identifying host-specific amino acid signatures for influenza A viruses using an adjusted entropy measure.

BACKGROUND: Influenza A viruses (IAV) exhibit vast genetic mutability and have great zoonotic potential to infect avian and mammalian hosts and are known to be responsible for a number of pandemics. A key computational issue in influenza prevention and control is the identification of molecular signatures with cross-species transmission potential. We propose an adjusted entropy-based host-specific signature identification method that uses a similarity coefficient to incorporate the amino acid substitution information and improve the identification performance. Mutations in the polymerase genes (e.g., PB2) are known to play a major role in avian influenza virus adaptation to mammalian hosts. We thus focus on the analysis of PB2 protein sequences and identify host specific PB2 amino acid signatures. RESULTS: Validation with a set of H5N1 PB2 sequences from 1996 to 2006 results in adjusted entropy having a 40% false negative discovery rate compared to a 60% false negative rate using unadjusted entropy. Simulations across different levels of sequence divergence show a false negative rate of no higher than 10% while unadjusted entropy ranged from 9 to 100%. In addition, under all levels of divergence adjusted entropy never had a false positive rate higher than 9%. Adjusted entropy also identifies important mutations in H1N1pdm PB2 previously identified in the literature that explain changes in divergence between 2008 and 2009 which unadjusted entropy could not identify. CONCLUSIONS: Based on these results, adjusted entropy provides a reliable and widely applicable host signature identification approach useful for IAV monitoring and vaccine development.

Identification and Synthesis of Leptotriene, a Unique Sesquiterpene Hydrocarbon from Males of the Leaffooted Bugs Leptoglossus zonatus and L. occidentalis.

The leaffooted bugs Leptoglossus zonatus and L. occidentalis (Hemiptera: Coreidae) cause substantial damage in tree nut crops in North America and pine seed orchards in North America and Europe, respectively. Sexually mature males of both species produce a number of aldehydes, esters, and sesquiterpenes, which are hypothesized to constitute an aggregation pheromone attractive to both sexes. Among the volatiles produced by males of both species, we identified a unique sesquiterpene hydrocarbon, given the common name "leptotriene" (5), which elicited strong responses from antennae of both sexes in electroantennogram assays. Here, we report its structure and its synthesis from (-)-(E)-ß-caryophyllene (1).

Major histocompatibility complex genes and locus organization in the Komodo dragon (Varanus komodoensis).

We performed a meta-analysis of the newly assembled Komodo dragon (Varanus komodoensis) genome to characterize the major histocompatibility complex (MHC) of the species. The MHC gene clusters of the Komodo dragon are gene dense, complex, and contain counterparts of many genes of the human MHC. Our analysis identified 20 contigs encompassing ~ 6.9 Mbp of sequence with 223 annotated genes of which many are predicted orthologs to the genes of the human MHC. These MHC contigs range in size from 13.2 kb to 21.5 Mbp, contain an average of one gene per 30 kb, and are thought to occur on at least two chromosomes. Eight contigs, each > 100 kb, could be aligned to the human MHC based on gene content, and these represent gene clusters found in each of the recognized mammalian MHC subregions. The MHC of the Komodo dragon shares organizational features of other non-mammalian taxa. Multiple class Iα and class IIß genes are indicated, with linkage between classical class I and immunoproteasome genes and between framework class I genes and genes associated with the mammalian class III subregion. These findings are supported in both Komodo genome assemblies and provide new insight into the MHC organization of these unique squamate reptiles.

Response of turkey pectoralis major muscle satellite cells to hot and cold thermal stress: Effect of growth selection on satellite cell proliferation and differentiation.

Satellite cell (SCs), the main progenitors for post-hatch poultry muscle growth, has maximal mitotic activity and sensitivity to temperature during the first week after hatch. The objective of the present study was to determine the effect of hot and cold temperatures on the proliferation and differentiation of SCs from pectoralis major (P. major) muscle of fast-growing 1-week-old Nicholas commercial (NC) turkeys compared to Randombred Control Line 2 (RBC2) turkeys representing commercial turkeys from 1966. Three temperature regimens were used: SCs proliferation at 38 °C (control) with differentiation at 43° or 33 °C; proliferation at 43° or 33 °C with differentiation at 38 °C; or both proliferation and differentiation at 43°, 38°, or 33°C. Satellite cell proliferation and differentiation increased at 43 °C and decreased at 33 °C in both lines. When a thermal challenge was administered during proliferation, greater stimulatory or suppressive effects on differentiation were observed compared to if the thermal challenge was applied only during differentiation in both lines. Expression of myoblast determination protein 1 during proliferation showed a higher increase in the NC line compared to the RBC2 line at 43 °C. Increased myogenin expression was observed in all hot treatment groups in the NC line but was only observed in the RBC2 line if the hot treatment was administered throughout proliferation and differentiation. Cold treatment suppressed myogenin expression independent of line. These results suggest turkey P. major muscle SCs are more sensitive to environmental temperatures during proliferation, and SCs from growth-selected NC turkeys are more sensitive to thermal stress compared to the RBC2 turkeys.

Strategies used by the Canadian food and beverage industry to influence food and nutrition policies.

BACKGROUND: Unhealthy food environments contribute to the rising rates of obesity and diet-related diseases. To improve the Canadian nutritional landscape, Health Canada launched the Healthy Eating Strategy in October 2016 which involved several initiatives including the restriction of unhealthy food marketing to children, the reduction of sodium in the food supply and the introduction of front-of-package labelling. Subsequently, various stakeholders engaged in discussions with Health Canada. This study sought to describe the interactions between Health Canada and industry and non-industry stakeholders and to identify the strategies used by industry to influence food and nutrition policy in Canada. METHODS: Documents such as correspondences and presentations exchanged in interactions between Health Canada and stakeholders regarding the Healthy Eating Strategy were obtained from Health Canada's Openness and Transparency website. The participating stakeholders of each interaction and the topics discussed were determined and described quantitatively. A directed content analysis was then conducted to identify the strategies employed by industry to influence policy. This was guided by a previously developed coding framework that was adapted during analysis. RESULTS: A total of 208 interactions concerning the Healthy Eating Strategy occurred between October 2016 and June 2018. Of the interactions for which documents were received (n = 202), 56% involved industry stakeholders, 42% involved non-industry stakeholders and 2% involved both. Industry stakeholders were more likely to initiate interactions with Health Canada (94% of their interactions) than non-industry stakeholders (49%). Front-of-package labelling was the most frequently discussed topic by industry stakeholders (discussed in 49% interactions involving industry) while non-industry stakeholders most frequently discussed the Healthy Eating Strategy as a whole (discussed in 37% of interactions involving non-industry). A wide variety of strategies were used by industry in their attempts to influence policy. Those most frequently identified included: "framing the debate on diet- and public health-related issues", "promoting deregulation", "shaping the evidence base", "stressing the economic importance of industry", and "developing and promoting alternatives to proposed policies". CONCLUSION: Industry stakeholders are highly active in their attempts to influence Canadian nutritional policies. Policymakers and public health advocates should be aware of these strategies so that balanced and effective food and nutrition policies can be developed.

Influence of Setback Distance on Antibiotics and Antibiotic Resistance Genes in Runoff and Soil Following the Land Application of Swine Manure Slurry.

The environmental spread of antibiotics and antibiotic resistance genes (ARGs) from the land application of livestock wastes can be a potential public health threat. The objective of this study was to assess the effects of setback distance, which determines how close manure may be applied in relation to surface water, on the transport of antibiotics and ARGs in runoff and soil following land application of swine manure slurry. Rainfall simulation tests were conducted on field plots covered with wheat residues, each of which contained an upslope manure region where slurry was applied and an adjacent downslope setback region that did not receive slurry. Results show that all three antibiotics (chlortetracycline, lincomycin, and tiamulin) and seven out of the ten genes tested (erm(B), erm(C), intI1, tet(O), tet(Q), tet(X), and the 16S rRNA gene) decreased significantly in runoff with increased setback distance. Only blaTEM, chlortetracycline, and tiamulin decreased significantly in surface soil with increased setback distance, while the other analytes did not exhibit statistically significant trends. By using linear regression models with field data, we estimate that a setback distance between 34-67 m may allow manure-borne antibiotics and ARGs in runoff to reach background levels under the experimental conditions tested.

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities.

The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and egg-associated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores.

Dual-Energy CT Urography With 50% Reduced Iodine Dose Versus Single-Energy CT Urography With Standard Iodine Dose.

OBJECTIVE: The purpose of this study was to compare dual-energy CT (DECT) urography with a 50% reduced iodine dose to single-energy CT (SECT) urography with a standard iodine dose with respect to attenuation of renal vascular and urinary tract structures and with respect to image quality. SUBJECTS AND METHODS: The study included 62 patients undergoing evaluation of urinary tract lithiasis, tumor, or hematuria. Thirty-one patients underwent DECT urography with a 50% reduced iodine dose and reconstruction at 50 and 77 keV. These subjects were sex, age, and size matched to a group of 31 patients who underwent 120-kVp SECT urography with a standard iodine dose. The mean iodine dose was 22 g for DECT and 44 g for SECT. Attenuation was measured at seven locations in the renal arteries, renal veins, and urinary tract. Two reviewers subjectively scored the image quality parameters image noise, sharpness of urinary tract contours, enhancement of urinary structures, and streak artifacts. RESULTS: Mean DECT attenuation at 50 keV was the same as or greater than SECT attenuation at each of the seven locations. Measured image noise was highest at 50-keV DECT but was the same for 77-keV DECT and 120-kVp SECT. Mean subjective scores for DECT image quality parameters were the same as or higher than those of SECT, except for streak artifact and sharpness of urinary tract contours. CONCLUSION: DECT urography with a 50% reduced iodine dose may result in measured renal vascular and urinary tract attenuation the same as or higher than and image quality measurements and scores similar to those obtained with 120-kVp SECT urography with a standard iodine dose.

Spatial Associations of Vines Infected With Grapevine Red Blotch Virus in Oregon Vineyards.

Spread and in-field spatial patterns of vines infected with grapevine red blotch virus (GRBV) were documented in Oregon vineyards using field sampling, molecular diagnostics, and spatial analysis. Grapevine petiole tissue collected from 2013 to 2016 was tested using quantitative polymerase chain reaction for GRBV. At Jacksonville in southern Oregon, 3.1% of vines were infected with GRBV in 2014, and GRBV incidence reached 58.5% of study vines by 2016. GRBV-infected plants and GRBV-uninfected plants were spatially aggregated at this site in 2015, and infected plants were spatially associated between years 2015 and 2016. In a southern Oregon vineyard near Talent, 10.4% of vines were infected with GRBV in 2014, and infection increased annually to 21.5% in 2016. At Talent, distribution of the infected vines was spatially associated across all years. GRBV infection was highest at Yamhill, in the Willamette Valley, where 31.7% of the tested vines had GRBV infection in 2014. By 2016, 59.2% of the vines tested positive for GRBV. Areas of aggregation increased and were spatially associated across all years. From 2013 to 2015, GRBV was not detected at Milton-Freewater in eastern Oregon. Spatial patterns of GRBV infection support evidence of spread by a mobile insect vector. GRBV is a significant threat to Oregon wine grape production because of its drastic year-over-year spread in affected vineyards.

3D printed testing aids for radiographic quality control.

Quality control testing of radiographic and fluoroscopic imaging systems requires positioning of test objects in the x-ray beam in a precise and repeatable fashion. In this work we present several three-dimensional (3D) printed testing aids that improve efficiency, accuracy, and repeatability of quality control testing. We also present a new device for determining the location of the perpendicular ray in radiographic systems. These devices were designed in an open source software program (OpenScad, http://www.openscad.org) and 3D models were saved in .stl format for printing. The models were printed on either a MakerBot Replicator 2 or Replicator Z18 printer (MakerBot Industries, LLC, Brooklyn, NY). The testing aids were printed using polylactic acid (PLA) filament. To investigate the radiographic characteristics of the PLA used, test articles were printed and used to measure the half-value layer (HVL) thicknesses in mm of PLA and half-value densities (HVD) in g/cm2 of PLA for two different colors and over a wide range of radiographic beam qualities, using a portable fluoroscopic c-arm system. HVL thicknesses of clear PLA ranged from approximately 20 mm at 50 kV nominal tube voltage to 27 mm at 120 kV nominal tube voltage. For green PLA, the HVL thickness was 19 mm at 50 kV tube voltage and 25.7 mm at 120 kV tube voltage. The HVD of clear PLA ranged from 2.37 g/cm2 at 50 kV nominal tube voltage to 3.19 g/cm2 at 120 kV nominal tube voltage. For green PLA, the HVD was 2.35 g/cm2 at 50 kV tube voltage and 3.17 g/cm2 at 120 kV tube voltage. The cost of the devices range from under $2 to approximately $20 in materials. The files used to create the models are freely available at https://github.com/Upstate3DLab/3D-Printed-Radiographic-Test-Tools.

Optimization of polyhydroxybutyrate production by experimental design of combined ternary mixture (glucose, xylose and arabinose) and process variables (sugar concentration, molar C:N ratio).

Conversion of lignocellulosic feedstocks to polyhydroxybutyrate (PHB) could make lignocellulosic biorefineries more profitable and sustainable. Glucose, xylose and arabinose are the main sugars derived from pretreatment and hydrolysis of herbaceous feedstocks. Burkholderia sacchari DSM 17165 is a bacterium that can convert these sugars into PHB. However, the effects of sugar ratio, sugar concentration, and molar C:N ratio on PHB production have not been studied. In this study, a seven-run mixture design for sugar ratio combined with a 32 full factorial design for process variables was performed to optimize PHB production. A polynomial model was built based on experimental data, and optimum conditions for different sugar streams were derived and validated. The highest PHB production (3.81 g/L) was achieved with arabinose at a concentration of 25.54 g/L and molar C:N ratio of 74.35. Results provide references for manipulation of sugar mixture and process control to maximize PHB production.

Entomological Opportunities and Challenges for Sustainable Viticulture in a Global Market.

Viticulture has experienced dramatic global growth in acreage and value. As the international exchange of goods has increased, so too has the market demand for sustainably produced products. Both elements redefine the entomological challenges posed to viticulture and have stimulated significant advances in arthropod pest control programs. Vineyard managers on all continents are increasingly combating invasive species, resulting in the adoption of novel insecticides, semiochemicals, and molecular tools to support sustainable viticulture. At the local level, vineyard management practices consider factors such as the surrounding natural ecosystem, risk to fish populations, and air quality. Coordinated multinational responses to pest invasion have been highly effective and have, for example, resulted in eradication of the moth Lobesia botrana from California vineyards, a pest found in 2009 and eradicated by 2016. At the global level, the shared pests and solutions for their suppression will play an increasing role in delivering internationally sensitive pest management programs that respond to invasive pests, climate change, novel vector and pathogen relationships, and pesticide restrictions.

Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas.

Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects. A total of eight dogs participated in the study and only two developed mild post-operative complications, which resolved with medical therapy. All canines underwent a single CED treatment of the cetuximab-IONPs over 3 days and did not receive any further adjuvant treatments. Volumetric analysis showed a median reduction in tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were euthanized due to recurrence of neurological signs other than seizures, two due to recurrent seizures, and one dog died in his sleep. Median survival time after surgery was 248 days (mean 367 days).

Conformational Effects on Gas-Phase Acidities of Isomeric C3 and C5 Alkanols.

The competitive threshold collision-induced dissociation technique is used to examine conformational effects on the relative gas-phase acidities of selected alcohols. By use of HF and H2O as reference acids in a local thermochemical network to obtain absolute acidities, the measured 0 K gas-phase acidities for the propanol and pentanol isomers are Δacid H0(CH3CH2CH2O-H) = 1563.9 ± 2.9 kJ/mol, Δacid H0((CH3)2CHO-H) = 1568.2 ± 2.7 kJ/mol, Δacid H0(CH3(CH2)4O-H) = 1556.4 ± 2.9 kJ/mol, and Δacid H0((CH3)2CHCH2CH2O-H) = 1556.5 ± 3.0 kJ/mol. Conformational stabilization during deprotonation results in the observed acidity differences between isomers, which can be compared with the "intrinsic" acidity strength defined as deprotonation of the extended all- anti staggered conformations without relaxation. The intrinsic acidities for the propanol and pentanol isomers are 1567 and 1562 kJ/mol, respectively. The difference in intrinsic and observed acidity is largely due to the result of a twisted geometry of the alkoxide ion, stabilized by electrostatic interaction between the electronegative terminal O atom and a H atom on the γ-carbon. These interactions are primarily due to internal rotation about the Cα-Cß bonds for n-propoxide and the primary pentoxides.