Validity of central pain processing biomarkers for predicting the occurrence of oncological chronic pain: a study protocol.

BACKGROUND: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. METHODS: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. DISCUSSION: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Respected physician in Syria, unemployed refugee in the Netherlands: An analysis of the integration of Syrian refugees with a medical degree in the Dutch medical field.

Refugees in the Netherlands are expected to integrate in society and find employment. Despite years of education, Syrian refugees who graduated in medicine (SRGMs') struggle to enter the Dutch medical field. To ensure patient safety, physicians with a medical degree obtained outside Europe are obliged to finish an 'assessment procedure' (AP) and might be forced to redo clinical internships, before being allowed to practice medicine. In this research, SRGMs' experiences were analysed using Bourdieu's capital theory. Semi-structured interviews were conducted with 17 SRGMs. In Syria, they acquired much capital as physicians, in the shape of financial means (economic capital), connections (social capital), medical degrees and skills (cultural capital), and status (symbolic capital). Their medical skills often provide the only capital that remains when arriving in the Netherlands, but it loses value as they have to prove their competence first in the AP. This is a long and arduous process. The mean duration, for those who had yet finished the AP, from arrival to employment was 4.5 years (n = 5, range 2.7-5.8 years). SRGMs experience difficulties in these AP years because they are forced to study from home and feel excluded from medical practice. They are unable to regain their economic, social and symbolic capital, whilst struggling to get their cultural capital acknowledged. Mentally this is challenging and when they do finish, this capital gap leaves them at a disadvantage when applying for competitive job applications. Once employed, SRGMs need time to adjust but are finally rebuilding their capital and integrating in Dutch society. Both SRGMs and Dutch society benefit when SRGMs' integration in the Dutch medical field improves. Although certain challenges for SRGMs seem inevitable, by offering a clinical internship before the assessment of SRGMs' skills, their capital acquisition might improve which would facilitate their integration.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Punto óptimo cardiorrespiratorio, composicion corporal y medidas bioquímicas: Un estudio con gemelos / Cardiorespiratory Optimal Point, Body Composition and Biochemical Measurements: A Study with Twins

El propósito de este estudio fue investigar la relación de la composición corporal y las variables bioquímicas con el POC, así como observar la tendencia de la heredabilidad. Estudio transversal con gemelos monocigóticos y dicigóticos adultos. Para obtener los valores del POC, la prueba de ejercicio cardiopulmonar fue realizada se realizó un protocolo con sobre cinta rodante. Para la composición corporal, se utilizaron laabsorciometríade energía dual y la antropometría. Para las inferencias, se realizaron la concordancia de Spearman y la prueba de hipótesisMann-Whitney.Los resultados mostraron que lasvariables de composición corporal no se correlacionaron significativamente con el punto óptimo cardiorrespiratorio. El Punto Óptimo Cardiorrespiratorio y las variables bioquímicas en general demostraron una mayor tendencia a ser influenciados por factores ambientales. El comportamiento de las variables de composición corporal demostró una mayor influencia de la heredabilidad. (AU)

The purpose of this study was to investigate the relationship of body composition and biochemical variables with the cardiorespiratory optimal point, as well as to observe the tendency of heritability. This is a descriptive study with a cross-sectional design with adult monozygotic and dizygotic twins. To obtain the COP values, the cardiopulmonary exercise test was performed using a treadmill ramp protocol. For body composition, dual energy absorptiometry and anthropometry were used. For inferences, the Spearman correlation and the Mann-Whitney hypothesis test were performed. The results showed that the body composition variables did not significantly correlate with the cardiorespiratory optimal point. The Cardiorespiratory Optimal Point and biochemical variablesdemonstrated a greater tendency to be influenced by environmental factors and the body composition variables showed a greater influence of heritability. (AU)

Sanitary sewage disinfection with ultraviolet radiation and ultrasound.

Currently, the world is facing a horrible situation due to SARS-CoV-2. Though its RNA was found in wastewater, there are still no studies on RNA contamination detected in sewage. Hence, a possible treatment of sewage is suggested in this work. The disinfection stage is extremely important in the treatment of effluents, minimizing the impacts on the receiving body of water and promoting public health. In this context, the sequential use of ultrasound and ultraviolet radiation, on a bench scale, was investigated as a way to improve the disinfection of anaerobically treated effluents. Two types of treated effluents were tested, by septic tank and anaerobic filter, for which, two ultrasound frequencies, 25 and 40 kHz, and four doses of UV, 3.6; 9.0; 18 and 36 mJ cm-2 were applied. Physicochemical and microbiological parameters were observed for individual and sequential assays. The better quality of the anaerobic filter effluent influenced the performance of both processes, decreasing the concentration of organic load and turbidity, even though a concentration of total coliforms and Escherichia coli occurred in the lowest quality effluent (septic tank). The application of ultrasound has a positive effect on the inactivation of total coliforms and E. coli up to 1.0 log and provides better conditions for ultraviolet radiation to be sequentially applied. The UV radiation applied for the septic tank and the anaerobic filter inactivates 2.5 log for total coliforms and 3.5 log for E. coli, respectively. It is suggested that the disinfection methods applied in this work to inactivate gram-negative bacteria (E. coli) can also be applied to secondary treatment effluents, as well as being better tested for viruses, protozoa, and helminths. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-021-03764-7.

A critical overview of household slow sand filters for water treatment.

Household, or point-of-use (POU), water treatments are effective alternatives to provide safe drinking water in locations isolated from a water treatment and distribution network. The household slow sand filter (HSSF) is amongst the most effective and promising POU alternatives available today. Since the development of the patented biosand filter in the early 1990s, the HSSF has undergone a number of modifications and adaptations to improve its performance, making it easier to operate and increase users' acceptability. Consequently, several HSSF models are currently available, including those with alternative designs and constant operation, in addition to the patented ones. In this scenario, the present paper aims to provide a comprehensive overview from the earliest to the most recent publications on the HSSF design, operational parameters, removal mechanisms, efficiency, and field experiences. Based on a critical discussion, this paper will contribute to expanding the knowledge of HSSF in the peer-reviewed literature.

HPV infection as a risk factor for atherosclerosis: A connecting hypothesis.

Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.

Drinking water treatment by multistage filtration on a household scale: Efficiency and challenges.

Universalising actions aimed at water supply in rural communities and indigenous populations must focus on simple and low-cost technologies adapted to the local context. In this setting, this research studied the dynamic gravel filter (DGF) as a pre-treatment to household slow-sand filters (HSSFs), which is the first description of a household multistage filtration scale to treat drinking water. DGFs (with and without a non-woven blanket on top of the gravel layer) followed by HSSFs were tested. DGFs operated with a filtration rate of 3.21 m3 m-2.d-1 and HSSFs with 1.52 m3 m-2.d-1. Influent water contained kaolinite, humic acid and suspension of coliforms and protozoa. Physical-chemical parameters were evaluated, as well as Escherichia coli, Giardia spp. cysts and Cryptosporidium spp. oocyst reductions. Removal was low (up to 6.6%) concerning true colour, total organic carbon and absorbance (λ = 254 nm). Nevertheless, HMSFs showed turbidity decrease above 60%, E. coli reduction up to 1.78 log, Giardia cysts and Cryptosporidium oocysts reductions up to 3.15 log and 2.24 log, respectively. The non-woven blanket was shown as an important physical barrier to remove solids, E. coli and protozoa.

Clinical Manifestations of Kawasaki Disease at Different Age Spectrum: A Ten-Year Study.

Background and objectives: The present study is the first known in Latin America to enroll a substantial number of Kawasaki disease (KD) patients with an extended follow-up. This study aimed to: (1) to expose the difficulties and delays in the diagnosis of KD in a developing country, (2) to describe and correlate the clinical features of this disorder with the children's age at the time of disease onset, (3) to correlate the frequent lack of early diagnosis with a delayed application of appropriate treatment, and (4) to describe the outcome and eventual recurrences of KD in our region. Materials and Methods: Three hundred and one participants (183 males and 118 females) included in the study were diagnosed and, subsequently, clinically followed for ten years (January 2007 to December 2016) at the Pediatric Rheumatology Walk-in Clinic of the Children's Hospital of Brasilia. Results: Episodes ranged from four months to two years. This rate of recurrence was well-above that disclosed by previous reports. Delay in diagnosis, in all age groups, caused an undesirable delay between the disease onset, the final diagnosis, and the administration of intravenous immunoglobulin (IVIG). KD recurred in 25 (8.3%) of the children during the first three years of follow-up. In seven patients, KD recurred twice, with an interval between episodes ranging from four months to two years. Conclusions: This rate of recurrence was well-above that disclosed by previous reports. In Latin America, aside from a handful of physicians and researchers, KD is being ignored. There is a pressing need to educate primary health care physicians and bring awareness to the fact that KD is not an exotic condition that affects only the Asian populations but a disorder that already exists among us and that frequently results in severe consequences.

Carbohydrate supplementation and psychophysiological responses during moderate exercise in hypoxia.

BACKGROUND: Rating of Perceived Exertion (RPE) is a subjective scale to monitor overload and fatigue during exercise. Hypoxia may worsen the perception of fatigue, compromising the self-reported perception of effort and increasing RPE. The objective was to evaluate the effects of carbohydrate (CHO) supplementation on RPE during exercise in hypoxia simulating 4200 m. METHODS: Eight male physically active volunteers performed two exercises at 50% VO2peak and 1% slope: exercise in hypoxia + placebo or exercise in hypoxia + CHO (6% maltodextrin) with supplementation at 20, 40, and 60 min during exercise. Oxygen Saturation (SaO2%) was assessed at baseline and after exercise, while RPE and HR were measured each 10 min during the trial. RESULTS: SaO2% decreased after exercise in both conditions of hypoxia compared to rest. The RPE did not differ between groups. However, the RPE increased in hypoxia after 20 min of exercise in relation to 10 min. The Area Under the Curve (AUC) of RPE was lower in hypoxia + CHO compared to hypoxia. The AUC of the HR/RPE ratio in the hypoxia + CHO group was higher in relation to hypoxia. CONCLUSIONS: Our results indicate that CHO supplementation does not change RPE induced by 60 min of exercise at 50% VO2peak in hypoxia equivalent to 4200 m at the different times analyzed. However, in hypoxia + CHO the (AUC)-60 min of total RPE decreased during exercise, while the heart rate/RPE ratio improved, indicating lower RPE in the hypoxic environment.

Single Nucleotide Polymorphisms Influence Histological Type and Grade of Canine Malignant Mammary Tumours.

Histological examination of canine mammary tumours is mandatory for determining the histological type and grade of the lesions, features that provide relevant information regarding the biological behaviour of the disease. Different histological classification systems and grading methods have been used to characterize canine mammary tumours. In this study, the relationship between the genetic profile of 87 female dogs (i.e. single nucleotide polymorphisms [SNPs] in genes known to be involved in mammary carcinogenesis) and the histological type and grade of malignant mammary tumours was assessed. The results demonstrated a significant relationship between genetic variation in genes RAD51, BRCA2, CHEK2, HER2, CDH1, COMT and PGR and these morphological features of the mammary lesions. Specifically, SNPs in RAD51 (rs23623251 and rs23642734), CHEK2 (rs397511718), HER2 (rs24537329) and PGR (rs8875007) were related to aggressive histotypes, with moderate to high histological grade. In contrast, SNPs in BRCA2 (rs23255542), HER2 (rs24537331), CDH1 (rs852280880 and rs850805755) and COMT (rs851328636, rs853133060 and rs85346495) were associated with tumour histotypes of good prognosis and of low histological grade. These data provide preliminary evidence for a genotypic-phenotypic correlation in canine mammary tumours, highlighting the mechanisms of their genesis, development and progression.

Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate.

Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.

PERFORMANCE OF THE INSTADOSETM DOSEMETER FOR INTERVENTIONAL RADIOLOGY AND CARDIOLOGY APPLICATION.

The aim of this article was to verify the performance of the Mirion InstadoseTM dosemeter under clinical conditions and to compare its response in typical X-ray fields used during interventional and cardiology procedures with the TLD-100, usually used for radiation dosimetry. It was also objective of this study to verify the feasibility of using the InstadoseTM dosemeter response at the chest level for estimation of occupational eye lens dose in cardiology and interventional radiology. Initially the response of the dosemeter was tested using continuous X-ray beams and the results showed that the Instadose dosemeter present a satisfactory behavior of the most important dosimetric properties based on the tests as described in the IEC 62387 standard. The measurements performed in clinical conditions showed that the InstadoseTM dosemeter response was comparable to that of TL dosemeters used in interventional radiology and cardiology procedures and there is a correlation between the eye lens doses and the chest doses measured with the InstadoseTM. Based on the results obtained, we recommend the use of the InstadoseTM dosemeter for purposes of occupational whole-body monitoring of medical staff in interventional radiology and cardiology procedures.

Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice.

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16-/- without treatment, group II: treated HPV16-/-, group III: HPV16+/- without treatment and group IV: treated HPV16+/-). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wild-type animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.

Malocclusion prevention through the usage of an orthodontic pacifier compared to a conventional pacifier: a systematic review.

AIM: This was to investigate the occurrence of malocclusion traits among children who were users of orthodontic or conventional pacifier by means of a systematic review. METHODS: Search for articles involved five electronic databases: Latin American and Caribbean Health Sciences (LILACS), PsycINFO, PubMed (including MedLine), Scopus and Web of Science. Grey literature was partially assessed. Observational studies with children aged 6-60 months who had used orthodontic or conventional pacifier were included. The risk of bias among included studies was assessed through the Joanna Briggs Institute Tool. RESULTS: From the 607 initially-identified papers only three were included after the selection process. All presented moderate risk of bias. Although an anterior open bite and accentuated overjet were identified among conventional users of pacifier in one study no differences were identified in the other two selected studies. Posterior crossbite frequency was not different in any of the included studies. There was also no difference regarding frequency and duration of use, except in the study that showed higher occurrence of open bite malocclusion in conventional pacifier users. CONCLUSIONS: The currently available evidence is insufficient to support the concept that the usage of orthodontic pacifiers is able to prevent malocclusion traits when compared to the usage of conventional pacifiers.

Metabolic syndrome in human immunodeficiency virus-infected patients.

The objective of this study was to investigate the factors underlying the development of metabolic syndrome (MetS) in HIV-infected patients. Two hundred and sixty-six clinical cases were selected for a retrospective study. The sample was classified using the Adult Treatment Panel III guidelines and the identification of risk or protective factors associated with MetS evaluated via multivariate logistic or multinomial regressions. HIV-infected individuals diagnosed with MetS tend to be older, overweight, or obese (85% have a BMI ≥ 25), with a waist circumference > 90 cm (96.5 [88.8-105.5] cm, median [interquartile range]). Blood testing these individuals revealed high fasting levels of insulin (8.1 [5.8-21.6] pg/ml), glucose (98.0 [84.0-116.0] mg/dl), triglycerides (201.0 [142.0-267.3] mg/dl), and high-density lipoprotein cholesterol (36.5 [29.8-43.3] mg/dl) in addition with higher levels of inflammatory mediators such as high-sensitivity C-reactive protein (2.5 [1.0-4.9] mg/dl) and interleukin-6 (3.4 [2.8-3.8] pg/ml). The likelihood of HIV-infected individuals who are virally suppressed developing MetS is about 60% higher than those with acute infection. Treatment with nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) increases the chance of developing MetS by around 2.4 times. Individuals with a lower antioxidant capacity (total antioxidant status [TAS] <1.33) have a 2.6 times higher risk of developing MetS. HIV-related chronic inflammation, a low TAS, and treatment with NRTIs in association with PIs are additional MetS risk factors.

Ozone therapy prevents the onset of dysplasia in HPV16-transgenic mice-A pre-clinical efficacy and safety analysis.

Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers. HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O3/O2 (80░mL/kg, at O3 50░µg/mL), once a day, for 5 consecutive days. The animals were sacrificed at 25 weeks-old, and skin samples were analyzed histologically to study tumour progression. Blood and internal organ samples were used to study toxicological parameters. 85.7% of untreated transgenic mice showed dysplastic skin lesions, compared with 28.6% of O3-treated mice. This was associated with a marked reduction of dermal inflammation associated with those lesions. No significant changes were observed in any toxicological parameters. These preliminary results support the hypothesis that O3 therapy is effective against papillomavirus-induced lesions, particularly against those induced by the most common high-risk virus, HPV16. Further studies are needed to confirm the mechanisms underlying these effects.

Long-term assessment of a modified tibial tuberosity advancement technique in dogs / Avaliação em longo prazo da técnica de avanço da tuberosidade tibial modificada em cães

The purpose of study was to assess long-term clinical and radiographic aspects of dogs' stifle joints which had undergone a modified tibial tuberosity advancement technique (mTTA). A total of 15 stifles that had undergone mTTA for CCL disease of 11 patients were included in this study. Assessments involved patient's gait analysis, cranial drawer and tibial compression tests, stifle goniometry range of articular motion, thigh and leg girth and radiographic evidence of progression of osteoarthrosis. Variables were compared between operated and healthy limbs and among moments (M0) on the early postop; (M1) 120 days postop; and (M2) approximately 5 years following surgery. A questionnaire regarding owner's perceptions after approximately 5 years of surgery was assessed. Most dogs presented positive response to cranial drawer and tibial compression tests on operated knees. There was also decrease on goniometry and thigh girth and increase in leg girth. Radiographic evidence of progression of osteoarthritis was seen especially on the long-term follow-up (M2). On gait analysis, most animals presented some degree of lameness in different conditions, in contrast to owners' perceptions. Osteoarthritis still develops in dogs following mTTA surgery for CCL disease. However, owners were overall satisfied with their recovery and would be willing to accept indication of mTTA for dogs with ruptured CCL.(AU)

O objetivo deste estudo foi avaliar, em longo prazo, aspectos clínicos e radiográficos do joelho de cães submetidos à técnica modificada de avanço da tuberosidade da tíbia (mTTA). Um total de 15 joelhos de 11 pacientes foram submetidos à mTTA para correção de doença do ligamento cruzado cranial. A avaliação envolvia análise de marcha do paciente, teste de compressão tibial e de gaveta, goniometria do joelho para amplitude articular, circunferência das pernas e coxas e evidência radiográfica de progressão da osteoartrose. As variáveis foram comparadas entre membros operados e saudáveis e entre os momentos (M0) no pós-operatório imediato; (M1) 120 dias de pós-operatório; e (M2) aproximadamente cinco anos após a cirurgia. Foi avaliado um questionário sobre as percepções do proprietário após aproximadamente cinco anos de cirurgia. A maioria dos cães apresentou resposta positiva aos testes de gavetas e de compressão tibial em joelhos operados. Houve também diminuição na goniometria e na circunferência da coxa e aumento do perímetro das pernas. Evidências radiográficas de progressão da osteoartrite foram observadas especialmente no seguimento de longo prazo (M2). Na análise de marcha, a maioria dos animais apresentou algum grau de claudicação em diferentes condições, em contraste com as percepções dos proprietários. A osteoartrite ainda se desenvolve em cães após a cirurgia de mTTA para doença CCL. No entanto, os proprietários estavam, em geral, satisfeitos com a recuperação dos animais e estavam dispostos a aceitar a indicação de mTTA para cães com doença do ligamento cruzado cranial.(AU)

Laryngeal Neuropathy in Adult Goats With Copper Deficiency.

The aim of this study was to elucidate the cause of a neurological syndrome characterized by stridor in adult goats with clinical signs of copper deficiency. The main clinical signs consisted of apathy, emaciation, pale mucous membranes, mucous nasal discharge, dyspnea, severe achromotrichia, diffuse alopecia, torpor, ataxia, and stridor. When the goats were forced to move, the stridor increased. In a herd of 194 Toggenburg goats, 10 adult goats with clinical signs of copper deficiency were removed from the herd and divided into 2 groups: group 1, which consisted of 4 nannies and 1 buck with stridor, and group 2, which consisted of 4 nannies and 1 buck without stridor. Group 3, used as a control, consisted of 5 adult goats from another flock without any clinical signs of disease. The mean serum copper concentrations were 1.3 ± 0.3 µmol/L in group 1, 8.1 ± 1.1 µmol/L in group 2, and 11.3 ± 2.2 µmol/L in group 3. The mean serum iron concentrations were 42.3 ± 14.2 µmol/L in group 1, 39.1 ± 8.2 µmol/L in group 2, and 20.6 ± 6.1 µmol/L in group 3. The main histological lesions in goats from group 1 were axonal degeneration of the recurrent laryngeal nerves and atrophy of the muscles of vocal folds and of the dorsal cricoarytenoid and right and left cricothyroid muscles. Goats with ataxia had neuronal degeneration and necrosis of cerebellar Purkinje cells and of the cranial cervical ganglion. We concluded that the stridor was caused by axonal degeneration of the recurrent laryngeal nerves due to the severe copper deficiency.