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  • 1.

    【2hr】The Interplay of Ethics, Animal Welfare, and IACUC Oversight on the Reproducibility of Animal Studies

    包量

    机译 伦理学，动物福利和IACUC对动物研究可重复性的监督之间的相互作用
    摘要：Reproducibility in animal studies has been defined as the ability of a result to be replicated through independent experiments within the same or among different laboratories. Over the past few years, much has been written and said about the lack of reproducibility of animal studies. Reasons that are commonly cited for this lack of reproducibility include inappropriate study design, errors in conducting the research, and potential fraud. In the quest to understand the basis for this lack of reproducibility, scientists have not fully considered the potential ramifications on ethical constructs for animal research, animal welfare considerations in animal research programs, the regulatory environment, and oversight by IACUCs. Here, we review how ethical theories behind animal research, policies, and practices meant to enhance animal welfare and the IACUC oversight process influence the reproducibility of animal studies, a previously undiscussed topic in the peer-reviewed literature.
  • 2.

    【2hr】Biochemical, Histopathologic, Physiologic, and Behavioral Effects of Nonsteroidal Antiinflammatory Drugs in Rainbow Trout (Oncorhynchus mykiss)

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    机译 非甾体类抗炎药在虹鳟鱼（Oncorhynchus mykiss）中的生化，组织病理学，生理和行为效应
    摘要：Because the number of fish being used in research is increasing rapidly, evaluating the analgesic and pathologic effects of NSAID in fish is essential. To determine the biochemical, histopathologic, physiologic and behavioral effects of 3 NSAID, 48 rainbow trout underwent anesthesia with tricaine methanesulfonate and exploratory celiotomy and were randomly assigned to receive flunixin (0.5 mg/kg IM), ketorolac (0.5 mg/kg IM), ketoprofen (2 mg/kg IM), or saline. Clinical pathologic variables were assessed 1 wk before surgery and 48 h after surgery. Histopathology was performed to evaluate the healing of the incision, tissue reaction at the injection site, and potential organ toxicity. Physiologic and behavioral parameters, including weight, feeding, opercular rate, and vertical position in the water, were measured to establish parameters for identifying pain in fish. The difference between the pre- and postoperative phosphorus concentrations was greater in the flunixin group than the saline group and was the only pathologic difference between treatment groups. Histopathology of incision site, injection site, and internal organs appeared normal, and healing did not appear to be inhibited by the drugs used. The physiologic parameters of opercular rate and weight were consistent and may be helpful in identifying pain in fish in future studies, whereas feeding and vertical position in the water were unhelpful as indicators of pain in this rainbow trout surgical model. Overall, according to clinical pathology and histopathology, the use of ketoprofen, ketorolac, and flunixin at the dosages used in this study lack negative effects in rainbow trout undergoing surgery.
  • 3.

    【2hr】Cystic Calculus in a Laboratory-housed Green Anole (Anolis carolinensis)

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    机译 实验室饲养的绿色Anole（Anolis carolinensis）中的囊性结石
    摘要：An adult, male, wild-caught, laboratory-housed green anole (Anolis carolinensis) on a locomotor performance study was presented for anorexia. The anole exhibited a 26% weight loss and a thin body condition but was otherwise alert and active. Despite supportive care, the anole's clinical condition deteriorated, necessitating euthanasia. Postmortem examination revealed a 4.5 mm × 2.5-mm cystic calculus, which consisted entirely of sodium urate. Here we describe the clinical findings and locomotor consequences of this disease in a green anole. Although urolithiasis has been reported clinically in reptiles, this report presents the first case of a cystic calculus in a laboratory-housed green anole.
  • 4.

    【2hr】Influence of Chronic Exposure to Simulated Shift Work on Disease and Longevity in Disease-Prone Inbred Mice

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    机译 慢性暴露对模拟轮班工作对病态自交系小鼠疾病和寿命的影响
    摘要：Shift work (SW) is viewed as a risk factor for the development of many serious health conditions, yet prospective studies that document such risks are rare. The current study addressed this void by testing the hypothesis that long-term exposure to repeated diurnal phase shifts, mimicking SW, will accelerate disease onset or death in inbred mice with genetic risk of developing cancer, diabetes, or autoimmune disease. The data indicate that 1) life-long exposure to simulated SW accelerates death in female cancer-prone AKR/J mice; 2) a significant proportion of male NON/ShiLtJ mice, which have impaired glucose tolerance but do not normally progress to type 2 diabetes, develop hyperglycemia, consistent with diabetes (that is, blood glucose 250 mg/dL or greater) after exposure to simulated SW for 8 wk; and 3) MRL/MpJ mice, which are prone to develop autoimmune disease, showed sex-related acceleration of disease development when exposed to SW as compared with mice maintained on a stable photocycle. Thus, long-term exposure to diurnal phase shifts that mimic SW reduces health or longevity in a wide variety of disease models. Our approach provides a simple way to assess the effect of chronic diurnal disruption in disease development in at-risk genotypes.
  • 5.

    【2hr】Effect of Isoflurane Anesthesia on Circadian Metabolism and Physiology in Rats

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    机译 异氟烷麻醉对大鼠昼夜代谢和生理的影响
    摘要：Isoflurane anesthesia alters the blood levels of several neuroendocrine hormones associated with normal metabolism and physiology and increases stress, but the effect of brief CO2 anesthesia on these parameters is unknown. In this study, we examined the effects of isoflurane (4%) compared with brief CO2 (70% CO2, 30% air) anesthesia on circadian rhythms of plasma measures of physiology and metabolism. Adult male Sprague–Dawley rats (Crl:SD; n = 6 per group) were maintained on a 12:12-h light:dark (300 lx; lights on, 0600) photoperiod. After 1 wk of acclimation, a series of 6 low-volume blood draws were collected by cardiocentesis under anesthesia using isoflurane (10 min or less) compared with CO2 (1 min or less) at a single circadian time point every 4 d (0400, 0800, 1200, 1600, 2000, or 2400) over 3 wk to assess arterial blood glucose, lactic acid, and potassium and plasma melatonin, leptin, insulin, total fatty acids, and corticosterone concentrations. Results revealed that plasma levels (mean ± SEM) of melatonin were low (11 ± 1 pg/mL) during the light phase in both groups but were significantly lower during the dark phase in the isoflurane group (48 ± 6 pg/mL) compared with the CO2 group (162 ± 18 pg/mL). In addition, prominent circadian rhythms of arterial plasma levels of corticosterone, glucose, total fatty acids, lactic acid, and potassium were altered in the isoflurane group compared with the CO2 group. These findings demonstrate that the normal circadian rhythms of endocrine physiology and metabolism observed during brief CO2 anesthesia in rats are markedly disrupted by isoflurane anesthesia.
  • 6.

    【2hr】Effects of Racecadotril on Weight Loss and Diarrhea Due to Human Rotavirus in Neonatal Gnotobiotic Pigs (Sus scrofa domesticus)

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    机译 雷卡卡地尔对新生生殖动物猪中人轮状病毒引起的体重减轻和腹泻的影响
    摘要：Diarrheal disease is the second leading cause of death in children younger than 5 y, and the most common cause of acute watery diarrhea in young children worldwide is rotaviral infection. Medicines to specifically reduce diarrhea would be a desirable adjunctive treatment to supportive fluid therapy to decrease the mortality rate of diarrheal diseases. In this study, we evaluated the efficacy of an antisecretory drug, racecadotril, in treating human rotavirus (HRV)-induced diarrhea in a neonatal gnotobiotic pig model. In total, 27 gnotobiotic pigs were randomly assigned (n = 9 per group) to receive either racecadotril, chlorpromazine (positive-control drug), or PBS (mock treatment) after inoculation with HRV. Pigs were weighed daily and rectal swabs were collected to determine fecal consistency scores and virus shedding. Rotaviral infection was confirmed by ELISA and cell culture immunofluorescence. Overall, the racecadotril-treated pigs had less severe illness than either the chlorpromazine- or mock-treated groups; this conclusion was supported by the lower fecal-consistency scores, shorter duration of diarrhea, and significant gain in body weight during the course of the study of the racecadotril-treated pigs. Through its influence on decreasing intestinal hypersecretion, racecadotril was better able to control the clinical signs of rotaviral infection in the gnotobiotic pigs. These results lend support for using racecadotril as a treatment for rotaviral diarrhea.
  • 7.

    【2hr】Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta)

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    机译 恒河猴（猕猴）长期，经皮，静态植入钛合金的局部和全身变化
    摘要：Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many alloys induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (duration, 0 to 14 y) were evaluated for changes in their hematology, coagulation, and serum chemistry profiles. Negative controls (n = 28) did not have implants. Macaques with implants had higher plasma D-dimer and lower antithrombin III concentrations than nonimplanted animals. In addition, animals with implants had higher globulin and lower albumin and calcium concentrations compared with nonimplanted macaques. Many of these changes were positively correlated with duration of implantation and the number of implants. Chronic bacterial infection of the skin was present around many of the implant sites and within deeper tissues. Representative histopathology around the implant site of 2 macaques revealed chronic suppurative to pyogranulomatous inflammation extending from the skin to the dura mater. X-ray fluorescence microscopy of tissue biopsies from the implant site of the same 2 animals revealed significantly higher levels of free metal ions in the tissue, including titanium and iron. The higher levels of free metal ions persisted in the tissues for as long as 6 mo after explantation. These results suggest that long-term skull-anchored percutaneous titanium alloy implants can be associated with localized inflammation, chronic infection, and leaching of metal ions into local tissues.
  • 8.

    【2hr】Well-differentiated Liposarcoma in a Bonnet Macaque (Macaca radiata)

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    机译 短尾猕猴（Macaca radiata）中的高分化脂肪肉瘤
    摘要：Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinical presentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque.
  • 9.

    【2hr】AALAS Position Statement on the Humane Care and Use of Laboratory Animals

    包量

    机译 AALAS关于人道关怀和使用实验动物的立场声明
    • 作者：
    • 刊名：Comparative Medicine
    • 2017年第2期
    摘要：
  • 10.

    【2hr】Erratum

    包量

    机译 勘误表
    • 作者：
    • 刊名：Comparative Medicine
    • 2017年第2期
    摘要：
  • 11.

    【2hr】Acute and Chronic Outcomes of Gas-Bubble Disease in a Colony of African Clawed Frogs (Xenopus laevis)

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    机译 非洲爪蛙（Xenopus laevis）群落中气泡疾病的急性和慢性结果
    摘要：Gas-bubble disease occurs in aquatic species that are exposed to water that is supersaturated with gases. In February 2007, municipal water supersaturated with gas was inadvertently pumped into the vivarium's aquatic housing systems and affected approximately 450 adult female Xenopus laevis. The inflow of supersaturated water was stopped immediately, the holding tanks aggressively aerated, and all experimental manipulations and feeding ceased. Within the first 6 h after the event, morbidity approached 90%, and mortality reached 3.5%. Acutely affected frogs showed clinical signs of gas-bubble disease: buoyancy problems, micro- and macroscopic bubbles in the foot webbing, hyperemia in foot webbing and leg skin, and loss of the mucous slime coat. All of the frogs that died or were euthanized had areas of mesenteric infarction, which resulted in intestinal epithelial necrosis and degeneration of the muscular tunic. Over the subsequent 2 wk, as gas saturation levels returned to normal, the clinical symptoms resolved completely in the remaining frogs. However, 3 mo later, 85% of them failed to lay eggs or produce oocytes, and the remaining 15% produced oocytes of low number and poor quality, yielding cytosolic extracts with poor to no enzymatic activity. Histology of the egg mass from a single 2- to 3-y-old frog at 3 mo after disease resolution revealed irregularly shaped oocytes, few large mature oocytes, and numerous small, degenerating oocytes. At 6 mo after the incident, the remaining frogs continued to fail to produce eggs of sufficient quantity or quality after hormonal priming. The researchers consequently opted to cull the remainder of the colony and repopulate with new frogs.
  • 12.

    【2hr】Age-Associated Differences in Hematopoietic Stem and Progenitor Cells of Mice

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    机译 小鼠造血干细胞和祖细胞的年龄相关差异。
    摘要：Establishing the appropriate yet minimal number of control mice for experiments is a critical step in experimental design. This decision is particularly important regarding the study of the hematopoietic system over time, given various age-associated changes in murine hematopoietic cell populations. Here we used flow cytometry to serially monitor the frequencies of hematopoietic stem cells, common lymphoid progenitor cells, and common myeloid progenitor cells and RT-PCR assays to study the levels of Ly6a(Sca1), Slamf1, Ikzf1, and Cebpa—4 genes that control the hematopoietic process—in wildtype male and female mice with a B6SJL genetic background. These analyses revealed many differences, both at the cellular and mRNA levels, between immature and mature mice at various developmental stages. In conclusion, although it is necessary to minimize the number of mice possible insofar as possible to reduce animal use and meet animal welfare requirements, the numerous differences shown by our findings highlight the need to establish controls for every time point selected for the study of the hematopoietic system cells. This need is especially crucial when comparing immature and mature stages of mouse development.
  • 13.

    【2hr】Use of the Rat Grimace Scale to Evaluate Neuropathic Pain in a Model of Cervical Radiculopathy

    包量

    机译 在大鼠神经根病模型中使用大鼠鬼脸量表评估神经性疼痛
    摘要：Although neck and low-back pain are common sources of neuropathic pain with high societal costs, the pathophysiology of neuropathic pain is not well-defined. Traditionally, most rodent pain studies rely on evoked reflex-based testing to measure pain. However, these testing methods do not reveal spontaneous pain, particularly early after injury. The rat grimace scale (RGS) for quantifying spontaneous pain has been validated after visceral, incisional, orthopedic, and inflammatory insults but not neuropathic pain. The current study used a rat model of radiculopathy to investigate the time course of RGS, the effect of the NSAID meloxicam on RGS, and the reliability and consistency of RGS across testers. RGS values at baseline and at 3, 6, 24, and 48 h after cervical nerve root compression (NRC) that induced robust evoked pain responses were compared with those obtained after sham surgery. The RGS was also evaluated at 6 h after NRC in another set of rats that had received meloxicam treatment prior to surgery. At 6 h, NRC induced higher RGS scores (1.27 ± 0.18) than did sham surgery (0.93 ± 0.20), and scores remained above baseline for as long as 48 h. Treatment with meloxicam before NRC reduced RGS at 6 h to sham levels, which were lower than those of injury without treatment. The RGS was associated with very good interobserver reliability (intraclass correlation coefficient, 0.91) and excellent internal consistency (Cronbach α, 0.87). These findings suggest that RGS is a useful approach to identifying and monitoring acute neuropathic pain in rats.
  • 14.

    【2hr】Shope Fibroma in the External Ear Canal of a Domestic Rabbit

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    机译 家兔外耳道中的Shope纤维瘤
    摘要：A 5-y-old, intact, 2.5-kg female domestic rabbit was presented because of blood spatter on the wall of its cage and the toenails of its right hind limb. Physical examination revealed a red, gelatinous mass that spanned the width of the right vertical ear canal. Radiographic images revealed a soft-tissue opacity at the base of the right ear, which was superimposed over the tympanic bulla and extended to the pinna. A CT scan revealed that the soft-tissue mass was within the vertical and horizontal portions of the right external ear canal and extended to the level of the tympanic membrane, with no bony involvement. An incisional biopsy of the mass and subsequent histopathology revealed heterophilic inflammation with bacteria, necrosis, and no evidence of neoplasia. The patient died during anesthesia for removal of the mass at 1 mo after the initial presentation. Necropsy with histopathology of the mass was consistent with Shope fibroma virus in light of the presence of typical intracytoplasmic eosinophilic inclusions. Electron microscopy of paraffin-embedded tissue revealed electron-dense intracytoplasmic structures within neoplastic cells consistent with the diagnosis of Leporipoxvirus. To our knowledge, this report is the first description of Shope fibroma virus invading the external ear canal of a domestic rabbit. Given the results of this case, Shope fibroma should be considered in rabbits presenting with abnormal tissue in the ear canal.
  • 15.

    【2hr】Assessment of Acute Kidney Injury and Renal Fibrosis after Renal Ischemia Protocols in Cats

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    机译 肾缺血方案对猫急性肾脏损伤和肾纤维化的评估
    摘要：In an attempt to identify a feline model of acute or chronic kidney disease, this study was designed to evaluate the effects of 15 or 30 min of bilateral renal ischemia (RI) and 60 min of unilateral RI with delayed contralateral nephrectomy as models of acute kidney injury and chronic interstitial fibrosis in cats. Adult, purpose-bred, USDA Class A cats (n = 14) were randomly assigned to receive bilateral RI for 15 min (n = 3) or 30 min (n = 3), unilateral RI for 60 min with a delayed (2 wk) contralateral nephrectomy (n = 5), or sham unilateral RI with a delayed contralateral nephrectomy (n = 3). Serum creatinine concentration, urine specific gravity, and plasma clearance of iohexol were assessed at several time points throughout the study. Renal interstitial inflammatory cell counts and descriptive histopathology were acquired in all cats. Histomorphometry was used to quantify renal interstitial fibrosis and collagen at 120 d after RI in cats undergoing unilateral RI. Renal histopathology was evaluated at 21 and 120 d after bilateral and unilateral RI, respectively. Neither duration of bilateral RI resulted in appreciable histologic renal damage at 21 d after ischemia. At 120 d after ischemia, variable amounts of renal fibrosis were noted after 60 min of unilateral RI with delayed contralateral nephrectomy. Neither of the tested methods is a suitable model of consistent renal interstitial fibrosis in cats. Healthy cats appear able to sustain bilateral RI for as long as 30 min with no apparent effects on renal morphology or function at 21 d after ischemia.
  • 16.

    【2hr】Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae)

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    机译 猫头鹰猴（Aotus nancymaae）不同年龄和性别的不同群体的外周血淋巴细胞的表型和功能表征
    摘要：Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.
  • 17.

    【2hr】Antimicrobial Use for and Resistance of Zoonotic Bacteria Recovered from Nonhuman Primates

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    机译 从非人类灵长类动物中回收的兽药和抗人畜共通细菌的抗药性
    摘要：As a growing threat to human and animal health, antimicrobial resistance (AMR) has become a central public-health topic. Large-scale surveillance systems, such as the National Antimicrobial Resistance Monitoring System (NARMS), are now established to monitor and provide guidance regarding AMR, but comprehensive literature on AMR among NHP is sparse. This study provides data regarding current antimicrobial use strategies and the prevalence of AMR in zoonotic bacteria recovered from NHP within biomedical research institutions. We focused on 4 enteric bacteria: Shigella flexneri, Yersinia enterocolitica, Y. pseudotuberculosis, and Campylobacter jejuni. Fifteen veterinarians, 7 biomedical research institutions, and 4 diagnostic laboratories participated, providing susceptibility test results from January 2012 through April 2015. Veterinarians primarily treated cases caused by S. flexneri, Y. enterocolitica, and Y. pseudotuberculosis with enrofloxacin but treated C. jejuni cases with azithromycin and tylosin. All isolates were susceptible to the associated primary antimicrobial but often showed resistance to others. Specifically, S. flexneri isolates frequently were resistant to erythromycin (87.5%), doxycycline (73.7%), and tetracycline (38.3%); Y. enterocolitica isolates to ampicillin (100%) and cefazolin (93.6%); and C. jejuni isolates to methicillin (99.5%) and cephalothin (97.5%). None of the 58 Y. pseudotuberculosis isolates was resistant to any tested antimicrobial. Notably, resistance patterns were not shared between this study's NHP isolates and human isolates presented by NARMS. Our findings indicate that zoonotic bacteria from NHP diagnostic samples are broadly susceptible to the antimicrobials used to treat the clinical infections. These results can help veterinarians ensure effective antimicrobial therapy and protect staff by minimizing occupational risk.
  • 18.

    【2hr】AALAS Position Statement on the Humane Care and Use of Laboratory Animals

    包量

    机译 AALAS关于人道关怀和使用实验动物的立场声明
    • 作者：
    • 刊名：Comparative Medicine
    • 2017年第1期
    摘要：
  • 19.

    【2hr】A Mouse Model for Human Unstable Hemoglobin Santa Ana

    包量

    机译 人类不稳定血红蛋白的小鼠模型Santa Ana
    摘要：In the present study, we described the phenotype, histologic morphology, and molecular etiology of a mouse model of unstable hemoglobin Santa Ana. Hematologic evaluation of anemic mice (Anem/+) discovered after N-ethyl-N-nitrosourea mutagenesis revealed moderate anemia with intense reticulocytosis and polychromasia, followed by anisocytosis, macrocytosis, hypochromia, and intraerythrocytic inclusion and Heinz bodies. The mice also demonstrated hemoglobinuria, bilirubinemia, and erythrocytic populations with differing resistance to osmotic lysis. Splenomegaly (particularly in older mutant mice) and jaundice were apparent at necropsy. Histopathologic examination revealed dramatically increased hematopoiesis and hemosiderosis in hematopoietic organs and intracellular iron deposition in tubular renal cells. These data are characteristic of a congenital hemolytic regenerative anemia, similar to human anemias due to unstable hemoglobin. Genetic mapping assigned the affected gene to mouse chromosome 7, approximately 50 cM from the Hbb locus. The sequence of the mutant Hbb gene exhibited a T→C transversion at nucleotide 179 in Hbb-b1, leading to the substitution of proline for leucine at amino acid residue 88 and thus homologous to the genetic defect underlying Santa Ana anemia in humans.
  • 20.

    【2hr】Effects of Chronic Diurnal Disruption and Acute Inflammatory Challenge on Mice with Latent Murine Gammaherpesvirus Infection

    包量

    机译 慢性昼夜干扰和急性炎症激发对小鼠潜伏性γ-疱疹病毒感染小鼠的影响
    摘要：People who engage in shift work (SW) have increased risk of developing illnesses, including infectious diseases and various inflammatory conditions. We hypothesized that exposure to repeated cycles of diurnal disruption, mimicking SW, influences viral clearance, latent viral load, or viral reactivation from latency in mice infected with murine gammaherpesvirus (MuGHV). To test this idea, we inoculated BALB/cByJ and C.129S7(B6)-Ifngtm1Ts/J (IFNgKO) mice with MuGHV and housed them under either a stable light:dark (LD) cycle or one mimicking SW. Compared with BALB/cByJ mice, IFNgKO mice generally had higher levels of lytic virus during the 6-wk period after inoculation. In addition, more IFNgKO mice were positive for replicating virus than were BALB/cByJ mice. Exposure to SW did not alter these measures consistently. After the virus had entered the latent phase of infection, mice received either LPS or pyrogen-free saline intraperitoneally. Mice exposed to SW and then injected with LPS during latent infection had greater viral loads and more replicating virus in the lung at 7 d after injection than did either mice that received pyrogen-free saline or those exposed to LD and then treated with LPS. Some cytokine and chemokine concentrations were changed in lung collected 1 d after but not at 7 d after LPS administration. These findings suggest that exposure to repeated chronic diurnal disruption and an acute inflammatory challenge during latent MuGHV infection, in the context of impaired host immune competence, contribute to enhanced viral reactivity and an increased viral load that might trigger ‘sickness behavior’ symptoms of infectious disease and perhaps contribute to chronic fatigue syndrome.
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