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The increasing study of emerging wildlife pathogens and a lack of policy or legislation regulating their translocation and use has heightened concerns about laboratory escape, species spillover, and subsequent epizootics among animal populations. Responsible self-regulation by research laboratories, in conjunction with institutional-level safeguards, has an important role in mitigating pathogen transmission and spillover, as well as potential interspecies pathogenesis. A model system in disease ecology that highlights these concerns and related amelioration efforts is research focused on amphibian emerging infectious diseases. Whereas laboratory escape of amphibian pathogens has not been reported and may be rare compared with introduction events from trade or human globalization, the threat that novel disease outbreaks with mass mortality effects pose to wild populations warrants thorough biosecurity measures to ensure containment and prevent spillover. Here, we present a case study of the laboratory biosecurity concerns for the emerging amphibian fungal pathogen Batrachochytrium salamandrivorans. We conclude that proactive biosecurity strategies are needed to integrate researcher and institutional oversight of aquatic wildlife pathogens generally, and we call for increased national and international policy and legislative enforcement. Furthermore, taking professional responsibility beyond current regulations is needed as development of legal guidance can be slow at national and international levels. We outline the need for annual laboratory risk assessments, comprehensive training for all laboratory personnel, and appropriate safeguards specific to pathogens under study. These strategies are critical for upholding the integrity and credibility of the scientific community and maintaining public support for research on wildlife diseases.

Submitted by CORREIA (icorreia@ubi.pt) on 2020-07-27T15:29:35Z No. of bitstreams: 1 2020 Mo Nanomed.pdf: 9202396 bytes, checksum: 0f8cd8715e2f5e700744536379365b25 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2020-07-27T15:31:07Z (GMT) No. of bitstreams: 1 2020 Mo Nanomed.pdf: 9202396 bytes, checksum: 0f8cd8715e2f5e700744536379365b25 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2020-07-27T15:33:20Z (GMT) No. of bitstreams: 1 2020 Mo Nanomed.pdf: 9202396 bytes, checksum: 0f8cd8715e2f5e700744536379365b25 (MD5) Made available in DSpace on 2020-07-27T15:33:21Z (GMT). No. of bitstreams: 1 2020 Mo Nanomed.pdf: 9202396 bytes, checksum: 0f8cd8715e2f5e700744536379365b25 (MD5) Previous issue date: 2020-06-18 info:eu-repo/semantics/publishedVersion

Background Therapeutic options in IBD are rapidly growing, causing new challenges including choice of first line therapy. Both adalimumab (ADM) and vedolizumab (VDZ) are effective at inducing and maintaining endoscopic remission in moderate-to-severe IBD. The VARSITY trial (Sands et al NEJM 2019) showed superiority of VDZ over ADM in achieving clinical remission and endoscopic improvement at W52 in UC patients. Our aim was to explore if these results withstand in a real world setting of UC patients, and if they are also valid in CD. Methods This retrospective cohort study included adult, biological-naive IBD patients starting ADM or VDZ between 2015-2019 in our referral IBD centre. Patients had moderate-to-severe disease (endoscopic Mayo sub score ≥ 2 for UC, presence of ulcerations for CD) prior to start of therapy. For UC, we assessed endoscopic remission (endoscopic Mayo sub score 0) and improvement (endoscopic Mayo sub score ≤ 1) at W52. For CD, we assessed endoscopic remission (absence of ulcerations) and improvement (markedly better endoscopy despite still presence of ulcerations) at weeks 26-52. Missing values were imputed as nonresponses for binary outcomes, and last-observation carried-forward was used for continuous outcomes. Results A total of 109 UC and 86 CD patients were included (Table 1). Endoscopic remission at W52 was significantly better for VDZ than ADM in UC (35% vs 15%, p=0.03), and also endoscopic improvement was numerically, yet not significantly, better for VDZ than ADM (56% vs 37%, p=0.08). At baseline, 23 UC patients (50%) in the ADM group and 40 (63%) in the VDZ group were on steroids. By W52, 83% and 78% (p=0.75) of UC patients respectively could discontinue steroids and steroid-free endoscopic remission was not different between groups (ADM: 22% vs VDZ: 23%, p=1.00). For CD patients, similar endoscopic remission (60% vs 48%, p=0.37) and improvement (77% vs 79%, p=1.00) rates at weeks 26-52 were seen between ADM and VDZ. Twenty-five (47%) CD patients in the ADM and 16 (48%) in the VDZ group were on steroids at baseline, and 88% of them in both groups could successfully stop steroids by W52. Again, no difference in steroid-free endoscopic remission was seen between ADM (56%) and VDZ (31%) treated CD patients (p=0.20). At the end of follow-up [81 (27-157) weeks], the rates of treatment persistence were significantly different between ADM and VDZ treatment groups in UC patients, though not in CD patients (Figure 1). Conclusion In a real-world cohort of bio-naive UC patients, VDZ was superior to ADM in achieving endoscopic remission at W52, while in bio-naive CD patients VDZ and ADM resulted in similar endoscopic outcomes.

Central hydrogen sulfide (H2S) has been reported to act as a gaseous neuromodulator involved in the ventilatory and cardiovascular control of normotensive rats, whereas no information is available in spontaneously hypertensive rats (SHR). We recorded minute ventilation (VE), mean arterial pressure (MAP) and heart rate (HR) before and after blocking of enzyme Cystathionine β-synthase (CBS) producing H2S in neural tissue by microinjection of aminooxyacetate (inhibitor of CBS) into the fourth ventricle of Wistar normotensive rats (WNR) and SHR followed by 30min of normoxia (21% inspired O2) or hypoxia (10% inspired O2) exposure. Microinjection of AOA or saline (1μL) did not change VE, MAP and HR during normoxia in both WNR and SHR. In WNR, hypoxia caused an increase in VE, HR and a decrease in MAP and these responses were unaltered by AOA. In SHR, hypoxia produced a higher increase of VE, and decrease in MAP and HR when compared to WNR, and these responses were all blunted by AOA. In conclusion, endogenous H2S plays important modulatory roles on hypoxia-induced ventilatory and cardiovascular responses, inhibiting the cardiovascular and stimulating the respiratory systems in SHR.

Background: Glycogen storage diseases (GSDs) are genetic disorders that result from defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. It also manifests with impaired neutrophil chemotaxis and neutropenic episodes which results in severe destruction of the supporting dental tissues, namely the periodontium. Although GSD Type Ib cannot be cured, associated symptoms and debilitating oral manifestations of the disease can be managed through collaborative medical and dental care where early detection and intervention is of key importance. This objective of the case report was to describe a child with GSD Ib and its associated oral manifestations with microbial, immunological and histological appearances. Case Presentation: An eight-year-old Hispanic male with a history of GSD type Ib presented with extensive intraoral generalized inflammation of the gingiva, ulcerations and bleeding, and intraoral radiographic evidence of bone loss. Tannerella forsythia was readily identifiable from the biofilm samples. Peripheral blood neutrophils were isolated and a deficient host response was observed by impaired neutrophil migration. Histological evaluation of the soft and hard tissues of the periodontally affected primary teeth showed unaffected dentin and cementum. Conclusions: This case illustrates the association between GSD Ib and oral manifestations of the disease. A multi-disciplinary treatment approach was developed in order to establish healthy intraoral conditions for the patient. Review of the literature identified several cases describing GSD and its clinical and radiographic oral manifestations; however, none was identified where also microbial, immunological, and histological appearances were described.

Background Switching between biological therapies is frequently observed in the routine management of inflammatory bowel disease (IBD). Yet, it is unknown whether sequential use of biologicals affects safety such as serious infections and malignancies. We aimed to compare the occurrence of serious infections and malignancies in regards to the number and classes of biologicals to which patients were exposed. Methods This retrospective cohort study included all IBD patients exposed to commercially available biologicals from 1999 to 2019 in a tertiary referral centre. Follow-up started at initiation of first biological. Exclusion criteria included: patients Results In total 1374 patients were included (Figure 1). During a median (IQR) follow-up of 8 (4–13) years, 373 serious infections and 127 malignancies were reported in 245 (19%) and 92 (7%) patients, leading to an incidence rate of 2.2 and 0.8 per 100.000 patients per year, respectively. The number of serious infections was dependent on prior exposure to immunomodulators (IM, p = 0.001), the number of biologicals (p = 0.042) and the number of biological classes to which the patient was exposed (p = 0.004, overall test Poisson model p = 0.0001). The risk of serious infections increased when a patient was exposed to three or more different biologicals or two or more different classes of biologicals. The number of malignancies was also affected by the number of biologicals (p = 0.028) to which the patient was exposed, with a higher risk of developing a malignancy with exposure to an increasing number of biologicals (Figure 2 and 3). Cox regression for the time to develop a first or second malignancy was independent of exposure to IM, number of biologicals as well as number of different biological classes to which the patient was exposed. Median (IQR) time to develop a first or second malignancy after the start of the first biological was 6 (3–9) and 6 (4–12) years. Conclusion In this large single-centre cohort study spanning 20 years, the overall risk of serious infections and malignancies in patients exposed to biologicals remains low, yet the risk increased with more and sequential use of biologicals so close vigilance is needed.

OBJECTIVE: The effect of chronic ethanol exposure on chemoreflexes has not been extensively studied in experimental animals. Therefore, this study tested the hypothesis that known ethanol-induced autonomic, neuroendocrine and cardiovascular changes coincide with increased chemoreflex sensitivity, as indicated by increased ventilatory responses to hypoxia and hypercapnia. METHODS: Male Wistar rats were subjected to increasing ethanol concentrations in their drinking water (first week: 5% v/v, second week: 10% v/v, third and fourth weeks: 20% v/v). At the end of each week of ethanol exposure, ventilatory parameters were measured under basal conditions and in response to hypoxia (evaluation of peripheral chemoreflex sensitivity) and hypercapnia (evaluation of central chemoreflex sensitivity). RESULTS: Decreased respiratory frequency was observed in rats exposed to ethanol from the first until the fourth week, whereas minute ventilation remained unchanged. Moreover, we observed an increased tidal volume in the second through the fourth week of exposure. The minute ventilation responses to hypoxia were attenuated in the first through the third week but remained unchanged during the last week. The respiratory frequency responses to hypoxia in ethanol-exposed rats were attenuated in the second through the third week but remained unchanged in the first and fourth weeks. There was no significant change in tidal volume responses to hypoxia. With regard to hypercapnic responses, no significant changes in ventilatory parameters were observed. CONCLUSIONS: Our data are consistent with the notion that chronic ethanol exposure does not increase peripheral or central chemoreflex sensitivity.

OBJECTIVE: Chemoreceptors play an important role in the autonomic modulation of circulatory and ventilatory responses to changes in arterial O2 and/or CO2. However, studies evaluating hemodynamic responses to hypoxia and hypercapnia in rats have shown inconsistent results. Our aim was to evaluate hemodynamic and respiratory responses to different levels of hypoxia and hypercapnia in conscious intact or carotid body-denervated rats. METHODS: Male Wistar rats were submitted to bilateral ligature of carotid body arteries (or sham-operation) and received catheters into the left femoral artery and vein. After two days, each animal was placed into a plethysmographic chamber and, after baseline measurements of respiratory parameters and arterial pressure, each animal was subjected to three levels of hypoxia (15, 10 and 6% O2) and hypercapnia (10% CO2). RESULTS: The results indicated that 15% O2 decreased the mean arterial pressure and increased the heart rate (HR) in both intact (n = 8) and carotid body-denervated (n = 7) rats. In contrast, 10% O2 did not change the mean arterial pressure but still increased the HR in intact rats, and it decreased the mean arterial pressure and increased the heart rate in carotid body-denervated rats. Furthermore, 6% O2 increased the mean arterial pressure and decreased the HR in intact rats, but it decreased the mean arterial pressure and did not change the HR in carotid body-denervated rats. The 3 levels of hypoxia increased pulmonary ventilation in both groups, with attenuated responses in carotid body-denervated rats. Hypercapnia with 10% CO2 increased the mean arterial pressure and decreased HR similarly in both groups. Hypercapnia also increased pulmonary ventilation in both groups to the same extent. CONCLUSION: This study demonstrates that the hemodynamic and ventilatory responses varied according to the level of hypoxia. Nevertheless, the hemodynamic and ventilatory responses to hypercapnia did not depend on the activation of the peripheral carotid chemoreceptors.

Made available in DSpace on 2021-07-14T10:34:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2016. Added 1 bitstream(s) on 2021-07-14T11:33:18Z : No. of bitstreams: 1 S1980-65742016000100018.pdf: 454204 bytes, checksum: b464171686482c0924312d61bcd612dc (MD5) This study examined the relationship between resting heart rate (RHRr) and anthropometric, metabolic and hemodynamic parameters in subjects aged 80 years and over. One hundred thirteen individuals were divided into two groups (RHR

Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5 mg/kg i.p.) in rats kept at an ambient temperature of 25 °C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS – responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.

Presents the formulation of a new triangular finite element for plate bending. The element has 15 degrees of freedom: six displacements at the corners and midside nodes and nine rotations normal to the element side, three along each element side. The element is based on the Kirchhoff theory for plate bending and the shape functions are derived from a complete quartic polynomial. Presents a numerical assessment of the element, showing that the element passes the patch test and that it possesses a good converge rate. The stiffness matrix is integrated exactly.

We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by PYR. When HF and control rats treated or untreated with PYR were exposed to 15% O2, all groups exhibited prompt increases in respiratory frequency (RF), tidal volume (TV) and PV. When HF rats were exposed to 10% O2 they showed greater PV response which was prevented by PYR. The hypercapnia triggered by either 5% CO2 or 10% CO2 promoted greater RF and PV responses in HF rats. PYR blunted the RF response in HF rats but did not affect the PV response. In conclusion, PYR prevented increased peripheral chemoreflex sensitivity, partially blunted central chemoreflex sensitivity and did not affect basal PV in HF rats.

Sympathetic hyperactivity and its outcome in heart failure have been thoroughly investigated to determine the focus of pharmacologic approaches targeting the sympathetic nervous system in the treatment of this pathophysiological condition. On the other hand, therapeutic approaches aiming to protect the reduced cardiac parasympathetic function have not received much attention. The present study evaluated rats with chronic heart failure (six to seven weeks after coronary artery ligation) and the effects of an increased parasympathetic function by pyridostigmine (an acetylcholinesterase inhibitor) on the following aspects: arterial pressure (AP), heart rate (HR), baroreceptor and Bezold-Jarisch reflex, pulse interval (PI) and AP variability, cardiac sympathetic and parasympathetic tonus, intrinsic heart rate (i-HR) and cardiac function. Conscious rats with heart failure exhibited no change in HR, Bezold-Jarisch reflex, PI variability and cardiac sympathetic tonus. On the other hand, these animals presented hypotension and reduced baroreflex sensitivity, power in the low frequency (LF) band of the systolic AP spectrum, cardiac parasympathetic tonus and i-HR, while anesthetized rats exhibited reduced cardiac performance. Pyridostigmine prevented the attenuation of all the parameters examined, except basal AP and cardiac performance. In conclusion, the blockade of acetylcholinesterase with pyridostigmine was revealed to be an important pharmacological approach, which could be used to increase parasympathetic function and to improve a number of cardiocirculatory parameters in rats with heart failure.

Made available in DSpace on 2013-08-28T14:12:09Z (GMT). No. of bitstreams: 1 WOS000300250500001.pdf: 706311 bytes, checksum: d18b433f1426cbf342153250b0b57808 (MD5) Made available in DSpace on 2013-09-30T18:09:53Z (GMT). No. of bitstreams: 2 WOS000300250500001.pdf: 706311 bytes, checksum: d18b433f1426cbf342153250b0b57808 (MD5) WOS000300250500001.pdf.txt: 29420 bytes, checksum: 8183576f358280ba056c671e285249b5 (MD5) Previous issue date: 2012-01-12 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:58:22Z No. of bitstreams: 2 WOS000300250500001.pdf: 706311 bytes, checksum: d18b433f1426cbf342153250b0b57808 (MD5) WOS000300250500001.pdf.txt: 29420 bytes, checksum: 8183576f358280ba056c671e285249b5 (MD5) Made available in DSpace on 2014-05-20T13:58:22Z (GMT). No. of bitstreams: 2 WOS000300250500001.pdf: 706311 bytes, checksum: d18b433f1426cbf342153250b0b57808 (MD5) WOS000300250500001.pdf.txt: 29420 bytes, checksum: 8183576f358280ba056c671e285249b5 (MD5) Previous issue date: 2012-01-12 Background: Recent studies have identified that a higher resting heart rate (RHR) is associated with elevated blood pressure, independent of body fatness, age and ethnicity. However, it is still unclear whether RHR can also be applied as a screening for other risk factors, such as hyperglycemia and dyslipidemia. Thus, the purpose of the presented study was to analyze the association between RHR, lipid profile and fasting glucose in obese children and adolescents.Methods: The sample was composed of 180 obese children and adolescents, aged between 7-16 years. Whole-body and segmental body composition were estimated by Dual-energy X-ray absorptiometry. Resting heart rate (RHR) was measured by heart rate monitors. The fasting blood samples were analyzed for serum triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose, using the colorimetric method.Results: Fasting glucose, TC, triglycerides, HDL-C, LDL-C and RHR were similar in both genders. The group of obese subjects with a higher RHR presented, at a lower age, higher triglycerides and TC. There was a significant relationship between RHR, triglycerides and TC. In the multivariate model, triglycerides and TC maintained a significant relationship with RHR independent of age, gender, general and trunk adiposity. The ROC curve indicated that RHR has a high potential for screening elevated total cholesterol and triglycerides as well as dyslipidemia.Conclusion: Elevated RHR has the potential to identify subjects at an increased risk of atherosclerosis development. UNESP Univ Estadual Paulista, Dept Phys Educ, Presidente Prudente, SP, Brazil UNESP Univ Estadual Paulista, Dept Phys Therapy, Presidente Prudente, SP, Brazil UNESP Univ Estadual Paulista, Dept Phys Educ, Rio Claro, SP, Brazil Univ São Paulo, Sch Med Ribeirao Preto, Dept Physiol, São Paulo, Brazil UNESP Univ Estadual Paulista, Dept Phys Educ, Presidente Prudente, SP, Brazil UNESP Univ Estadual Paulista, Dept Phys Therapy, Presidente Prudente, SP, Brazil UNESP Univ Estadual Paulista, Dept Phys Educ, Rio Claro, SP, Brazil

INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons.

Made available in DSpace on 2022-04-29T07:20:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-01 This study compared autonomic modulation in swimmers and non-Athletes in relation to body composition. A total of 28 athletes with a mean age of 19.7 ± 2.9 years were evaluated who had at least 2 years of swimming training, trained approximately 7,000 m per day, with a frequency of 5 days per week, and who competed at national level. The control group was made up of 21 volunteers (23.0 ± 2.5 years), who did not practice regular physical activity (

Made available in DSpace on 2013-08-12T18:37:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-01 Made available in DSpace on 2013-09-30T19:12:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:30:35Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T15:30:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-01-01 This study investigated if overfed rats present morphological and histochemical muscle adaptation similar to normally fed, both submitted to two different weekly frequencies of training. Thirty male Wistar rats were fed either with standard chow (SCO) or with hypercaloric diet (HCO). They were subdivided into six subgroups: sedentary (SCO and HCO), trained twice/week (SC2 and HC2) and trained five times/week (SC5 and HC5). The trained groups swam 60 min/day, during 10 weeks. Twenty four hours after the last training, samples of Gastrocnemius were excised and stained with HE, NADH-TR and m-ATPase, and the capillary density was calculated. Total heart mass (HM) and the mass of atrium (AM), left (LV) and right (RV) ventricles were excised and weighted. The comparisons were made by ANOVA and by Covariance analysis, adjusting the variables by body weight. The results showed that the HCO achieved higher BM, however, absolute HM did not differ post training. Irrespective of the diet, rats that were trained twice a week presented significantly greater increase in the AM. In general, the SC5 and HC5 groups showed higher HM, LV, RV, proportion of oxidative fibres and capillary density, compared to the sedentary and twice week trained groups. A higher proportion of injuries (splitting) was noted in the HC2 and HC5 compared to SC2 and SC5. These results indicate that the frequency of training influenced the skeletal and heart adaptation and larger changes were observed in the 5x/week group, which ingested the standard diet. The 5x/week training groups also presented large amount of muscle fibres damage. São Paulo State Univ, UNESP, Dept Phys Educ, São Paulo, Brazil São Paulo State Univ, UNESP, Dept Phys Educ, São Paulo, Brazil