A need for standardized reporting of introgression: Insights from studies across eukaryotes.

With the rise of affordable next-generation sequencing technology, introgression-or the exchange of genetic materials between taxa-has become widely perceived to be a ubiquitous phenomenon in nature. Although this claim is supported by several keystone studies, no thorough assessment of the frequency of introgression across eukaryotes in nature has been performed to date. In this manuscript, we aim to address this knowledge gap by examining patterns of introgression across eukaryotes. We collated a single statistic, Patterson's D, which can be used as a test for introgression across 123 studies to further assess how taxonomic group, divergence time, and sequencing technology influence reports of introgression. Overall, introgression has mostly been measured in plants and vertebrates, with less attention given to the rest of the Eukaryotes. We find that the most frequently used metrics to detect introgression are difficult to compare across studies and even more so across biological systems due to differences in study effort, reporting standards, and methodology. Nonetheless, our analyses reveal several intriguing patterns, including the observation that differences in sequencing technologies may bias values of Patterson's D and that introgression may differ throughout the course of the speciation process. Together, these results suggest the need for a unified approach to quantifying introgression in natural communities and highlight important areas of future research that can be better assessed once this unified approach is met.

An Indian lineage of Histoplasma with strong signatures of differentiation and selection.

Histoplasma, a genus of dimorphic fungi, is the etiological agent of histoplasmosis, a pulmonary disease widespread across the globe. Whole genome sequencing has revealed that the genus harbors a previously unrecognized diversity of cryptic species. To date, studies have focused on Histoplasma isolates collected in the Americas with little knowledge of the genomic variation from other localities. In this report, we report the existence of a well-differentiated lineage of Histoplasma occurring in the Indian subcontinent. The group is differentiated enough to satisfy the requirements of a phylogenetic species, as it shows extensive genetic differentiation along the whole genome and has little evidence of gene exchange with other Histoplasma species. Next, we leverage this genetic differentiation to identify genetic changes that are unique to this group and that have putatively evolved through rapid positive selection. We found that none of the previously known virulence factors have evolved rapidly in the Indian lineage but find evidence of strong signatures of selection on other alleles potentially involved in clinically-important phenotypes. Our work serves as an example of the importance of correctly identifying species boundaries to understand the extent of selection in the evolution of pathogenic lineages. IMPORTANCE: Whole genome sequencing has revolutionized our understanding of microbial diversity, including human pathogens. In the case of fungal pathogens, a limiting factor in understanding the extent of their genetic diversity has been the lack of systematic sampling. In this piece, we show the results of a collection in the Indian subcontinent of the pathogenic fungus Histoplasma, the causal agent of a systemic mycosis. We find that Indian samples of Histoplasma form a distinct clade which is highly differentiated from other Histoplasma species. We also show that the genome of this lineage shows unique signals of natural selection. This work exemplifies how the combination of a robust sampling along with population genetics, and phylogenetics can reveal the precise genetic changes that differentiate lineages of fungal pathogens.

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

A narrow window for geographic cline analysis using genomic data: Effects of age, drift, and migration on error rates.

The use of genomic and phenotypic data to scan for outliers is a mainstay for studies of hybridization and speciation. Geographic cline analysis of natural hybrid zones is widely used to identify putative signatures of selection by detecting deviations from baseline patterns of introgression. As with other outlier-based approaches, demographic histories can make neutral regions appear to be under selection and vice versa. In this study, we use a forward-time individual-based simulation approach to evaluate the robustness of geographic cline analysis under different evolutionary scenarios. We modelled multiple stepping-stone hybrid zones with distinct age, deme sizes, and migration rates, and evolving under different types of selection. We found that drift distorts cline shapes and increases false positive rates for signatures of selection. This effect increases with hybrid zone age, particularly if migration between demes is low. Drift can also distort the signature of deleterious effects of hybridization, with genetic incompatibilities and particularly underdominance prone to spurious typing as adaptive introgression. Our results suggest that geographic clines are most useful for outlier analysis in young hybrid zones with large populations of hybrid individuals. Current approaches may overestimate adaptive introgression and underestimate selection against maladaptive genotypes.

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort.

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.

Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.

BACKGROUND: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. MATERIAL AND METHODS: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. RESULTS: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ±â€¯12.8 vs 11.6 ±â€¯10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ±â€¯0.5 vs 4 ±â€¯0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ±â€¯32 vs 29.1 ±â€¯25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. CONCLUSIONS: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

BACKGROUND AND PURPOSE: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). METHODS: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. RESULTS: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). CONCLUSIONS: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Magnetic compression anastomosis as a nonsurgical treatment for esophageal atresia.

BACKGROUND: We describe a unique technique to promote a nonsurgical esophageal anastomosis with magnets in children with esophageal atresia. OBJECTIVE: To evaluate the efficacy of magnetic lengthening of atretic esophageal ends to produce an anastomosis and to communicate our results after more than 2 years of follow-up. MATERIALS AND METHODS: Between September 2001 and March 2004, five children were selected for treatment. Two of the children had esophageal atresia without fistula (type A) and three had atresia with fistula converted to type A surgically; however, surgeons failed to achieve an anastomosis because of the width of the gap. Neodymium-iron-boron magnets were used. Daily chest radiographs were taken until union of the magnets was observed. They were then replaced with an orogastric tube. RESULTS: Anastomosis was achieved in all patients in an average of 4.8 days. One patient, with signs of early sepsis, was successfully treated with antibiotics. In four of the five patients, esophageal stenosis developed. At the time of this report, two patients were free of treatment and on an oral diet (after 26 months), two patients required periodic balloon dilatation, and one patient had recently undergone surgery due to recurrent esophageal stenosis not amenable to balloon dilatation. CONCLUSION: Magnetic esophageal anastomosis is a feasible method in selected patients with esophageal atresia. Esophageal anastomosis was achieved in all patients. The only observed complication of significance was esophageal stenosis. One patient needed surgery because of stenosis.

[Infections of the central nervous system in emergency department]. / Infecciones del sistema nervioso central en urgencias.

Infections of the central nervous system are frequent diseases in emergency care. They can have a bacterial, parasitic or viral origin. Initial symptoms can be non-specific, which can complicate and delay diagnosis, hence the extreme importance of all the information that can be obtained through anamnesis and physical exploration, with frequent complementary explorations. In the last hundred years, with the introduction of antibiotic drugs, there has been a significant fall in mortality secondary to meningoencephalitis, but in spite of that they continue to provoke high morbidity and mortality. Other phenomena, such as vaccination campaigns, migratory movements, infection by HIV and other states of immunosuppression, have given rise to important epidemiological changes such as the virtual disappearance of some infections or the appearance of others that rarely existed previously. The list of potential infections of the central nervous system is extensive, which is why in this review we set out, from the clinical, diagnostic and therapeutic point of view, those that are most frequent in our environment and some that, although very infrequent, might require emergency attention due to their severity.

[Movement disorders in the emergency department]. / Los trastornos del movimiento en urgencias.

Acute or sub-acute movement disorders represent a small percentage of neurological emergencies but it is necessary to be aware of their existence because a failure in their diagnosis or treatment can result in significant morbidity and mortality. Clinical presentation of acute movement disorders can be diverse. In some cases acinesia or rigidity predominates, while others are characterized by dystonia, chorea o balism. The type of movement disorder suggest a specific aetiology. Drugs represent the most frequent etiologic factor and are the cause of neuroleptic malignant syndrome and serotoninergic syndrome. Emergencies secondary to Parkinson's disease are reviewed, including parkinsonism-hyperpirexia syndrome, acute psychosis and the emergencies derived from deep brain stimulators. Different aetiologies of acute dystonia and chorea are also covered and, finally, acute movement disorders due to stroke are reviewed.

Infecciones del sistema nervioso central en urgencias / Infections of the central nervous system in emergency department

Las infecciones del sistema nervioso central son enfermedades frecuentes en la atención urgente, pudiendo ser de origen bacteriano, parasitario o vírico. Los síntomas iniciales pueden ser inespecíficos, lo que puede dificultar y retrasar su diagnóstico, por lo que es de suma importancia toda la información que pueda obtenerse a través de la anamnesis y exploración física y con frecuencia exploraciones complementarias. En los últimos cien años, con la introducción de fármacos antibióticos ha disminuido de forma importante la mortalidad secundaria a meningoencefalitis, pero a pesar de ello siguen provocando alta morbi-mortalidad. Otros fenómenos, como las campañas de vacunación, movimientos migratorios, infección por el virus de la inmunodeficiencia humana y otros estados de inmunosupresión, han dado lugar a importantes cambios epidemiológicos como son la práctica desaparición de algunas infecciones o la aparición de otras previamente casi inexistentes. La lista de infecciones potenciales de sistema nervioso central es extensa por lo que en este artículo de revisión expondremos desde el punto de vista clínico, diagnóstico y terapéutico las más frecuentes en nuestro medio y algunas que, aunque poco frecuentes, pueden requerir atención urgente por su gravedad (AU)

Infections of the central nervous system are frequent diseases in emergency care. They can have a bacterial, parasitic or viral origin. Initial symptoms can be non-specific, which can complicate and delay diagnosis, hence the extreme importance of all the information that can be obtained through anamnesis and physical exploration, with frequent complementary explorations. In the last hundred years, with the introduction of antibiotic drugs, there has been a significant fall in mortality secondary to meningoencephalitis, but in spite of that they continue to provoke high morbidity and mortality. Other phenomena, such as vaccination campaigns, migratory movements, infection by HIV and other states of immunosuppression, have given rise to important epidemiological changes such as the virtual disappearance of some infections or the appearance of others that rarely existed previously. The list of potential infections of the central nervous system is extensive, which is why in this review we set out, from the clinical, diagnostic and therapeutic point of view, those that are most frequent in our environment and some that, although very infrequent, might require emergency attention due to their severity (AU)

Los trastornos del movimiento en urgencias / Movement disorders in the emergency department

Los pacientes que acuden a urgencias con un cuadro clínico en el que predomina un trastorno del movimiento de instauración aguda o subaguda suponen un porcentaje pequeño de las urgencias neurológicas. Sin embargo, su conocimiento es importante ya que en muchos de estos casos un error en el diagnóstico o tratamiento puede conllevar una importante morbilidad e incluso mortalidad. La forma clínica de presentación de estos trastornos es variada y en algunos predomina la acinesia o la rigidez mientras que en otros casos son los movimientos anormales en forma de discinesias o balismos lo que caracterizan al cuadro clínico. El tipo de trastorno del movimiento orienta hacia una determinada etiología. El consumo de determinados fármacos o tóxicos supone una de las principales causas de trastorno agudo del movimiento dentro de las que se incluyen el síndrome neuroléptico maligno y el síndrome serotoninérgico. En esta revisión se ha dedicado un apartado a las urgencias que plantea la enfermedad de Parkinson y que incluyen el síndrome parkinsonismo-hiperpirexia, la psicosis aguda y las urgencias de los pacientes con neuroestimuladores. Las distonías y corea-balismo agudas son también abordadas, y por último se dedica un apartado a las trastornos del movimiento como forma de presentación de un ictus (AU)

Acute or sub-acute movement disorders represent a small percentage of neurological emergencies but it is necessary to be aware of their existence because a failure in their diagnosis or treatment can result in significant morbidity and mortality. Clinical presentation of acute movement disorders can be diverse. In some cases acinesia or rigidity predominates, while others are characterized by dystonia, chorea o balism. The type of movement disorder suggest a specific aetiology. Drugs represent the most frequent etiologic factor and are the cause of neuroleptic malignant syndrome and serotoninergic syndrome. Emergencies secondary to Parkinson’s disease are reviewed, including parkinsonism-hyperpirexia syndrome, acute psychosis and the emergencies derived from deep brain stimulators. Different aetiologies of acute dystonia and chorea are also covered and, finally, acute movement disorders due to stroke are reviewed (AU)

Recurrent angioedema due to lysozyme allergy.

A 54-year-old woman suffered an episode of dyspnea and edema affecting her eyelids, tongue, and lips a few minutes after intake of Lizipaina (bacitracin, papain, and lysozyme). She was treated with intravenous drugs and her symptoms improved within 2 hours. She had experienced 3 to 4 bouts of similar symptoms related to the ingestion of cured cheeses or raw egg. Specific serum immunoglobulin (Ig) E against lysozyme was present at a concentration of 0.45 kU/L, and no specific IgE was found against egg white and yolk, ovalbumin, or ovomucoid. Skin prick tests were positive with commercial extracts of egg white and lysozyme but doubtful with yolk, ovalbumin, and ovomucoid. Prick-to-prick tests with raw egg white and yolk gave positive results, but negative results were obtained with cooked egg white and yolk and 5 brands of cheese (3 of them containing lysozyme and the other 2 without lysozyme). Controlled oral administration of papain, bacitracin, and cheeses without lysozyme was well tolerated. We suggest that the presence of lysozyme in a pharmaceutical preparation, cured cheese, and raw egg was responsible for the symptoms suffered by our patient, probably through an IgE-mediated mechanism.

Severe immediate reaction to nabumetone.

Nabumetone is a nonsteroidal antiinflammatory (NSAID) prodrug that inhibits cyclooxygenase-2. It has been recommended as a safe alternative in most patients with hypersensitivity reactions to NSAIDs. Systemic reactions caused by nabumetone are not frequent. We report 2 cases of immediate systemic reactions due to nabumetone. The first case involved a 68-year-old woman who developed immediate generalized pruritus, erythema, morbilliform eruption, swollen tongue sensation, diarrhea, and hypotension after the ingestion of a single dose of nabumetone. In the second case, a 77-year-old woman developed generalized pruritus, palm erythema, colic abdominal pain, diarrhea, dizziness, tightness of the chest, dyspnea, and hypotension immediately after oral intake of nabumetone. Both patients had previously tolerated this drug. Since these episodes, they have avoided nabumetone. Skin prick tests with nabumetone (10 and 100 mg/mL) were negative. Oral challenge tests with other NSAIDs, even of the same group as nabumetone, were negative in both patients. The mechanisms responsible for the reaction were not established.

[Neurocysticercosis. An emergent disease]. / Neurocisticercosis. Una enfermedad emergente.

Neurocysticerosis is an affection of the central nervous system by the larvae of the Taenia solium. Although its diagnosis in our country is exceptional, in recent years a notable increase in the number of cases diagnosed has been observed, due to the phenomenon of immigration from countries where the disease is endemic. The most frequent form of presentation of neurocysticercosis is seizures, followed by headache. To diagnose it we must evaluate the epidemiological data, the clinical record and confirm this through neuroimage and immunological studies. The treatment selected should be pharmacological, principally with albendazole, and surgery reserved for cases where the former fails. Hygienic measures and the treatment of patients with teniasis are of great importance. Neurocysticerosis has ceased to be an exceptional diagnosis and given the foreseeable increase of its incidence in our milieu, health professionals must understand this disease and include it at higher levels of the algorithms of differential diagnosis.

Neurocisticercosis. Una enfermedad emergente / Neurocysticercosis. An emergent disease

La neurocisticercosis es una afectación del sistema nervioso central por las larvas de la Taenia solium. Aunque en nuestro país su diagnóstico era excepcional, en los últimos años se ha observado un notable incremento en el número de casos diagnosticados, debido al fenómeno de la inmigración desde países donde la enfermedad es endémica. La forma de presentación más frecuente de la neurocisticercosis es la crisis epiléptica, seguida de la cefalea. Para el diagnóstico de sospecha debemos valorar los datos epidemiológicos y la clínica y confirmarlo mediante los estudios de neuroimagen e inmunológicos. El tratamiento de elección debe ser farmacológico, principalmente con albendazol, y reservar la cirugía para los casos en el que el primero falla. Las medidas higiénico-sanitarias y el tratamiento de los pacientes con teniasis son de suma importancia. La neurocisticercosis ha dejado de ser uno de esos diagnósticos excepcionales y dado el previsible aumento de su incidencia en nuestro medio, los profesionales sanitarios debemos conocer dicha enfermedad e incluirla en niveles más altos de los algoritmos de diagnóstico diferencial (AU)

Ataques isquémicos transitorios / Transitory ischaemic attacks

No disponible

Abl kinase but not PI3-kinase links to the cytoskeletal defects in Bcr-Abl transformed cells.

OBJECTIVE: The purpose of this study was to investigate the contribution of Abl kinase and phosphatidylinositol 3-kinase (PI3-kinase) to the altered adhesive properties and cytoskeletal defects in a Bcr-Abl transformed fibroblast cell model. MATERIALS ANID METHODS: Two fibroblast cell lines stably transfected with Bcr-Abl were compared to their parental counterparts for alterations in their adhesive properties in an attachment assay and for abnormalities in their cytoskeletal architecture by immunofluorescence microscopy. Cells then were treated with specific inhibitors of either the Abl kinase CGP57148 or the PI3-kinase LY294002 to determine whether these treatments would restore normal cytoarchitecture and adhesion. RESULTS: [corrected] Significant defects in cytoskeletal architecture were observed using this fibroblast model of Bcr-Abl expression. Specific changes include loss of stress fibers and focal adhesions, which correlated with an adhesive defect. [corrected] Treatment of Bcr-Abl expressing cells with CGP57148, but not LY294002, resulted in reversion of cells to a near-normal phenotype, as assessed by immunofluorescence and attachment of Bcr-Abl transformed fibroblasts. CONCLUSIONS: Our studies demonstrate that Bcr-Abl tyrosine kinase but not PI3- kinase activity is required for maintenance of cytoskeletal rearrangements resulting from Bcr-AbI expression. Further, inhibition of Abl kinase restored normal adhesive properties to the Bcr-Abl-expressing cells, demonstrating the contribution of Bcr-Abl kinase activity to abnormal cytoskeletal function.