Detection of Horizontal Gene Transfer Mediated by Natural Conjugative Plasmids in E. coli.

Conjugation represents one of the main mechanisms facilitating horizontal gene transfer in Gram-negative bacteria. This work describes methods for the study of the mobilization of naturally occurring conjugative plasmids, using two naturally-occurring plasmids as an example. These protocols rely on the differential presence of selectable markers in donor, recipient, and conjugative plasmid. Specifically, the methods described include 1) the identification of natural conjugative plasmids, 2) the quantification of conjugation rates in solid culture, and 3) the diagnostic detection of the antibiotic resistance genes and plasmid replicon types in transconjugant recipients by polymerase chain reaction (PCR). The protocols described here have been developed in the context of studying the evolutionary ecology of horizontal gene transfer, to screen for the presence of conjugative plasmids carrying antibiotic-resistance genes in bacteria found in the environment. The efficient transfer of conjugative plasmids observed in these experiments in culture highlights the biological relevance of conjugation as a mechanism promoting horizontal gene transfer in general and the spread of antibiotic resistance in particular.

The effect of reducing attentional resources on selective suppression in the Simon task.

Studies using reaction times (RTs) distribution methods find that the Simon effect is greater for fast RTs and becomes smaller or reversed for slow RTs. However, the exact mechanisms responsible for this reduction are under debate. This study addressed the issue of whether attentional resources play a role in reduction of the Simon effect over time by investigating whether it is influenced by attentional constraints in a dual-task paradigm. Participants were instructed to perform a Simon task concurrently with a secondary task. Secondary task characteristics were manipulated by varying the overlap between the secondary task and the Simon task. Specifically, secondary tasks varied in their stimulus modality (auditory or visual) and/or response type (verbal or manual and lateralised or not). Distribution analyses of RTs, in the form of delta-plot functions, were performed for both the single- and dual-task conditions. Results showed that the more attention the secondary task demanded, the less the Simon effect was reduced, even for slower RTs. This suggests that the mechanisms responsible for the reduction of Simon effect over time are under top-down control.

Dissociable effects of positive feedback on the capture and inhibition of impulsive behavior in adolescents with ADHD versus typically developing adolescents.

The present study investigated how enhancing motivation by delivering positive feedback (a smiley) after a successful trial could affect interference control in adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and in their typically developing (TD) peers. By using a Simon task within the theoretical framework of the "activation-suppression" model, we were able to separately investigate the expression and the inhibition of impulsive motor behavior. The experiment included 19 adolescents with ADHD and 20 TD adolescents in order to explore whether data found in adolescents with ADHD were similar to those found in TD adolescents. Participants performed the Simon task in two conditions: a condition with feedback delivered after each successful trial and a condition with no feedback. The main findings were that increasing motivation by delivering positive feedback increased impulsive response in both groups of adolescents. It also improved the efficiency of impulsive motor action inhibition in adolescents with ADHD but deteriorated it in TD adolescents. We suggest that 1/increased motivation could lead adolescents to favor fast responses even if incorrect, and 2/the differential effect of feedback on the selective suppression of impulsive motor action in both groups could be due to different baseline DA levels.

Dynamic profiles and predictive values of some biochemical and haematological quantities in COVID-19 inpatients.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in some hospitalized patients has shown some important alterations in laboratory tests. The aim of this study was to establish the most relevant quantities associated with the worst prognosis related to COVID-19. MATERIALS AND METHODS: This was a descriptive, longitudinal, observational and retrospective study, in a cohort of 845 adult inpatients from Bellvitge University Hospital (L'Hospitalet de Llobregat, Barcelona, Spain). A multivariate regression analysis was carried out in demographic, clinical and laboratory data, comparing survivors (SURV) and non-survivors (no-SURV). A receiver operating characteristic analysis was also carried out to establish the cut-off point for poor prognostic with better specificity and sensibility. Dynamic changes in clinical laboratory measurements were tracked from day 1 to day 28 after the onset of symptoms. RESULTS: During their hospital stay, 18% of the patients died. Age, kidney disease, creatinine (CREA), lactate-dehydrogenase (LD), C-reactive-protein (CRP) and lymphocyte (LYM) concentration showed the strongest independent associations with the risk of death in the multivariate regression analysis. Established cut-off values for poor prognosis for CREA, LD, CRP and LYM concentrations were 75.0 µmol /L, 320 U/L, 80.9 mg/L and 0.69 x109/L. Dynamic profile of laboratory findings, were in agreement with the consequences of organ damage and tissue destruction. CONCLUSIONS: Age, kidney disease, CREA, LD, CRP and LYM concentrations in COVID-19 patients from the southern region of Catalonia provide important information for their prognosis. Measurement of LD has demonstrated to be very good indicator of poor prognosis at initial evaluation because of its stability over time.

Prevalence and associations of metabolic syndrome in patients with alcohol use disorder.

Excessive alcohol consumption has been associated with different components of the metabolic syndrome (MetS) such as arterial hypertension, dyslipidemia, type 2 diabetes or obesity. We aimed to analyze the prevalence and associations of MetS in patients with Alcohol Use Disorder (AUD). Cross-sectional study in heavy drinkers admitted for the treatment of AUD between 2013 and 2017. Medical comorbidity, anthropometric data, alcohol use and biological parameters were obtained. MetS was established according to the harmonized definition. A total of 728 patients (22% women) were included; median age was 47 years (IQR: 40-53.5), median alcohol consumption was 160 g/day (IQR: 115-240) and prevalence of MetS was 13.9%. The multivariate analysis showed a significant dose-response effect of estimated glomerular filtration (eGFR) and MetS: relative to patients with eGFR > 90 mL/min, those with eGFR (60-90 mL/min) and those with eGFR < 60 mL/min were 1.93 times (95% CI 1.18-3.15) and 5.61 times (95% CI 1.66-19.0) more likely to have MetS, respectively. MetS was significantly associated with hyperuricemia (OR 2.28, 95% CI 1.36-3.82) and elevated serum GGT (OR 3.67, 95% CI 1.80-7.46). Furthermore, for every increase of 1 year in age, the probability of MetS increased significantly (OR 1.03, 95% CI 1.01-1.05). MetS in heavy drinkers is independently associated with reduced kidney function and metabolic risk factors including hyperuricemia and elevated serum GGT.

Cannabis hyperemesis syndrome: Incidence and treatment with topical capsaicin. / Síndrome de hiperémesis por cannabis: incidencia y tratamiento con capsaicina tópica.

There are few studies in Spain on cannabinoid hyperemesis syndrome (CHS), as well as on the use of topical capsaicin as a treatment. METHODS: Retrospective study of patients over 14 years of age seen in a hospital emergency department during 2018 and 2019 with a diagnosis of CHS based on the following criteria: compatible clinical picture, cannabis use less than 48h and positive urine cannabis test. Epidemiological and clinical variables, attendance times and treatment (including use of topical capsaicin 0.075%) were collected. RESULTS: Fifty-nine attendances were studied, from 29 patients (4.4 cases/10,000 visits, 95% CI 2.8-4.7). Fifty per cent returned for CHS, differing only in more tobacco (P=.01) and cocaine (P=.031) use. Capsaicin was used in 74.6% of visits. The mean time to resolution of vomiting after application was 17.87min. CONCLUSIONS: Although probably underdiagnosed, CHS has a low incidence in the emergency department in Spain, with high patient recurrence. The use of capsaicin ointment is efficient and safe.

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that individuals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in individuals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients' diagnosis, follow-up, and longitudinal assessment in the clinical setting.

Stronger impulse capture and impaired inhibition of prepotent action in children with ADHD performing a Simon task: An electromyographic study.

OBJECTIVE: A deficit in interference control is commonly reported in children with attention deficit hyperactivity disorder (ADHD). This has mainly been interpreted as a difficulty in inhibiting inappropriate responses. However, it could be due to at least two distinct and independent processes, which are often confounded: The activation or suppression of impulsive responses. The aim of the present study was to separate the contribution of these two processes. METHOD: We compared performance of 26 children with ADHD to that of 26 nonADHD children using a novel approach based on electromyographic activity (EMG) analysis. EMG allows two distinct indices to be computed: Incorrect activation rate, which is an index of the intensity of impulse capture and correction rate, which provides a direct measure of the ability to suppress automatic responses. RESULTS: Children with ADHD were slower, committed more errors, and had a larger interference effect than nonADHD children. Moreover, we observed a greater incorrect activation rate and a lower correction rate in the ADHD group. CONCLUSIONS: Our data suggest that the difficulties in interference control found in children with ADHD are explained by both impaired inhibitory processes and a greater propensity to activate automatic responses. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Differential response to pharmacological intervention in ADHD furthers our understanding of the mechanisms of interference control.

The deficit in "interference control" found in children with Attention Deficit Hyperactivity Disorder (ADHD) could be due to two distinct processes, which are not disentangled in most studies: a larger susceptibility to activating prepotent response impulses and a deficit in suppressing them. Here, we investigated the effect of 1/ADHD and 2/ methylphenidate (MPH), on these two components of interference control. We compared interference control between untreated children with ADHD, children with ADHD under MPH, and typically developing children performing a Simon task. The main findings were that 1/ children with ADHD were more susceptible to reacting impulsively and less efficient at suppressing impulsive actions, and 2/ MPH improved the selective inhibition of impulsive actions but did not modify the strength of response impulse. This work provides an example of how pharmacological interventions and selective responses to them can be used to investigate and further our understanding of cognitive processing.

Derretimiento corneal como complicación de queratitis ulcerativa periférica en un paciente con artritis reumatoide / Corneal melt as a complication of a peripheral ulcerative keratitis in a patient with rheumatoid arthritis

RESUMEN Las manifestaciones oculares de la artritis reumatoide son manifestaciones graves que requieren manejo agresivo. En el presente reporte presentamos un caso de queratitis asociada a derretimiento corneal desencadenado por suspensión abrupta de su medicación reumatológica y cirugía no ocular, que respondió de forma favorable al manejo con metil-prednisolona y ciclofosfamida.

ABSTRACT Ocular signs of rheumatoid arthritis are severe extra-articular manifestations, which usually require aggressive management. In this report, A case is presented here of patient with peripheral ulcerative keratitis associated with corneal melt syndrome triggered by abrupt suspension of antirheumatic medication and non-ocular surgery. They symptoms responded favourably to methylprednisolone and cyclophosphamide.

Two sides of the same coin: ADHD affects reactive but not proactive inhibition in children.

Children with attention-deficit/hyperactivity disorder (ADHD) present a deficit in inhibitory control. Still, it remains unclear whether it comes from a deficit in reactive inhibition (ability to stop the action in progress), proactive inhibition (ability to exert preparatory control), or both.We compared the performance of 39 children with ADHD and 42 typically developing children performing a Simon choice reaction time task. The Simon task is a conflict task that is well-adapted to dissociate proactive and reactive inhibition. Beyond classical global measures (mean reaction time, accuracy rate, and interference effect), we used more sophisticated dynamic analyses of the interference effect and accuracy rate to investigate reactive inhibition. We studied proactive inhibition through the congruency sequence effect (CSE).Our results showed that children with ADHD had impaired reactive but not proactive inhibition. Moreover, the deficit found in reactive inhibition seems to be due to both a stronger impulse capture and more difficulties in inhibiting impulsive responses. These findings contribute to a better understanding of how ADHD affects inhibitory control in children.

Caracterización de pacientes con enfermedad de ojo seco en una institución de referencia en la ciudad de Medellín, Colombia / Characterization of patients with dry eye disease from distinguished ophthalmology clinic in Medellín, Colombia

Introducción: La enfermedad de ojo seco ha sido definida como una entidad multifactorial en la cual se pierde la homeostasis de la película lagrimal. Objetivo: Caracterizar a los pacientes con enfermedad de ojo seco atendidos en la unidad de ojo seco de la Clínica de Oftalmología Sandiego. Materiales y métodos: Estudio observacional, descriptivo, de cohorte retrospectiva. Se documentaron pruebas cualitativas, cuantitativas, cuestionario OSDI y tipo de ojo seco de los pacientes que consultaron en el periodo de marzo de 2016 a diciembre de 2017 con diagnóstico confirmado de enfermedad de ojo seco. Resultados: En 107 pacientes se confirmó el diagnóstico de ojo seco, 80.4% fueron mujeres. La mediana de edad fue 53 años (38-69). El 64.5% tenía ojo seco evaporativo, 12.2% acuodeficiente y 23.4% mixto. El OSDI fue mayor a 33 en 67 pacientes. La osmolaridad lagrimal y la MMP-9 estuvieron alteradas en 78.5 y 76.6%, respectivamente. Conclusión: La realización de pruebas clínicas, laboratorio y cuestionarios de síntomas, permiten realizar el diagnóstico integral de la enfermedad ojo seco según las recomendaciones del DEWS II, apoyando la clasificación del mismo, reconocimiento de factores de riesgo y planteamiento de posibles etiologías que ayudan en el tratamiento.

ackground: Dry eye disease has been defined by DEWS II as a multifactorial entity in which tear film homeostasis is altered. Objective: To characterize patients with dry eye disease evaluated in the dry eye unit of Clínica de Oftalmología Sandiego. Materials and methods: Observational, descriptive, retrospective cohort study. Information was collected from patients who consulted the dry eye unit in the period from March 2016 to December 2017 and who were diagnosed with dry eye disease. The results of qualitative and quantitative tests, as well as the dry eye symptoms questionnaire, were documented.

How Is Temporal Processing Affected in Children with Attention-deficit/hyperactivity Disorder?

We compared the performance of children with ADHD and typically developing children on two temporal tasks, a bisection task and a reproduction task, in auditory and visual modalities. Children with ADHD presented a larger variability when performing auditory and visual temporal tasks. Moreover, they overestimated the durations in bisection tasks and underproduced duration intervals in the visual reproduction task. In the context of the pacemaker-accumulator model, these results suggest that temporal deficits might result from a dysfunction in the switch and/or memory impairment.

Clinical Management of Prostate Cancer Metastasis to Pineal Gland: Case Report and Review of Literature.

BACKGROUND: Prostate cancer is the most common cancer among American men, with an incidence of approximately 233,000 cases per year. Intracranial metastases are rare and, specifically, metastasis to the pineal gland has only been reported in 2 postmortem cases in the literature. CASE DESCRIPTION: We present the first documented case of confirmed prostate cancer metastasis to the pineal gland in a living patient. The patient underwent an endoscopic third ventriculostomy and pineal lesion biopsy with complete resolution of his hydrocephalus and presenting symptoms. His biopsy results confirmed the prostate origin of the metastasis, and he subsequently underwent stereotactic radiosurgery for treatment of this lesion. CONCLUSIONS: This is the first report of the clinical management of metastatic prostate cancer to the pineal region and description of the clinical outcome. Although prostate cancer is the most common cancer in American men, metastasis to the pineal has only been reported twice from autopsy examinations. Overall, pineal tumors in the geriatric population are exceedingly rare and the age and comorbidities in this patient made management quite unique.

Manipulating the Alpha Level Cannot Cure Significance Testing.

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

Reduced TH expression and α-synuclein accumulation contribute towards nigrostriatal dysfunction in experimental hepatic encephalopathy.

PURPOSE: The present work examines α-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and α-synuclein expression were sought. METHODS: Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), α-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub). RESULTS: In the control rats, TH immunoreactivity was detected in the neuronal cell bodies and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH-positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of α-synuclein-immunoreactive neurons in the SNc; some of the TH-positive neurons also showed α-synuclein immunoreactivity. In addition, α-synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas α-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure. CONCLUSION: α-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation.

Strongyloides hyperinfection syndrome in an immunocompetent host resulting in bandemia and death.

Strongyloides stercoralis infection is usually asymptomatic but can result in a hyperinfection syndrome, most commonly triggered by acquired or iatrogenic immunosuppression. Here, we present a case of a man aged 60 years originally from a strongyloides endemic area with a medical history of alcohol abuse who presents with strongyloides hyperinfection syndrome (SHS) complicated by partial small bowel obstruction, pulmonary haemorrhage, large bandemia without eosinophilia and cardiac arrest resulting in death. This case is notable for the presence of bandemia and absence of eosinophilia, lack of historical risk factors for hyperinfection, specifically corticosteroid immunosuppressants, and dramatic decline in clinical status which ultimately resulted in the patient's death. Clinicians should suspect SHS in immunocompetent patients who are from an endemic area and who have persistent gastrointestinal and/or pulmonary manifestations in the absence of a clear cause.

Targeting IgE in Severe Atopic Dermatitis with a Combination of Immunoadsorption and Omalizumab.

Patients with atopic dermatitis (AD) tend to have greatly elevated levels of serum immunoglobulin E (IgE). However, the role of IgE in the pathogenesis of AD is debated. This investigator-initiated open-label pilot study evaluates an anti-IgE-treatment approach by combining extracorporeal immunoadsorption and anti-IgE antibody omalizumab in 10 patients with severe, therapy-refractory AD. IgE levels decreased after immunoadsorption and decreased continuously in all patients during anti-IgE therapy. The reverse trend was observed during 6 months follow-up without treatment. In parallel with these observations, an improvement in AD was observed during the treatment period, with aggravation during follow-up. Further research is needed, based on the principle of reducing IgE levels in order to improve clinical symptoms, using a combination anti-IgE treatment approach, adjusted according to IgE levels.

Ammonia Affects Astroglial Proliferation in Culture.

Primary cultures of rat astroglial cells were exposed to 1, 3 and 5 mM NH4Cl for up to 10 days. Dose- and time-dependent reductions in cell numbers were seen, plus an increase in the proportion of cells in the S phase. The DNA content was reduced in the treated cells, and BrdU incorporation diminished. However, neither ammonia nor ammonia plus glutamine had any effect on DNA polymerase activity. iTRAQ analysis showed that exposure to ammonia induced a significant reduction in histone and heterochromatin protein 1 expression. A reduction in cell viability was also noted. The ammonia-induced reduction of proliferative activity in these cultured astroglial cells seems to be due to a delay in the completion of the S phase provoked by the inhibition of chromatin protein synthesis.