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A retrospective cross-sectional study was conducted to assess the frequency of low-dose dexamethasone suppression test (LDDST) patterns in canine patients that had clinicopathologic signs consistent with Cushing's syndrome (CS). Medical records for patients of interest (N = 128) were reviewed between January 2014 and December 2020 to analyse and classify LDDST results based upon the following patterns: lack of suppression, partial suppression, complete suppression, escape, or inverse. Complete suppression, lack of suppression, partial suppression, escape, and inverse patterns were identified in 39.1%, 31.2%, 14.1%, 10.1% and 5.5% of cases respectively. LDDST results were also evaluated with respect to clinical signs, serum alkaline phosphatase (ALP) activity, urine specific gravity (USG) and adrenal ultrasonographic findings. There was no association between LDDST patterns and clinical signs (p = 0.11), increased ALP (p = 0.32), USG (p = 0.33) or adrenal ultrasonographic findings (p = 0.19). In all dogs that demonstrated complete suppression or an inverse pattern, CS was excluded by the attending clinician. The diagnosis of CS was also excluded without further exploration in 23.1%, 7.5% and 5.6% of dogs that demonstrated an escape pattern, lack of suppression and partial suppression pattern, respectively. These results suggest that the clinical significance of LDDST patterns, particularly escape and inverse patterns, are misunderstood by some clinicians, leading them to prematurely exclude the diagnosis of CS., Competing Interests: Declaration of competing interest The authors declare not conflict of interests. This work was supported by FCT—Fundação para a Ciência e Tecnologia IP, grant UIDB/00276/2020 and by LA/P/0059/2020—AL4AnimalS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This systematic review and meta-analysis aimed to evaluate if rapid maxillary expansion improves the activity of the masticatory muscles (masseter and temporal) in patients with unilateral posterior crossbite., Material and Methods: Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane Library, and grey literature. A manual search of orthodontic journals was also performed. Randomized clinical trials or longitudinal prospective studies were eligibles. Meta-analyses were conducted using R software with the "Meta" package, applying mean differences with a 95% confidence interval. Risk of bias was assessed using the Newcastle-Ottawa scale, and evidence certainty was evaluated using GRADE., Results: Nine articles were included. Qualitative analysis showed that RME treatment in patients with unilateral posterior crossbite showed a positive correlation with improvement in masseter and temporalis muscle activity. Meta-analyses indicated a significant difference for all models of muscle activity after treatment with rapid maxillary expansion, except for the temporal muscle in the force exerted on the maximum voluntary clenching on cotton rolls. The studies showed low bias risk, and the evidence certainty for each analysis was generally low to very low., Conclusions: This investigation demonstrated the benefits of R rapid maxillary expansion in treating unilateral posterior crossbite and its potential therapeutic effects on the masticatory muscles. Key words: Rapid maxillary expansion, masticatory muscles, unilateral posterior crossbite, systematic review, meta-analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Medicina Oral S.L.)

Background: The diagnosis of multiple myeloma (MM) in dogs may be challenging and complex. The cell blocks are a diagnostic technique that allows the characterization of neoplastic cells and, therefore, might help in the diagnosis of atypical MM., Objective: The objective of the present work is to describe three clinical cases in which the cell blocks and immunohistochemistry contributed to the definitive diagnosis of canine MM., Methods: Three dogs, one female and two males, with different clinical signs, were presented for consultation with anemia, hyperproteinemia with monoclonal gammopathy, and the presence of plasmacytosis in the bone marrow. Cytologic analysis of the spleen was performed in two dogs and was suggestive of the presence of lymphocytes or plasma cells of a neoplastic nature in one of the cases and plasma cell hyperplasia associated with extramedullary hematopoiesis in the other. Given the hypotheses of lymphoid neoplasms with a plasma cell phenotype, cell blocks from aspiration punctures were performed for immunohistochemical analysis with anti-CD3, CD20, CD79αcy, PAX5, and MUM1 antibodies., Results: The results revealed positive staining for MUM1 in 80% of the cells in the spleen cell block and for CD20 and MUM1 in 70% of the cells in the bone marrow cell blocks, with negative staining for the other antibodies. The immunophenotyping results allowed the diagnosis of MM in the three cases and excluded other lymphoid neoplasms., Conclusions: This work reinforces the importance of using cell blocks in the diagnosis of neoplasms by demonstrating their potential to aid the diagnosis of MM., (© 2024 American Society for Veterinary Clinical Pathology.)

This retrospective study evaluated factors responsible for mortality of dogs hospitalized for Canine Leishmaniosis. Medical records of 31 dogs with leishmaniosis from a Portuguese Veterinary Teaching Hospital were examined between August 2018 and January 2022. Females (n = 18) and pure breed dogs (n = 27) were overrepresented, with higher frequency of Labrador Retriever (n = 4). Median age was 7 years (interquartile range=7). Most had historical findings of lethargy (n = 26) and the commonest clinicopathological abnormality was hypoalbuminemia (n = 26). Eleven dogs were classified as LeishVet stage II, 10 stage III and 10 stage IV. Fourteen dogs (45.2%) died or were euthanized, with azotemia, leukocytosis, stage IV, absence of diagnosis before hospitalization and lack of leishmaniosis specific treatment during hospitalization contributing to mortality. Absence of hypoalbuminemia and stages II/III increased survival. Mean hospitalization length prior to discharge was 5.41days ( ± 1.84) and diarrhea prolonged hospital stay., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no competing interests. Over the last two years, ROL and MJD were involved in two research trials on Canine Leishmaniosis (Nestle Purina and Bioiberica), both unrelated with this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

SARS-CoV-2 infection and its resulting sequelae have increased the prevalence of people with respiratory symptoms, with impacts on functional capacity, quality of life, anxiety, depression, and mental health. To mitigate this problem, one challenge has been the design and implementation of interventions that simultaneously allow for education, rehabilitation, and monitoring of people with long COVID, at a time when health services were on the verge of rupture due to the volume of people with active COVID and in need of intensive care. Telerehabilitation emerged as a mode for providing rehabilitative care that brought professionals closer to patients and enabled continuity of care. The present study aimed to evaluate the results of a telerehabilitation intervention for people with injuries associated with SARS-CoV-2 infection in hospital-community transitions, considering their degree of dependence in performing activities of daily living, respiratory symptoms, fatigue, gait capacity, muscle strength, and experience with anxiety and depression. A pre-post study with a non-equivalent control group was carried out with a total of 49 participants (intervention group n = 24; control group n = 25). The post-intervention results showed an increase in saturation, a decrease in heart rate, an improvement in the impact of post-COVID functionality, a decrease in fatigue, a decrease in perceived effort, and a decrease in depressive and anxiety symptoms. The telerehabilitation intervention, which combined educational strategies with respiratory and motor rehabilitation, helped improve global functionality and self-care, with clinical and functional impacts.

Background: Pheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats., Objectives: We evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC-MS-MS)., Methods: Urine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at -80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs-to-creatinine ratios., Results: The PL-MN and PL-NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U-MN/Creat and U-NMN/Creat ratios were 70 and 139 μg/g, respectively. The PheoCat had a PL-MN of 3.68 nmol/L, PL-NMN of 66.27 nmol/L, U-MN/Creat of 179 μg/g, and U-NMN/Creat of 1262 μg/g. The PheoCat had markedly increased concentrations of both PL and U MNs when compared to the healthy cats. No significant difference was found between U MNs measured in urine samples that underwent 24 hours of refrigeration in comparison to those that were frozen immediately., Conclusions: We report preliminary reference intervals for PL and U MNs in cats using LC-MS-MS and the potential clinical applicability of these biomarkers for the diagnosis of PCC in cats., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Already in early 2000s, concerns have been growing in the EU about increasing use of cocaine and it is estimated that below 1 % of the population administer the drug by smoking crack cocaine. New available data suggests an increase in the use of crack cocaine and an increase in the number of crack cocaine users entering treatment has been reported in several European countries. Robust estimations of crack cocaine use are however not available yet. The use of crack cocaine has long been associated with severe adverse socio-economic conditions as well as mental health problems, such as suicide ideation and depression. The aim of this study was to assess spatial trends in population-normalized mass loads of crack cocaine biomarkers (i.e., anhydroecgonine and anhydroecgonine methyl ester) in 13 European cities in six countries (the Netherlands, Belgium, Ireland, Portugal, Spain and Italy). Furthermore, temporal trends over a five-year period were evaluated through the analysis of historic samples collected in the Netherlands. Finally, the stability of the crack cocaine biomarkers in wastewater was investigated through batch experiments. The samples were analyzed with a new developed and validated hydrophilic interaction liquid chromatography coupled to mass spectrometry method. Targeted crack cocaine biomarkers were found in all cities. Also, crack cocaine biomarker was detected in wastewater from 2017 to 2021 in the Netherlands, but no significance between the years were found. With respect to biomarker in-sample stability, AEME was found to be stable in wastewater. This study assessed crack cocaine use for the first time on a broad scale, both temporal and in cities across Europe, with wastewater-based epidemiology and it shows the importance of wastewater analysis to monitor community loads of crack cocaine use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was overrepresented (25/68; 37%), followed by endocrinopathies (20/68; 29%). Adrenomegaly was bilateral in 53% (36/68) of cases. In unilateral cases (32/68; 47%), it was more prevalent on the left side (23/32; 72%), with a normal-sized contralateral adrenal gland. Left adrenal demonstrated a larger size and a tendency to oval shape. This study assesses the prevalence of adrenomegaly in clinically ill cats, reinforcing it can be an incidental ultrasound finding.

Objective: To evaluate signalment, clinical presentation, location and type of nasal foreign bodies identified by rhinoscopy in dogs., Materials and Methods: We retrospectively reviewed medical records from dogs that presented for consultation between April 2012 and June 2019 and were diagnosed with nasal foreign body via rhinoscopy., Results: Forty-two dogs met the study's inclusion criteria. Thirty (71.4%; 30/42) were purebreds. Males accounted for 59.5% (25/42) of cases. The median age was 4.0 years old and 76.2% (32/42) were dogs up to 7 years of age. Mean bodyweight was 21.8 kg and dogs weighing more than 10 kg were overrepresented (78.6%; 33/42). Sneezing occurred in 78.6% (33/42) of cases. Foreign body retrieval was achieved by rhinoscopy in all cases. The foreign body was extracted from the right nasal cavity in 52.4% (22/42) of cases and from the left one in 42.9% (18/42). Two dogs (4.8%; 2/42) presented with one foreign body in each nasal cavity. Most nasal cavity foreign bodies (90.5%; 38/42) were grass awns. Three (7.2%; 3/42) were mineral and one (1/42) was fabric. Follow-up was documented for 35 patients, of which 97.1% (34/35) experienced resolution of clinical signs. Seven cases (16.7%; 7/42) were lost to follow-up., Clinical Significance: Nasal foreign bodies were more common in dogs up to 7 years of age and heavier than 10 kg. Sneezing was the primary clinical sign. The vast majority of foreign bodies were grass awns and rhinoscopy was an effective means of nasal cavity foreign body retrieval., (© 2020 British Small Animal Veterinary Association.)

Background: Activity of 1,2-O-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase in serum shows good agreement with pancreatic lipase (cPL) in dogs. Although prednisolone therapy does not seem to affect serum cPL concentration, its influence on DGGR lipase is unclear., Objectives: The aim of the study was to evaluate the effect of prednisolone therapy on DGGR lipase serum activity in dogs., Animals: Thirty-four dogs were used, of which 17 dogs received prednisolone (study group) and 17 healthy dogs did not receive treatment., Methods: A prospective cohort study measured DGGR lipase activity in both groups at 3 time points: T0, T1, and T2, corresponding to days 0, 7-10, and 21-30, respectively. Dogs from study group presented a medical reason that justified the use of prednisolone for at least 3 weeks. Initial prednisolone dose was .5-2.0 mg/kg/day PO with a reduction at T1 to a final dose that was maintained until T2. DGGR lipase activity >160 U/L was defined as clinically relevant., Results: In the study group, DGGR lipase activity increased significantly from T0 to T1 (P = .02) and decreased significantly from T1 to T2 (P = .02). Median DGGR activity at each time point (T0, T1, and T2) was 24.74 (14.45-31.48), 36.82 (23.8-80.16), and 29.52 (15.91-48.48) U/L, respectively. In the control group, no significant changes were observed over time (P = .93). The DGGR lipase activity and prednisolone doses were not correlated for both T0-T1 (r s = .371, P = .14) and T1-T2 (r s = 0.390, P = .12)., Conclusion and Clinical Importance: DGGR lipase activity was affected by prednisolone administered orally in dogs. However, this variation was not clinically important as values remained below the relevant upper limit., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The consumption of psychoactive substances is considered a growing problem in many communities. Moreover, new psychoactive substances (NPS) designed as (legal) substitutes to traditional illicit drugs are relatively easily available to the public through e-commerce and retail shops, but there is little knowledge regarding the extent and actual use of these substances. This study aims to gain new and complementary information on NPS and traditional illicit drug use at six music festivals across Europe by investigating wastewater and pooled urine. Samples were collected, between 2015 and 2018, at six music festivals across Europe with approximately 465.000 attendees. Wastewater samples were also collected during a period not coinciding with festivals. A wide-scope screening for 197 NPS, six illicit drugs and known metabolites was applied using different chromatography-mass spectrometric strategies. Several illicit drugs and in total 21 different NPS, mainly synthetic cathinones, phenethylamines and tryptamines, were identified in the samples. Ketamine and the traditional illicit drugs, such as amphetamine-type stimulants, cannabis and cocaine were most abundant and/or frequently detected in the samples collected, suggesting a higher use compared to NPS. The analyses of urine and wastewater is quick and a high number of attendees may be monitored anonymously by analysing only a few samples which allows identifying the local profiles of use of different drugs within a wide panel of psychoactive substances. This approach contributes to the development of an efficient surveillance system which can provide timely insight in the trends of NPS and illicit drugs use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data., Design: Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017., Setting and Participants: Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries., Measurements: Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ 9 -tetrahydrocannabinol (11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol) were measured in wastewater using liquid chromatography-tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world-wide, and temporal trends were discerned at European level by comparing 2011-13 drug loads versus 2014-17 loads., Findings: Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge., Conclusions: The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data., (© 2019 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Menopause induces osteoporosis, sarcopenia, insulin resistance, and dyslipidemia. Ovariectomized (OVX) rat is an animal model, which mimetics postmenopausal conditions. The present study aimed to test the effects of strength training protocol on bone mineral density and metabolic parameters in OVX rats. Female Wistar rats were randomly separated in four groups: non-ovariectomized rats (Sham); ovariectomized rats (OVX); OVX treated with 17β-estradiol (HR); and OVX trained group (TR). At 70-days-old OVX groups were submitted to a bilateral ovariectomy. Hormonal replacement and strength training were performed three times per week, for 60 days. 17β-estradiol was administered by intramuscular injection (50 μg/kg of BW) and strength training protocol was composed by four series of 12 repetitions with 65-75% of 1RM. As expected, OVX impaired glucose homeostasis, promoted weight and adiposity gain, dyslipidemia, sarcopenia and osteoporosis, but hormonal replacement and strength training improved most of these parameters. Both HR and TR normalize glucose homeostasis; however, only TR restores blood insulin. OXV also reduced the maximum force in 42%, but TR improved this parameter in 110%, in addition TR prevents sarcopenia and fat mass gain. Interestingly, strength training was able to improve significantly BMD. Taken together, these data suggest that strength training can be effective in the treatment of damage caused by OVX, which in a translational context, becomes an effective non-pharmacological strategy to improve the health of postmenopausal women, reducing costs with secondary symptoms, mainly caused by weight gain, sarcopenia and osteoporosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relation between optical properties, population receptive fields (pRFs), visual function, and subjectively perceived quality of vision after cataract surgery., Methods: The study includes 30 patients who had recently undergone bilateral sequential cataract surgery. We used functional magnetic resonance imaging and pRF modelling methods to assess pRF sizes across visual cortical regions (V1-V3). Subjects also performed a complete ophthalmologic and psychophysical examination and answered a quality of vision questionnaire., Results: Subjects with worse optical properties had, as predicted, larger pRF sizes. In addition, analysis in the primary visual cortex revealed significantly larger mean pRF sizes for operated subjects with worse contrast sensitivity (P = 0.038). In contrast, patients who scored high in the subjective "bothersome" dimension induced by dysphotic symptoms had surprisingly lower pRF size fitting interception (P = 0.012) and pRF size fitting slopes (P = 0.020), suggesting a dissociation between objective quality of vision and subjective appraisal., Conclusions: Optical properties of the eye influence pRF size. In particular, visual aberrations have a negative impact on visual cortical processing. A novel dissociation between subjective reports of quality of vision and pRF sizes was further identified. This suggests that patients with better cortical resolution may have a negative subjective response possibly because of improved perception of dysphotic phenomena. pRF properties represent a valuable quantitative measure to objectively evaluate quality of vision but do not necessarily predict subjective complaints.

A method for the simultaneous determination of 11 illicit drugs, using the dried blood spot (DBS) sampling technique combined with the UPLC-MS/MS technology was developed to study its applicability within the forensic toxicology. The DBS samples, prepared from a blood volume of 50μL and using the Whatman® BFC 180 bloodstain cards, were extracted with a methanol/acetonitrile mixture. The chromatographic separation was performed using an Acquity UPLC ® HSS T3 column (100mm×2.1mm, 1.8μm) and an acetonitrile/2mM ammonium formate (0.1% formic acid) gradient. The detection was accomplished with a TQ Detector, operating in the ESI+ and MRM modes. The method was validated in terms of selectivity, matrix effect, extraction recovery (42%-91%), carryover, LOD and LOQ (0.5-1ng/mL and 1-5ng/mL, respectively), linearity (LOQ to 500ng/mL), intraday and interday precision (3.8-14% and 5.3-13%, respectively), accuracy (-9.3% to 7.9%) and dilution integrity. An eight months stability study at room temperature, 2-8°C and -10°C, was also performed, with the best results obtained at -10°C. The procedure was applied to 64 real samples (92 positive results for substances included in this study). The results were compared with the methodologies routinely applied in the laboratory and the statistical analysis allowed to establish an acceptable correlation. This study permitted to determine that the DBS can represent an alternative or a complement to conventional analytical and sampling techniques, responding to some of the present issues concerning the different forensic toxicology applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Context: Crack cocaine is an illicit drug derived from cocaine, in which use and abuse have increased around the world, especially in developing countries., Objectives: The aim of this study was to evaluate genomic damage in multiple organs of mice following acute exposure to crack cocaine. For this purpose, single cell gel (comet) assay in peripheral blood, liver, kidney, and brain cells was performed and micronucleus test for bone narrow and liver cells was also made in this setting., Material and Methods: A total of 20 C57BL/10 male mice were distributed into four groups, as follows: 0, 4.5, 9, and 18 mg/kg b.w. of crack cocaine dissolved to 1% dimethyl sulfoxide by intraperitoneal (i.p.) route. All animals were sacrificed 24 h after i.p. injection., Results: The results showed that crack cocaine induced DNA damage in peripheral blood, and brain cells for higher doses used as depicted by single cell gel (comet) assay data. Analysis of kidney cells showed no genetic damage for all groups tested. The number of micronucleated cells did not increase after crack cocaine exposure in bone narrow or liver cells., Conclusion: In summary, crack cocaine is a genotoxic agent in peripheral blood, liver, and brain cells but not mutagenic in multiple organs of mice.

Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats.

Objective: Analyze the progress of hearing and language in a group of children with cerebral palsy (CP) who have received cochlear implants (CI) and compare their progress in the clinical and functional domains., Methods: This is a prospective transdisciplinary study developed within a tertiary referral center, with a group of nine cochlear-implanted children with CP, two- to seven-year-old. The assessments undertaken included audiological, language, and communication assessments complemented by the assessment of functional abilities and the level of independence as evaluated by the Pediatric Evaluation of Disability Inventory (PEDI) and Gross Motor Function Classification System (GMFCS)., Results: The outcomes varied, as two children achieved hearing comprehension in open-set evaluations. These children presented the same type of CP, athetosis, but with different functional skills and GMFCS levels. Only one of the subjects had any spoken language at the single-word level., Conclusions: A holistic view of change and development is central to understanding progress made in children with CP who received cochlear implants (CI). The functional evaluation of these children with CP is a useful tool for monitoring their progress and measuring their outcomes with CI., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To present a seven-cases serie of Mowat-Wilson syndrome (MWS)., Method: All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization., Results: A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7)., Conclusion: Physicians who care for patients with mental retardation and epilepsy should be aware of SMW.

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

The aim of this study was to evaluate cytotoxicity and genotoxicity in multiple organs of rats induced by municipal effluent released by submarine outfall in city of Santos. A total of 20 male Wistar rats were exposed to effluents by drinking water ad libitum at concentrations of 0, 10, 50, and 100 % for 30 days. Microscopic analysis revealed severe lesions such as necrosis and hemorrhagic areas in liver and kidney from animals exposed to effluent at 50 and 100 % concentration. DNA damage in peripheral blood, liver, and kidney cells were detected by comet assay at higher concentrations of effluent. Moreover, a decrease DNA repair capacity was detected in liver cells. Significant statistical differences (p<0.05) for micronucleated cells from liver were noticed at 50 % concentration of effluent. Taken together, our results demonstrate that municipal effluent is able to induce cytotoxicity and genotoxicity in multiple organs of Wistar rats.

An UPLC-MS/MS method using ESI+ionization and MRM was developed and fully validated according to international guidelines for the qualitative and quantitative analysis of nine synthetic cannabinoids and/or their metabolites in urine samples (1mL). Prior to extraction the samples were subjected to an enzymatic hydrolysis using β-glucuronidase followed by a SPE procedure using Oasis(®) HLB 3cc (60mg) columns. The chromatographic separation was performed with an Acquity UPLC(®) HSS T3 (50mm×2.1mm i.d., 1.8μm) reversed-phase column using a gradient with methanol-ammonium formate 2mM (0.1% formic acid) and with a run time of 9.5min. The method was validated in terms of selectivity, capacity of identification, limits of detection (0.01-0.5ng/mL) and quantification (0.05-0.5ng/mL), recovery (58-105%), carryover, matrix effect, linearity (0.05-50ng/mL), intra-assay precision, inter-assay accuracy and precision (CV<20%). The method was applied to 80 authentic samples, five of them (6.2%) were confirmed or suspected to be positive for the metabolites JWH-018 N-hydroxypentyl and JWH-018 N-pentanoic acid of JWH-018 and for the metabolite JWH-122 N-(5-hydroxypentyl) of JWH-122, and three of them in association with THC and/or THCCOOH (substances included in the method, together with the 11-OH-THC). Additionally, 17 spice products were analyzed, for which were confirmed the presence of the following substances: AM-2201, JWH-018, JWH-022 JWH-073, JWH-122, JWH-203, JWH-210, JWH-250, HU-210 and RCS-4, according to the comparison with authentic reference material and published data. The analytical method developed allowed the analysis of synthetic cannabinoids and the notification of the first cases in Portugal., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years) who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88%) cases. Of these, 19 (53%) used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051). Incomplete elementary school education was reported by two (11%) mothers in the exposed group and by three (14%) mothers in the unexposed group (P=0.538). The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively). One (5%) case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively), lack of emotional tearing (47% and 36%, respectively), and lagophthalmos (32% and 41%, respectively). Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups.

Background: While the causes of falls in old hospitalized patients are multifactorial, medication has been considered as one of the most significant factors. Given the large impact that this phenomenon has on the lives of the elderly and organizations, it is important to explore such phenomenon in greater depth., Objective: The objective of this study was to explore the association between medication and falls and the recurrent falls (n≥2), and identify medication related risk for fall in hospitalized patients, in a large acute hospital., Design: Retrospective and quantitative study from June 2008 to December 2010., Setting: The study was conducted in a private hospital for acute patients in Lisbon, Portugal., Participants: The study included a sample of 214 episodes of fall event notifications which occurred in 193 patients., Methods: The current study was conducted through the "face to face consensus" technique which emerged the treatment groups to investigate. Regarding the data analysis we used Student's t test, ANOVA and Odds Ratio. In the violation of the premises for the use of parametric statistics we used the Kruskal-Wallis test. To assess the fall risk, and the medication-related fall risk, we used the Morse Fall Risk Scale, and the Medication Fall Risk Score., Results: Patients who received drugs from the therapy group of "Central Nervous System", are 10 times more likely to have fall risk (OR 9. 90, 95% CI 1.6-60.63). Association was found between falls (OR 6.09, 95% CI 1.30-28.54) and its recurrence (OR 3.32, 95% CI 1.61-6.85), among patients receiving haloperidol and receiving tramadol for recurrent falls (OR 3.10, 95% CI 1.59-6.07). In 34% of the patients the medication fall risk score was 6 or higher., Conclusions: This current study allowed identifying medication-related risk factors for falls, that nurses should consider when prescribing interventions to prevent falls and its recurrence, when patients are admitted to acute care hospitals., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Moebius syndrome (MS) is a rare congenital condition that is characterised by facial hypomimia and congenital strabismus caused by complete or partial impairment of the 6th and 7th cranial nerves. MS may be further associated with other nerves or malformations, mainly involving the extremities. The objective of this study was to quantify the decrease in oral motor performance in people with MS compared with normoreactive individuals using the Oral Motor Assessment Scale (OMAS)., Methods: The study group comprised 33 subjects between the ages of 2 and 20 years (average age: 10 ± 5 years) with MS along with 46 age- and gender-matched control subjects., Results: The study group displayed a lower average functional score than the control group (P < 0.0001). A significant lack of lip closure (P = 0.03) and anterior lingual seal during swallowing (P = 0.03) occurred in the study group; in most cases, the individuals with MS were classified as 'subfunctional'. In addition, individuals with MS in the older age group displayed better functional scores than those in the younger group (P = 0.05)., Conclusions: Functional damage to oral motor function in individuals with MS is evident, but differs among patients with respect to severity and the movements that are compromised. However, overall, improvements in the functional patterns of these individuals can be observed as they mature in age., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Our objective was to determine the presence of psychoactive substances in blood of drivers killed in road crashes in four European countries. Data from 1118 drivers of car and vans, killed between 2006 and 2009, were collected in Finland, Norway, Portugal and Sweden. The prevalence of any psychoactive substance ranged between 31 and 48%. Alcohol (≥ 0.1 g/L) was the most common finding, 87% had a blood alcohol concentration (BAC) ≥ .5 g/L. Benzodiazepines (1.8-13.3%) and amphetamines (0-7.4%) were the most prevalent psychoactive medicines and illicit drugs, respectively. Alcohol-drug and drug-drug combinations were rather prevalent. Differences in alcohol/drug findings seemed to reflect differences in use in the countries. More research should be done to develop preventive strategies to reduce the number of alcohol- and drug-related traffic accidents targeting at-risk groups, such as drivers with very high BACs and novice drivers.

The interdisciplinary nature of bioinformatics makes it an ideal framework to develop activities enabling enquiry-based learning. We describe here the development and implementation of a pilot project to use bioinformatics-based research activities in high schools, called "Bioinformatics@school." It includes web-based research projects that students can pursue alone or under teacher supervision and a teacher training program. The project is organized so as to enable discussion of key results between students and teachers. After successful trials in two high schools, as measured by questionnaires, interviews, and assessment of knowledge acquisition, the project is expanding by the action of the teachers involved, who are helping us develop more content and are recruiting more teachers and schools.

Objectives: Deletion of the chromosome 15q11-q13, the most common genetic mechanism associated with Angelman syndrome (AS), is highly associated with a severe phenotype. However, deletion is not a genetically homogeneous group as it is composed by two main groups: Class I with breakpoints at BP1 (proximal) and BP3 (distal) and Class II present breakpoints at BP2 (proximal) and BP3 (distal). In this study, we aimed to evaluate the impact of the breakpoint on the electroclinical profile., Methods: We evaluated 16 patients with AS caused by 15q11-13 deletion (6 were Class I; 10 were Class II). We characterized epilepsy features by clinical history obtained from parents and caretakers with a pre-standard questionnaire. These data were corroborated by medical records, contact with previous physicians, and video-EEG monitoring. Suggestive EEG patterns for AS were classified according to the classical description of Boyd et al. (1988)., Results: AS patients with BP1-BP3 deletion had significantly more daily and disabling seizures than AS patients with BP1-BP2 deletion. They also presented a significant higher frequency of status epilepticus and epilepsy aggravated by fever. Need for polytherapy was significantly more frequent in BP1-BP3 patients. EEG features were similar in both groups., Conclusion: This study shows a significant correlation between the two deletion classes and AS clinical, but not the electrographic phenotype. Epilepsy is more severe and refractory to treatment in patients with larger deletions. Deletion is not a homogeneous group and knowledge on the breakpoint may have a clinical implication and represent an important factor in parental counseling., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Misoprostol is a pharmaceutical synthetic compound, analog of prostaglandin E1, frequently used as an abortifacient in not medically supervised or self-induced abortions, particularly in countries with restrictive abortion laws representing a serious public health problem. The aim of this study was to develop and validate a sensitive analytical method for the determination of misoprostol acid in whole blood samples. The samples were prepared by SPE and the chromatographic separation was performed by UPLC-MS/MS using ESI- and MRM mode with an Acquity UPLC(®) BEH C18 (50mm×2.1mm i.d., 1.7μm) column using a methanol-ammonium 0.1% solution gradient in a total run time of 7.0min. The method showed to be selective and linear in range 25-2000ng/L. The LOD and LOQ were 10ng/L and 25ng/L, respectively. The recovery ranged from 89 to 97%. No carryover and significant matrix effect were observed. The intra- and inter-assay precisions and the inter-assay accuracy results were 4.0% and 5.4%, 5.5% and 4.1%, and -1.4% and -2.8%, for the concentrations 50 and 500ng/L, respectively. The method developed allows the analysis of misoprostol acid in whole blood samples with adequate sensitivity to the concentration range obtained from therapeutic doses. The method was successfully used in a controlled misoprostol administration study and has been applied in our laboratory in the forensic toxicology field., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A qualitative and quantitative analytical method was developed for the simultaneous determination of Δ(9) -tetrahydrocannabinol (THC), 11-hydroxy-Δ(9) -tetrahydrocannabinol (11-OH-THC) and l1-nor-9-carboxy-Δ(9) -tetrahydrocannabinol (THC-COOH) in whole blood. The samples were prepared by solid-phase extraction followed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) analysis using positive ion electrospray ionization and multiple reaction monitoring. The chromatographic separation was performed with an Acquity UPLC® HSS T3 (50 × 2.1 mm i.d., 1.8 µm) reversed-phase column using a methanol/2 mM ammonium formate (formic acid 0.1%) gradient in a total run time of 9.5 min. MS/MS detection was achieved with two precursor-product ion transitions per substance. The method was fully validated, including selectivity and capacity of identification, according to the identification criteria (two transitions per substance, signal-to-noise ratio, relative retention time and ion ratio) without the presence of interferences, limit of detection (0.2 µg/L for THC and 0.5 µg/L for 11-OH-THC and THC-COOH), limit of quantitation (0.5 µg/L for all cannabinoids), recovery (53-115%), carryover, matrix effect (34-43%), linearity (0.5-100 µg/L), intra-assay precision (CV < 10% for the relative peak area ratios and <0.1% for the relative retention time), inter-assay accuracy (mean relative error <10%) and precision (CV <11%). The method has already been successfully used in proficiency tests and subsequently applied to authentic samples in routine forensic analysis., (Copyright © 2011 John Wiley & Sons, Ltd.)

Transformation requires specialized proteins to facilitate the binding and uptake of DNA. The genes of the Bacillus subtilis comG operon (comGA-G) are required for transformation and to assemble a structure, the pseudopilus, in the cell envelope. No role for the pseudopilus has been established and the functions of the individual comG genes are unknown. We show that among the comG genes, only comGA is absolutely required for DNA binding to the cell surface. ComEA, an integral membrane DNA-binding protein plays a minor role in the initial binding step, while an unidentified protein which communicates with ComGA must be directly responsible for binding to the cell. We show that the use of resistance to DNase to measure 'DNA uptake' reflects the movement of transforming DNA to a protected state in which it is not irreversibly associated with the protoplast, and presumably resides outside the cell membrane, in the periplasm or associated with the cell wall. We suggest that ComGA is needed for the acquisition of DNase resistance as well as for the binding of DNA to the cell surface. Finally, we show that the pseudopilus is required for DNA uptake and we offer a revised model for the transformation process., (© 2011 Blackwell Publishing Ltd.)

Transformable (competent) cells of Bacillus subtilis are blocked in cell division because the traffic ATPase ComGA prevents the formation of FtsZ rings. Although ComGA-deficient cells elongate and form FtsZ rings, cell division remains blocked at a later stage and the cells become mildly filamented. Here we show that the highly conserved protein Maf is synthesized predominantly in competent cells under the direct control of the transcription factor ComK and is solely responsible for the later block in cell division. In vivo and in vitro data show that Maf binds to both ComGA and DivIVA. A point mutation in maf that interferes with Maf binding to DivIVA also interferes with the ability of Maf to inhibit cell division. Based on these findings, we propose that Maf and ComGA mediate mechanisms for the inhibition of cell division in competent cells with Maf acting downstream of ComGA. We further suggest that Maf must interact with DivIVA to inhibit cell division., (© 2011 Blackwell Publishing Ltd.)

Möbius sequence is a congenital facial and abducens nerve palsy, frequently associated to abnormalities of extremities. Arthrogryposis multiplex congenital is defined as a congenital fixation of multiple joints seldom of neurogenic origin. Both sequences must have a genetic origin, but usually are sporadic cases related to environmental factors such as drugs exposition and maternal trauma. A 5-year-old girl and a 1-year-old boy were born with Möbius sequence and arthrogryposis multiplex congenital, respectively. During pregnancies, the mother had vaginal bleeding at 7 weeks and used crack (free-based cocaine) in the first trimester, respectively. The girl also has equinovarus talipes and autistic behavior. The boy has arthrogryposis with flexion contractures of the feet and knees. A vascular disruption, due to hemorrhage and cocaine exposure, causing a transient ischemic insult to embryos in a critical period of development may be responsible for distinct phenotypes in these cases.

The aim of the present study was to investigate antiinflammatory activity of the methylene chloride extract of Morus nigra in animal models. Carrageenan-induced paw edema as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the antiinflammatory activity of Morus nigra extract (MnE) in rats. A HPLC fingerprint was used for phytochemical analysis of the extracts. The MnE at test doses of 100-300 mg/kg p.o. clearly demonstrated antiinflammatory effects by reduced paw edema induced by carragenan and significantly inhibited the formation of granulomatous tissue. In addition, chemical compounds isolated from Morus nigra, including betulinic acid, β-sitosterol and germanicol, may be responsible for the antiinflammatory effect of the extract., (Copyright © 2010 John Wiley & Sons, Ltd.)

The aim of the study was to analyze the epidemiologic, clinical, laboratory and development profile of Guillain-Barré syndrome series studied at the Child Institute, between 1989 and 2000. From the 61 patients that fulfilled the selection criteria, aged between 7 months and 13 years old, no sexual or seasonal variation was observed. Clinical events prior to neurological symptoms (with an average time gap of 20.7 days) were observed in 62.3%, 55% had cranial nerve disturbances, 27.9% dysautonomic symptoms, and 27.9% respiratory dysfunction. Installation time varied from 2-40 days, plateau from 0-28 days and recuperation from 30-480 days; 94% of patients had a complete clinical recuperation. Electrophysiology in 20 patients disclosed an abnormal demyelination pattern in 15, an exclusively motor axonal pattern in 4 and a mixed pattern in 1 patient. The results obtained did not differ from those in the literature but it was observed that boys and older children had a longer recuperation time. It was not possible to correlate electroneurography with clinical abnormalities and evolution due to the reduced number of patients.

Introduction: Churg-Strauss syndrome (CSS) is a systemic granulomatous vasculitis rarely described in children, particularly associated with neurological involvement, exceptionally chorea. To our knowledge there are only 35 children and adolescent patients with CSS described in the literature. During a 25-year period 5283 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and only one (0.02%) presented CSS., Case Report: A 7-year-old boy suffered from severe asthma, eosinophilia, history of allergy, recurrent non-fixed pulmonary infiltrates, several nodular lesions in both lungs and maxillary sinusitis. Transthoracic biopsy of the right lung revealed necrotizing extravascular eosinophilic infiltrates and the diagnosis of CSS was established. During the follow-up he had persistent vasculitis skin lesions and hemichorea. Despite the treatment with immunosuppressive drugs and intravenous immunoglobulin, he died because of pulmonary abscess and sepsis., Discussion: A rare case of CSS with chorea was reported, reinforcing the possibility of this disease in children with asthma, allergic rhinitis, hypereosinophilia and cutaneous vasculitis.

Morus nigra has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of dichloromethane extract from leaves of M. nigra. The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice. The extract at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. The extract administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.), which supports previous claims for its traditional use.

A qualitative and quantitative analytical method was developed for the simultaneous determination of 24 illicit drugs and medicines, in preserved oral fluid samples collected with the StatSure Saliva Sampler collection device. The samples were prepared by liquid-liquid extraction followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. The chromatographic separation was performed with an Atlantis T3 (100 x 2.1 mm i.d., 3 microm) reversed-phase column using an acetonitrile/2 mM ammonium formate buffer pH 3.4 gradient and the MS/MS detection was achieved with two precursor-product ion transitions per substance. The method was fully validated, including specificity and capacity of identification, limit of detection (0.2-2.1 microg/L), limit of quantitation (0.8-6.4 microg/L), recovery (34-98%), carryover, linearity (the method was linear in the range 1-200 microg/L), intra-assay precision (coefficient of variance (CV) <20% for 20 microg/L and CV <10% for 100 microg/L) and inter-assay accuracy (mean relative error <15%) and precision (CV <20%). The method showed to be specific and sensitive. It has already been successfully used in four proficiency tests and subsequently applied to oral fluid samples collected from road traffic volunteers in the driving population of Portugal (districts of Lisbon, Coimbra and Porto), within the DRUID project., (Copyright (c) 2009 John Wiley & Sons, Ltd.)