Prader-Willi syndrome in a large sample from Spain: general features, obesity and regular use of psychotropic medication.

BACKGROUND: Prader-Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross-sectional study was to describe the characteristics of the first large national sample of persons with PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors, particularly with obesity and the regular use of psychotropic medication. METHODS: Participants were recruited among all members of the Spanish Prader-Willi Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient (IQ), anthropometric measures, lifestyle habits, behavioural disturbances (with the Aberrant Behavior Checklist) and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. RESULTS: The cohort included 177 participants (aged 6-48 years), that is, 90 (50.8%) males and 87 (49.2%) females. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only-child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone (GH) treatment. Participants taking any psychotropic medication were characterised by more frequent age ≥30 years, high level of hyperactivity and a psychiatric diagnosis. CONCLUSIONS: Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long-term application of GH therapy and the rational use of psychotropic medication.

Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

Clinical, virological and phylogenetic characterization of a multiresistant HIV-1 strain outbreak in naive patients in southern Spain.

BACKGROUND: We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the 'Costa del Sol'), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned. RESULTS: Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded. CONCLUSIONS: We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.

[Knowledge level of hypertensive patients about hypertension. Relationship between knowledge level and hypertension control]. / Estudio Conocimiento: grado de conocimiento sobre hipertensión arterial de nuestros pacientes. Relación con el nivel de control de la misma.

OBJECTIVE: To assess the knowledge of the hypertensive patients about their hypertension and their relation to its control. MATERIAL AND METHODS: Cross-sectional study among 400 hypertensive patients, all over 18 years, selected from 50 primary-care centres, who responded to an hypertension-related survey. Included variables were survey items, age, gender, educational level, professional occupation, blood pressure data and antihypertensive treatment. The obtained differences were analyzed using the chi-square test, Kruskal-Wallis, Wilcoxon, Anova and Bonferroni methods. RESULTS: There were 323 valid surveys. 52.9% of respondents were women, the average age: 65.4 years (SD: 11.2), 54.8% of them had primary education. 39.6% were aware of the objectives of systolic BP control. Only 19.6% having knowledge of those for diastolic BP control, with no differences between controlled and uncontrolled (systolic BP: 39% vs 38.1%, P=.887; diastolic BP: 19.2% vs 21%, P=.721). Over 70% knew about lifestyle changes, without significant differences between controlled and uncontrolled respondents. 82% of controlled respondents, and 79% of those uncontrolled, recognized the chronical nature of the treatment (P=.548), but 15.1% of the controlled respondents and 12.4% of uncontrolled respondents did not see the relation between the treatment and hypertension control (P=.525). 31.1% believed to be well-controlled, but in fact was not. CONCLUSIONS: Our patients doesn't know blood pressure targets of control. There isn't relationship between this knowledge and control of hypertension.

Estudio Conocimiento: grado de conocimiento sobre hipertensión arterial de nuestros pacientes. Relación con el nivel de control de la misma / Knowledge level of hypertensive patients about hypertension. Relationship between knowledge level and hypertension control

Objetivo: Evaluar el conocimiento de nuestros pacientes hipertensos sobre su HTA y su relación con el control de la misma. Material y métodos: Estudio descriptivo transversal con 400 hipertensos, mayores de edad, seleccionados de forma sistemática consecutiva de 50 consultas de atención primaria, que respondieron una encuesta sobre HTA. Las variables recogidas fueron los ítems de la encuesta, edad, sexo, nivel educacional, ocupación, cifras de presión arterial y tratamiento antihipertensivo. Las diferencias se analizaron con los test ji-cuadrado, Kruskal-Wallis, Wilcoxon, Anova y Bonferroni según distribución normal. Resultados: Fueron válidas 323 encuestas. El 52,9% fueron mujeres, edad media de 65,4años (DE: 11,2). El 54,8% contaban con estudios primarios. El 39,6% conocían los objetivos de control de PA sistólica, y solo el 19,6% los de PA diastólica, sin diferencias entre controlados y no controlados (PA sistólica: 39% vs 38,1%, p = 0,887; PA diastólica: 19,2% vs 21%, p = 0,721). Más del 70% conocían las modificaciones del estilo de vida, sin diferencias entre controlados y no controlados. El 82% de los controlados y el 79% de los no controlados reconocieron la cronicidad del tratamiento (p = 0,548), pero el 15,1% de los controlados y el 12,4% de los no controlados no lo relacionaban con el control de la HTA (p = 0,525). El 31,1% creían estar bien controlados aunque no lo estaban. Conclusiones: Los pacientes hipertensos conocen en baja frecuencia cuáles son los objetivos de control, sin encontrar relación entre el conocimiento del problema y el control del mismo

Objective: To assess the knowledge of the hypertensive patients about their hypertension and their relation to its control. Material and methods: Cross-sectional study among 400 hypertensive patients, all over 18 years, selected from 50 primary-care centres, who responded to an hypertension-related survey. Included variables were survey items, age, gender, educational level, professional occupation, blood pressure data and antihypertensive treatment. The obtained differences were analyzed using the chi-square test, Kruskal-Wallis, Wilcoxon, Anova and Bonferroni methods. Results: There were 323 valid surveys. 52.9% of respondents were women, the average age: 65.4 years (SD: 11.2), 54.8% of them had primary education. 39.6% were aware of the objectives of systolic BP control. Only 19.6% having knowledge of those for diastolic BP control, with no differences between controlled and uncontrolled (systolic BP: 39% vs 38.1%, P = .887; diastolic BP: 19.2% vs 21%, P = .721). Over 70% knew about lifestyle changes, without significant differences between controlled and uncontrolled respondents. 82% of controlled respondents, and 79% of those uncontrolled, recognized the chronical nature of the treatment (P = .548), but 15.1% of the controlled respondents and 12.4% of uncontrolled respondents did not see the relation between the treatment and hypertension control (P = .525). 31.1% believed to be well-controlled, but in fact was not. Conclusions: Our patients doesn’t know blood pressure targets of control. There isn’t relationship between this knowledge and control of hypertension

Síndrome de Terson y ecografía orbitaria / Terson syndrome and ocular ultrasound

No disponible

Tacalcitol in the treatment of acquired perforating collagenosis.

Acquired perforating collagenosis (APC) is a rare perforating dermatosis characterized by transepidermal collagen elimination. We describe a 65-year-old patient, with long-standing type 2 diabetes mellitus and a 2-year history of itchy hyperkeratotic nodules situated on the back, who was subsequently diagnosed with APC. Treatment included topical corticosteroids and antihistamines, without improvement of the lesions. However, therapy with topical tacalcitol administered for 2 months produced a significant response leading to complete remission of APC.

Prognosis value of early diffusion MRI in Legg Perthes Calvé disease.

PURPOSE: To evaluate diffusion MRI of the proximal femoral epiphysis and metaphysis as a prognosis factor in Legg Calvé Perthes (LCP) disease. METHODS: Thirty-one children (mean age 5.5 years, range 2.5-10.5) with unilateral LCP were included in a prospective, consecutive series. Radiographs were analysed and classified as per Herring criteriae. Mean follow-up was 19 months (range 6-30). Forty-nine MRI scans were performed at either the condensation or fragmentation stage. Apparent Diffusion Coefficient (ADC) of both the femoral epiphysis and metaphysis were measured bilaterally and ADC ratio were calculated, then compared to the Herring group. RESULTS: Sixteen hips were rated Herring A or B, 3 Herring B-C and 12 Herring C. ADC was increased in affected hips compared to unaffected sides, both at the femoral epiphysis (P<0.001) and metaphysis (P<0.0001). ADC ratio of the femoral metaphysis was positively correlated to Herring classification: if superior to 1.63, it was associated with a bad prognosis (Herring B-C or C) (P=0.0017, sensitivity=89%, specificity=58%). Interobserver reliability of ADC measurement was excellent. The 1.63 threshold could be determined as early as the condensation stage. CONCLUSIONS: Diffusion presents several advantages including being non radiating and non invasive. It does not need contrast medium administration and it can be performed without anaesthesia. The origin of the increased ADC remains unknown. Basically, it reflects molecular changes (true diffusion) but it is also influenced by the vascular supply (pseudo-diffusion). ADC ratio could provide an early prognosis before Herring classification is applicable. LEVEL OF EVIDENCE: Level III. Prospective uncontrolled study.

A quantitative speciation model for the adsorption of organic pollutants on activated carbon.

Granular activated carbon (GAC) is commonly used as adsorbent in water treatment plants given its high capacity for retaining organic pollutants in aqueous phase. The current knowledge on GAC behaviour is essentially empirical, and no quantitative description of the chemical relationships between GAC surface groups and pollutants has been proposed. In this paper, we describe a quantitative model for the adsorption of atrazine onto GAC surface. The model is based on results of potentiometric titrations and three types of adsorption experiments which have been carried out in order to determine the nature and distribution of the functional groups on the GAC surface, and evaluate the adsorption characteristics of GAC towards atrazine. Potentiometric titrations have indicated the existence of at least two different families of chemical groups on the GAC surface, including phenolic- and benzoic-type surface groups. Adsorption experiments with atrazine have been satisfactorily modelled with the geochemical code PhreeqC, assuming that atrazine is sorbed onto the GAC surface in equilibrium (log Ks = 5.1 ± 0.5). Independent thermodynamic calculations suggest a possible adsorption of atrazine on a benzoic derivative. The present work opens a new approach for improving the adsorption capabilities of GAC towards organic pollutants by modifying its chemical properties.

Diffusion MRI of the neck of the femur in Legg-Calve-Perthes disease: a preliminary study.

PURPOSE: To evaluate diffusion MR imaging of the neck of the femur in Legg-Calve-Perthes disease (LCPD). MATERIAL AND METHODS: This is a prospective study in 27 children followed for unilateral LCPD. Forty-six MRIs were carried out with bilateral quantification of the apparent diffusion coefficient (ADC) of the neck of the femur. The intra- and inter-observer variability of the ADC measurements was evaluated. The association between the ADC and age as well as the healthy or pathological status of the neck of the femur and the Catterall classification were looked for. RESULTS: Intra- and inter-observer reproducibility of the ADC measurements was excellent. A statistically significant negative correlation between the ADC of the healthy neck of the femur and age was found. There was a significant increase in the ADC of the pathological neck of the femur compared to the healthy neck. The ratio of the pathological neck ADC and the healthy neck ADC was significantly associated with the Catterall classification. CONCLUSION: The quantification of the ADC of the neck of the femur is reproducible. This could be useful in the treatment of LCPD, where there is an early and significant increase in the ADC on the pathological side. This increase could have a prognostic value, as it is correlated with the Catterall classification.

Diversity of culturable halophilic archaea isolated from Rambla Salada, Murcia (Spain).

We have studied the diversity of culturable halophilic Archaea at Rambla Salada, Murcia (south-eastern Spain). We made 8 samplings at different places in this habitat during the years 2006 and 2007 and isolated a total of 49 strains, which were identified by means of phenotypic tests and the hypervariable V1-V3 region of the 16S rRNA gene sequences (around 500 bp). The ribosomal data showed that the isolates belonged to 12 genera within the Halobacteriaceae family, with Haloferax and Natrinema being the most abundant. Five strains showed less than 97% sequence identity with validly described species and may well represent new taxa. All the strains grew best with around 25% w/v salts, required high concentrations of NaCl and magnesium and produced red to pink colonies. They were facultative anaerobes with both respiratory and fermentative metabolisms. The diversity of the archaeal community was analysed with the MOTHUR package. We identified 14 OTUs at the 3% genetic distance level and found quite high diversity. Rarefaction curves of richness estimators and diversity indices demonstrated that our collection of isolates represented the archaeal community at Rambla Salada that can be isolated under the conditions used in this work. This is the first report to be published on the culturable archaea at Rambla Salada, an area of considerable ecological interest.

Cyclin-dependent kinase 1 expression is inhibited by p16(INK4a) at the post-transcriptional level through the microRNA pathway.

The p16(INK4a) protein regulates cell cycle progression mainly by inhibiting the activity of G1-phase cyclin-dependent kinases (CDKs) 4 and 6, the subsequent retinoblastoma protein (pRb) phosphorylation and E2F transcription factor release. The p16(INK4a) protein can also repress the activity of other transcription factors, such as c-myc, nuclear factor-kappaB and c-Jun/AP1. Here, we report that, in two p16(-/-), pRb(WT) and p53(WT) cell lines (MCF7 and U87), p16(INK4a) overexpression induces a dramatic decrease in CDK1 protein expression. In response to p16(INK4a), the decreased rate of CDK1 protein synthesis, its unchanged protein half-life, unreduced CDK1 mRNA steady-state levels and mRNA half-life allow us to hypothesize that p16(INK4a) could regulate CDK1 expression at the post-transcriptional level. This CDK1 downregulation is mediated by the 3'-untranslated region (3'UTR) of CDK1 mRNA as shown by translational inhibition in luciferase assays and is associated with a modified expression balance of microRNAs (miRNAs) that potentially regulate CDK1, analyzed by TaqMan Human microRNA Array. The p16(INK4a)-induced expression of two miRNAs (miR-410 and miR-650 chosen as an example) in MCF7 cells is confirmed by individual reverse transcription-qPCR. Furthermore, we show the interaction of miR-410 or miR-650 with CDK1-3'UTR by luciferase assays. Endogenous CDK1 expression decreases upon both miRNA overexpression and increases with their simultaneous inhibition. The induction of miR-410, but not miR-650 could be related to the pRb/E2F pathway. These results demonstrate the post-transcriptional inhibition of CDK1 by p16(INK4a). We suggest that p16(INK4a) may regulate gene expression by modifying the functional equilibrium of transcription factors and consequently the expression balance of miRNAs.

Diagnóstico coproparasitológico de Fasciola hepática en ganado bovino en una empresa pecuaria cubana / Coproparasitological diagnosis of Fasciola Hepatica in cattle in a cuban livestock farm

Con el objetivo de comparar el método coproparasitológico de sedimentación de Benedek con el kit inmunoenzimático FasciDIG para el diagnóstico de Fasciola hepática en ganado bovino de una empresa pecuaria cubana, se realizó un estudio descriptivo transversal entre febrero y marzo de 2008. Se colectó muestras de heces a 254 bovinos Jersey, Holstein y mestizos. Se encontró 16 (6.3%) animales positivos mediante el FasciDIG y 10 (3.9%) por la técnica de sedimentación de Benedek. Se concluye que el método inmunoenzimático (FasciDIG) demostró mayor detectabilidad diagnóstica que el método de sedimentación.

The aim of the study was to compare the coproparasitological method of Benedek sedimentation against the immunoenzimeassay for the diagnosis of Fasciola hepaticain cattle from a Cuban livestock large farm. A descriptive cross-sectional study was conducted in February-March 2008 and faecal samples were collected to 254 Jersey, Holstein, and crossbreed animals. Sixteen positive cases (6.3%) were detected using FasciDIG whereas only 10 (3.9%) using the Benedek sedimentation method. It was concluded that the immunoassay method (FasciDIG) showed better diagnostic sensitivity than the Benedek sedimentation test.

Molecular evolution of nitric oxide synthases in metazoans.

Nitric oxide synthases (NOS), the enzymes responsible for the NO synthesis, are present in all eukaryotes. Three isoforms (neuronal, inducible and endothelial), encoded by different loci, have been described in vertebrates, although the endothelial isoform seems to be restricted to tetrapods. In invertebrates, a variety of NOS isoforms have been variably annotated as "inducible" or "neuronal", while others lack precise annotation. We have performed an exhaustive collection of the available NOS amino-acid sequences in order to perform a phylogenetic analysis. We hypothesized that the NOS isoforms reported in vertebrates derive from 1) different invertebrate NOS, 2) a single invertebrate ancestral gene, through an event related to the double whole genomic duplication that occurred at the origin of vertebrates, and 3) the endothelial form of NOS appeared late in the evolution of vertebrates, after the split of tetrapods and fishes. Our molecular evolution analysis strongly supports the second scenario, the three vertebrate NOS isoforms derived from a single ancestral invertebrate gene. Thus, the diverse NOS isoforms in invertebrates can be explained by events of gene duplication, but their characterization as "inducible" or "neuronal" should only be justified by physiological features, since they are evolutionarily unrelated to the homonym isoforms of vertebrates.