Salivary Cortisol and Anxiety in Canadian Dentists over 1 Year of COVID-19.

The dental profession has endured unprecedented disruption amid COVID-19. Novel stressors have included a high risk of occupational exposure to COVID-19, financial losses, and stricter infection prevention and control requirements. The present study investigated the longitudinal impact of COVID-19 on the stress and anxiety levels of a cohort of Canadian dentists (N = 222) between September 2020 and October 2021. Salivary cortisol was selected as a biomarker of mental stress, and 10 sets of monthly saliva samples (2,131 in total) were self-collected, sent to our laboratory in prepaid courier envelopes, and analyzed by enzyme-linked immunosorbent assay. To assess COVID-19 anxiety, 9 monthly online questionnaires were administered, comprising a general COVID-19 anxiety instrument and 3 items regarding the impact of dentistry-related factors. Bayesian log-normal mixed effect models were fitted to estimate the longitudinal trajectory of salivary cortisol levels and their association with the disease burden of COVID-19 in Canada. After accounting for age, sex, vaccination status, and the diurnal rhythm of cortisol secretion, a modest positive association was found between dentists' salivary cortisol levels and the count of COVID-19 cases in Canada (96% posterior probability). Similarly, the self-reported impact of dentistry-related factors, such as fear of getting COVID-19 from a patient or coworker, was greatest during peaks of COVID-19 waves in Canada; however, general COVID-19 anxiety decreased consistently throughout the study period. Interestingly, at all collection points, the majority of participants were not concerned about personal protective equipment. Overall, participants reported relatively low rates of psychological distress symptoms in relation to COVID-19, a result that should be reassuring for the dental community. Our findings strongly suggest a link between self-reported and biochemical measurements of stress and anxiety in Canadian dentists during the COVID-19 pandemic.

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma.

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

Consensus on domains, formation objectives and contents in cariology for undergraduate dental students in Colombia.

OBJECTIVE: To achieve a consensus for an undergraduate cariology teaching curriculum between Colombian dental schools in line with the 2015 Global Alliance for a Cavity-Free Future goal: '90% of dental schools adopting the current caries paradigm'. MATERIALS AND METHODS: First phase: Four-regional 2-day workshops were conducted with 4 representative teachers (cariology, clinics, basic-science, public health and specialisations) from each of the 24-ACFO schools (Colombian Dental Schools Association) as follows: Presentations: -Main Colombian cariology teaching barriers, -Caries and public health current paradigms; -Schools' cariology teaching descriptions; -European Cariology Curriculum. Five main-domain subgroup discussions: (i) the knowledge base; (ii) risk assessment, diagnosis and synthesis; (iii) decision-making, preventive non-surgical therapy; (iv) decision-making, surgical therapy; and (v) evidence-based cariology in clinical and public health practice, to adapt domains, objectives and contents to Colombian curriculum, public health and national health system needs. These 4-regional plus 24-school consensuses sent 1 month afterwards were adapted into a preliminary document. 2nd-phase: 10 peer review by national faculty in cariology, and 10 curriculum, basic sciences, research, clinical management and public health experts. School participants and deans reviewed the draft document and suggestions were discussed and adapted into a final consensus document officially presented to the academic community at the ACFO National-Research-Meeting (September, 2012). RESULTS: 24 schools and 92 teachers participated. The Colombian Cariology Curriculum was agreed by 23 schools. It positioned public health into one domain. A general focus on social determination was included, and more relevance was given to fluorosis than erosion. CONCLUSIONS: A consensus on cariology teaching for undergraduate dental students was achieved in Colombia and work to promote its adoption has commenced.

Iron status in blood donor dogs.

BACKGROUND: Despite the popularity of canine blood donor (BD) programs, there is scarce scientific information regarding iron status in this canine population of dogs. OBJECTIVE: To assess iron status in dogs used in a blood donor program. ANIMALS: A total of 130 healthy dogs (75 BD, 55 controls [C]) were included. A subset of dogs (n = 12) were used to evaluate the effects of repetitive donations by having a second and more recent sample analyzed. METHODS: Serum iron concentration (SI), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), and percentage transferrin saturation (%SAT) were obtained. Values were compared using a 2-way ANOVA (factors: BD status, breed). For the subset of BD, the first sample (less frequent donors -LD-, after a mean of 3.8 donations) was compared to a second sample (experienced donors -ED-, mean 13.6 donations) using a paired t-test. RESULTS: SI (183.7 ± 55.3 µg/dL) and %SAT (55.7 ± 17.4%) were higher and UIBC (152.6 ± 73.3 µg/dL) was lower in BD dogs than in C (153.9 ± 51.7 µg/dL, 43.8 ± 17.8%, and 224.1 ± 120.6 µg/dL, respectively). Also, UIBC and TIBC were lower, and %SAT higher in Greyhounds when compared with non-Greyhounds. ED had decreased %SAT and increased UIBC and TIBC when compared with LD. CONCLUSIONS AND CLINICAL IMPORTANCE: Our canine BD population did not have iron deficiency and had higher SI concentration than C. However, ED (~14 consecutive blood donations every ~8 weeks) developed a mild iron deficiency, although values were still within canine reference intervals. Greyhounds have higher %SAT than non-Greyhounds, which might be a breed-specific peculiarity.

Effects of racing on reticulocyte concentrations in Greyhounds.

BACKGROUND: Greyhounds have several hematologic variables that are outside of the respective reference intervals of other dog breeds. In addition, increases in HCT, total protein and HGB concentration, and RBC and WBC counts occur immediately after exercise; these values return to resting values within a few hour after racing. OBJECTIVE: This study evaluated the effects of exercise on the concentration of reticulocytes in circulating blood in racing Greyhounds. We hypothesized that reticulocyte numbers are significantly increased immediately after a race, and return to baseline within one to 2 h postrace. METHODS: Fifty actively racing Greyhounds at the Wheeling Island Racetrack and Casino were included in the study. Samples were collected by jugular venipuncture one day prior to racing at the kennel (resting), immediately after racing, and one to 2 h after the race (recovery). Reticulocyte counts were determined with an IDEXX ProCyte Dx Hematology Analyzer (IDEXX Laboratories, Inc., Westbrook, ME, USA). Due to a nonparametric distribution, the results were statistically compared using the Friedman test. RESULTS: Reticulocyte concentrations were significantly different among the 3 sample collection times (P < .0001). There was a significant increase in reticulocyte concentration immediately after racing (P < .001); one to 2 h after racing, the reticulocyte numbers decreased significantly (P < .001) to counts comparable to resting samples. CONCLUSION: The increase in reticulocyte concentration is probably related to splenic contraction secondary to the release of catecholamines, although premature bone marrow release could also account for these changes. Thus, it is important to consider a Greyhound's activity and degree of excitement when interpreting selected hematologic data in a clinical setting.

Is "intra-operating room" thromboelastometry useful in liver transplantation? A case-control study in 303 patients.

Coagulation monitoring during liver transplantation (LT) is, even today, fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a proven technique for controlling the various parameters that influence coagulation. However, there are no studies linking "intra-operating room" TEM (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft recipients analyzing variables associated with operative complications and long-term LT outcomes. The results showed that orTEM reduced the use of blood products in patients with Model for End-Stage Liver Disease scores of ≥ 21, retransplantation, and high surgical difficulty and important intraoperative bleeding. In addition, results in survival and postoperative complications were better when orTEM was used. In conclusion, we confirm that use of orTEM is associated with less use of blood products and a lower rate of complications after LT.

Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts.

INTRODUCTION: The use of grafts from donors older than 70 years of age is increasing due to the decrease in the number of donors and the increase in waiting list patients. MATERIAL AND METHODS: We undertook a univariate and multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them from donors aged 70 years or older. RESULTS: No differences were found in patient survival compared with recipients of younger grafts. There were no higher rates of rejection, vascular or biliary complications, postoperative bleeding, or infections, but older grafts were associated with graft dysfunction (P = .01) and a higher frequency of postoperative refractory ascites (P = .007), but without a greater need for retransplantation. As graft-associated factors, the joint presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04-0.117), hypertension (P = .00; CI = 0.22-0.39), and weight of more than 90 kg (P = .031; CI = 0.05-0.104) were suggestive of poor prognostic factors in recipient survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older than 60 years was worse with donors aged older than 70 years, although not significantly so. With grafts from donors aged older than 80 years (n = 15), although patient survival rate was good (70% at 10 years), there was a higher rate of retransplantation (20%) and the early mortality rate was 13.3%. CONCLUSIONS: Use of grafts from donors aged older than 70 years is safe, with similar survival to patients with younger grafts. The appearance of initial dysfunction with prolonged ascites may be due to a delay in reaching a correct functionality, but was not associated with increased mortality, complications, or need for retransplantation. It should also be avoided in recipients older than 60 years or with HCV. Grafts older than 80 years were associated with a good long-term patient survival but at the expense of a higher rate of retransplantation. However, it helps to reduce the time on the waiting list and, thus, mortality. We noted decreased survival associated with donor hypertension, diabetes, and obesity, so these donors should be selected more rigorously.

Markers of iron metabolism in retired racing Greyhounds with and without osteosarcoma.

BACKGROUND: Greyhounds have well-described clinicopathologic idiosyncrasies, including a high prevalence of osteosarcoma (OSA). Hematocrit, HGB, and HGB oxygen affinity are higher than in other dogs, while haptoglobin concentration is lower, so we hypothesized that Greyhounds have a different iron metabolism. To our knowledge, there are no reports on serum iron profiles in Greyhounds. OBJECTIVES: To elucidate iron metabolism in Greyhounds, we wanted to compare serum iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (%SAT) in healthy retired racing Greyhounds (RRGs) with OSA (RRGs - OSA), and also with non-Greyhounds (NGs), without and with OSA (NGs - OSA). METHODS: Serum iron concentration and unsaturated iron-binding capacity (UIBC) were measured by standard methods, and TIBC and %SAT were calculated in RRGs (n = 25), RRGs - OSA (n = 28), NGs (n = 30), and NGs - OSA (n = 32). RESULTS: TIBC was lower in RRGs than in NGs (P < .0001), and in RRGs - OSA than in NGs - OSA (P < .0001). NGs - OSA had lower TIBC than healthy NGs (P = .003). Percent SAT was higher in RRGs than in NGs (P < .0001) and in RRGs - OSA (P = .008), and %SAT was also lower in NGs than in NGs - OSA (P = .004). Percent SAT was also higher in RRGs - OSA than in NGs - OSA (P = .001). Both RRGs - OSA (P = .02) and NGs - OSA (P < .0001) had lower serum iron concentrations than their healthy counterparts. CONCLUSION: Lower TIBC and higher %SAT may constitute another Greyhound idiosyncrasy compared with other dogs. In this study, all dogs with OSA had higher serum iron concentrations and %SAT than healthy dogs.

Haematological and biochemical values in North American Scottish deerhounds.

OBJECTIVE: Sighthounds, including deerhounds, have unique physiological traits that result in laboratory test results that may lie outside reference intervals for the general dog population. Although reference intervals for most analytes are thought to be similar among sighthounds, breed-specific reference intervals are available mainly for greyhounds. The aim of this study was to establish reference intervals for haematology and serum biochemical profiles in deerhounds. METHODS: Venous blood samples were collected from healthy deerhounds. Haematological and biochemical analytes were examined and reference intervals were established using the 5th and 95th percentiles. RESULTS: The reference intervals obtained from 96 dogs for platelets, reticulocytes, total thyroxine, chloride, gamma glutamyl transferase, bilirubin and glucose were lower than the general dog population. Reference intervals for mean cell volume, potassium, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and cholesterol were higher than the general dog population. Reference intervals for eosinophils and globulin were wider than that of the general population. CLINICAL SIGNIFICANCE: These results confirm that differences in haematological and biochemical values exist in the deerhound. Some appear to be shared by all sighthounds but others may be unique to this breed.

Antitumor efficacy of mammalian target of rapamycin inhibitor therapy in liver transplant recipients with oncological disease: a case-control study.

INTRODUCTION: The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer. METHODS: We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL. RESULTS: No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05). DISCUSSION: Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or "de novo" neoplasms.

Clinical pathology of Greyhounds and other sighthounds.

Owing to the development of Greyhounds as racing sighthounds, these dogs have acquired unique physiologic adaptations that distinguish them from other breeds. Reference intervals for many analytes in retired racing Greyhounds (RRGs) differ from those of other breeds; most of the hematologic differences have also been described in other sighthounds. In this review, we provide a survey of the literature on clinical pathology of Greyhounds and other sighthounds and results of laboratory testing, including analysis of CBCs, biochemical profiles, coagulation tests, and blood gases, in RRGs at The Ohio State University. Major clinicopathologic differences in this breed include higher RBC mass, creatinine concentration, glomerular filtration rate, activities of hepatic enzymes, and concentration of cardiac troponin, as well as lower WBC, neutrophil, and platelet counts, thromboelastographic values, and concentrations of serum haptoglobin, total globulins, and T4.

Results of liver transplantation with donors older than 70 years: a case-control study.

Older donors are a growing part of the total pool but no definite consensus exists on the age limit for their acceptance. This retrospective case-control unicenter study compared the outcomes of 72 orthotopic liver transplantations (OLTs) from April 1990 to April 2010 using donors older than 70 years versus 738 chronologically correlated OLTs performed with donors younger than 60 years. The percentage of refusal was greater among older than younger donors (48.2 vs 14.3%; P < .001). No difference was observed in mean cold ischemia times between older (370.5 minutes) versus younger groups (389.2 minutes). or in postoperative complications of rejection or renal insufficiency except for sepsis and mortality. Long-term survival was lower among transplant recipients from donors older than 70 years (P = .001) and these cases showed more blood requirements associated with prolonged cold ischemia (P = .02). Multivariate analysis revealed graft dysfunction, mortality, and reduced survival to be associated with donor weight and recipient MELD (Model for End-stage Liver Disease) (P < .05). Interestingly, the mortality related to hepatitis C virus recurrence was not greater among patients whose donors were older than 70. Septuagenarians' livers can be used safely, but careful donor and recipient evaluation are required to avoid additional risk factors.

Liver transplantation in patients with cryptogenic cirrhosis: long-term follow-up.

OBJECTIVE: The objective of this study was to evaluate long-term survival, histological diagnoses, and mobility of patients with cryptogenic cirrhosis (CC) treated with orthotopic liver transplantation (OLT). PATIENTS AND METHODS: We performed a retrospective analysis of 35 patients who underwent transplantation with CC among 800 OLT patients. There were no differences in gender, mean age of 47 years, average MELD (Model for End-stage Liver Disease) of 16, and hepatocellular carcinoma incidence (8%). RESULTS: In 28.6% of patients, the diagnosis of CC was wrong. There was no incidence of an acute rejection episode and a low incidence of complications, although the postoperative mortality rate was 20%, of chronic rejection was 25%, and recurrence of disease was 4%. Cumulative at 3-, 5-, and 10-year survivals were lower than the other OLT. Survival was lower in patients receiving suboptimal grafts. CONCLUSIONS: One of 3 patients who underwent transplantation for CC had a specific etiologic diagnosis. The chronic rejection rate and postoperative mortality rate were higher than other etiologies, and survivals at 5, 10, and 15 years were lower than other OLT.

Efficacy, tolerance, and safety of mammalian target of rapamycin inhibitors as rescue immunosuppressants in liver transplantation.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias. MATERIALS AND METHODS: Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes. RESULTS: There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia. CONCLUSIONS: mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.

Serum cardiac troponin I concentration in retired racing greyhounds.

BACKGROUND: Cardiac troponin I (cTnI) is a polypeptide found specifically in cardiac muscle tissue that has been used as a diagnostic and prognostic indicator of cardiomyopathy. Increases in cTnI are associated with myocardial pathologic processes. However, high serum cTnI concentrations have been observed in normal Greyhounds. HYPOTHESIS: We hypothesized that Greyhounds have cTnI concentrations higher than non-Greyhound dogs, and that a separate reference range should be established for Greyhounds. ANIMALS: Blood samples were collected from the jugular vein from a group of 20 healthy Greyhound blood donors. METHODS: Analysis of serum cTnI was performed with an immunoassay system with a detection level of 0.01 ng/mL, as described previously. The Greyhound values were compared with 2 groups of Boxers with and without arrhythmogenic right ventricular cardiomyopathy (ARVC), and to a group of non-Boxer control dogs from a previous study. RESULTS: The mean cTnI concentration in Greyhounds was significantly higher (P < .0001) than that in non-Greyhound control dogs, although not significantly different from normal Boxers (P= .50), or Boxers with ARVC (P= .58). Greyhound serum cTnI concentrations were in the range found in Boxers with ARVC. The proposed reference range for cTnI in Greyhounds is 0.05-0.16 ng/mL. CONCLUSIONS AND CLINICAL IMPORTANCE: Greyhounds have a reference range for serum cTnI concentrations that differs from that of other previously published reference ranges for dogs of other breeds. Until a broader database and more precise reference range can be established, caution should be exercised in interpreting serum cTnI concentrations in Greyhounds with suspected cardiac disease.

Effects of time of collection and sample processing on von Willebrand factor concentration in retired racing greyhounds.

BACKGROUND: Concentrations of von Willebrand factor (vWF) are less than 30% in approximately 10% of Greyhounds. HYPOTHESIS: That sample collection, processing, and storage can affect the concentration of vWF in plasma of Greyhounds. ANIMALS: Nineteen healthy former racing Greyhounds. METHODS: Prospective study: Blood samples were obtained from the jugular vein of dogs at 4 times during the day. Samples were divided and processed in each of 3 ways. The 1st tube was centrifuged immediately, the 2nd tube was kept in a household refrigerator, and the 3rd tube was kept at room temperature for 3 hours before centrifugation and processing. RESULTS: There were no significant differences in the vWF concentration between different sample storage and processing (P = 5.31). There was no statistically significant diurnal variation in vWF concentration in the samples evaluated (P = .37). CONCLUSIONS AND CLINICAL IMPORTANCE: Time of sample collection and short-term storage temperature do not influence the vWF concentration in retired racing Greyhounds.

Intact glycans from cestode antigens are involved in innate activation of myeloid suppressor cells.

During helminthic infections, strong Th2 type-biased responses concomitant with impaired cell-proliferative responses to parasitic and unrelated antigens are major immunological hallmarks. Parasite glycan structures have been proposed to play a role in modulating these responses. To understand early events related to immune modulation during cestode infection, we have examined the role of intact glycans of antigens from Taenia crassiceps in the recruitment of innate cells. Soluble antigens from this cestode contained higher levels of carbohydrates than proteins. Intraperitoneal injection of the antigens rapidly recruited a cell population expressing F4/80(+)/Gr-1(+)surface markers, which adoptively suppressed naïve T-cell proliferation in vitro in response to anti-CD3/CD28 MAb stimulation in a cell-contact dependent manner. Soluble antigens with altered glycans by treatment with sodium periodate significantly reduced the recruitment of F4/80(+)/Gr1(+)cells, concomitantly their suppressive activity was abrogated, indicating that glycans have a role in the early activation of these suppressor cells. Using C3H/HeJ and STAT6-KO mice, we found that expansion and suppressive activity of F4/80(+)Gr1(+)cells induced by T. crassiceps intact antigens was TLR4 and Th2-type cytokine independent. Together with previous studies on nematode and trematode parasites, our data support the hypothesis that glycans can be involved on a similar pathway in the immunoregulation by helminths.