Evaluating injuries and illnesses that occurred during the Yukon Quest International sled dog race, 2018-2020.

Introduction: The purpose of this study was to evaluate medical record data from the 2018-2020 Yukon Quest International Sled Dog race to examine injury patterns and risk factors for dogs competing in multi-day ultra-endurance events. Specifically, we summarized injuries and illnesses that resulted in canine athletes being removed ("dropped") from competition, and in orthopedic injuries diagnosed in both dropped and finished dogs. Methods: The records of 989 dogs that started the race were examined, but only records from dogs in teams that went on to finish the race were included, for a total of 711 records. Results and discussion: Three hundred and sixty five dogs (51.3%) were noted to have at least one abnormal finding in their veterinary medical record during the race. Orthopedic injuries were most common, and 291 injuries were ultimately diagnosed in 234 dogs (32.9%). Ultimately, 206 dogs (29%) were dropped from competition, for any reason. The most common reasons for dropping dogs were orthopedic injuries (156 dogs; 188 injuries), gastrointestinal illness (22 dogs), and cardiorespiratory disease (7 dogs). Most orthopedic injuries in dropped dogs occurred in the thoracic limb (n = 121 dogs; 151 injuries). Of those, injuries to the shoulder were most common (n = 77), followed by injuries to the carpus (n = 59), and injury to the pelvic limb (n = 32). Carpal injuries were the most prevalent injury diagnosed in dogs that went on to finish the race (71 of 85 injuries). Carpal injuries were the most prevalent injuries overall in 2018 (51%) and 2019 (52%). In 2020, shoulder injuries were most prevalent (27%), suggesting that trail conditions may have differed between years. The majority of dogs with an orthopedic injury ultimately were removed from competition (156 of 234, or 66.6%), but the likelihood of finishing the race with an injury depended on the type of injury sustained; 71 of 130 dogs (54.6%) with a carpal injury went on to finish the race, whereas only 9 of 86 dogs with a shoulder injury (10.5%) went on to finish. The results of this study can assist mushers and veterinarians in preparing for races, and in decision making during endurance sled dog races.

Are American transplant centers willing to transplant prisoners.

INTRODUCTION: The United Network for Organ Sharing (UNOS) is tasked with ensuring fair and equitable access to organs for patients seeking transplant. Despite UNOS' position statement clearly stating that prisoner status should not preclude transplant evaluation, prisoners continue to face significant barriers. The goal of this survey was to discover how many American transplant centers are willing to evaluate, list, and transplant prisoners. MATERIALS AND METHODS: All adult kidney transplant centers listed as active on the UNOS website were contacted to participate in a survey asking if they were willing to evaluate, list, and transplant prisoners, and why or why not. RESULTS: A total of 122 centers responded. Forty-nine were willing to evaluate, 43 willing to list, and 42 willing to transplant prisoners. Fourteen centers said yes, but on a case-by-case basis only. Things they reported considering were type of crime, length of sentence, and likelihood of release. Frequently cited reasons for not treating inmates were: inadequate follow up (28), insurance/funding (16), transportation (12), medication compliance (9), security (8), patient safety (8), and lack of social support (5). Twenty-four centers refused to disclose their policy or did not have one. CONCLUSIONS: Prisoners continue to face barriers to evaluation, listing, and receiving kidney transplants. A lack of understanding of contraindications to transplant or a lack of knowledge about the prisoner system on behalf of transplant centers may contribute to these barriers. We feel as transplant professionals it is our responsibility to assist vulnerable patients in overcoming barriers to transplantation and work to ensure equitable access to organs, regardless of prisoner status.

Effects of hyperthermia and acidosis on mitochondrial production of reactive oxygen species.

Exercise is associated with the development of oxidative stress, but the specific source and mechanism of production of pro-oxidant chemicals during exercise has not been confirmed. We used equine skeletal muscle mitochondria to test the hypothesis that hyperthermia and acidosis affect mitochondrial oxygen consumption and production of reactive oxygen species (ROS). Skeletal muscle biopsies were obtained at rest, after an acute episode of fatiguing exercise, and after a 9-wk conditioning program to increase aerobic fitness. Mitochondrial oxygen consumption and ROS production were measured simultaneously using high-resolution respirometry. Both hyperthermia and acidosis increased nonphosphorylating (LEAK) respiration (5.8× and 3.0×, respectively, P < 0.001) and decreased efficiency of oxidative phosphorylation. The combined effects of hyperthermia and acidosis resulted in large decreases in phosphorylating respiration, further decreasing oxidative phosphorylation efficiency from 97% to 86% (P < 0.01). Increased aerobic fitness reduced the effects of acidosis on LEAK respiration. Hyperthermia increased and acidosis decreased ROS production (2× and 0.23×, respectively, P < 0.001). There was no effect of acute exercise, but an aerobic conditioning program was associated with increased ROS production during both nonphosphorylating and phosphorylating respiration. Hyperthermia increased the ratio of ROS production to O2 consumption during phosphorylating respiration, suggesting that high-temperature impaired transfer of energy through the electron transfer system despite relatively low mitochondrial membrane potential. These data support the role of skeletal muscle mitochondria in the development of exercise-induced oxidative stress, particularly during forms of exercise that result in prolonged hyperthermia without acidosis.NEW & NOTEWORTHY The results of this study provide evidence for the role of mitochondria-derived ROS in the development of systemic oxidative stress during exercise as well as skeletal muscle diseases such as exertional rhabdomyolysis.

Biomarkers of heatstroke-induced organ injury and repair.

NEW FINDINGS: What is the topic of this review? The status and potential role of novel biological markers (biomarkers) that can help identify the patients at risk of organ injury or long-term complications following heatstroke. What advances does it highlight? Numerous biomarkers were identified related to many aspects of generalized heatstroke-induced cellular injury and tissue damage, and heatstroke-provoked cardiovascular, renal, cerebral, intestinal and skeletal muscle injury. No novel biomarkers were identified for liver or lung injury. ABSTRACT: Classic and exertional heatstroke cause acute injury and damage across numerous organ systems. Moreover, heatstroke survivors may sustain long-term neurological, cardiovascular and renal complications with a persistent risk of death. In this context, biomarkers, defined as biological samples obtained from heatstroke patients, are needed to detect early organ injury, and predict outcomes to develop novel organ preservation therapeutic strategies. This narrative review provides preliminary insights that will guide the development and future utilization of these biomarkers. To this end, we have identified numerous biomarkers of widespread heatstroke-associated cellular injury, tissue damage and repair (extracellular heat shock proteins 72 and 60, high mobility group box protein 1, histone H3, and interleukin-1α), and other organ-specific biomarkers including those related to the cardiovascular system (cardiac troponin I, endothelium-derived factors, circulation endothelial cells, adhesion molecules, thrombomodulin and von Willebrand factor antigen), the kidneys (plasma and urinary neutrophil gelatinase-associated lipocalin), the intestines (intestinal fatty acid-binding protein 2), the brain (serum S100ß and neuron-specific enolase) and skeletal muscle (creatine kinase, myoglobin). No specific biomarkers have been identified so far for liver or lung injury in heatstroke. Before translating the identified biomarkers into clinical practice, additional preclinical and clinical prospective studies are required to further understand their clinical utility, particularly for the biomarkers related to long-term post-heatstroke health outcomes.

Acylcarnitine profile in Alaskan sled dogs during submaximal multiday exercise points out metabolic flexibility and liver role in energy metabolism.

Alaskan sled dogs develop a particular metabolic strategy during multiday submaximal exercise, allowing them to switch from intra-muscular to extra-muscular energy substrates thus postponing fatigue. Specifically, a progressively increasing stimulus for hepatic glycogenolysis and gluconeogenesis provides glucose for both fueling exercise and replenishing the depleted muscle glycogen. Moreover, recent studies have shown that with continuation of exercise sled dogs increase their insulin-sensitivity and their capacity to transport and oxidize glucose and carbohydrates rather than oxidizing fatty acids. Carnitine and acylcarnitines (AC) play an essential role as metabolic regulators in both fat and glucose metabolism; they serve as biomarkers in different species in both physiologic and pathologic conditions. We assessed the effect of multiday exercise in conditioned sled dogs on plasma short (SC), medium (MC) and long (LC) chain AC by tandem mass spectrometry (MS/MS). Our results show chain-specific modification of AC profiles during the exercise challenge: LCACs maintained a steady increase throughout exercise, some SCACs increased during the last phase of exercise and acetylcarnitine (C2) initially increased before decreasing during the later phase of exercise. We speculated that SCACs kinetics could reflect an increased protein catabolism and C2 pattern could reflect its hepatic uptake for energy-generating purposes to sustain gluconeogenesis. LCACs may be exported by muscle to avoid their accumulation to preserve glucose oxidation and insulin-sensitivity or they could be distributed by liver as energy substrates. These findings, although representing a "snapshot" of blood as a crossing point between different organs, shed further light on sled dogs metabolism that is liver-centric and more carbohydrate-dependent than fat-dependent and during prolonged submaximal exercise.

Glucocentric Metabolism in Ultra-Endurance Sled Dogs.

The total energy expenditure of a racing sled dog can exceed 500 kcal/kg bodyweight during typical events spanning a week or more. Based on early research, as well as practical considerations, modern commercial diets are formulated to meet these energy requirements using fat and protein. However, more recent research provides a clear picture of a canine athlete with glucocentric metabolism, including many conditioning-induced adaptations oriented toward sustaining submaximal exercise with glucose as the primary metabolic fuel despite the consumption of fat as the primary dietary energy source. The specific strategies used by racing sled dogs to maintain a robust supply of glucose during exercise, as well as the possible role of fat in facilitating that metabolic priority, is the subject of ongoing research.

Orthopedic and ultrasonographic examination findings in 128 shoulders of 64 ultra-endurance Alaskan sled dogs.

OBJECTIVE: To determine the location and periarticular shoulder-muscle-abnormalities detected via orthopedic examinations and ultrasonography in ultra-endurance Alaskan sled-dogs, returned from an ultra-endurance sled-dog-race prior to finishing it. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Sixty-four dogs (128 shoulders). METHODS: Dogs were classified based on clinical evidence of shoulder pain (SP versus control). Orthopedic examination findings, shoulder-abduction-angles (SAA; before- and during-anesthesia), and ultrasonographic findings were recorded. Relationships between orthopedic and ultrasonographic abnormalities were compared. RESULTS: Pain was elicited on 55/128 shoulders; 73 shoulders were pain-free. The most common painful structures included the biceps-tendon (BT; 30%), triceps-muscle (28%), and infraspinatus-muscle (25%). SAA ranged between 25° and 75° among groups, including pain-free shoulders in dogs without lameness. SAA was greater when dogs were anesthetized (46.3° ± 14.0° vs. 47.8° ± 12.0°; p = .03), especially in SP (mean increase of 3.49° ± 8.85°) compared to control (0.03° ± 7.71°, p = .009). Overall, 103 ultrasonographic abnormalities were detected (SP: 44; control: 59). The most common ultrasonographic abnormality was fluid surrounding the biceps tendon, similarly distributed between groups (SP: 39/44; control: 57/59). Most chronic ultrasonographic abnormalities affected the BT (15/103 abnormalities). No associations were detected between ultrasonographic abnormalities and clinical findings. CONCLUSION: Shoulder abduction varied greatly and reached up to 75° in normal joints. Ultrasonographic shoulder-muscle abnormalities were common but did not seem associated with clinical findings. CLINICAL SIGNIFICANCE: Interpretation of shoulder abduction warrants caution, and the presence of fluid around the BT may reflect a physiologic adaptation to racing, rather than a pathologic change in ultra-endurance Alaskan sled-dogs.

Effect of conditioning and physiological hyperthermia on canine skeletal muscle mitochondrial oxygen consumption.

Exercise often causes skeletal muscle hyperthermia, likely resulting in decreased efficiency of mitochondrial respiration. We hypothesized that athletic conditioning would improve mitochondrial tolerance to hyperthermia. Skeletal muscle biopsies were obtained from six Alaskan sled dogs under light general anesthesia before and after a full season of conditioning and racing, and respiration of permeabilized muscle fibers was measured at 38, 40, 42, and 44°C. There was no effect of temperature on phosphorylating respiration, and athletic conditioning increased maximal phosphorylating respiration by 19%. Leak respiration increased and calculated efficiency of oxidative phosphorylation decreased with increasing incubation temperature, and athletic conditioning resulted in higher leak respiration and lower calculated oxidative phosphorylation efficiency at all temperatures. Conditioning increased skeletal muscle expression of putative mitochondrial leak pathways adenine nucleotide transporter 1 and uncoupling protein 3, both of which were correlated with the magnitude of leak respiration. We conclude that athletic conditioning in elite canine endurance athletes results in increased capacity for mitochondrial proton leak that potentially reduces maximal mitochondrial membrane potential during periods of high oxidative phosphorylation. This effect may provide a mechanistic explanation for previously reported decreases in exercise-induced muscle damage in well-conditioned subjects.NEW & NOTEWORTHY Athletic conditioning is expected to increase exercise capacity through improved function of cardiopulmonary and musculoskeletal tissues. Our finding of decreased calculated efficiency of skeletal muscle mitochondria in one of the premier mammalian athletes suggests that this mandate for improved function may take the form of sacrificing capacity for maximal oxidative phosphorylation to minimize exercise-induced muscle damage caused by mitochondrial oxidative stress.

Initial Presentation and Outcomes of Testicular Cancer among Different Racial and Ethnic Groups at a Tertiary Care Facility in New Mexico.

INTRODUCTION: This study explored differences in testicular cancer presentation, treatment, compliance and outcomes among ethnicities in New Mexico. METHODS: A retrospective review of patients with testicular cancer treated between 2002 and 2015 was performed. Data included demographics, stage, delays in care, treatments, insurance status and nonadherence rates. RESULTS: Of 186 patients Hispanics and Native Americans presented at higher stage (p <0.01) and delayed treatment (p=0.02). Retroperitoneal lymph node dissection for stage I disease was 28% while stage II was 30%, compared to 18% and 58% nationally, respectively. Of stage II in Hispanic patients 24.5% received retroperitoneal lymph node dissection compared to 41.3% of Caucasians (p <0.05). Regarding chemotherapy Caucasian patients at stage I were more likely than Hispanics to receive chemotherapy (p <0.05). Hispanics had higher rates of nonadherence (p <0.01). Insurance rates did not differ among groups. However, insurance increased the likelihood for receiving chemotherapy/retroperitoneal lymph node dissection only for Caucasians. Lack of insurance increased active surveillance rates for stage I in Hispanics. The incidence of testicular cancer in Hispanics rose by 58% after 2009 (p <0.05). CONCLUSIONS: Minority groups presented at higher stages and delayed treatment. Retroperitoneal lymph node dissection rates differed nationally compared to this cohort with Hispanic patients at higher stage being less likely to receive retroperitoneal lymph node dissection. Meanwhile, Hispanics with stage I are less likely to obtain chemotherapy. Insurance rates did not differ among ethnicities but having insurance did not increase rates of chemotherapy/retroperitoneal lymph node dissection for Hispanics unlike for Caucasians. Meanwhile, lack of insurance increased stage I rates of active surveillance suggesting cultural/financial factors contribute to treatment decisions. Increased health literacy, outreach and access may aid in alleviating these disparities.

Contrast therapy: Tissue heating and cooling properties within the equine distal limb.

BACKGROUND: Rehabilitation of tendon injuries in horses often involves cryotherapy to reduce inflammation and occasionally tissue heating to increase collagen extensibility. The application of alternating cold and hot (ie contrast therapy) is widely used in human physical therapy; however, its utility in equine rehabilitation is largely unknown. OBJECTIVES: The objectives of this study were to (a) assess if the equipment could achieve therapeutic tissue temperatures (<15 and >40°C) at different tissue depths relative to the digital flexor tendons and (b) evaluate the time-temperature profiles during serial heating and cooling cycles using a contrast therapy device. STUDY DESIGN: In vivo experiment. METHODS: In 4 adult horses with normal forelimb digital flexor tendons, fine-wire temperature probes were placed superficially on the skin and implanted subcutaneously, deep to the superficial digital flexor tendon (SDFT) and deep to the deep digital flexor tendon (DDFT). Temperatures were recorded over three complete thermal (hot-cold) cycles. Minimum and maximum temperatures were recorded and the rate of temperature changes and the areas underneath the time-temperature curves (ie thermal load) were calculated. RESULTS: Minimum and maximum tissue temperatures (°C) included: superficial skin [12.6 ± 1.0; 42.4 ± 2.4], subcutaneous tissues [14.1 ± 0.8; 42.3 ± 2.2], deep to the SDFT [15.6 ± 0.8; 41.7 ± 2.6] and deep to DDFT [25.1 ± 2.0; 38.0 ± 3.5]. An initial rapid rate of tissue temperature change between 3.2 and 4.3°C/min occurred within tissues to the depth of the DDFT. Tissue thermal loads during heating ranged from 255 to 607°C*second and from 309 to 780°C*second during tissue cooling, with the lower values noted deep to the DDFT. MAIN LIMITATIONS: Unknown clinical efficacy in diseased tissues. CONCLUSIONS: The applied contrast therapy was consistently able to induce cooling and heating of tissues to the depth of the DDFT.

Comparison of Postexercise Cooling Methods in Working Dogs.

BACKGROUND: Overheating is a common form of injury in working dogs. The purpose of this study was to evaluate the relative efficacy of three postexercise cooling methods in dogs with exercise-induced heat stress. METHODS: Nine athletically conditioned dogs were exercised at 10kph for 15 minutes on a treadmill in a hot environmental chamber (30°C) three times on separate days. After exercise, the dogs were cooled using one of three methods: natural cooling, cooling on a 4°C cooling mat, and partial immersion in a 30°C water bath for 5 minutes. RESULTS: Time-weighted heat stress was lower for immersion cooling compared with the cooling mat and the control. The mean time required to lower gastrointestinal temperature to 39°C was 16 minutes for immersion cooling, 36 minutes for the cooling mat, and 48 minutes for control cooling. CONCLUSION: Water immersion decreased postexercise, time-weighted heat stress in dogs and provided the most rapid cooling of the three methods evaluated, even with the water being as warm as the ambient conditions. The cooling mat was superior to cooling using only fans, but not as effective as immersion. The placement of simple water troughs in working- dog training areas, along with specific protocols for their use, is recommended to reduce the occurrence of heat injury in dogs and improve the treatment of overheated dogs.

Advanced Resuscitative Care in Tactical Combat Casualty Care: TCCC Guidelines Change 18-01:14 October 2018.

TCCC has previously recommended interventions that can effectively prevent 4 of the top 5 causes of prehospital preventable death in combat casualties-extremity hemorrhage, junctional hemorrhage, airway obstruction, and tension pneumothorax- and deaths from these causes have been markedly reduced in US combat casualties. Noncompressible torso hemorrhage (NCTH) is the last remaining major cause of preventable death on the battlefield and often causes death within 30 minutes of wounding. Increased use of whole blood, including the capability for massive transfusion, if indicated, has the potential to increase survival in casualties with either thoracic and/or abdominopelvic hemorrhage. Additionally, Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) can provide temporary control of bleeding in the abdomen and pelvis and improve hemodynamics in casualties who may be approaching traumatic cardiac arrest as a result of hemorrhagic shock. Together, these two interventions are designated Advanced Resuscitative Care (ARC) and may enable casualties with severe NCTH to survive long enough to reach the care of a surgeon. Although Special Operations units are now using whole blood far-forward, this capability is not routinely present in other US combat units at this point in time. REBOA is not envisioned as care that could be accomplished by a unit medic working out of his or her aid bag. This intervention should be undertaken only by designated teams of advanced combat medical personnel with special training and equipment.

Effect of Endurance Conditioning on Insulin-mediated Glucose Clearance in Dogs.

INTRODUCTION: Physical activity has been shown to improve insulin sensitivity in subjects with insulin resistance, but the effect of athletic conditioning on subjects with normal insulin sensitivity has received less scrutiny. Because strenuous exercise can be limited by the availability of substrates, it is reasonable to hypothesize that conditioning would increase the capacity for muscle uptake of substrates like glucose and to the extent that improvement in this process would include upregulation of the portions of the glucose uptake pathway in muscle, this increased capacity would also be reflected in insulin sensitivity. Therefore, we tested the hypothesis that conditioning for endurance exercise would result in increased insulin sensitivity using elite racing sled dogs. METHODS: A frequent-sampled intravenous glucose tolerance test was performed on these dogs before and after a full 7-month season of conditioning in preparation for a 1600-km race. RESULTS: Compared with the results in unconditioned dogs, conditioned dogs rapidly cleared the intravenous glucose bolus through increases in both glucose mediated (7.6%·min ± 3.4%·min vs 3.0%·min ± 2.2%·min, P = 0.008) and insulin-mediated (36.3 ± 18.4 × 10 L·min·mU vs 11.5 ± 8.0 × 10 L·min·mU, P = 0.007) mechanisms. The more modest increase in serum insulin after the intravenous glucose bolus in conditioned dogs failed to suppress lipolysis and serum concentrations of nonesterified fatty acids remained constant in the conditioned dogs throughout the 4-h test. CONCLUSIONS: These results, in particular the increase in insulin-independent peripheral uptake of glucose, describe novel alterations in metabolism induced by athletic conditioning that arguably result in near-continuous provision of oxidizable substrates to peripheral muscle in support of sustained muscular work typical of these dogs.

Effect of brachycephaly and body condition score on respiratory thermoregulation of healthy dogs.

OBJECTIVE To evaluate the effect of brachycephaly and body condition score on respiratory thermoregulation of healthy dogs. DESIGN Prospective study. ANIMALS 52 brachycephalic and 53 nonbrachycephalic dogs. PROCEDURES All dogs were exposed to a cool treatment (temperature, 21.8 ± 1.7°C [71.2 ± 3.1°F]; relative humidity, 62.2 ± 9.7%; and ambient enthalpy, 47.7 ± 6.6 kcal/kg) and then a hot treatment (temperature, 32.9 ± 1.7°C [91.2 ± 3.1°F]; relative humidity, 51.9 ± 9.8%; and ambient enthalpy, 74.8 ± 8.7 kcal/kg; heat stress) at least 1 hour later. For each treatment, dogs were allowed to acclimatize to the environment for 15 minutes and then were placed in a sealed whole-body plethysmograph for continuous measurement of the respiratory pattern for 10 minutes. Treatment was discontinued if a dog developed signs of respiratory distress. Respiratory variables and body temperature were compared between the 2 breed types (brachycephalic and nonbrachycephalic) and between treatments. RESULTS Body condition score was positively associated with body temperature independent of environmental conditions or breed type and negatively associated with tidal volume. Brachycephalic dogs had a greater increase in respiratory rate in response to heat stress than did nonbrachycephalic dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that brachycephalic dogs had decreased capacity for thermoregulation, compared with nonbrachycephalic dogs, but body condition score was a greater determinant of body temperature than breed type. Nevertheless, both upper airway conformation and body condition score should be considered when evaluating whether an individual dog is capable of tolerating heat stress.

Lessons Still Being Learned: Acute Pulmonary Tumor Embolus During Renal Cell Carcinoma Resection.

Renal cell carcinoma (RCC) is the most common primary renal neoplasm and is associated with the intraluminal growth into the venous system with possible extension into the inferior vena cava or even right heart. Intraoperative pulmonary embolism is a complication of resection of RCC, which may be mitigated by the use of the cardiopulmonary bypass with or without deep hypothermic circulatory arrest. We present a case of unexpected pulmonary embolism diagnosed during RCC surgery. The case highlights the central importance of intraoperative transesophageal echocardiography use and the need for proper preoperative planning for the use of cardiopulmonary bypass.

Gastritis and Gastric Ulcers in Working Dogs.

Gastritis and gastric ulcers are an important cause of morbidity and mortality in canine athletes. Although the majority of scientific work on this condition has been performed in ultraendurance racing sled dogs, this condition has been identified in other canine athletes, including sled dogs competing in shorter events and dogs performing off-leash explosive detection duties. The cause of the syndrome is unknown, but current hypotheses propose a link between exercise-induced hyperthermia and loss of gastric mucosal barrier function as an early event in the pathogenesis. Treatment is focused on prevention of clinical disease using acid secretion inhibitors, such as omeprazole, which has excellent efficacy in controlled clinical studies.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants.

RATIONALE: Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. METHODS: Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 10(7) FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. RESULTS: Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and hyperplasia, peribronchial lymphocyte infiltration, and syncytial cells, were consistent with those described previously for lambs and infants. CONCLUSION: This work demonstrates that M37 hRSV replication in the lower airways of newborn lambs is robust with peak replication on day 3 and sustained until day 6. These findings, along with the similarities of lamb lung to those of infants in terms of alveolar development, airway branching and epithelium, susceptibility to human RSV strains, lesion characteristics (bronchiolitis), lung size, clinical parameters, and immunity, further establish the neonatal lamb as a model with key features that mimic RSV infection in infants.

A technology-enabled adherence enhancement system for people with bipolar disorder: results from a feasibility and patient acceptance analysis.

OBJECTIVE: As poor medication adherence is common in bipolar disorder (BD), technology-assisted approaches may help to monitor and enhance adherence. This study evaluated preliminary feasibility, patient satisfaction and effects on adherence, BD knowledge, and BD symptoms associated with the use of a multicomponent technology-assisted adherence enhancement system. METHODS: This prospective study tested the system in five BD patients over a 15-day period. System components included: 1) an automated pill cap with remote monitoring sensor; 2) a multimedia adherence enhancement program; and 3) a treatment incentive program. This study evaluated system usability, patient satisfaction and effects on adherence (Morisky scale), knowledge (treatment knowledge test [TKT]), and symptoms (internal state scale [ISS]). RESULTS: Mean age of the sample was 62 years, 4/5 (80%) Caucasian, and 4/5 (80%) single/divorced or widowed. Most participants (4/5, 80%) were on a single BD medication. Participants had BD for an average of 21 years. Challenges included attaching the pill sensor to standard pharmacy bottles for individuals using very large pill containers or those with multiday pill boxes. Three of five (60%) individuals completed the full 15-day period. Usability scores were high overall. Mean Morisky scores improved. Means on all four subscales of the ISS were all in the direction of improvement. On the TKT, there was a 40% increase in mean scores. CONCLUSION: A multicomponent technology-assisted BD adherence enhancement system is feasible. Challenges include accommodating multiple types of pill containers and monitoring multiple drugs simultaneously. The system can also generate adherence information that is potentially useful for treatment planning.