Probiotic Characteristics and Antimicrobial Potential of a Native Bacillus subtilis Strain Fa17.2 Rescued from Wild Bromelia sp. Flowers.

In the present study, we identified the Bacillus subtilis strain annotated Fa17.2 isolated from Bromelia flower inflorescences collected from the subtropical humid mesothermal region, Santo Domingo de Los Tsachilas Province, Ecuador. The probiotic capacity and antimicrobial potential against four foodborne pathogens were assessed. The cell culture of Fa17.2 is highly resistant to synthetic gastric acid (pH 2.5, 3.0, and 3.5), bile salts (0.3%), tolerating different sodium chloride concentrations (1, 3, and 5%), and growth conditions (15 °C and 45 °C), suggesting its potential probiotic features. The isolate showed no antibiotic resistance and was considered safe as no hemolysis was detected on sheep blood agar. The optimum medium for bacterial growth and the release of antimicrobial compounds was MRS with 10% glucose. The active components released in the neutralized crude extract (NCE) were insensitive to organic solvents, surfactants, and nonproteolytic enzymes and sensitive to proteolytic enzymes suggesting their proteinaceous nature. The antimicrobial activity was enhanced by heat and maintained active over a wide range of pH (2.0-8.0). Moreover, the crude extract (CE) showed inhibitory activity against several Gram-negative and Gram-positive bacteria. The molecular weight of partially purified precipitated bacteriocin-like substances (BLISs) was about 14 kDa in 20% Tricine-SDS-PAGE. The CE obtained from Fa17.2 inhibits the growth of four foodborne pathogens, Staphylococcus aureus, Escherichia coli, Kosaconia cowanii, and Shigella dysenteriae, which implies its potential as an antimicrobial producer strain.

Eye-of-the-Tiger Sign with an Unexpected Pathological Diagnosis.

BACKGROUND: Clinical diagnosis of atypical parkinsonisms may be challenging. The eye-of-the-tiger sign on brain MRI, typical of neurodegeneration with brain iron accumulation, has been anecdotally observed in cases clinically diagnosed as atypical parkinsonisms. OBJECTIVES: To show how clinical syndromes and even neuroimaging sometimes may lead the neurologist to a misunderstanding, just as to emphasize the important role of pathology to establish the final diagnosis in these cases. METHODS: Clinico-pathological case. RESULTS: A 67-year-old-woman presented with progressive painful stiffness and allodynia in her left arm. On examination, she presented parkinsonism without tremor with greater involvement of left limbs. She developed dystonia, with myoclonic tremor and hypoesthesia involving her left arm, as well as an impairment of balance with falls, a significant axial involvement with disabling rigidity, supranuclear gaze abnormalities, facial dystonia, dysphonia, severe dysphagia, and anarthria. There was no response to levodopa. Syndromic diagnosis and findings on neuroimaging are discussed. Afterwards, the underlying pathology is revealed. CONCLUSIONS: We present the first case of neuropathologically confirmed multiple system atrophy with the eye-of-the-tiger sign on brain MRI. The presence of supranuclear vertical gaze palsy further complicated a correct clinical diagnosis. A pathological postmortem study remains essential to establish a definite diagnosis in atypical parkinsonisms.

A single Epley manoeuvre can improve self-perceptions of disability (quality of life) in patients with pc-BPPV: A randomised controlled trial in primary care / Impacto de la maniobra de Epley en la discapacidad autopercibida en pacientes con vértigo posicional paroxístico benigno: un ensayo controlado aleatorio en atención primaria

Objective: The purpose of the study was to compare the impact of the EM and a sham manoeuvre in primary care on self-perceived disability. Design: Randomised, double-blind, sham-controlled clinical trial conducted in primary care with a follow-up of 1 year. Participants: Patients aged ≥18 years old diagnosed with pc-BPPV according to the Dix–Hallpike test (DHT) were randomised to: Interventions: Intervention (EM) group or a control (sham manoeuvre) group. Main measurements: The main study covariates were age, sex, history of depression and anxiety, presence of nystagmus in the DHT, patient-perceived disability assessed with the Dizziness Handicap Inventory – screening version (DHI-S). Data were analyzed using bivariate and multivariate mixed Tobit analyses. Results: Overall, 134 patients were studied: 66 in the intervention group and 68 in the control group. Median age was 52 years (interquartile range [IQR], 38.25–68.00 years. standard deviation, 16.98) and 76.12% of the patients were women. The DHT triggered nystagmus in 40.30% of patients. The median total DHI-S score for the overall sample at baseline was 16 (IQR, 8.00–22.00); 16 [IQR, 10.5–24.0] vs 10 [6.0–14.0] for women vs men (P<.001). Patients treated with the EM experienced a mean reduction of 2.03 points in DHI-S score over the follow-up period compared with patients in the sham group. Conclusions: Pc-BPPV affects the quality of life of primary care patients. A single EM can improve self-perceptions of disability by around 2 points on the DHI-S scale.(AU)

Objetivo: El propósito del estudio fue comparar el impacto de la ME y una maniobra simulada en Atención Primaria sobre la discapacidad autopercibida. Diseño: Ensayo clínico aleatorizado, doble ciego y controlado realizado en Atención Primaria con un seguimiento de un año. Participantes:Los pacientes ≥18 años diagnosticados de pc-BPPV según la prueba de Dix-Hallpike (DHT) fueron aleatorizados para: Intervenciones: Grupo de intervención (EM) o un grupo de control (maniobra simulada). Variables principales: Las principales variables del estudio fueron la edad, el sexo, los antecedentes de depresión y ansiedad, la presencia de nistagmo en la DHT, la discapacidad percibida por el paciente, evaluada con la versión de cribado del Inventario de discapacidad del vértigo (DHI-S). Los datos se analizaron mediante análisis Tobit mixtos bivariados y multivariados. Resultados: Se estudió a 134 pacientes: 66 en el grupo de intervención y 68 en el grupo de control. La mediana de edad fue de 52 años (rango intercuartílico [IQR], 38,25-68,00 años; desviación estandar 16,98) y el 76,12% de los pacientes eran mujeres. La DHT desencadenó nistagmo en el 40,30% de los pacientes. La media del DHI-S para la muestra general al inicio del estudio fue de 16 (IQR 8,00-22,00); 16 (RIQ, 10,5-24,0) frente a 10 (6,0-14,0) para mujeres frente a hombres (p<0,001). Los pacientes tratados con ME experimentaron una reducción media de 2,03 puntos en la puntuación DHI-S durante el período de seguimiento en comparación con los pacientes del grupo simulado. Conclusiones: El Pc-BPPV afecta a la calidad de vida de los pacientes de Atención Primaria. Una sola ME puede mejorar la autopercepción de la discapacidad en alrededor de 2 puntos en la escala DHI-S.(AU)

Responses to the Dix-Hallpike test in primary care: A comparison between subjective and objective benign paroxysmal positional vertigo / Detección de nistagmo en respuesta a la prueba de Dix-Hallpike en atención primaria: una comparación entre vértigo posicional paroxístico benigno subjetivo y objetivo

Patients who experience both vertigo and nystagmus in the Dix-Hallpike test (DHT) are diagnosed with objective benign paroxysmal positional vertigo (BPPV). This test provokes only vertigo in between 11% and 48% of patients, who are diagnosed with subjective BPPV. Detection of nystagmus has important diagnostic and prognostic implications. To compare the characteristics of patients diagnosed with objective and subjective BPPV in primary care. Cross-sectional descriptive study. Two urban primary care centers. Adults (≥18 years) diagnosed with objective or subjective BPPV between November 2012 and January 2015. DHT results (vertigo or vertigo plus nystagmus; dependent variable: nistagmus as response to DHT), age, sex, time since onset, previous vertigo episodes, self-reported vertigo severity (Likert scale, 0–10), comorbidities (recent viral infection, traumatic brain injury, headache, anxiety/depression, hypertension, diabetes mellitus, dyslipidemia, cardiovascular disease, altered thyroid function, osteoporosis, cervical spondylosis, neck pain). In total, 134 patients (76.1% women) with a mean age of 52 years were included; 59.71% had subjective BPPV. Objective BPPV was significantly associated with hypertension, antihypertensive therapy, and cervical spondylosis in the bivariate analysis and with cervical spondylosis (OR=3.94, p=0.021) and antihypertensive therapy (OR 3.02, p=0.028) in the multivariate analysis. Patients with subjective BPPV were more likely to be taking benzodiazepines [OR 0.24, p=0.023]. The prevalence of subjective BPPV was higher than expected. Cervical spondylosis and hypertensive therapy were associated with objective BPPV, while benzodiazepines were associated with subjective BPPV.(AU)

A los pacientes que experimentan tanto vértigo como nistagmo en la prueba de Dix-Hallpike (DHT) se les diagnostica vértigo posicional paroxístico benigno objetivo (VPPB). Esta prueba provoca solamente vértigo entre el 11 y el 48% de los pacientes a los que se les diagnostica VPPB subjetivo. La detección de nistagmo tiene importantes implicaciones diagnósticas y pronósticas. Comparar las características de los pacientes diagnosticados de VPPB objetivo y subjetivo en Atención Primaria. Estudio descriptivo transversal. Ubicación: 2 centros urbanos de Atención Primaria. Participantes: adultos (≥18 años) diagnosticados de VPPB objetivo o subjetivo entre noviembre del 2012 y enero del 2015. Resultados de la DHT (vértigo o vértigo más nistagmo; variable dependiente: nistagmo como respuesta a la DHT), edad, sexo, tiempo desde el inicio, episodios de vértigo previos, gravedad del vértigo autoinformada (escala Likert, 0-10), comorbilidades (infección viral reciente, lesión cerebral traumática, dolor de cabeza, ansiedad/depresión, hipertensión, diabetes mellitus, dislipidemia, enfermedad cardiovascular, función tiroidea alterada, osteoporosis, espondilosis cervical, cervicalgia). Se incluyó a 134 pacientes (76,1% mujeres) con una edad media de 52 años. El 59,71% presentaba VPPB subjetivo. El VPPB objetivo se asoció significativamente con hipertensión, tratamiento antihipertensivo y espondilosis cervical en el análisis bivariado y con espondilosis cervical (OR=3,94, p=0,021) y tratamiento antihipertensivo (OR=3,02, p=0,028) en el análisis multivariado. Los pacientes con VPPB subjetivo tenían más probabilidades de estar tomando benzodiacepinas (OR=0,24, p=0,023). La prevalencia de VPPB subjetivo fue superior a la esperada. La espondilosis cervical y la terapia hipertensiva se asociaron con VPPB objetivo, mientras que las benzodiacepinas se asociaron con VPPB subjetivo.(AU)

Responses to the Dix-Hallpike test in primary care: A comparison between subjective and objective benign paroxysmal positional vertigo.

Patients who experience both vertigo and nystagmus in the Dix-Hallpike test (DHT) are diagnosed with objective benign paroxysmal positional vertigo (BPPV). This test provokes only vertigo in between 11% and 48% of patients, who are diagnosed with subjective BPPV. Detection of nystagmus has important diagnostic and prognostic implications. To compare the characteristics of patients diagnosed with objective and subjective BPPV in primary care. Cross-sectional descriptive study. Two urban primary care centers. Adults (≥18 years) diagnosed with objective or subjective BPPV between November 2012 and January 2015. DHT results (vertigo or vertigo plus nystagmus; dependent variable: nistagmus as response to DHT), age, sex, time since onset, previous vertigo episodes, self-reported vertigo severity (Likert scale, 0-10), comorbidities (recent viral infection, traumatic brain injury, headache, anxiety/depression, hypertension, diabetes mellitus, dyslipidemia, cardiovascular disease, altered thyroid function, osteoporosis, cervical spondylosis, neck pain). In total, 134 patients (76.1% women) with a mean age of 52 years were included; 59.71% had subjective BPPV. Objective BPPV was significantly associated with hypertension, antihypertensive therapy, and cervical spondylosis in the bivariate analysis and with cervical spondylosis (OR=3.94, p=0.021) and antihypertensive therapy (OR 3.02, p=0.028) in the multivariate analysis. Patients with subjective BPPV were more likely to be taking benzodiazepines [OR 0.24, p=0.023]. The prevalence of subjective BPPV was higher than expected. Cervical spondylosis and hypertensive therapy were associated with objective BPPV, while benzodiazepines were associated with subjective BPPV.

A single Epley manoeuvre can improve self-perceptions of disability (quality of life) in patients with pc-BPPV: A randomised controlled trial in primary care.

Posterior canal benign paroxysmal positional vertigo (pc-BPPV) causes physical, functional, and emotional impairment. The treatment is the Epley manoeuvre (EM). OBJECTIVE: The purpose of the study was to compare the impact of the EM and a sham manoeuvre in primary care on self-perceived disability. DESIGN: Randomised, double-blind, sham-controlled clinical trial conducted in primary care with a follow-up of 1 year. PARTICIPANTS: Patients aged ≥18 years old diagnosed with pc-BPPV according to the Dix-Hallpike test (DHT) were randomised to: INTERVENTIONS: Intervention (EM) group or a control (sham manoeuvre) group. MAIN MEASUREMENTS: The main study covariates were age, sex, history of depression and anxiety, presence of nystagmus in the DHT, patient-perceived disability assessed with the Dizziness Handicap Inventory - screening version (DHI-S). Data were analyzed using bivariate and multivariate mixed Tobit analyses. RESULTS: Overall, 134 patients were studied: 66 in the intervention group and 68 in the control group. Median age was 52 years (interquartile range [IQR], 38.25-68.00 years. standard deviation, 16.98) and 76.12% of the patients were women. The DHT triggered nystagmus in 40.30% of patients. The median total DHI-S score for the overall sample at baseline was 16 (IQR, 8.00-22.00); 16 [IQR, 10.5-24.0] vs 10 [6.0-14.0] for women vs men (P<.001). Patients treated with the EM experienced a mean reduction of 2.03 points in DHI-S score over the follow-up period compared with patients in the sham group. CONCLUSIONS: Pc-BPPV affects the quality of life of primary care patients. A single EM can improve self-perceptions of disability by around 2 points on the DHI-S scale.

SURINPARK: Safinamide for Urinary Symptoms in Parkinson's Disease.

BACKGROUND: Urinary symptoms are common, disabling and generally unresponsive to treatment in Parkinson´s disease (PD). Safinamide is approved as an add-on therapy to levodopa to improve fluctuations. METHODS: Retrospective analysis of electronic records of nondemented PD patients seen consecutively in a Movement Disorders Unit (November 2018-February 2019). All were assessed with Scale for Outcomes in Parkinson's disease for Autonomic Symptoms-Urinary subscale (SCOPA-AUT-U) by the attending neurologist, and a month afterwards by an independent researcher blinded to treatment and clinical records in a routine clinical practice setting. Clinical variables were compared among patients who were prescribed safinamide (SA+) for the treatment of motor fluctuations and those with different treatment regimes (SA-). RESULTS: From 169 patients screened initially, 54 were excluded due to severe incontinence, absence of urinary symptoms or previous safinamide treatment. Thirty-five patients were included in SA+ and 79 in SA-. Both groups were comparable in terms of clinical variables, except in basal urinary symptoms, with more severity in the SA+ group. In the follow-up assessment, total SCOPA-AUT-U, as well as urgency, incontinence, frequency and nocturia subscales improved significantly in the SA+ group, while the SA- group remained unchanged. CONCLUSIONS: Safinamide could be helpful in the improvement of urinary symptoms in PD.

Effectiveness of a brief advance directive intervention in primary care: a randomized clinical trial.

OBJECTIVE: To measure the effectiveness of a brief intervention aimed at increasing interest in and use of advanced directives (AD) among primary care patients. METHODS: Randomized controlled trial. In the intervention arm, patients were given brief oral information and a leaflet on AD by General Practitioners (GPs), in the control group were briefly informed about the study's purpose. Outcome variables were the proportion of patients who expressed interest in AD and those who completed one. Covariates were sex, age, education, race, Charlson comorbidity index (CCI), religion, and possession of financial will. RESULTS: Overall, 332 patients were recruited; 58 in the intervention and 36 in the control group expressed interest in AD (p = 0.033) and 18 (5.4 %) made an AD (nine in each group). Variables associated with interest were Caucasian race (odds ratio [OR], 1.88), the intervention (OR, 1.86), and CCI extreme scores (OR, 0.36). Variables associated with AD completion were primary education/no schooling (OR, 5.69) and fewer children (OR, 0.57). CONCLUSIONS: A brief oral and written intervention delivered by GP significantly increased interest in AD and achieved a completion rate of 5.4 %, without differences with the control group. PRACTICE IMPLICATIONS: AD interventions should focus on individuals already likely to be motivated.

Long-term outcomes and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation: a prospective study in a pilot cohort.

INTRODUCTION: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood. PATIENTS AND METHODS: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT. RESULTS: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported. CONCLUSION: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.

Novel mutations in the KCNJ10 gene associated to a distinctive ataxia, sensorineural hearing loss and spasticity clinical phenotype.

KCNJ10 encodes the inward-rectifying potassium channel (Kir4.1) that is expressed in the brain, inner ear, and kidney. Loss-of-function mutations in KCNJ10 gene cause a complex syndrome consisting of epilepsy, ataxia, intellectual disability, sensorineural deafness, and tubulopathy (EAST/SeSAME syndrome). Patients with EAST/SeSAME syndrome display renal salt wasting and electrolyte imbalance that resemble the clinical features of impaired distal tubular salt transport in Gitelman's syndrome. A key distinguishing feature between these two conditions is the additional neurological (extrarenal) manifestations found in EAST/SeSAME syndrome. Recent reports have further expanded the clinical and mutational spectrum of KCNJ10-related disorders including non-syndromic early-onset cerebellar ataxia. Here, we describe a kindred of three affected siblings with early-onset ataxia, deafness, and progressive spasticity without other prominent clinical features. By using targeted next-generation sequencing, we have identified two novel missense variants, c.488G>A (p.G163D) and c.512G>A (p.R171Q), in the KCNJ10 gene that, in compound heterozygosis, cause this distinctive EAST/SeSAME phenotype in our family. Electrophysiological characterization of these two variants confirmed their pathogenicity. When expressed in CHO cells, the R171Q mutation resulted in 50% reduction of currents compared to wild-type KCNJ10 and G163D showed a complete loss of function. Co-expression of G163D and R171Q had a more pronounced effect on currents and membrane potential than R171Q alone but less severe than single expression of G163D. Moreover, the effect of the mutations seemed less pronounced in the presence of Kir5.1 (encoded by KCNJ16), with whom the renal Kir4.1 channels form heteromers. This partial functional rescue by co-expression with Kir5.1 might explain the lack of renal symptoms in the patients. This report illustrates that a spectrum of disorders with distinct clinical symptoms may result from mutations in different parts of KCNJ10, a gene initially associated only with the EAST/SeSAME syndrome.

Disability perceived by primary care patients with posterior canal benign paroxysmal positional vertigo.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo. Little is known on how posterior canal BPPV affects health-related quality of life in patients diagnosed and treated at primary care facilities or on whether patients with subjective and objective disease perceive the effects differently. This study was designed to describe how patients diagnosed with posterior canal BPPV in primary care perceive disability. METHODS: Cross-sectional descriptive study performed at two urban primary care centers. Participants were patients aged 18 years or older with suspected posterior canal BPPV recruited for baseline evaluation in a clinical trial on the effectiveness of the Epley maneuver in primary care. The recruitment period was from November 2012 to January 2015. Perceived disability was evaluated using the Dizziness Handicap Inventory - Screening version (DHI-S). Other variables collected were age and sex, a history or diagnosis of anxiety or depression, treatment with antidepressants and/or anxiolytics, and results of the Dix-Hallpike (DH) test, which was considered positive when it triggered vertigo with or without nystagmus and negative when it triggered neither. RESULTS: The DH test was positive in 134 patients, 40.30% of whom had objective BPPV (vertigo with nystagmus). The median age of the patients was 52 years (interquartile range [IQR], 39.00-68.50 years) and 76.1% were women. The median total score on the DHI-S was 16 out of 40 (IQR, 8.00-22.00). Scores were higher (greater perceived disability) in women (p < 0.001) and patients with subjective BPPV (vertigo without nystagmus) (p = 0.033). The items perceived as causing the greatest disability were feeling depressed (67.1%) and worsening of the condition on turning over in bed (88%). CONCLUSIONS: Patients diagnosed with posterior canal BPPV in primary care perceive their condition as a disability according to DHI-S scores, with higher levels of disability reported by women and patients with subjective BPPV. Feelings of depression and turning over in bed were associated with the greatest perceived difficulties. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01969513. Retrospectively registered. First Posted: October 25, 2013. https://clinicaltrials.gov/ct2/show/NCT01969513.

Transcranial sonography in atypical parkinsonism: How reliable is it in real clinical practice? A multicentre comprehensive study.

INTRODUCTION: Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the three AP (progressive supranuclear palsy, PSP, multiple system atrophy, MSA, corticobasal degeneration, CBD). Previous references lack homogeneous criteria and data are incomprehensive. METHODS: Analysis of TCS performed in routine clinical practice in AP and PD patients from two tertiary hospitals. Expert recommendations were strictly followed. Previous literature was critically analysed. RESULTS: 155 AP (98 PSP, 40 MSA, 14 CBD), 254 PD, 145 control subjects were included. We confirmed good sensitivity for SN+ in PD (80%), but specificity was lower than reported (61%). LN+ and 3V + had moderate sensitivity for AP and PSP diagnosis respectively (65%, 63%), but specificity was higher than reported (87%, 91%). We confirmed high specificity and positive predictive value of the combination SN/LN (98%, 93% AP; 83%, 86% PD). The combinations of two or three echofeatures, previously unreported, showed high specificity but lower sensitivity (SN/3V: 75% sensitivity, 87% specificity PD; 42% sensitivity, 98% specificity PSP) (SN + LN+: 79% sensitivity, 86% specificity CBD) (SN/3V/LN: 67% sensitivity, 89% specificity PD; 29% sensitivity, 99% specificity PSP; 41% sensitivity, 95% specificity MSA; 57% sensitivity 91% specificity CBD). CONCLUSIONS: We present a large comprehensive study of TCS, confirming its usefulness and certain limitations in AP diagnosis. Adherence to consensus criteria is critical to implement TCS for clinical and research purposes.

Benchmarking Particle Filter Algorithms for Efficient Velodyne-Based Vehicle Localization.

Keeping a vehicle well-localized within a prebuilt-map is at the core of any autonomous vehicle navigation system. In this work, we show that both standard SIR sampling and rejection-based optimal sampling are suitable for efficient (10 to 20 ms) real-time pose tracking without feature detection that is using raw point clouds from a 3D LiDAR. Motivated by the large amount of information captured by these sensors, we perform a systematic statistical analysis of how many points are actually required to reach an optimal ratio between efficiency and positioning accuracy. Furthermore, initialization from adverse conditions, e.g., poor GPS signal in urban canyons, we also identify the optimal particle filter settings required to ensure convergence. Our findings include that a decimation factor between 100 and 200 on incoming point clouds provides a large savings in computational cost with a negligible loss in localization accuracy for a VLP-16 scanner. Furthermore, an initial density of ∼2 particles/m 2 is required to achieve 100% convergence success for large-scale (∼100,000 m 2 ), outdoor global localization without any additional hint from GPS or magnetic field sensors. All implementations have been released as open-source software.

Tumor Budding: Prognostic Value in Muscle-invasive Bladder Cancer.

OBJETIVES: To assess if "tumor budding" (TB) behaves as a poor prognostic factor in muscle-invasive bladder carcinoma (MIBC). TB is the presence of tumor cells isolated or in small groups of fewer than 5 cells located at the tumor invasion front. MATERIAL AND METHODS: Retrospective study of 106 patients with MIBC who underwent radical cystectomy. A cytokeratin AE1/AE3 immunostaining was applied to identify and quantify TB by the "hot-spot" method. The variables evaluated were: age, gender, Tumour, Node, Metastasis Classification (TNM) stage, associated Carcinoma in situ, differentiation degree, tumor size, tumor location, lymphatic, venous or perineural invasion, p53, Ki67, molecular subtype (basal/luminal) and chemotherapy. Main variables were overall and cancer-specific survival. RESULTS: The mean follow-up time was 47 ± 46.45 months. The mean TB count was 32.3 ± 25.9 "buds." The ROC curve established 14 "buds" as the cut-off point: the median survival rate for the "low-grade TB" group (≤14 "buds") was 69.5 months, and for the "high-grade TB" group (>14 "buds") was 18.5 months (P= .003). In the multivariate analysis, independent predictive variables regarding mortality were: age, TB, and TNM stage. Patients with more than 14 "buds" had 2.27 times more risk of mortality, 95%CI:1.19-4.34, P = .013. In addition, the risk of mortality rises progressively as the number of "buds" increases, at a rate of 2% per "bud." CONCLUSION: According to our results, TB becomes an independent predictor factor for cancer-specific mortality in MIBC, with a cut-off point of 14 "buds."

Land use shapes the resistance of the soil microbial community and the C cycling response to drought in a semi-arid area.

The aim of this study was to understand the responses of the microbial community of soil under different land uses to drought in a semi-arid Mediterranean area. In a laboratory incubation, soil samples from different land uses (natural forest, drip-irrigated orchard, rain-fed almond tree cultivation and abandoned area) were maintained at 20% and 60% of the WHC. The microbial biomass and potential enzyme activities were determined after four and fifty days of soil incubation. The diversity and composition of the microbial community were studied after 50 days of incubation. The total mineralisation of soil organic C (SOC), as well as, the mineralisation of fresh organic matter (FOM) and the "priming effect" were analysed after addition of 13C-enriched plant tissue. Both land use and drought had significant effects in the soil microbial community, but the effect of land use was stronger than that of drought. The PLFA content (microbial biomass) of the forests soil was greater under drought. After 50 days of soil incubation, the microbial biomass and most of potential enzyme activities of the almond tree and abandoned soil samples were not significantly affected by drought contrary to those in orchard soil. The total and FOM mineralisation were on average lower in soil under drought than under optimal moisture for all land uses. However, the responses of the priming effect to drought were dependent on the land use. Overall, we conclude that the resistance to drought of the soil microbial community from an agroecosystem having a semi-arid climate is strongly influenced by the previous land use.

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly.

Drug-induced parkinsonism (DIP) and tardive dyskinesia (TD) are iatrogenic consequences of antidopaminergic drugs. Both are particularly prevalent among the elderly and those with dementia. However, despite their prevalence, these disorders are often overlooked. Both entities share risk factors, physiopathological mechanisms and, to some degree, therapeutic approaches. Withdrawing the causal agent, reducing the dose or switching to a less potent antidopaminergic drug should be the first therapeutic options. Here we review both entities and emerging therapies including the recently approved drugs deutetrabenazine and valbenazine. We discuss relevant aspects for clinical practice such as new diagnostic techniques and the latest advances in the understanding of DIP and TD.

Quantification of the Light Subunit of Neurofilament Protein in Cerebrospinal Fluid of Huntington's Disease Patients.

 Neurofilament light proteins (NFL) are a structural element of the neuronal cytoskeleton and are released with neuronal damage. Its levels are increased in cerebrospinal fluid (CSF) in the setting of neurodegenerative diseases. We investigated the CSF-NFL levels of Huntington´s disease (HD) patients (participating in a clinical trial SAT-HD) as well as of premanifest carriers and compared their results with a sample of healthy controls and correlated CSF-NFL levels with demographic and clinical variables (baseline demographic characteristics and HD measures of disease severity). CSF levels were significantly higher in all HD subjects [5014.4 (1557.3) ng/l] and pre-manifest carriers [1050 (212.13) ng/l as compared to controls [331.4 (200.2) ng/l] (p<0.00) and were correlated with age (correlation coefficient -0.37, p<0.01) and CAG triplet number (0,51, p<0.05) in the subset of HD patients. NFL levels were not correlated with age in the control group. We did not find any correlation with the remaining variables. These results indicate, as in previous studies, that CSF-NFL levels are a marker of neuronal damage in HD. It seems to be a highly sensitive, but non-specific marker of axonal damage. One of the limitations of our study is a very small number of patients in pre-symptomatic group and lack of individuals with very advanced HD. Further investigations should focus on study of CSF-NFL levels in advanced patients, tracking prospectively CSF-NFL levels and analysing its correlation with the clinical course and usefulness to monitor disease progression, validation and quantification of NFL levels in more accessible biofluids.

Docencia e Investigación en Odontología Legal en Chile: Situación y Desafíos Actuales / Teaching and Research in Legal Dentistry in Chile: Current Situation and Challenges

RESUMEN: El objetivo de este estudio es describir las características de las instituciones y el equipo de investigación y docencia que imparten Odontología Legal (OL) a nivel pregrado en Chile. Estudio cualitativo realizado durante el 2017. Desde las páginas web institucionales de las universidades que imparten la carrera de odontología en Chile, se obtuvo información sobre el cuerpo docente del ramo de OL a nivel pregrado. Cuando la información no estuvo disponible, se solicitó vía correo electrónico. Se realizó una búsqueda de publicaciones chilenas sobre OL y Forense en las bases de datos Medline, SciELO, Lilacs y Cochrane, y se identificó aquellas realizadas por docentes ejerciendo en Chile. La asignatura de OL se imparte a nivel pregrado en 17 de las 21 universidades que imparten la carrera de Odontología, siendo un curso obligatorio en 16 de ellas, y electivo en una de ellas. De los 29 docentes que imparten el ramo a nivel pregrado en Chile, sólo tres tiene la especialidad de OL. Se encontraron sólo 28 publicaciones científicas en el área en los últimos diez años, cuya autoría corresponde a cinco de los docentes del ramo a nivel pregrado. En Chile, la docencia de OL, a nivel pregrado, es impartida mayoritariamente por cirujano-dentistas no especializados en el área, en concordancia con que la especialidad comenzó a impartirse en el año 2015. Es imperioso aumentar la investigación en OL entre los docentes, de manera de desarrollar el área a nivel universitario, aumentando el conocimiento en la disciplina y consolidándola como ciencia.

ABSTRACT: The aim of this study was to describe the characteristics of the universities and the research and education teams imparting "Forensic Odontology" at undergraduate level in Chile. A qualitative cross-sectional study was conducted during 2017. Information was sought from the institutional websites of universities that impart Dentistry degrees. When the information was not available, it was requested via email to the respective authorities. A search was conducted to identify Chilean publications that deal with the topic of forensic dentistry, in the Medline, SciELO, Lilacs and Cochrane databases. Those authored or co-authored by academic(s) teaching in Chile were identified. "Forensic Odontology" is taught at undergraduate level in 17 of the 21 universities that impart the career of Dentistry in Chile, being mandatory in 16 of schools, and an elective in one of them. Of the 29 academics who teach the subject at undergraduate level in Chile, only three have the specialty of OL. Only 28 scientific publications in the area were found in the last ten years, whose authorships correspond to five academics in the field, teaching at undergraduate level. In Chile, "Forensic Odontology" at the undergraduate level, is mainly imparted by dental surgeons not specialized in the subject, in accordance with the fact that the specialty began to be taught in Chile only in 2015. It is imperative to increase the amount of research in forensic odontology conducted by the academics, in order to develop the area at the university level, to improve knowledge in this discipline and consolidate it as a science.

Does normal substantia nigra echogenicity make a difference in Parkinson's disease diagnosis? A real clinical practice follow-up study.

OBJECTIVES: Substantia nigra hyperechogenicity (SN+) detected by transcranial ultrasound (TUS) is useful for Parkinson's disease (PD) diagnosis. Approximately 15% false negative results of unknown significance are reported. However, most TUS studies are transversal, and diagnosis of PD may change during follow-up. METHODS: Analysis of our prospective registry of TUS in clinical practice, selecting patients with sufficient bone window, to whom TUS was performed because of suspected PD, and a minimum of 3-year follow-up. Subjects were classified regarding SN echogenicity (SN+/SN-). RESULTS: 172 patients (122 SN+, 50 SN-), mean age 71 years (25-90), were included. At the end of follow-up, PD diagnosis was retained by 91% SN+ vs. 54% SN- subjects (p < 0.0001), while final diagnosis of atypical parkinsonism (3%SN+ vs. 16%SN-, p:0.0059) was more frequent in SN-. Dopaminergic therapy response was associated with SN+ (88% SN+ vs. 50% SN-, p < 0.0001), as were abnormal DaTSCANs (90%SN+ vs. 56%SN-, p 0.0027). SN echogenicity had 80% sensitivity and 68% specificity for PD diagnosis, while SPECT had 91% and 73%, respectively. SN+ was the only baseline predictor of keeping PD diagnosis at the end of follow-up, with an odds ratio of 12 (95% CI 3-42) (p < 0.001). CONCLUSIONS: In our sample of patients with suspected PD, SN hyperechogenicity predicted PD diagnosis in the long term with a high odds ratio. Conversely, a baseline normal SN echogenicity was associated with a poorer response to PD therapy and change to a different diagnosis from PD. Normal SN appears to be a caveat for clinicians to check for atypical parkinsonism features during follow-up.