Dogs can detect an odor profile associated with Staphylococcus aureus biofilms in cultures and biological samples.

Introduction: The study investigated the utilization of odor detection dogs to identify the odor profile of Staphylococcus aureus (S. aureus) biofilms in pure in vitro samples and in in vivo biosamples from animals and humans with S. aureus periprosthetic joint infection (PJI). Biofilms form when bacterial communities aggregate on orthopedic implants leading to recalcitrant infections that are difficult to treat. Identifying PJI biofilm infections is challenging, and traditional microbiological cultures may yield negative results even in the presence of clinical signs. Methods: Dogs were trained on pure in vitro S. aureus biofilms and tested on lacrimal fluid samples from an in vivo animal model (rabbits) and human patients with confirmed S. aureus PJI. Results: The results demonstrated that dogs achieved a high degree of sensitivity and specificity in detecting the odor profile associated with S. aureus biofilms in rabbit samples. Preliminary results suggest that dogs can recognize S. aureus volatile organic compounds (VOCs) in human lacrimal fluid samples. Discussion: Training odor detection dogs on in vitro S. aureus, may provide an alternative to obtaining clinical samples for training and mitigates biosecurity hazards. The findings hold promise for culture-independent diagnostics, enabling early disease detection, and improved antimicrobial stewardship. In conclusion, this research demonstrates that dogs trained on in vitro S. aureus samples can identify the consistent VOC profile of PJI S. aureus biofilm infections. The study opens avenues for further investigations into a retained VOC profile of S. aureus biofilm infection. These advancements could revolutionize infectious disease diagnosis and treatment, leading to better patient outcomes and addressing the global challenge of antimicrobial resistance.

Assessing Different Chronic Wasting Disease Training Aids for Use with Detection Dogs.

Chronic wasting disease (CWD) is a highly infectious, fatal prion disease that affects cervid species. One promising method for CWD surveillance is the use of detection dog-handler teams wherein dogs are trained on the volatile organic compound signature of CWD fecal matter. However, using fecal matter from CWD-positive deer poses a biohazard risk; CWD prions can bind to soil particles and remain infectious in contaminated areas for extended periods of time, and it is very difficult to decontaminate the affected areas. One solution is to use noninfectious training aids that can replicate the odor of fecal matter from CWD-positive and CWD-negative deer and are safe to use in the environment. Trained CWD detection dogs' sensitivity and specificity for different training aid materials (cotton, GetXent tubes, and polydimethylsiloxane, or PDMS) incubated with fecal matter from CWD-positive and CWD-negative deer at two different temperatures (21 °C and 37 °C) for three different lengths of time (6 h, 24 h, and 48 h) were evaluated. Cotton incubated at 21 °C for 24 h was identified as the best aid for CWD based on the dogs' performance and practical needs for training aid creation. Implications for CWD detection training and for training aid selection in general are discussed.

The effect of repeated testing on judgement bias in domestic dogs (Canis familiaris).

Judgement bias paradigms are increasingly being used as a measure of affective state in dogs. Approach to an ambiguous stimulus is commonly used as a measure of affect, however, this may also be influenced by learning. This study directly measured the impact of learning on a commonly used judgement bias paradigm in the absence of an affective state manipulation. Dogs (N = 15) were tested on a judgement bias task across five sessions. The dogs' latency to approach a bowl placed in one of three ambiguous locations between non-baited (negative) and baited (positive) locations was measured. Results show that session number had a significant effect on the dogs' latencies to reach the ambiguous bowl locations, with post-hoc tests revealing that dogs were significantly slower to approach the locations as the number of sessions increased. Session number also had a significant effect on the number of times the dogs did not approach the bowl within 30 s of being released, with the number of no approaches generally increasing across sessions. When dog identity was included as a fixed effect, a significant effect on latency to approach was found, suggesting that some dogs were consistently faster than others across sessions. To assess whether the paradigm produced repeatable results, Intraclass Correlation Coefficients were used. A low degree of reliability was found between latencies to approach each bowl position across sessions. This study demonstrates that dogs learned that the ambiguous locations were not rewarded with repeated exposures, and that this impacted their responses. We conclude that this judgement bias paradigm may require further consideration if applied across multiple exposures and that repeated results should be interpreted with caution as they are likely impacted by learning.

Dogs can discriminate between human baseline and psychological stress condition odours.

Previous research suggests that dogs can detect when humans are experiencing stress. This study tested whether baseline and stress odours were distinguishable to dogs, using a double-blind, two-phase, three-alternative forced-choice procedure. Combined breath and sweat samples were obtained from participants at baseline, and after a stress-inducing (mental arithmetic) task. Participants' stress was validated with self-report and physiological measures recorded via a Biopac MP150 system. Thirty-six participants' samples were presented to four dogs across 36 sessions (16, 11, 7 and 2 sessions, respectively). Each session consisted of 10 Phase One training trials and 20 Phase Two discrimination trials. In Phase One, the dog was presented with a participant's stress sample (taken immediately post-task) alongside two blanks (the sample materials without breath or sweat), and was required to identify the stress sample with an alert behaviour. In Phase Two, the dog was presented with the stress sample, the same participant's baseline sample (taken pre-task), and a blank. Which sample (blank, baseline, or stress) the dog performed their alert behaviour on was measured. If dogs can correctly alert on the stress sample in Phase Two (when the baseline sample was present), it suggests that baseline and stress odours are distinguishable. Performance ranged from 90.00% to 96.88% accuracy with a combined accuracy of 93.75% (N trials = 720). A binomial test (where probability of success on a single trial was 0.33, and alpha was 0.05) showed that the proportion of correct trials was greater than that expected by chance (p < 0.001). Results indicate that the physiological processes associated with an acute psychological stress response produce changes in the volatile organic compounds emanating from breath and/or sweat that are detectable to dogs. These results add to our understanding of human-dog relationships and could have applications to Emotional Support and Post Traumatic Stress Disorder (PTSD) service dogs.

Altered Mental Status: An Important but Overlooked Presenting Symptom of COVID-19 in Older Adults.

OBJECTIVES: To determine whether altered mental status (AMS) as a presenting symptom in older adults with COVID-19 is independently associated with adverse outcomes. METHODS: A retrospective single center observational study of admitted patients (n = 421) age greater than 60 and a positive COVID-19 test. Outcomes included mortality, intubation, acute respiratory distress syndrome, acute kidney injury, and acute cardiac injury. Multivariate regression analysis was used to determine if presenting with AMS was associated with adverse outcomes. RESULTS: There was an increased risk of mortality (RR 1.29, 95% CI 1.05-1.57), intubation (RR 1.52, 95% CI 1.09-2.12) and AKI (RR 1.42, 95% CI 1.13-1.78) in patients that presented with AMS. CONCLUSIONS: During a global pandemic, prognostic indicators are vital to help guide the clinical course of patients, reduce healthcare cost, and preserve life. Our study suggests that AMS can play a major role in diagnostic algorithms in older adults with COVID-19.

Dog Owners' Survey reveals Medical Alert Dogs can alert to multiple conditions and multiple people.

Medical Alert Dogs (MADs) are a promising support system for a variety of medical conditions. Emerging anecdotal reports suggest that dogs may alert to additional health conditions and different people other than those that they were trained for or initially began alerting. As the use of medical alert dogs increases, it is imperative that such claims are documented empirically. The overall aims of this study were to record the proportion of MAD owners who have a dog that alerts to multiple health conditions or to people other than the target person and to determine whether any sociodemographic variables were associated with dogs alerting to multiple conditions, multiple people, or both. MAD owners completed an online survey that contained a series of forced choice questions. Sixty-one participants reported a total of 33 different conditions to which dogs alerted. Eighty-four percent of participants reported that their dog alerted to multiple conditions and 54% reported that their dog alerted to multiple people. This is the first study to document that a large percentage of people report that their MAD alerts to multiple conditions and/or to multiple people. We present a discussion of how these alerting abilities could develop, but questions about the underlying mechanisms remain.

Non-invasive positive pressure ventilation versus endotracheal intubation in treatment of COVID-19 patients requiring ventilatory support.

IMPORTANCE: Initial guidelines recommended prompt endotracheal intubation rather than non-invasive ventilation (NIV) for COVID-19 patients requiring ventilator support. There is insufficient data comparing the impact of intubation versus NIV on patient-centered outcomes of these patients. OBJECTIVE: To compare all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation first, intubation after NIV, or NIV only. DESIGN: Retrospective study of patients admitted in March and April of 2020. SETTING: A teaching hospital in Brooklyn, New York City. PARTICIPANTS: Adult COVID-19 confirmed patients who required ventilator support (non-invasive ventilation and/or endotracheal intubation) at discretion of treating physician, were included. EXPOSURES: Patients were categorized into three exposure groups: intubation-first, intubation after NIV, or NIV-only. PRIMARY OUTCOME: 30-day all-cause mortality, a predetermined outcome measured by multivariable logistic regression. Data are presented with medians and interquartile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables, respectively. Covariates for the model were age, sex, qSOFA score ≥ 2, presenting oxygen saturation, vasopressor use, and greater than three comorbidities. A secondary multivariable model compared mortality of all patients that received NIV (intubation after NIV and NIV-only) with the intubation-first group. RESULTS: A total of 222 were enrolled. Overall mortality was 77.5% (95%CI, 72-83%). Mortality for intubation-first group was 82% (95%CI, 73-89%; 75/91), for Intubation after NIV was 84% (95%CI, 70-92%; 37/44), and for NIV-only was 69% (95%CI, 59-78%; 60/87). In multivariable analysis, NIV-only was associated with decreased all-cause mortality (odds ratio [OR]: 0.30, 95%CI, 0.13-0.69). No difference in mortality was observed between intubation-first and intubation after NIV. Secondary analysis found all patients who received NIV to have lower mortality than patients who were intubated only (OR: 0.44, 95%CI, 0.21-0.95). CONCLUSIONS & RELEVANCE: Utilization of NIV as the initial intervention in COVID-19 patients requiring ventilatory support is associated with significant survival benefit. For patients intubated after NIV, the mortality rate is not worse than those who undergo intubation as their initial intervention.

The impact of obesity on COVID-19 complications: a retrospective cohort study.

BACKGROUND: Obesity is an epidemic in New York City, the global epicenter of the coronavirus pandemic. Previous studies suggest that obesity is a possible risk factor for adverse outcomes in COVID-19. OBJECTIVE: To elucidate the association between obesity and COVID-19 outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients tested between March 10 and April 13, 2020. SETTING: SUNY Downstate Health Sciences University, a COVID-only hospital in New York. PARTICIPANTS: In total, 684 patients were tested for COVID-19 and 504 were analyzed. Patients were categorized into three groups by BMI: normal (BMI 18.50-24.99), overweight (BMI 25.00-29.99), and obese (BMI ≥ 30.00). MEASUREMENTS: Primary outcome was 30-day in-hospital mortality, and secondary outcomes were intubation, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute cardiac injury (ACI). RESULTS: There were 139 patients (27%) with normal BMI, 150 patients who were overweight (30%), and 215 patients with obesity (43%). After controlling for age, gender, diabetes, hypertension, and qSOFA score, there was a significantly increased risk of mortality in the overweight (RR 1.4, 95% CI 1.1-1.9) and obese groups (RR 1.3, 95% CI 1.0-1.7) compared with those with normal BMI. Similarly, there was a significantly increased relative risk for intubation in the overweight (RR 2.0, 95% CI 1.2-3.3) and obese groups (RR 2.4, 95% CI 1.5-4.0) compared with those with normal BMI. Obesity did not affect rates of AKI, ACI, or ARDS. Furthermore, obesity appears to significantly increase the risk of mortality in males (RR 1.4, 95% CI 1.0-2.0, P = 0.03), but not in females (RR 1.2, 95% CI 0.77-1.9, P = 0.40). CONCLUSION: This study reveals that patients with overweight and obesity who have COVID-19 are at increased risk for mortality and intubation compared to those with normal BMI. These findings support the hypothesis that obesity is a risk factor for COVID-19 complications and should be a consideration in management of COVID-19.

Differences in the Search Behavior of Cancer Detection Dogs Trained to Have Either a Sit or Stand-Stare Final Response.

Recent literature has demonstrated that dogs have the potential to detect, and communicate the presence of, various human diseases. However, there is a lack of investigation into whether commonplace training differences within the field could influence a dog's behavior during a biomedical detection task. Here we report on the behavior of four dogs trained to alert to blood plasma samples taken from individuals with ovarian cancer. One hundred trials per dog were selected from routine video recordings collected over a period of 13 months. Videos were coded frame by frame to quantify sample checking, alerting behavior, and durations of alert. Dogs had previously been trained to elicit a final response behavior once they had located the target odor. Two dogs had a "sit" response while the other two had a "stand-stare" response. Alert behavior was categorized as true positive (a correct alert to a cancer sample) or false positive (an incorrect alert to biological and non-biological controls and distractors). Hesitations were also recorded, where the dog either checks the sample twice or, spends a longer duration of time sniffing the sample than a true pass without carrying out their final response. Results show individual variation in the total frequency of false alerts elicited. However, the rate of hesitations appears to be influenced by alert style, with stand-stare dogs carrying out 40 and 32, respectively (total = 72) and sit dogs carrying out 7 and 8, respectively (total = 15). The stand-stare dogs had a non-significant difference in the duration of their true and false positive alerts. In contrast, the sit dogs showed a significant difference (p < 0.001), maintaining their false alerts for, on average, two times the duration of their true alerts. Stand-stare dogs increased the duration of time spent in contact with the port when plasma samples were present, whereas sit dogs spent on average 0.3 s in contact with the port regardless of what sample type it contained. These findings suggest that the type of operant response a biomedical detection dog has been trained may influence their sample checking and response behavior.

An Owner-Independent Investigation of Diabetes Alert Dog Performance.

Objective: To quantify Diabetes Alert Dog (DAD) performance by using owner-independent measures. Research Design and Methods: Eight owners of accredited DADs used a FreeStyle Libre Flash Glucose Monitoring System (FGMS). Concurrent Closed Circuit Television (CCTV) footage was collected for between 5 and 14 days in each owner's home or workplace. The footage was blind-coded for dogs' alerting behaviors. The sensitivity, False Positive Rate and Positive Predictive Values (PPV) of dogs' alerts to out-of-range (OOR) episodes were calculated. Ratings for 11 attributes describing participant's lifestyle and compliance (taken from each dog's instructor) and the percentage of DAD alerts responded to by the owner as per training protocol (taken from CCTV footage) were assessed for association with dog performance. Results: Dogs alerted more often when their owners' glucose levels were outside vs. inside target range (hypoglycaemic 2.80-fold, p = 0.001; hyperglycaemic 2.29-fold, p = 0.005). Sensitivity to hypoglycaemic episodes ranged from 33.3 to 91.7%, the mean was 55.9%. Mean PPV for OOR episodes was 69.7%. Sensitivity and PPV were associated with aspects of the dog and owner's behavior, and the owner's adherence to training protocol. Conclusions: Owner-independent methods support that some dogs alert to hypo- and hyperglycaemic events accurately, but performance varies between dogs. We find that DAD performance is affected by traits and behaviors of both the dog and owner. Combined with existing research showing the perceived psychosocial value and reduced critical health care needs of DAD users, this study supports the value of a DAD as part of a diabetes care plan. It also highlights the importance of ongoing training and continued monitoring to ensure optimal performance.

Author Correction: Domestic horses (Equus caballus) prefer to approach humans displaying a submissive body posture rather than a dominant body posture.

In the original publication, data availability text was incorrectly published. The correct text should read as below.

Domestic horses (Equus caballus) prefer to approach humans displaying a submissive body posture rather than a dominant body posture.

Signals of dominance and submissiveness are central to conspecific communication in many species. For domestic animals, sensitivities to these signals in humans may also be beneficial. We presented domestic horses with a free choice between two unfamiliar humans, one adopting a submissive and the other a dominant body posture, with vocal and facial cues absent. Horses had previously been given food rewards by both human demonstrators, adopting neutral postures, to encourage approach behaviour. Across four counterbalanced test trials, horses showed a significant preference for approaching the submissive posture in both the first trial and across subsequent trials, and no individual subject showed an overall preference for dominant postures. There was no significant difference in latency to approach the two postures. This study provides novel evidence that domestic horses may spontaneously discriminate between, and attribute communicative significance to, human body postures of dominance; and further, that familiarity with the signaller is not a requirement for this response. These findings raise interesting questions about the plasticity of social signal perception across the species barrier.

Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy.

Photodynamic therapy, mediated by exogenously administered aminolevulinic acid (ALA-PDT), followed by exposure to a laser or broadband light source, is a promising modality for treatment of many types of cancers; however, it remains inadequate to treat large, deep, solid tumors. In this article, we report that calcitriol, the active form of vitamin D3, can be administered before ALA as a nontoxic preconditioning regimen to markedly increase the efficacy of ALA-PDT. Using mouse models of squamous cell skin cancer for preclinical proof of concept, we showed that calcitriol, delivered topically or intraperitoneally, increased tumoral accumulation of the PDT-activated ALA product protoporphyrin-IX (PpIX) up to 10-fold, mainly by altering expression of the porphyrin-synthesis enzymes coproporphyrinogen oxidase (increased) and ferrochelatase (decreased). Calcitriol-pretreated tumors underwent enhanced apoptotic cell death after ALA-based PDT. Mechanistic studies have documented activation of the extrinsic apoptotic pathway, with specific cleavage of caspase-8 and increased production of TNF-α in tumors preconditioned by calcitriol treatment before receiving ALA-PDT. Very low doses of calcitriol (0.1-1 µg/kg body weight) were sufficient to elicit tumor-selective enhancement to ALA-PDT efficacy, rendering toxicity concerns negligible. Our findings define a simple, nontoxic, and highly effective preconditioning regimen to enhance the response of epithelial tumors to ALA-PDT, possibly broadening its clinical applications by selectively enhancing accumulation of photosensitizer PpIX together with TNF-α in tumors.