Leukocyte kinetics and bacterial clearance during S. pneumoniae pneumonia and contributions of ICAM-1.

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is highly expressed on the pulmonary capillary endothelium, alveolar epithelium and other cell types within the lung. ICAM-1 plays important roles in leukocyte adhesion, migration, and motility. To determine the contributions of ICAM-1 to bacterial clearance and leukocyte kinetics during pneumonia, mice were inoculated with S. pneumoniae and evaluated 1, 4 and 7 days later. Our results show that Icam1-/-mice have a greater number of viable bacteria within the lung at each time point. The impaired clearance observed in Icam1-/- mice was not due to an impediment in leukocyte recruitment. In fact, Icam1-/- mice had a greater number of neutrophils and recruited inflammatory macrophages in the lung tissue and the alveoli/airways on day 7. In contrast, fewer alveolar macrophages were present in the BAL of Icam1-/-mice. The loss of body weight and the concentrations of inflammatory mediators in the BAL were also significantly greater in Icam1-/- mice. Mechanistic studies to understand the defect in clearance show that neutrophils and macrophage subpopulations had no defect in phagocytosis or acidification of phagosomes. RNA sequencing reveals many differences in gene expression, but no suggestion of a defect in phagocytosis or killing. Thus, that ICAM-1 is necessary for the clearance of S. pneumoniae and for the resolution of pneumonia, but is not required for the recruitment of neutrophils or inflammatory macrophages into the pneumonic lung parenchyma or the alveoli/airways during S. pneumoniae-induced pneumonia.

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single-dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single-dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

Topographical Features of Pediatric Electroencephalography during High Initial Concentration Sevoflurane for Inhalational Induction of Anesthesia.

BACKGROUND: High-density electroencephalographic (EEG) monitoring remains underutilized in clinical anesthesia, despite its obvious utility in unraveling the profound physiologic impact of these agents on central nervous system functioning. In school-aged children, the routine practice of rapid induction with high concentrations of inspiratory sevoflurane is commonplace, given its favorable efficacy and tolerance profile. However, few studies investigate topographic EEG during the critical timepoint coinciding with loss of responsiveness-a key moment for anesthesiologists in their everyday practice. The authors hypothesized that high initial sevoflurane inhalation would better precipitate changes in brain regions due to inhomogeneities in maturation across three different age groups compared with gradual stepwise paradigms utilized by other investigators. Knowledge of these changes may inform strategies for agent titration in everyday clinical settings. METHODS: A total of 37 healthy children aged 5 to 10 yr underwent induction with 4% or greater sevoflurane in high-flow oxygen. Perturbations in anesthetic state were investigated in 23 of these children using 64-channel EEG with the Hjorth Laplacian referencing scheme. Topographical maps illustrated absolute, relative, and total band power across three age groups: 5 to 6 yr (n = 7), 7 to 8 yr (n = 8), and 9 to 10 yr (n = 8). RESULTS: Spectral analysis revealed a large shift in total power driven by increased delta oscillations. Well-described topographic patterns of anesthesia, e.g., frontal predominance, paradoxical beta excitation, and increased slow activity, were evident in the topographic maps. However, there were no statistically significant age-related changes in spectral power observed in a midline electrode subset between the groups when responsiveness was lost compared to the resting state. CONCLUSIONS: High initial concentration sevoflurane induction causes large-scale topographic effects on the pediatric EEG. Within the minute after unresponsiveness, this dosage may perturb EEG activity in children to an extent where age-related differences are not discernible.

Impact of and research priorities in early onset epilepsy: An investigation of parental concerns.

[Background and aim] Early onset epilepsy is a neurological condition with significant developmental consequences, and presents affected children and families with challenges which pervade many aspects of family life. Whilst the concerns of parents and the impact on quality of life is well documented in qualitative research, little emphasis has been placed on the context of 'early onset', and the implications of these concerns for research priority setting. We aimed to explore parental perspectives regarding concerns and the impact of early onset epilepsy on the child and family, and to identify priorities for future paediatric epilepsy research. [Methods] The Brain development in Early Epilepsy: Parent Priorities (BEE-PP) project employed a mixed methods approach to collect information on parents' experience of having a child diagnosed with early onset epilepsy before 36 months old and aged up to 16 years old. Parents completed an online survey (n = 15) followed by a focus group (n = 5) to explore their main concerns regarding early onset epilepsy, the impact on family life and research priorities. [Results] A thematic analysis of the focus group data generated eight themes related to concerns of parents, the impact on the family and research priorities. The three main concerns identified were the expected trajectory of their child's development, a lack of seizure control following diagnosis and adverse behavioural side effects of medication. Within family life, early onset epilepsy had an impact on sibling autonomy and psychosocial adaptation, poorer parental wellbeing and restricted social and personal activities. The need for clearer information regarding their child's developmental trajectory, and managing the side effects of medication and their interactions with behaviour over time were topics of priority for future epilepsy research. [Interpretation] The impact of early onset epilepsy on the family is pervasive and requires the provision of appropriate healthcare service-led support for families to improve quality of life and children's adjustment to epilepsy. Regular monitoring of the concerns of parents and the impact of the diagnosis would be beneficial for addressing epilepsy-related and psychosocial needs of the wider family throughout their child's development. Implications for future research priority setting with regards to improved clinician-to-parent information sharing and managing the behavioural side effects of medication are discussed.

Sexual Identity Development and Social Ecological Facilitators and Barriers of PrEP Uptake and Adherence Among Latinx Men Who Have Sex with Men.

Latinx gay, bisexual, and other men who have sex with men (LMSM) report lower pre-exposure prophylaxis (PrEP) use than their white, non-Latinx counterparts. We hypothesize that this disparity is partially attributable to social ecological factors that can be addressed via prevention interventions. In this retrospective study, we first examined data from 253 LMSM to determine whether theorized associations existed between acquisition of a PrEP prescription (uptake) in relation to several social ecological factors based on a conceptual framework of determinants of access to and uptake of PrEP for LMSM. We also explored relations between frequency of PrEP use (adherence) and social ecological factors with a subsample of 33 LMSM who had initiated PrEP 12 months prior to assessment. In this study, individual-level factors from this framework included age and socioeconomic status. Perceived access to medical care represented both individual- and community-level determinants of PrEP uptake and adherence. Interpersonal-level factors were social support and relationship status. Structural/cultural-level factors were sexual identity development status, the masculinity norm of heterosexual self-presentation, traditional Latinx masculine gender role beliefs of machismo and caballerismo, racial identity, and immigration status. Results indicated that older men and those who endorsed the synthesis/integration status of sexual identity development were more likely to acquire a PrEP prescription during their lifetime in comparison to peers. PrEP adherence was linked with being older, reporting higher socioeconomic status, reporting more appraisal social support, self-identifying as white-Latinx, being U.S.-born, and endorsing less sexual identity uncertainty and more heterosexual self-presentation. Results specify modifiable factors that may inform tailored, community-based prevention efforts to increase PrEP use and decrease existing HIV/AIDS disparities among LMSM.

Opioid Misuse by Adults with Chronic Pain: The Impact of Illness and Medication Beliefs.

BACKGROUND: Why do some adults with chronic pain misuse their prescription opioids when others do not? Based on the extended Common-Sense Model, the study evaluated whether adults' beliefs about their pain have an indirect effect on risk of opioid misuse through beliefs about opioids when controlling for depression. METHODS: The sample included 297 adult participants in the U.S. recruited from Prolific, an online crowdsourcing website. Study measures included the Illness Perception Questionnaire-Revised (IPQ-R; protective and threat-related illness beliefs about chronic pain), the Beliefs about Medicines Questionnaire-Specific subscale (BMQ-Specific; concern and necessity medication beliefs about prescription opioids), and the Current Opioid Misuse Measure (COMM; risk of current opioid misuse). This cross-sectional parallel mediation analysis was conducted using MPlus. RESULTS: After controlling for depression, the indirect effect of protective illness beliefs on opioid misuse risk through concern medication beliefs (b = -0.01, 95% CI (-0. 038, -0.001), and the indirect effect of threat-related illness beliefs on opioid misuse risk through necessity medication beliefs (b = 0.02, 95% CI (0.004, 0.036) were significant. The full model explained 35% of the variance of opioid misuse risk. CONCLUSIONS: Adults with chronic pain with stronger protective beliefs about pain were less likely to have concerns about their opioids and were at lower risk for opioid misuse, while those with greater threat-related beliefs about pain were more likely to believe that their opioids were necessary and be at greater risk for opioid misuse. Results have implications for medical and mental health providers and future research.

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia.

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions. Forty-two newly diagnosed AML patients were enrolled in the investigator-initiated High Dose Discontinuation Azacitidine+Venetoclax (HiDDAV) Study (clinicaltrials gov. Identifier: NCT03466294). Patients received one to three "induction" cycles of venetoclax 600 mg daily with azacitidine. Responders received MRD-positive or MRDnegative "maintenance" arms: azacitidine with 400 mg venetoclax or 400 mg venetoclax alone, respectively. The toxicity profile of HiDDAV was similar to 400 mg venetoclax. The overall response rate was 66.7%; the duration of response (DOR), event-free survival (EFS) and overall survival were 12.9, 7.8 and 9.8 months, respectively. The MRD negativity rate was 64.3% by flow cytometry and 25.0% when also measured by droplet digital polymerase chain recation. MRD-negative patients by flow cytometry had improved DOR and EFS; more stringent measures of MRD negativity were not associated with improved OS, DOR or EFS. Using MRD to guide azacitidine discontinuation did not lead to improved DOR, EFS or OS compared to patients who discontinued azacitidine without MRD guidance. Within the context of this study design, venetoclax doses >400 mg with azacitidine were well tolerated but not associated with discernible clinical improvement, and MRD may not assist in recommendations to discontinue azacitidine. Other strategies to optimize, and for some patients, de-intensify, venetoclax+azacitidine regimens are needed.

Masculine Drinking Norms and Alcohol Use in a National Sample of NCAA Male Student-Athletes.

Objectives: Participation in sports can increase young adults' risk for heavy alcohol use and related consequences. Among student-athletes, more men report heavy drinking than women. These gender differences may reflect men's expression of masculinity which can encompass excessive consumption. While a growing body of research indicates that general masculine norms are positively associated with alcohol use and consequences among men, the extent to which alcohol-specific masculine norms can increase student-athletes' risk for elevated drinking and related outcomes is not yet known. Thus, we examined how masculine drinking norms are associated with alcohol use and related consequences while accounting for demographics and multiple dimensions of general masculine norms. Methods: 1,825 NCAA student-athletes (White=79%, Mage=20.1/SDage=1.3; 50 colleges/universities) completed a confidential online survey which included questions regarding masculine drinking norms of excess and control and conformity to general masculine norms. Results: We created latent constructs and tested a path model in SEM. Results indicated that, after accounting for demographics and multiple dimensions of general masculine norms, the masculine drinking norm of excess was positively associated with alcohol use and consequences. Conversely, control was negatively related to alcohol use but unrelated to consequences. Compared to control and other dimensions of general masculine norms, excess was most strongly related to alcohol use and consequences. Conclusions: A move from assessing general masculine norms toward alcohol-specific masculine norms can further researchers' and practitioners' knowledge of masculine norms and their link to drinking behaviors, and enhance the application of masculine norms in alcohol intervention and prevention programs.

TBK1 Is Required for Host Defense Functions Distinct from Type I IFN Expression and Myeloid Cell Recruitment in Murine Streptococcus pneumoniae Pneumonia.

Bacterial pneumonia induces the rapid recruitment and activation of neutrophils and macrophages into the lung, and these cells contribute to bacterial clearance and other defense functions. TBK1 (TANK-binding kinase 1) performs many functions, including activation of the type I IFN pathway and regulation of autophagy and mitophagy, but its contribution to antibacterial defenses in the lung is unclear. We previously showed that lung neutrophils upregulate mRNAs for TBK1 and its accessory proteins during Streptococcus pneumoniae pneumonia, despite low or absent expression of type I IFN in these cells. We hypothesized that TBK1 performs key antibacterial functions in pneumonia apart from type I IFN expression. Using TBK1 null mice, we show that TBK1 contributes to antibacterial defenses and promotes bacterial clearance and survival. TBK1 null mice express lower concentrations of many cytokines in the infected lung. Conditional deletion of TBK1 with LysMCre results in TBK1 deletion from macrophages but not neutrophils. LysMCre TBK1 mice have no defect in cytokine expression, implicating a nonmacrophage cell type as a key TBK1-dependent cell. TBK1 null neutrophils have no defect in recruitment to the infected lung but show impaired activation of p65/NF-κB and STAT1 and lower expression of reactive oxygen species, IFNγ, and IL12p40. TLR1/2 and 4 agonists each induce phosphorylation of TBK1 in neutrophils. Surprisingly, neutrophil TBK1 activation in vivo does not require the adaptor STING. Thus, TBK1 is a critical component of STING-independent antibacterial responses in the lung, and TBK1 is necessary for multiple neutrophil functions.

Effect of distance and daily periods on heat-stressed pigs and pre-slaughter losses in a semiarid region.

Effective planning animal transport is essential to safeguard animal welfare and reduce production losses. Environmental conditions, specifically extreme temperatures in combination with ranges of relative humidity are highlighted as one of the main risk factors for production losses during transport (e.g., fatalities). The majority of research evaluating both welfare and production impacts of pig transport have been primarily undertaken in Europe and North America, which cover a relatively limited range of distinct climates (e.g., temperate, sub-arctic, etc.). As a result, research on pig transport in semi-arid conditions is lacking. In this study, we evaluated the effects of both distance (short, 30 km; and long, 170 km) and transport daily periods (morning, (05:00-11:00); afternoon (12:00-17:00); and night, (23:00-04:00)) on the preslaughter losses and heat stress of pigs in commercial transport in a semiarid region. Across 19 journeys of standard slaughter-weight pig loads (124.0 ± 2.8 kg), 684 focal animals (36 per journey) were evaluated. For each journey, the load's thermal profile (THIadj and enthalpy) and physiological responses of individual pigs were recorded. On arrival at designated slaughterhouses, the percentage pig of non-ambulatory non-injured (NANI), non-ambulatory injured (NAI), death on arrival (DOA), and total losses were recorded. Short journeys in the afternoon were shown to be more detrimental to the thermal comfort of pigs, with higher rectal temperatures recorded. The highest percentage of total losses and DOA occurred in afternoon journeys, irrespective of distance, followed by the morning, with the lowest losses observed in pigs transported at night. Additionally, total losses and DOA were further exacerbated by journey distance, with higher rates observed in short journeys. Higher percentage averages of NANI and NAI were observed in shorter journeys, but daily periods effects were only observed for NANI. These results further demonstrate the welfare and production loss risks associated with journey distance and time of day (representing varying environmental conditions) during road transport of pigs, whilst providing novel data in semiarid conditions. Careful and effective planning for pig transportation is essential to minimize heat stress and production losses. Consideration of the thermal environment on the day of travel, as well as providing flexibility to adjust travel times (e.g., early morning or evening), should help to mitigate risks of heat stress and production losses during pig transport.

Associations between Impulsivity and Exercise Addiction, Disordered Eating, and Alcohol Use Behaviors: A Latent Profile Analysis.

BackgroundDespite the known negative consequences of exercise addiction and preliminary evidence suggesting that it may co-occur with other health risk behaviors, no studies to date have examined exercise addiction among college students in conjunction with disordered eating behaviors and alcohol use. The aim of this study was to describe which college students are most at-risk for co-occurring health risk behaviors to enhance the efficiency of health risk prevention efforts. Method: Guided by multidimensional theories of impulsivity and substance use models of comorbidity, this study used latent profile analysis to examine whether separate, conceptually meaningful profiles of risk for exercise addiction, disordered eating behaviors, and alcohol use would emerge among 503 college students from a large public university. Results: The best-fitting model supported three profiles. MANOVA results revealed significant profile differences based on exercise addiction, binge eating, purging, laxative/pill/diuretic use, exercising longer than 60 minutes, negative urgency, and problematic alcohol use. Profile 3 students (n = 29), labeled the Affect Driven Health Risk-Takers, demonstrated the highest levels of impulsivity (i.e., negative urgency, lack of premeditation, lack of perseverance, and sensation seeking) and the most risk behaviors compared to the other two profiles. Profile membership was associated with distinct levels of negative urgency, exercise addiction, disordered eating behaviors, and problematic alcohol use. A small proportion of undergraduates demonstrated co-occurring exercise addiction, disordered eating behaviors, and problematic alcohol use. Profile membership also predicted the health outcomes of clinically significant exercise addiction and hazardous alcohol use. Conclusions: Findings illuminated how patterns of risk behavior engagement were associated with clinically significant exercise addiction and hazardous alcohol use and will inform prevention efforts and clinical interventions with at-risk college students.

Formation and contraction of multicellular actomyosin cables facilitate lens placode invagination.

Embryonic morphogenesis relies on the intrinsic ability of cells, often through remodeling the cytoskeleton, to shape epithelial tissues during development. Epithelial invagination is an example of morphogenesis that depends on this remodeling but the cellular mechanisms driving arrangement of cytoskeletal elements needed for tissue deformation remain incompletely characterized. To elucidate these mechanisms, live fluorescent microscopy and immunohistochemistry on fixed specimens were performed on chick and mouse lens placodes. This analysis revealed the formation of peripherally localized, circumferentially orientated and aligned junctions enriched in F-actin and MyoIIB. Once formed, the aligned junctions contract in a Rho-kinase and non-muscle myosin dependent manner. Further molecular characterization of these junctions revealed a Rho-kinase dependent accumulation of Arhgef11, a RhoA-specific guanine exchange factor known to regulate the formation of actomyosin cables and junctional contraction. In contrast, the localization of the Par-complex protein Par3, was reduced in these circumferentially orientated junctions. In an effort to determine if Par3 plays a negative role in MyoIIB accumulation, Par3-deficient mouse embryos were analyzed which not only revealed an increase in bicellular junctional accumulation of MyoIIB, but also a reduction of Arhgef11. Together, these results highlight the importance of the formation of the multicellular actomyosin cables that appear essential to the initiation of epithelial invagination and implicate the potential role of Arhgef11 and Par3 in their contraction and formation.

Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study.

BACKGROUND: Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. METHODS: This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 - 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. RESULTS: Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 - 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 - 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 - 1.38). CONCLUSION: As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.

Nickel(II)-SNS Thiolate Complexes: Reactivity and Solution Dynamics.

Nickel coordination chemistry with a biomimetic thiolate-imine-thioether SNSMe ligand is accompanied by diverse reactivity and multidentate ligand dynamics. Reaction of Ni(acac)2 with 2 equiv of 2-(methylthio)-phenyl-benzothiazolidine (MPB) affords the bis(arylimino-phenylene-thiolate) complex Ni(κ2-SNSMe)2 (1; acac = acetylacetonate). Thermolysis of 1 in refluxing toluene is accompanied by imine C-C bond formation, yielding [Ni(N2S2)] (2) with a redox-active ligand. Protonation of 1 with NHTf2 at a low temperature released 1 equiv of MPB, yielding crystals of the dimeric dication {[Ni(µ-κ3-SNSMe)]2}(NTf2)2 (3; Tf = SO2CF3) in high yield. In contrast, the same reaction at room temperature gave also paramagnetic complexes {Ni[µ-Ni(κ3-SNSMe)2]2}(NTf2)2 (4) and {Ni[µ-Ni(κ3-SNSMe)2]3}(NTf2)2 (5) that feature coordination of two or three pseudo-octahedral, paramagnetic Ni(κ3-SNSMe)2 units to a central Ni(II) dication via thiolate bridges. Remarkably, dissolution of 3 in a variety of solvents, including weakly coordinating CH2Cl2, rapidly generates a mixture of 4 and Ni(NTf)2. Treatment of this mixture with Lewis bases L gave high yields of dimers {[Ni(µ-κ3-SNSMe)L]2}(NTf2)2 for L = CNXylyl (6a) and {[Ni(µ-κ3-SNSMe)]2(µ-dmpm)}(NTf2)2 (6b; dmpm = bis(dimethylphosphino)methane) or monomers [Ni(κ3-SNSMe)L](NTf2) for L = PMe3 (7a) and P(OMe)3 (7b). Addition of 2 equiv of the strong donor N-heterocyclic carbene ligand, IPr, to 3, however, led to thioether demethylation, affording neutral dithiolate complex Ni(κ3-SNS)(IPr) (8). Reaction products were characterized by NMR and mass spectrometry and complexes 1-5, 6a, 6b, 7a, and 8 by single-crystal X-ray diffraction.

Identification of trailer heat zones and associated heat stress in weaner pigs transported by road in tropical climates.

Heat stress is major welfare concern during transport of pigs in tropical climates, which can also lead to direct production costs. This study evaluated the dynamics of heat zones through the load and their relationship with heat stress of weaner pigs during road transport in a tropical climate. Both environmental (e.g. temperature and relative humidity) and physiological (e.g. respiratory frequency and lactate) measures were recorded from four vehicle journeys (70 km distance, 216 weaner pigs within each trailer load) within Ceará, northeastern Brazil. Geostatistics and fluid dynamics simulation techniques were applied to understand the dynamics of heat zones and ventilation patterns the truckload. Statistics based on canonical discriminant analysis and ANOVA were performed to verify the relationship between heat zones and heat stress in pigs. The results showed that, during transport, the generation of heat zones occurred with different magnitudes along the load (P < 0.05), which was harmonized by the ventilation dynamics. There was a heat core with high energy content, in the front region of the lower deck (LD) of the trailer. In this zone, weaners pigs had higher rectal temperature (+1.8 °C temperature difference), respiratory frequency (LD = 94 ± 1.3 breaths/min; UD = 86 ± 1.3 breaths/min), and blood cortisol concentration (LD = 32.9 ± 0.8 ng/mL; UD = 30.18 ± 0.6 ng/mL) (all P < 0.05). Weaners pigs transported in the upper deck (UD) compartments had the highest skin temperature (LD = 38.13 ± 0.3 °C; UD = 38.9 ± 0.22 °C) and the highest mean values of blood lactate (LD = 65.5 ± 1.11 m/M; UD = 71.60 ± 1.19 m/M) and Creatine kinase (LD = 3891.23 ± 69U/L; UD = 4107.43 ± 62U/L) (P < 0.05). Weaners transported in compartments of the LD of trailer were more susceptible to heat stress, while weaners in the UD compartments were more susceptible to physical stress and muscle exhaustion. These results provide additional evidence of heat zones within trailer compartments and highlight the requirement for the planning of pig transport operations in tropical climates to mitigate risks of heat stress.

Veterinary Student Opinions Regarding Ethical Dilemmas Encountered by Veterinarians and the Benefits of Ethics Instruction.

Recognizing and addressing ethical conflicts is an emerging concern for veterinarians. Veterinary students (N = 284) from four US schools were surveyed regarding their opinions on ethical dilemmas encountered by veterinarians and the benefits of ethics instruction. The majority of respondents had encountered all clinical scenarios that may be associated with ethical dilemmas that were provided. The most common ethical dilemma experienced was compromise of patient care because of financial limitations. Students with at least 12 months of experience were more likely to believe that practitioners encounter ethical dilemmas regularly. Although 92% of 271 respondents indicated that veterinarians should prioritize patient interests when the interests of clients and patients conflict, 84% of respondents reported that veterinarians most often prioritize client interests. Most (78%) respondents indicated having received training in ethical theories and approaches to address ethical dilemmas. The majority of respondents agreed that they feel better prepared to identify (80%) and address (55%) ethical dilemmas as a result of their ethics training. Most respondents (81%) identified experiencing moral stress in relation to how animals were treated. Only 46% of respondents reported receiving training in tools for coping with moral stress. Most of these respondents (54%) agreed that such training would be effective in helping to manage moral stress. Results suggested that educators should prepare students for the contrast in advocacy preferences they are apt to encounter when they enter practice. It is recommended that ethics training and tools for coping with moral stress be core components of the veterinary curriculum.

Cigarillos Compromise the Mucosal Barrier and Protein Expression in Airway Epithelia.

Smoking remains a leading cause of preventable morbidity and mortality worldwide. Despite a downward trend in cigarette use, less-regulated tobacco products, such as cigarillos, which are often flavored to appeal to specific demographics, such as younger people, are becoming increasingly popular. Cigar/cigarillo smoking has been considered a safer alternative to cigarettes; however, the health risks associated with cigar in comparison with cigarette smoking are not well understood. To address this knowledge gap, we characterized the effects of multiple brands of cigarillos on the airway epithelium using ex vivo and in vivo models. To analyze these effects, we assessed the cellular viability and integrity of smoke-exposed primary airway cell cultures. We also investigated the protein compositions of apical secretions from cigarillo-exposed airway epithelial cultures and BAL fluid of cigarillo-exposed mice through label-free quantitative proteomics and determined the chemical composition of smoke collected from the investigated cigarillo products. We found that cigarillo smoke exerts similar or greater effects than cigarette smoke in terms of reduced cell viability; altered protein levels, including those of innate immune proteins; induced oxidative-stress markers; and greater nicotine delivery to cells. The analysis of the chemical composition of the investigated cigarillo products revealed differences that might be linked to the differential effects of these products on cell viability and protein abundance profiles, which have been associated with a range of health risks in the context of airway biology. These findings contradict the assumption that cigarillos might be safer and less harmful than cigarettes. Instead, our results indicate that cigarillo smoke is associated with equal or greater health risks and the same or increased airway toxicity compared with cigarette smoke.

Propionic acid production by Propionibacterium freudenreichii using sweet sorghum bagasse hydrolysate.

Propionic acid, a widely used food preservative and intermediate in the manufacture of various chemicals, is currently produced from petroleum-based chemicals, raising concerns about its long-term sustainability. A key way to make propionic acid more sustainable is through fermentation of low-cost renewable and inedible sugar sources, such as lignocellulosic biomass. To this end, we utilized the cellulosic hydrolysate of sweet sorghum bagasse (SSB), a residue from a promising biomass source that can be cultivated around the world, for fermentative propionic acid production using Propionibacterium freudenreichii. In serum bottles, SSB hydrolysate supported a higher propionic acid yield than glucose (0.51 vs. 0.44 g/g, respectively), which can be attributed to the presence of additional nutrients in the hydrolysate enhancing propionic acid biosynthesis and the pH buffering capacity of the hydrolysate. Additionally, SSB hydrolysate supported better cell growth kinetics and higher tolerance to product inhibition by P. freudenreichii. The yield was further improved by co-fermenting glycerol, a renewable byproduct of the biodiesel industry, reaching up to 0.59 g/g, whereas volumetric productivity was enhanced by running the fermentation with high cell density inoculum. In the bioreactor, although the yield was slightly lower than in serum bottles (0.45 g/g), higher final concentration and overall productivity of propionic acid were achieved. Compared to glucose (this study) and hydrolysates from other biomass species (literature), use of SSB hydrolysate as a renewable glucose source resulted in comparable or even higher propionic acid yields. KEY POINTS: • Propionic acid yield and cell growth were higher in SSB hydrolysate than glucose. • The yield was enhanced by co-fermenting SSB hydrolysate and glycerol. • The productivity was enhanced under high cell density fermentation conditions. • SSB hydrolysate is equivalent or superior to other reported hydrolysates.

Arthrographis kalrae Keratitis Complicated by Endophthalmitis: A Case Report With Literature Review.

OBJECTIVES: To report the first case of Arthrographis kalrae keratitis complicated by endophthalmitis in the UK and to review the current literature. METHODS: A case report with literature review. RESULTS: A 65-year-old male patient, with a background of treated B-cell lymphoma and herpes simplex virus-related neurotrophic keratopathy, presented with a large infiltrative corneal ulcer in the right eye. The patient was immediately commenced on empirical antifungal treatment in view of the clinical suspicion of fungal keratitis (FK). The initial corneal scrape identified the organism as nonspecific "mold," and the identity of A. kalrae was subsequently confirmed using matrix-assisted laser/desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). During the clinical course, the patient received topical, intrastromal, intracameral, and systemic antifungal treatment, repeat therapeutic corneal cross-linking treatment, and three penetrating keratoplasties. Although a temporary improvement was achieved with therapeutic corneal cross-linking treatment, the FK progressed relentlessly and was ultimately complicated by an endophthalmitis despite maximum medical and surgical treatment, eventuating in an enucleation. CONCLUSIONS: A. kalrae keratitis is an exceptionally rare clinical entity that poses significant therapeutic challenges. MALDI-TOF-MS serves as a useful diagnostic technique in identifying this rare organism. Although the literature suggested that A. kalrae keratitis may sometimes be controlled with antifungal medical treatment alone, this approach was proven to be futile in our immunocompromised patient with pre-existing neurotrophic keratopathy, suggesting that early surgical intervention such as therapeutic keratoplasty may be required in these cases.

Associations among Negative Urgency, Sensation Seeking, Alcohol Use, Self-Esteem, and Casual Sexual Behavior for College Students.

Background: The present study proposed a moderated mediation model of relations among negative urgency, sensation seeking, alcohol use, self-esteem, and casual sexual behavior among college students. We hypothesized students' alcohol use would mediate a positive relation between two facets of impulsivity, negative urgency and sensation seeking, with casual sexual behavior. We also examined the influence of self-esteem on alcohol use and casual sexual behavior to determine if self-esteem may serve as a point of intervention. We hypothesized that self-esteem might moderate the relation between casual sexual behavior and alcohol use, such that students who report high alcohol use in addition to low self-esteem would engage in more casual sexual behavior than individuals who report relatively higher levels of self-esteem. Methods: Data were collected in 2015 from 413 undergraduate students at a large Northeastern public university. Structural equation modeling tested the moderated mediation model. Results: Contrary to hypotheses, the theorized model demonstrated an inadequate fit to the data when self-esteem was included. A second structural model was calculated to test alcohol use as a mediator of associations between negative urgency and sensation seeking, and casual sexual behavior. As hypothesized, students' alcohol use was found to be a mediator of the positive associations between negative urgency and casual sexual behavior and sensation seeking and casual sexual behavior. Conclusions: Findings suggest that alcohol use, negative urgency, and sensation seeking may serve as points of intervention to address casual sexual behavior, as appropriate, among college student populations.