- Invited Review - Pig meat production in the European Union-27: current status, challenges, and future trends.

The main objective of this study was to present data on the current situation and future trends of pig meat production in the European Union-27 (EU). Pig production has played an important social and economic role for centuries in many states of the EU. In 2022, pig meat production in the EU reached 23 M tons, which represented 21% of total production worldwide. The two key reasons that justify such amount of pork produced, are the acceptance and high consumption of the meat by the local population and the high quality of the meat produced which facilitated pork export. However, current data show a reduction in pork production for the last three years, as a consequence of a series of events that include i) problems with the chain of ingredients supply, ii) uncontrolled increase in African Swine Fever (ASF) outbreaks, iii) fast recovery of pig production in China, iv) increasing concerns by the rural population on the high cost to meet future requirements of the EU legislation on farm management, environmental sustainability and animal welfare, v) increased cost of all inputs involved in pig production and vi) limited interest of the new farmer generation to work on the pig sector. Consequently, pork production is expected to decrease in the EU for the next years, although sales will be maintained at a relative high level because pork is the meat preferred by local consumers in most EU countries. In order to maintain the favourable position of the pork industry in the near future, strategies to implement include: i) maintain the quality of the meat destinated to export markets, ii) improve the control of outbreaks of ASF and other swine diseases, iii) implementation of technological innovations to improve working conditions making more attractive to work in the pork sector of the food chain to the new generation of farmers and workers.

A reply to "Relevant factors in the eutrophication of the Uruguay River and the Río Negro".

A recent paper by Beretta-Blanco and Carrasco-Letelier (2021) claims that agricultural eutrophication is not one of the main causes for cyanobacterial blooms in rivers and artificial reservoirs. By combining rivers of markedly different hydrological characteristics e.g., presence/absence and number of dams, river discharge and geological setting, the study speculates about the role of nutrients for modulating phytoplankton chlorophyll-a. Here, we identified serious flaws, from erratic and inaccurate data manipulation. The study did not define how erroneous original dataset values were treated, how the variables below the detection/quantification limit were numerically introduced, lack of mandatory variables for river studies such as flow and rainfall, arbitrary removal of pH > 7.5 values (which were not outliers), and finally how extreme values of other environmental variables were included. In addition, we identified conceptual and procedural mistakes such as biased construction/evaluation of model prediction capability. The study trained the model using pooled data from a short restricted lotic section of the (large) Uruguay River and from both lotic and reservoir domains of the Negro River, but then tested predictability within the (small) Cuareim River. Besides these methodological considerations, the article shows misinterpretations of the statistical correlation of cause and effect neglecting basic limnological knowledge of the ecology of harmful algal blooms (HABs) and international research on land use effects on freshwater quality. The argument that pH is a predictor variable for HABs neglects overwhelming basic paradigms of carbon fluxes and change in pH because of primary productivity. As a result, the article introduces the notion that HABs formation are not related to agricultural land use and water residence time and generate a great risk for the management of surface waterbodies. This reply also emphasizes the need for good practices of open data management, especially for public databases in view of external reproducibility.

[Postraumatic epidural arachnoid spinal cyst: case report]. / Quiste aracnoideo espinal epidural postraumático: presentación de un caso.

INTRODUCTION: Extradural arachnoid spinal cysts are unfrequent lesions that are associated with spinal trauma, surgery and less frequently with congenital anomalies. The clinical manifestations are similar to those seen with other compressive spinal cord lesions. Magnetic resonance techniques allow to diagnose correctly this pathology and to define its thopographic situation. The pathologic history of the patient is essencial to establish the ethiology. Surgery is the elective treatment in most cases. CLINICAL CASE: The patient is a 35 years old man who has a medical history of penetrating spinal trauma two years ago. In that instance he suffered an unilateral spinal cord section at D2-D3 level with the corresponding Brown Sequard syndrome. A small wound was detected at the skin dorsal level and it was closed without difficulties. At the beginning, he improved his motor right leg function with rehabilitation and vitamins. After two years of good recovery he came to our hospital suffering a neurological deterioration of six months of evolution. The physical examination revealed an spastic paraparesis. Magnetic resonance was performed demonstrating a cystic extradural collection compressing the spinal cord at D3-D4 level. Surgical decompressive treatment allowed to excise the cyst and it was possible to define a dural tear that was closed successfully. The outcome was good with restoration of the initial motor function that he had after the spinal trauma. CONCLUSIONS: Surgical management of postraumatic epidural arachnoid spinal cyst allows to detect the meningeal tear and to close it, which is highly effective on these kinds of lesions.

Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex.

BACKGROUND: Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. OBJECTIVES: To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. METHODS: Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. RESULTS: KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. CONCLUSIONS: This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

Quiste aracnoideo espinal epidural postraumático: presentación de un caso / Postraumatic epidural arachnoid spinal cyst: case report

Introducción. Los quistes aracnoideos extradurales espinales son lesiones poco frecuentes. Clínicamentese caracterizan por un cuadro mielopático progresivo,asociado o no a crisis radiculares. Para su diagnóstico radiológico las técnicas de resonancia magnética actuales posibilitan definirlos adecuadamente y conocer sulocalización topográfica. Los antecedentes patológicos del paciente son esenciales para establecer se etiología encontrándose en muchos casos una historia de traumaespinal, cirugía y menos frecuentemente anomalías con-génitas asociadas. El tratamiento en la mayoría de los casos es quirúrgico. Caso clínico. Presentamos el caso de un paciente de 35 años con antecedentes de una hemisección medular dorsal por arma blanca hace dos años. Evolutivamente se deterioran sus funciones motoras presentándose con una paraparesia espástica. Los estudios radiológicos mostraron la presencia de la lesión quística extradural comprimiendo el cordón medular a nivel dorsal (D3-D4). Se realizó cirugía descompresiva y se identificó un desgarro meníngeo a ese nivel que fue suturado. La evolución postoperatoria fue satisfactoria. Conclusiones. El tratamiento quirúrgico efectivo de estas lesiones está dado por la detección del defectomeníngeo y su cierre (AU)

Introduction. Extradural arachnoid spinal cysts are unfrequent lesions that are associated with spinal trauma, surgery and less frequently with congenital anomalies. The clinical manifestations are similar to those seen with other compressive spinal cord lesions. Magnetic resonance techniques allow to diagnose correctly this pathology and to define its thopographic situation. The pathologic history of the patient is essencial to establish the ethiology. Surgery is the elective treatment in most cases. Clinical case. The patient is a 35 years old man who has a medical history of penetrating spinal trauma two years ago. In that instance he suffered an unilateral spinal cord section at D2-D3 level with the corresponding Brown Sequard syndrome. A small wound was detected at the skin dorsal level and it was closed without difficulties. At the beginning, he improved his motor right leg function with rehabilitation and vita- mins. After two years of good recovery he came to our hospital suffering a neurological deterioration of six months of evolution. The physical examination revea- led an spastic paraparesis. Magnetic resonance was performed demonstrating a cystic extradural collection compressing the spinal cord at D3-D4 level. Surgical decompressive treatment allowed to excise the cyst and it was possible to define a dural tear that was closed successfully. The outcome was good with restoration of the initial motor function that he had after the spinal trauma. Conclusions. Surgical management of postraumatic epidural arachnoid spinal cyst allows to detect the meningeal tear and to close it, which is highly effective on these kinds of lesions (AU)

X-linked ichthyosis along with recessive dystrophic epidermolysis bullosa in the same patient.

X-linked ichthyosis (XLI) is a relatively common keratinization disorder which is caused, in the vast majority of cases, by a total deletion of the sulfatase steroid (STS) gene. Dystrophic epidermolysis bullosa (DEB) is a scarring form of epidermolysis bullosa of either autosomal recessive or dominant inheritance secondary to collagen VII gene mutations. We report the first case of a patient with both XLI and DEB in whom a partial deletion of the STS gene and a recessive point mutation in COL7A1 were demonstrated.

The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in COL7A1. The clinical manifestations are highly variable from nail dystrophy to life-threatening blistering, making early molecular diagnosis and prognosis of utmost importance for the affected families. Mutation identification is mandatory for prenatal testing. OBJECTIVES: To conduct the first mutational analysis of COL7A1 in a Spanish cohort, to assess mutation consequences at protein/mRNA level and to establish genotype-phenotype correlations. METHODS: Forty-nine Spanish patients with DEB were studied. Antigen mapping was performed on patient skin biopsies. COL7A1 mutation screening in genomic DNA was performed by polymerase chain reaction (PCR) and direct sequencing. Mutation consequences were determined by reverse transcriptase-PCR. RESULTS: Eight patients belonged to three unrelated families with dominant DEB. Forty-one were affected with recessive DEB (RDEB). Specifically, 27 displayed the severe generalized subtype, eight the other generalized subtype and six a localized phenotype (two pretibial, three acral and one inversa). Thirty-five mutations were identified, 20 of which are novel. The pathogenic mutation c.6527insC accounted for 46.3% of Spanish RDEB alleles. A consistent genotype-phenotype correlation was established. CONCLUSIONS: Although the COL7A1 database indicates that most DEB mutations are family specific, the pathogenic mutation c.6527insC was highly recurrent in our cohort. This level of recurrence for a single genetic defect has never previously been reported for COL7A1. Our findings are essential to the clinicians caring for patients with DEB in Spain and in the large population of Spanish descendants in Latin America. They also provide geneticists a molecular clue for a priority mutation screening strategy.

[Usefulness of the 14-3-3 test for the diagnosis of sCJD evaluated by a Spanish reference center]. / Utilidad del inmunoensayo de la proteína 14-3-3 en el diagnóstico de la enfermedad de Creutzfeldt-Jakob examinada desde un centro de referencia nacional.

INTRODUCTION: The performance of the 14-3-3 protein test has been shown to be adequate for sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis in selected populations, but its routine validity has been questioned. METHODS: One thousand and sixty-eight patients with clinically suspected sCJD were analyzed in a Spanish reference center. In order to explore the influence of the clinical context on the performance of the immunoassay, the patients were classified at sample reception according to the World Health Organization (WHO) diagnostic criteria excluding the 14-3-3 test results. The yield of the immunoassay was evaluated in each subgroup with criteria of probable, possible sCJD or non-sCJD. RESULTS: In the set of patients with suspicion of sCJD the inclusion of the 14-3-3 test produces a significant increase in the diagnosis certainty (positive likelihood ratio: 10.1) compared to the WHO's criteria, excluding the 14-3-3 test. For patients classified at sample reception as probable sCJD (n=166), possible sCJD (n=129) and non-sCJD (n=773), the positive predictive values for the test were 98.4%, 97.5% and 31%, and the negative predictive values were 22.2%, 73.4% and 100%, respectively. CONCLUSIONS: The predictive values of the assay vary according to the previous diagnostic certainty. Therefore, in order to interpret correctly the test, it is necessary to evaluate the degree of initial clinical suspicion of the patient at the moment of the cerebrospinal fluid (CSF) extraction. This study offers up-to-date information, referenced to the Spanish population, and in useful format, and it is intended to serve as a guideline for 14-3-3 test results interpretation to the clinicians in our community.

Utilidad del inmunoensayo de la proteína 14-3-3 en el diagnóstico de la enfermedad de Creutzfeldt-Jakob examinada desde un centro de referencia nacional / Usefulness of the 14-3-3 test for the diagnosis of sCJD evaluated by a Spanish reference center

Introducción. El inmunoensayo de la proteína 14-3-3 en líquido cefalorraquídeo (LCR) muestra un rendimiento óptimo para el diagnóstico de la enfermedad de Creutzfeldt- Jakob esporádica (ECJe) en poblaciones seleccionadas, pero su validez en la práctica rutinaria ha sido cuestionada. Método. Se estudiaron 1.068 pacientes con sospecha de ECJe procedentes de distintas instituciones españolas. Para explorar la influencia del contexto clínico sobre la validez del inmunoensayo los pacientes fueron clasificados en el momento de la recepción de la muestra de acuerdo con los criterios de certeza diagnóstica establecidos por la Organización Mundial de la Salud (OMS), excluyendo la prueba de la proteína 14-3-3. El rendimiento del immunoensayo se evaluó en cada subgrupo con criterios de ECJe probable, posible o no ECJe. Resultados. En el conjunto de pacientes con sospecha de ECJe la inclusión del inmunoensayo supone un aumento significativo en la certeza diagnóstica (razón de verosimilitud positiva: 10,1) sobre los criterios de la OMS sin incluir dicha prueba. En los subgrupos de pacientes clasificados a la recepción de la muestra como ECJe probable (n=166), ECJe posible (n=129) y no ECJe (n=773) los valores predictivos positivos de la prueba de la proteína 14-3-3 fueron 98,4, 97,5 y 31% y los valores predictivos negativos fueron 22,2, 73,4 y 100%, respectivamente. Conclusiones. Los valores predictivos de la prueba varían según el grado de certeza diagnóstica previa de cada paciente. Por ello, para interpretar correctamente el ensayo es necesario valorar el grado de sospecha clínica del paciente en el momento de la extracción del LCR. Este estudio pretende facilitar la interpretación de los resultados de la prueba de la proteína 14-3-3 a los especialistas clínicos, ofreciendo una información actualizada, referenciada a la población española y en formato de utilidad práctica (AU)

Introduction: The performance of the 14-3-3 protein test has been shown to be adequate for sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis in selected populations, but its routine validity has been questioned. Methods: One thousand and sixty-eight patients with clinically suspected sCJD were analyzed in a Spanish reference center. In order to explore the influence of the clinical context on the performance of the immunoassay, the patients were classified at sample reception according to the World Health Organization (WHO) diagnostic criteria excluding the 14-3-3 test results. The yield of the immunoassay was evaluated in each subgroup with criteria of probable, possible sCJD or non-sCJD. Results: In the set of patients with suspicion of sCJD the inclusion of the 14-3-3 test produces a significant increase in the diagnosis certainty (positive likelihood ratio: 10.1) compared to the WHO's criteria, excluding the 14-3-3 test. For patients classified at sample reception as probable sCJD (n=166), possible sCJD (n=129) and non-sCJD (n=773), the positive predictive values for the test were 98.4%, 97.5% and 31%, and the negative predictive values were 22.2%, 73.4% and 100%, respectively. Conclusions: The predictive values of the assay vary according to the previous diagnostic certainty. Therefore, in order to interpret correctly the test, it is necessary to evaluate the degree of initial clinical suspicion of the patient at the moment of the cerebrospinal fluid (CSF) extraction. This study offers up-to-date information, referenced to the Spanish population, and in useful format, and it is intended to serve as a guideline for 14-3-3 test results interpretation to the clinicians in our community (AU)

CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathies.

Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/microl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/microl and one of 20 cells/microl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/microl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests.

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters. METHODS: CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls. RESULTS: The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity. CONCLUSIONS: The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.

Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease.

To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM1 patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2.

Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt-Jakob disease.

OBJECTIVE: To determine the concentrations of microtubule associated protein tau and multiple phosphorylated tau epitopes in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease (sCJD), dementias, and controls, in order to evaluate their diagnostic use and clinical relevance. METHODS: The CSF concentrations of total tau and phosphorylated tau at epitope 181 were determined by enzyme linked immunosorbent assay in 66 definite and nine probable sCJD patients, and in 97 controls. Other phosphorylated tau epitopes were investigated by western blot. RESULTS: In the sCJD population, determination of 14-3-3 protein and total tau protein concentrations was of the highest diagnostic value, with a sensitivity of 96% and 92%, respectively, and a specificity of 94% and 97%. Two distinct subgroups could be identified among the 75 sCJD patients based on the detection of phosphorylated tau at threonine 181 and serines 199, 202, and 404. A high phosphorylated tau concentration was clinically correlated with a significantly shorter disease duration, early onset of akinetic mutism, and a higher rate of typical EEGs (p < 0.05). CONCLUSIONS: Although the determination of phosphorylated tau levels cannot be used as a diagnostic biomarker, it may prove useful for estimating the prognosis of an sCJD patient. These experiments reconfirm that sCJD is a disease with a complex pathology.