Prognosis in meningoencephalitis of unknown origin in dogs: Risk factors associated with survival, clinical relapse, and long-term disability.

BACKGROUND: Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging. OBJECTIVES: Identify clinical prognostic variables in dogs with MUO. ANIMALS: A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO. METHODS: Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse. RESULTS: Eighty-two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P = .03), epileptic seizures (P < .001), paresis (P < .001), and higher neurodisability scale (NDS) score (P < .001) at presentation were negatively associated with survival to 6 months. Dogs with persistent deficits had higher NDS scores on presentation (P = .001). Median follow-up time was 11 months (interquartile range [IQR], 1-24) and 50.6% (160/316) relapsed during treatment (median time to relapse, 7 months; IQR, 2-15). Incomplete resolution of the clinical signs during the 6 months after diagnosis (P < .001), higher NDS score (P < .001), and longer duration of the clinical signs (P < .001) were associated with relapse. CONCLUSIONS AND CLINICAL IMPORTANCE: Knowledge of risk factors associated with survival, incomplete recovery and clinical relapse in MUO can help guide monitoring and treatment and improve owner communications regarding prognosis for this debilitating disease.

Prevalence, clinical presentation, and etiology of myelopathies in 224 juvenile dogs.

BACKGROUND: Intervertebral disc herniation is widely recognized as the most common cause of myelopathy in dogs older than 2 years; however, the prevalence of various causes of myelopathy in younger dogs has not been reported. HYPOTHESIS/OBJECTIVES: To describe the prevalence, clinical presentation, and etiology of myelopathy in dogs aged 18 months or less. Secondarily, to investigate which clinical features were associated with each of the most common etiologies. ANIMALS: Two hundred twenty-four dogs aged 18 months or less with myelopathy were included in the study. METHODS: Retrospective review of clinical records from 4 referral institutions. Multivariable logistic regression analyses assessed which clinical features were associated with each diagnosis. RESULTS: French bulldogs (n = 51, 22.8%), pugs (n = 18, 8.0%), crossbreeds (n = 12, 5.4%), and English bulldogs (n = 11, 4.9%) were the most frequently affected breeds. Overall, 31 diagnoses were reached. The 5 most frequent diagnoses were vertebral malformation (VM; n = 42, 18.8%), spinal arachnoid diverticulum (SAD; n = 28, 12.5%), traumatic fracture of the vertebral column (n = 22, 9.8%), atlantoaxial instability (n = 18, 8.0%), and osseous-associated cervical spondylomyelopathy (n = 17, 7.6%). Intervertebral disc extrusion (IVDE) accounted for 4.5% of cases (n = 10). A final diagnosis of VM was associated with younger, screw-tailed, and pug breeds with chronic signs of T3-L3 myelopathy. SAD was associated with screw-tailed and pug breeds with nonpainful clinical signs. Intervertebral disc extrusion was associated with older, screw-tailed, and pug breeds with shorter duration of clinical signs. CONCLUSIONS AND CLINICAL IMPORTANCE: Prioritization of differential diagnoses for dogs presenting with signs of myelopathy when aged 18 months or less should differ to those for older dogs, with IVDE not the most common cause in the former.

Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin.

Introduction: Canine meningoencephalitis of unknown origin (MUO) is a debilitating disease associated with high mortality. The prognostic value of magnetic resonance imaging (MRI) findings for predicting survival at 12 months and long-term relapse remains uncertain. Methods: This was a retrospective cohort study evaluating the prognostic value of different MRI variables using multivariable logistic regression and Cox proportional hazards analysis. Results: In total, 138 dogs were presumptively diagnosed with MUO. The most common location for lesions identified on MRI were the white matter tracts of the corona radiata and corpus callosum, followed by the frontal, sensorimotor and temporal cortices. Lower T2 lesion load (p = 0.006, OR = 0.942, CI = 0.902-0.983) was associated with longer survival and higher T1 post-contrast lesion load (p = 0.023, OR = 1.162, CI = 1.021-1.322) was associated with relapse. Discussion: This study has identified prognostic factors that may help identify dogs at higher risk of death and relapse and therefore guide treatment recommendations.

Can pharmaceutical care decrease the oxidative stress in type 2 diabetes mellitus?

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder characterized by an increase in oxidative stress, which is itself related to development of T2D's main chronic complications. Oxidative stress caused by elevated production of reactive species of oxygen and decrease of antioxidant defense system level, leads to activation of lipid peroxidation (LPO) and oxidative lipoprotein modification with increasing atherogenicity. Therefore, the aim of this study was to evaluate whether pharmacotherapeutic follow-up in patients with T2D, users and non-users of insulin, interferes with the levels of oxidative stress, measuring lipid peroxidation and protein oxidation, nitric oxide and superoxide dismutase levels. After the follow-up, there was a decrease in nitric oxide levels and an increase in superoxide dismutase concentration for the group with insulin therapy. Accordingly, these results show that the proposed pharmaceutical care program reduced the oxidative stress levels, mainly in patients in insulin therapy, as a consequence, can impact in the surging of the main chronic complications in T2D.

Clinical signs, causes, and outcome of central cord syndrome in 22 cats.

OBJECTIVE: To describe the signalment, clinical findings, presumptive or definitive diagnosis, and outcome in cats with central cord syndrome (CCS). ANIMALS: 22 cats. CLINICAL PRESENTATION: Cats evaluated for CCS at 7 referral hospitals between 2017 and 2021 were included. Information retrieved from medical records included signalment, physical and neurological examination findings, diagnostic investigations, definitive or presumptive diagnosis, treatment, and follow-up. RESULTS: Median age at presentation was 9 years. Two neuroanatomical localizations were associated with CCS: C1-C5 spinal cord segments in 17 (77.3%) cats and C6-T2 spinal cord segments in 5 (22.7%) cats. Neuroanatomical localization did not correlate with lesion location on MRI in 8 (36.3%) cats. The most common lesion location within the vertebral column was over the C2 and C4 vertebral bodies in 6 (27.2%) and 5 (22.7%) cats, respectively. Peracute clinical signs were observed in 11 (50%) cats, acute in 1 (4.5%), subacute in 4 (18%), and chronic and progressive signs were seen in 6 (40.9%) cats. The most common peracute condition was ischemic myelopathy in 8 (36.3%) cats, whereas neoplasia was the most frequently identified chronic etiology occurring in 5 (22.7%) cats. Outcome was poor in 13 (59%) cats, consisting of 4 of 11 (36.6%) of the peracute cases, 3 of 4 (75%) of the subacute cases, and 6 of 6 of the chronic cases. CLINICAL RELEVANCE: Central cord syndrome can occur in cats with lesions in the C1-C5 and C6-T2 spinal cord segments. Multiple etiologies can cause CCS, most commonly, ischemic myelopathy and neoplasia. Prognosis depends on the etiology and onset of clinical signs.

The value of a head turn in neurolocalization.

BACKGROUND: A head turn is a clinically relevant abnormality identified on neurological examination and historically has been an isolated or concomitant sign of ipsilateral forebrain dysfunction. Experimental studies in quadrupedal mammals suggest that changes in head posture may be identified as originating in other parts of the central nervous system (CNS). OBJECTIVES: To identify whether other locations within the CNS could give rise to a head turn and whether the head turn identified is isolated or concomitant with other deviations in head and body posture. ANIMALS: Forty-nine client-owned dogs with a presentation of a head turn, from 6 veterinary referral centers. METHODS: Multicenter observational prospective study including dogs with photographic evidence of a head turn, full neurological examination, and advanced imaging. RESULTS: Of the population, 15/49 had head turn only, 9/49 had head turn and head tilt only, 12/49 had head turn and body turn only, and 13/49 had head turn, head tilt, and body turn. Nearly all dogs with forebrain disease (23/24), and, all with brainstem and cerebellar disease, had an ipsilateral head turn and body turn (if present). In the cerebellar group, all head tilts were contralateral to the lesion location. In the cervical spinal cord group, all head turns, body turns and head tilts were contralateral to the lesion location. CONCLUSION: A head turn, although most likely associated with, is not exclusively seen with forebrain disease. Certain combinations of head turn, head tilt and body turn suggest a neurolocalization other than the forebrain, with appropriate classification needed.

Research Note: Comparative effects of liquid and dry applications of a combination of lysolecithin, synthetic emulsifier, and monoglycerides on growth performance, nutrient digestibility, and litter moisture in broilers fed diets of differing energy density.

Supplementation of a combination of lysolecithin, a synthetic emulsifier, and monoglycerides (LEX) in liquid and dry form to broiler diets with different energy levels was investigated to determine their effect on performance, litter quality and subsequent occurrence of footpad lesions. One thousand two hundred and forty-eight-day-old Ross 308 broilers were assigned to 1 of 6 treatments for a 42-day study: a basal diet with a normal energy content (NE); NE + 300 g/t LEX in liquid form (LEL); NE + 500 g/t LEX in dry form (LED); a basal diet with low energy (LE, -90 kcal/kg starter, -100 kcal/kg grower, finisher), LE + 300 g/t LEL and a LE + 500 g/t LED. Each treatment consisted of 13 pens of 16 birds each. Diets were fed in 3 phases (starter d 0-10, grower d 11-21, finisher d 22-42). Feed intake and weight were measured on d 0, 10, 21, and 42. On d 42 a litter sample was collected from each pen and 2 birds per pen were assessed for footpad lesions and breast scald. Data were analyzed using JMP 16, with means separation achieved using Tukey's HSD; significance was assumed at P < 0.05. Results showed a higher (P < 0.05) cumulative bodyweight gain with LEX supplementation (NE CON = 2,718 g, NE+LED = 2,829, NE+LEL = 2,895, LE CON = 2,722, LE+LED = 2,787, LE+LEL = 2,893; P = 0.0027). An increased feed intake was observed for the LE diets, however cumulative FCR of LE+LED and LE+LEL remained equal to the NE control (1.657 NE CON, 1.657 LE+LED, 1.623 LE+LEL; P > 0.05), suggesting LEX enabled the birds to compensate for the energy gap. Litter dry matter was significantly improved with both LED and LEL supplementation compared to the control groups, and resulted in lower (P < 0.05) occurrence and severity of footpad lesions and breast scalds. Considering the income over feed cost (IOFC) of the NE treatment as the reference point for comparison, all other treatments improved profitability, with NE+LEL and LE+LEL achieving the greatest IOFC with 154.58 and 175.96 €/1,000 birds respectively. In conclusion, feeding broilers a combination of lysophospholipids, a synthetic emulsifier and monoglycerides resulted in improved bird performance. The use of the LEX also improved litter quality and footpad health, therefore improving animal welfare indicators such as breast scald and footpad measurements.

Serological investigation of vaccine-induced antibodies for measles, rubella, and yellow fever viruses in children vertically exposed to Zika virus or with down syndrome.

Background: Vaccination schedules, as well as their effectiveness and contraindications, need to be evaluated regularly, especially in specific situations. Congenital Zika Syndrome (CZS) is a severe condition that results in extensive functional and neurological impairment of fetuses and newborns due to Zika virus tropism for fetal neural progenitor cells. Down Syndrome (DS) is the leading genetic cause of intellectual disability. The immune impairment in DS has already been described, but little is known about the immune response of CZS children. Thus, CZS and DS are specific conditions that can be considered for a reassessment of the available immunizations. Here, we carried out serological analyses of attenuated vaccines-induced antibodies for measles, rubella, and yellow fever viruses in children aged 2-7, grouped into asymptomatic controls, DS children, and CZS children. Methods: Plasma samples were taken, and vaccination records were compiled during clinical follow-up. Enzymatic immunoassays for quantifying anti-measles and anti-rubella IgG were performed to assess the response to the Measles, Mumps, and Rubella (MMR) vaccine. Plaque Reduction Neutralization Test (PRNT) was performed to investigate neutralizing antibodies in response to the Brazilian vaccine strain of yellow fever (YF-17DD). Results: We highlight similar levels of anti-measles IgG and neutralizing antibodies for YF-17DD among CZS, DS, and asymptomatic children, although low positivity of measles data was seen in the three groups. In DS children, the 2-4-year-old group had an increased level of anti-measles IgG compared to the older group of children aged five to seven years. Lower anti-rubella IgG levels were observed in CZS and DS children compared to asymptomatic children. For anti-rubella IgG, the good performance of vaccination in asymptomatic children is due to younger ones rather than older ones. Conclusions: There were no reports of adverse events after the use of the MMR and YF-17DD indicating that CZS and DS could continue to receive these vaccines, but our data draws attention to the necessity of monitoring the vaccination response in CZS and DS children over time and the possible need to adhere to national measles vaccination campaigns. Scientific research needs to continue to help develop appropriate CZS and DS health guidelines.

Pharmaceutical care improves medication adherence and quality of life in type 2 diabetes mellitus

Aims: This study aimed to evaluate whether pharmacotherapeutic follow-up in patients with T2DM in primary care interferes in metabolic control, cardiovascular risk, medication adherence and quality of life. Methods: A prospective clinical study was conducted at two Primary Health Units in Vitória, Espírito Santo, Brazil with 75 patients with T2DM between 40 and 70 years old. The parameters of metabolic control evaluated included fasting blood glucose, HbA1c, triglyceride/HDL-c and total cholesterol/HDL-c ratio. The cardiovascular risk was calculated based on the Framingham risk score. Adherence to medication was measured using the Brief Medication Questionnaire and quality of life was evaluated by applying the World Health Organization Quality of Life-Bref. Results: After the follow-up, there was a significant decreasing in cardiovascular risk (p=0.048) and total cholesterol/HDL-c ratio (p=0.024) and a discrete improvement in fast glucose and HbA1c levels. The quality of life scores increased for all domains (p<0.0001) and the treatment adherence also improved with 12.00% of the patients classified as low adherence in the final time, against 41.33% before the meetings. Conclusion: These results show the proposed pharmacotherapeutic follow-up influenced positively cardiovascular risk, adherence to therapy and quality of life in all domains, and, therefore, may contribute to delay the onset of the main chronic complications of the disease (AU)

Characterization of phenolic compounds in Eugenia uniflora leaves by ESI(-) FT-ICR MS, analysis of cytotoxic activity on gastric adenocarcinoma (AGS cells), and anti-Helicobacter pylori activity.

Eugenia uniflora leaves are a source of flavonoids and ellagitannins, and the Brazilian population uses them to treat various diseases, including gastrointestinal disorders. This study aimed to determine if the ethanol extract and other derivatives are effective cytotoxic agents against gastric adenocarcinoma (AGS cells) and anti-H. pylori agent, its chemical composition, and mass spectrometry characterization of the more abundant compounds. The results were compared with the literature. The aqueous fraction, rich in Oenothein B and Gemin D/Hippomanin A, showed anti-H. pylori activity and higher cytotoxicity on AGS cells compared to the other samples analysed. Furthermore, the ESI(-) FT-ICR MS characterized the more abundant phenolic compounds, including Quinic Acid, Myricitrin, Gemin D/Hippomanin A, and Oenothein. Therefore, the activity of the ethanolic extract and aqueous fraction for gastric cancer and against H-pylori seems to originate from the antiproliferative and bacteriostatic effects of tannins and flavonoids.

Idiopathic and structural episodic nonintentional head tremor in dogs: 100 cases (2004-2022).

BACKGROUND: Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT). HYPOTHESIS/OBJECTIVES: Describe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT. ANIMALS: One hundred dogs with IEHT (n = 71) or SEHT (n = 29). METHODS: Retrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022. RESULTS: Lesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P < .001 for all) compared to IEHT dogs. Two SEHT dogs had only tremor. In IEHT dogs, 8/10 owners reported that the tremor decreased or abated over time (range, 106-2315 days) without treatment. Tremor remission occurred in SEHT dogs treated for underlying meningoencephalitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Presence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination.

Atypical case of acute posterior multifocal placoid pigment epitheliopathy with intraretinal fluid.

Acute posterior multifocal placoid pigment epitheliopathy is a rare inflammatory chorioretinopathy, classified as a white dot syndrome, in which ischaemia of the choriocapillaris leads to atrophy of the external retinal layers, including the retinal pigment epithelium.A male patient in his 20s presented with sudden severe loss of vision in the left eye. Funduscopy revealed with yellow placoid lesions in the macula and near periphery. Spectral-domain optical coherence tomography and fluorescein angiography revealed the presence of central intraretinal fluid in the left eye and multiple areas of macular ischaemia bilaterally. Treatment with oral corticosteroids was initiated, and the anatomical changes, including the intraretinal fluid, improved steadily over the following weeks.Although rare, the presence of subretinal or intraretinal fluid should not decrease the suspicion of acute posterior multifocal placoid pigment epitheliopathy. Reabsorption of the fluid is usually accompanied by the improvement of the remaining anatomical changes and the visual function.

Synthesis, Docking Studies and Evaluation of Chalcones as Anti-Helicobacter pylori and antitumoral Agents.

Helicobacter pylori colonizes the gastric epithelium of 50 % of world population and it is the main etiological agent of human chronic gastritis, peptic ulcer, and gastric cancer. In this study, we synthesized and characterized a series of 14 chalcones and evaluated their anti-H. pylori, NO inhibition (in vitro and in silico), and AGS cells cytotoxic effects. Compounds 3b and 3h showed MIC of 8 µg/mL. We observed structure-activity relationships, mainly related to the influence of methoxy substituent at C-2 (3b) and the nitro group at C-4 (3h) in chalcone scaffold. The fourteen chalcones inhibited the NO production in LPS-stimulated macrophages and showed potential for interaction on the active site of the iNOS enzyme. Finally, 3b and 3h showed the highest selectivity to the AGS cell lines. Thus, ours results suggest 3b and 3h as potential candidates for design of new and effective agents against H. pylori and related diseases.

In Vitro and In Silico Evaluation of Red Algae Laurencia obtusa Anticancer Activity.

Studies estimate that nearly 2 million new cases of gastric cancer will occur worldwide during the next two decades, which will increase mortality associated with cancer and the demand for new treatments. Marine algae of the Laurencia genus have secondary metabolites known for their cytotoxic action, such as terpenes and acetogenins. The species Laurencia obtusa has demonstrated cytotoxicity against many types of tumors in previous analyses. In this study, we determined the structure of terpenes, acetogenins, and one fatty acid of Laurencia using mass spectrometry (ESI-FT-ICR/MS). In vitro cytotoxicity assays were performed with adenocarcinoma gastric cells (AGS) to select the most cytotoxic fraction of the crude extract of L. obtusa. The Hex:AcOEt fraction was the most cytotoxic, with IC50 9.23 µg/mL. The selectivity index of 15.56 shows that the Hex:AcOEt fraction is selective to cancer cells. Compounds obtained from L. obtusa were tested by the analysis of crystallographic complexes. Molecular docking calculations on the active site of the HIF-2α protein showed the highest affinity for sesquiterpene chermesiterpenoid B, identified from HEX:AcOEt fraction, reaching a score of 65.9. The results indicate that L. obtusa presents potential compounds to be used in the treatment of neoplasms, such as gastric adenocarcinoma.

Trabeculectomy Vs Non-penetrating Deep Sclerectomy for the Surgical Treatment of Open-Angle Glaucoma: A Long-Term Report of 201 Eyes.

Introduction: Glaucoma is the second leading cause of vision loss worldwide. The reduction of intraocular pressure remains the backbone of its therapy. Among surgical techniques for its treatment, deep non-penetrating sclerotomy is the most widely practiced non-penetrating surgery. The purpose of this study was to evaluate the long-term efficacy and safety of deep non-penetrating sclerotomy compared to standard trabeculectomy in patients with open-angle glaucoma. Patients and methods: Retrospective study including 201 eyes with open-angle glaucoma. Closed-angle and neovascular cases were excluded. Absolute success was considered when intraocular pressure under 18 mmHg, or a reduction of at least 20% in patients with a baseline intraocular pressure below 22 mmHg, was obtained after 24 months, without the use of medication. Qualified success was considered when those targets were met with or without the use of hypotensive medication. Results: Deep non-penetrating sclerectomy showed a slightly lower long-term hypotensive effect compared to standard trabeculectomy, with significant differences at 12 months, but not at 24 months of follow-up. The absolute and qualified success rates were 51.85% and 65.43% for the trabeculectomy group and 50.83% and 60.83% for the deep non-penetrating sclerectomy, without significant differences. Regarding postoperative complications, mainly due to postoperative hypotonia, or related to the filtration bleb, they were significantly different between groups, with 10.8% and 24.7%, in deep-nonpenetrating sclerectomy and trabeculectomy groups, respectively. Conclusion: Deep non-penetrating sclerectomy seems to be an effective and safe surgical option for patients with open-angle glaucoma unable to be controlled by non-invasive strategies. Data suggests that the intraocular pressure-lowering effect of this technique may be marginally lower than that of trabeculectomy, but the achieved efficacy outcomes were similar, with a significantly lower risk of complications.

Determining the prevalence and risk factors for positive bacterial culture in canine discospondylitis: 120 cases.

BACKGROUND: Identification of the aetiologic agent in canine discospondylitis is infrequent; and risk factors for a positive bacterial culture have not previously been reported. METHODS: Medical records at three institutions were searched to identify clinical features of dogs with discospondylitis diagnosed via radiography or cross-sectional imaging. Inclusion in this retrospective case-control study required culture of one or more samples. Multivariable binary logistic regression identified features associated with a positive culture. RESULTS: Fifty (42%) of 120 dogs had one or more positive culture results obtained from either urine (28/115), blood (25/78), intervertebral disc aspiration (10/34) or cerebrospinal fluid (1/18). A positive culture was associated with higher bodyweight (p = 0.002, odds ratio [OR] = 1.054, 95% confidence interval [CI]: 1.019-1.089), more sample types cultured (p = 0.037, OR = 1.806, 95% CI: 1.037-3.147) and institution (p = 0.021). The presence of possibly associated preceding events (e.g., surgery), pyrexia, number of disc sites affected and serum C-reactive protein result, among other features, were not statistically significant. LIMITATIONS: All isolates cultured were included since differentiation of true aetiologic agents from contaminants was not possible without histological confirmation and culture from surgical or postmortem biopsies. CONCLUSIONS: Clinical features typically associated with infection were not identified as risk factors for positive culture in canine discospondylitis. The statistical significance of the institution suggests that standardisation of sampling protocols is necessary.

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale.

BACKGROUND: Meningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity. OBJECTIVES: Design a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome. ANIMALS: One hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation. METHODS: Medical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome. RESULTS: The most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68-0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56-0.83). No association was found between NDS score and long-term outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: The NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified.

Complications associated with cerebrospinal fluid collection in dogs.

BACKGROUND: This study aimed to identify complications associated with cerebrospinal fluid (CSF) collection in dogs. METHODS: This was a prospective, observational multicentre study using data collected from 102 dogs undergoing CSF collection for the investigation of neurological disease. CSF was collected from the cerebellomedullary cistern (CMC), lumbar subarachnoid space (LSAS) or both sites. Pre-, intra- and postprocedural data were collected. Descriptive statistics were performed to outline complications associated with CSF collection. RESULTS: CSF sampling was attempted on 108 occasions, and CSF was acquired on 100 occasions (92.6%). Collection from the CMC was more likely to be successful than that from the LSAS. No dogs exhibited neurologic deterioration following CSF collection. There was no significant difference between pre- and post-CSF collection short-form Glasgow composite measure pain scores in ambulatory dogs (p = 0.13). LIMITATIONS: The scarcity of complications limited the ability to quantify the incidence of some potential complications reported elsewhere. CONCLUSIONS: Our results may be used to inform clinicians and owners that CSF sampling is associated with a low frequency of complications when performed by trained personnel.

Anti-Candida, docking studies, and in vitro metabolism-mediated cytotoxicity evaluation of Eugenol derivatives.

The high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti-Candida potential and the cytotoxic profile of eugenol derivatives. Anti-Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol-14-α-demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti-Candida activity against both strains with MIC ranging from 50 to 100 µg ml-1 . SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol-14-α-demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti-Candida agent prototypes.