Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Massive deep vein thrombosis in pregnant women: The importance of individualizing the action plan.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially lethal condition to be taken into account in pregnant women, where the situation is favored by the characteristic physiological changes of the pregnancy, childbirth and the puerperium. The management of this pathology in this type of patient is based on anticoagulation, with the benefits and drawbacks that this implies. We present the case of a pregnant woman with massive DVT and the issues are discussed, such as the method of delivery (vaginal vs. cesarean section) or the management of treatment (LMWH vs. UFH) in order to obtain the safest situation for the patient.

Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia.

Iatrogenic tracheal rupture (ITR) is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of ITR depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-Cov-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Bioactive compounds and antibacterial activities in crystallized honey liquefied with ultrasound.

The effect of ultrasound on the crystal size, phenols, flavonoids, Maillard products and antibacterial activity of crystallized honeys was studied. Three multifloral honeys (M), one monofloral (MO) and one honeydew (HD) honey were used. Ultrasound was performed at 42 kHz for different times (0, 5, 10 and 15 min). The antibacterial activities were tested against Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus and Escherichia coli. In all honeys, the parameters analyzed had significant differences ((P < 0.05)). After 15 min of ultrasound the HD had increments of 44 mg of gallic acid/100 g of honey in phenols, and some M showed increase in flavonoids (5.64 mg of quercitin /100 g of honey) and improvement in inhibition against Salmonella typhimurium was 13.1%. In some honeys the correlation between phenols or flavonoids and antibacterial activity were significant ((P < 0.05)). No correlation was found between Maillard products and antibacterial activity. The ultrasound treatment effect on the crystal size, phenols, flavonoid, Maillard products, and antibacterial activity of crystallized honeys were different in each honey.

Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia. / Rotura traqueal iatrogénica en paciente con síndrome de distrés respiratorio agudo por neumonía SARS-CoV-2.

Iatrogenic tracheal rupture is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of iatrogenic tracheal rupture depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-CoV-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Acute airway obstruction in a patient with forestier disease. Case report. / Obstrucción aguda de vía aérea en paciente con enfermedad de Forestier. Caso clínico.

Ossification of the anterior longitudinal ligament of the spine, known as Forestier disease or diffuse idiopathic skeletal hyperostosis, is usually an asymptomatic disorder. The area most frequently affected is the thoracic spine, followed by lumbar and cervical regions. In the case of cervical involvement with clinical manifestations, the most common symptoms include dysphagia, dyspnoea, dysphonia, and can exceptionally cause an acute airway obstruction. The airway management of these patients represents a great anaesthetic challenge. The case is reported of an eighty-five-year-old patient who had an acute airway obstruction associated with Forestier disease. A fibre-optic-assisted intubation was accomplished under sevoflurane inhaled anaesthesia, maintaining spontaneous ventilation, with subsequent tracheostomy performed by ENT surgeons.

Modulatory effect of three probiotic strains on infants' gut microbial composition and immunological parameters on a placebo-controlled, double-blind, randomised study.

The gut microbiota plays a crucial role in gastrointestinal health. Current use of probiotics is aimed at modulating the bacterial gut composition to alleviate specific diseases. The safety and tolerance of three probiotic strains (Bifidobacterium longum subsp. infantis R0033, Lactobacillus helveticus R0052 and Bifidobacterium bifidum R0071) has recently been described. The objective of the present study was to analyse the microbiological composition and immunological parameters of faecal samples obtained from healthy infants from 3 to 12 months of age after receiving either one of the three probiotic strains or placebo for 8 weeks. 16S ribosomal RNA gene sequencing and multiplexing technology was used for analysis. Faecal sample analysis showed that the most abundant genus in all four groups of infants pre- and post-intervention was Bifidobacterium, representing approximately 50% of the sequences. After the intervention period the microbial composition of faecal samples in the probiotic groups did not display notable changes. In contrast, a decrease in different Bifidobacterium species, such as B. bifidum and Bifidobacterium breve and an increase in Bacteroides, Blautia, Clostridium, Coprococcus and Faecalibacterium genera was observed in the placebo group. The analysis of a wide range of immune factors in faecal samples suggests a modulatory effect by these three probiotic strains during the intervention period. The anti-inflammatory ratio interleukin (IL)-10/IL-12 increased at the end of the intervention period in the B. infantis R0033 group while the TNF-α/IL-10 ratio increased in the L. helveticus R0052 group. The decrease of the IL-10/IL-12 ratio together with the increase of the tumour necrosis factor alpha (TNF-α)/IL-10 ratio demonstrated a pro-inflammatory profile in the placebo group. In conclusion, the species profile of the microbiome observed in all three probiotic groups resembled that of a younger infant, similar to an unweaned infant, when compared to the placebo group which may also be related with an anti-inflammatory effect.

Transcriptomic changes in Cucurbita pepo fruit after cold storage: differential response between two cultivars contrasting in chilling sensitivity.

BACKGROUND: Zucchini fruit is susceptible to chilling injury (CI), but the response to low storage temperature is cultivar dependent. Previous reports about the response of zucchini fruit to chilling storage have been focused on the physiology and biochemistry of this process, with little information about the molecular mechanisms underlying it. In this work, we present a comprehensive analysis of transcriptomic changes that take place after cold storage in zucchini fruit of two commercial cultivars with contrasting response to chilling stress. RESULTS: RNA-Seq analysis was conducted in exocarp of fruit at harvest and after 14 days of storage at 4 and 20 °C. Differential expressed genes (DEGs) were obtained comparing fruit stored at 4 °C with their control at 20 °C, and then specific and common up and down-regulated DEGs of each cultivar were identified. Functional analysis of these DEGs identified similarities between the response of zucchini fruit to low temperature and other stresses, with an important number of GO terms related to biotic and abiotic stresses overrepresented in both cultivars. This study also revealed several molecular mechanisms that could be related to chilling tolerance, since they were up-regulated in cv. Natura (CI tolerant) or down-regulated in cv. Sinatra (CI sensitive). These mechanisms were mainly those related to carbohydrate and energy metabolism, transcription, signal transduction, and protein transport and degradation. Among DEGs belonging to these pathways, we selected candidate genes that could regulate or promote chilling tolerance in zucchini fruit including the transcription factors MYB76-like, ZAT10-like, DELLA protein GAIP, and AP2/ERF domain-containing protein. CONCLUSIONS: This study provides a broader understanding of the important mechanisms and processes related to coping with low temperature stress in zucchini fruit and allowed the identification of some candidate genes that may be involved in the acquisition of chilling tolerance in this crop. These genes will be the basis of future studies aimed to identify markers involved in cold tolerance and aid in zucchini breeding programs.

Safety and tolerance of three probiotic strains in healthy infants: a multi-centre randomized, double-blind, placebo-controlled trial.

Some strains of species belonging to the genera Bifidobacterium and Lactobacillus are used in order to maintain health. Although these organisms have a long record of safe use, it is important to assess their safety and tolerance in potentially vulnerable populations, such as infants. The objective of this study was to evaluate the safety and tolerance of three probiotic strains (Bifidobacterium longum subsp. infantis R0033, Bifidobacterium bifidum R0071 and Lactobacillus helveticus R0052) in healthy infants aged 3 to 12 months. A multi-centre randomized, double-blind, placebo-controlled intervention study with 221 healthy full-term infants was conducted. Infants received either a placebo or one of the 3 probiotic strains (3×109 cfu) daily during an 8 week intervention period. Growth (weight, height and head circumference), adverse events (AEs)/serious adverse events (SAEs), concentrations of D-lactic acid in urine samples, characteristics of the stools and use of medication were collected for safety evaluation. All 4 groups were homogeneous with respect to age, gender, feeding type, ethnicity, height, weight and head circumference at the start of the study. The results showed that changes in growth (weight, height and head circumference) were equivalent in all 4 groups. No SAEs were reported. Total number of AEs recorded was equivalent in all groups. Thus, the use of B. infantis R0033, L. helveticus R0052 and B. bifidum R0071 in infancy is safe, and well tolerated.

Genetic divergence between Mexican Opuntia accessions inferred by polymerase chain reaction-restriction fragment length polymorphism analysis.

Molecular methods are powerful tools in characterizing and determining relationships between plants. The aim of this study was to study genetic divergence between 103 accessions of Mexican Opuntia. To accomplish this, polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis of three chloroplast intergenic spacers (atpB-rbcL, trnL-trnF, and psbA-trnH), one chloroplast gene (ycf1), two nuclear genes (ppc and PhyC), and one mitochondrial gene (cox3) was conducted. The amplified products from all the samples had very similar molecular sizes, and there were only very small differences between the undigested PCR amplicons for all regions, with the exception of ppc. We obtained 5850 bp from the seven regions, and 136 fragments were detected with eight enzymes, 37 of which (27.2%) were polymorphic. We found that 40% of the fragments from the chloroplast regions were polymorphic, 9.8% of the bands detected in the nuclear genes were polymorphic, and 20% of the bands in the mitochondrial locus were polymorphic. trnL-trnF and psbA-trnH were the most variable regions. The Nei and Li/Dice distance was very short, and ranged from 0 to 0.12; indeed, 77 of the 103 genotypes had the same genetic profile. All the xoconostle accessions (acidic fruits) were grouped together without being separated from three genotypes of prickly pear (sweet fruits). We assume that the genetic divergence between prickly pears and xoconostles is very low, and question the number of Opuntia species currently considered in Mexico.

Milk and blood biomarkers associated to the clinical efficacy of a probiotic for the treatment of infectious mastitis.

Previous studies have shown the efficacy of oral administration of selected lactobacilli strains to treat mastitis. The objective of this study was to find microbiological, biochemical and/or immunological biomarkers of the probiotic effect. Women with (n=23) and without (n=8) symptoms of mastitis received three daily doses (10(9) cfu) of Lactobacillus salivarius PS2 for 21 days. Samples of milk, blood and urine were collected before and after the probiotic intervention, and screened for a wide spectrum of microbiological, biochemical and immunological parameters. In the mastitis group, L. salivarius PS2 intake led to a reduction in milk bacterial counts, milk and blood leukocyte counts and interleukin (IL)-8 level in milk, an increase in those of immunoglobulin (Ig)E, IgG3, epidermal growth factor and IL-7, a modification of the milk electrolyte profile, and a reduction of some oxidative stress biomarkers. Such biomarkers will be useful in future clinical studies involving a larger cohort.

Towards an unsupervised device for the diagnosis of childhood pneumonia in low resource settings: automatic segmentation of respiratory sounds.

Pneumonia remains the worldwide leading cause of children mortality under the age of five, with every year 1.4 million deaths. Unfortunately, in low resource settings, very limited diagnostic support aids are provided to point-of-care practitioners. Current UNICEF/WHO case management algorithm relies on the use of a chronometer to manually count breath rates on pediatric patients: there is thus a major need for more sophisticated tools to diagnose pneumonia that increase sensitivity and specificity of breath-rate-based algorithms. These tools should be low cost, and adapted to practitioners with limited training. In this work, a novel concept of unsupervised tool for the diagnosis of childhood pneumonia is presented. The concept relies on the automated analysis of respiratory sounds as recorded by a point-of-care electronic stethoscope. By identifying the presence of auscultation sounds at different chest locations, this diagnostic tool is intended to estimate a pneumonia likelihood score. After presenting the overall architecture of an algorithm to estimate pneumonia scores, the importance of a robust unsupervised method to identify inspiratory and expiratory phases of a respiratory cycle is highlighted. Based on data from an on-going study involving pediatric pneumonia patients, a first algorithm to segment respiratory sounds is suggested. The unsupervised algorithm relies on a Mel-frequency filter bank, a two-step Gaussian Mixture Model (GMM) description of data, and a final Hidden Markov Model (HMM) interpretation of inspiratory-expiratory sequences. Finally, illustrative results on first recruited patients are provided. The presented algorithm opens the doors to a new family of unsupervised respiratory sound analyzers that could improve future versions of case management algorithms for the diagnosis of pneumonia in low-resources settings.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

Observed costs and health care use of children in a prospective cohort study on community-acquired pneumonia in Geneva, Switzerland.

QUESTIONS UNDER STUDY: Despite various efforts to estimate cost-effectiveness of pneumococcal conjugate vaccines, only scarce information on the cost burden of paediatric community acquired pneumonia (CAP) exists. The objective of this study was to prospectively calculate direct and indirect costs associated with treatment of CAP from a society perspective in children between 2 months and 16 years of age seeking care at a tertiary hospital in Geneva, Switzerland between December 2008 and May 2010. METHODS: This cost of illness study population comprised children aged from 2 months to 16 years of age seeking care for CAP at the University Children's Hospital Geneva from January 2008 through May 2010 (a subset of patients taken from a larger multicentre prospective cohort). Hospital-associated costs for episodes of pneumonia were computed according to the REKOLE® system. Non-hospital costs were estimated by parental interviews at baseline and follow-up on day 14. RESULTS: The overall cost for one episode of CAP was 11'258 CHF; 23'872 CHF for inpatient treatment and 1009 CHF for outpatient treatment. Severe pneumonia cases per World Health Organisation (WHO) definition used significantly more hospital resources than non-severe cases: 21'842 CHF versus 3'479 CHF (p <0.0001). CONCLUSION: Childhood CAP results in a significant medical cost burden that may have been underestimated in previous cost-effectiveness analyses of pneumococcal vaccine strategies.

Effects of amoxicillin treatment on the salivary microbiota in children with acute otitis media.

Amoxicillin is a first-line antibiotic treatment for acute otitis media in children and one of the most commonly used antibiotics for human bacterial infections. We investigated changes in salivary bacterial communities among children treated with amoxicillin for acute otitis media (n = 18), using a culture-independent approach based on pyrosequencing of the V3 region of the bacterial 16S rRNA gene. The control group consisted of children with acute otitis media who were not given antibiotics (n = 15). One species-level phylotype assigned to the genus Streptococcus was identified across all (n = 99) saliva samples. Two additional species-level phylotypes from the genera Gemella and Granulicatella were shared by all (n = 45) samples of control subjects. Amoxicillin treatment resulted in reduced species richness and diversity, and a significant shift in the relative abundance of 35 taxa at different ranks from phylum to species-level phylotype. At the phylum level, prevalence of TM7 and Actinobacteria decreased at the end of treatment, whereas Proteobacteria had a higher relative abundance post-treatment. Multivariate analysis showed that samples from the same control subject taken over time intervals tended to cluster together. Among antibiotic-treated subjects, samples taken before and at the end of amoxicillin treatment formed two relatively well-separated clusters both of which greatly overlapped with samples taken about 3 weeks post-treatment. Our results point to a substantial but incomplete recovery of the salivary bacterial community from the antibiotic about 3 weeks after the end of treatment.

Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays.

OBJECTIVES: To assess the concordance of procalcitonin values at 3 cut-off ranges in a cohort of pediatric samples presenting with fever without source, using two different automated immunoassays. DESIGN AND METHODS: 65 frozen samples from children presenting with fever without source were thawed, tested on both Kryptor and VIDAS systems, and compared using a regression analysis, a Bland-Altman difference plot, and analysis of concordance at the clinically relevant cut-off points. RESULTS: Kryptor and VIDAS PCT results correlated remarkably well (r=0.952), with no significant difference in the frequency distribution over the 3 cut-off ranges (p=0.1384). The strength of the agreement was good (κ=0.759) with an overall concordance of 84.6%. CONCLUSION: Correlation and concordance of PCT values measured by both systems were good. This finding allows clinical implementation of both techniques with the same nominal PCT cut-off values for detection of serious bacterial infection in children presenting with fever without source.

Different cardiovascular protective effects of quercetin administered orally or intraperitoneally in spontaneously hypertensive rats.

We tested whether the administration procedure of quercetin affects its metabolite profile and antihypertensive activity. Spontaneously hypertensive rats (SHR) were randomly assigned to four experimental treatments: (1) 1 mL of 1% methylcellulose by oral gavage and 2% DMSO i.p. (control group); (2) 10 mg kg⁻¹ quercetin by oral gavage once daily and 2% DMSO i.p.; (3) 10 mg kg⁻¹ quercetin by oral gavage divided in two daily doses (5 + 5 at 12 h intervals) and 2% DMSO i.p.; (4) 1 mL of 1% methylcellulose by oral gavage and 10 mg kg⁻¹ quercetin i.p. injection. Rats were treated daily for 5 weeks. Single dose and two daily doses, in a long-term oral treatment were equally efficient, both restoring the impaired aortic endothelium-dependent vasodilatation and reducing mesenteric contractile response to phenylephrine, systolic blood pressure, heart rate, and heart and kidney hypertrophy. Attenuation of vascular NADPH oxidase-driven O2⁻ production was also found in orally treated rats. Intraperitoneal administration reduced, to lesser extent than oral administration, the increased systolic blood pressure, being without effect to the endothelial dysfunction and vascular oxidative stress. In contrast, greater levels of metabolites were quantified following intraperitoneal compared to oral administration at any time point, except for higher plasma methylated quercetin aglycone in oral as compared to intraperitoneal administration at 2 but not at 8 h. In conclusion, oral quercetin was superior to intraperitoneal administration for the protection from cardiovascular complications in SHR. No differences were found between the oral administration as a single daily dose or divided into two daily doses.

Analysis of flavonoids in foods and biological samples.

Flavonoids are a major class of plant phenolics that are widely distributed in the human diet and have been related to health promotion. They may occur in their natural sources in free forms (aglycones), as glycosylated or acylated derivatives, or as oligomeric and polymerized structures. This structural diversity affects their physicochemical behaviour and complicates their analysis. Thus, there is not a single standardized procedure that can be recommended for all flavonoid groups and/or type of samples, and the procedures have to be optimized depending on the nature of the sample and the target analytes. Furthermore, when dealing with the analysis of flavonoids biological samples (i.e., human and animal fluids and tissues) some differential aspects have to be taken into account; the nature of the compounds that can be found in those samples may differ from that present in plants and food, and flavonoids and metabolites occur in much lower concentrations, which make their analysis still more challenging. In this review the main techniques for extraction and analysis of flavonoids in foodstuffs and biological fluids are revised, as well as their occurrence in foods and beverages and available databases.

[Multicenter validation of the clinical dehydration scale for children]. / Validation multicentrique du score clinique de déshydratation pédiatrique.

INTRODUCTION: Dehydration is an important complication for sick children. The Clinical Dehydration Scale for children (CDS) measures dehydration based on 4 clinical signs: general appearance, eyes, saliva, and tears. OBJECTIVE: To validate the association between the CDS and markers of dehydration in children aged 1 month to 5 years visiting emergency departments (EDs) for vomiting and/or diarrhea. METHOD: An international prospective cohort study conducted in 3 university-affiliated EDs in 2009. Participants were a convenience sample of children aged 1-60 months presenting to the ED for acute vomiting and/or diarrhea. Following triage, a research nurse obtained informed consent and evaluated dehydration using the CDS. A few days after recovery, another research assistant weighed participants at home. The primary outcome was the percentage of dehydration calculated by the difference in weight at first evaluation and after recovery. Secondary outcomes included proportion of blood test measurements, intravenous use, hospitalization, and inter-rater agreement. RESULTS: During the study period, 264 children were recruited and data regarding weight and dehydration scores were complete for 219 (83%). According to the CDS, 88 had no dehydration, 159 some dehydration, and 15 moderate or severe dehydration. A Chi-square test showed a statistical association between CDS and weight gain, the occurrence of blood tests, intravenous rehydration, hospitalization, and abnormal plasmatic bicarbonate. Good inter-rater correlation was found among participants (linear weighted Kappa score of 0.65; (95% CI, 0.43-0.87). CONCLUSION: CDS categories correlate with markers of dehydration for young children complaining of vomiting and/or diarrhea in the ED.

[Experimental models in Alzheimer's disease]. / Modelos experimentales de la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer s disease (AD) is the most common neurodegenerative disease and (it accounts for 60-80 %). The certain diagnosis is made thanks to the brain patients study. Since 1970 there have been developed experimental models that have done a deep approach of this disease and new therapeutic researching. METHODS: We review all the papers published about experimental models in AD, and all the new therapeutical approaches base don them using the database Pubmed. RESULTS: Animal models aim to replicate the symptoms, the lesions or the cause(s) of AD. It has been described many experimental models in AD. There are animal models based on the metabolism of the amyloid precursor protein (APP) (human APPwild type wt- o the mutants forms), other based on Presenilin (PS) (transgenic mice that overexpress the form wild-type or the mutant ones), the double mutants PS/APP that develop the lesions earlier. There are other based on tau protein (tau-JNPL3) or the triple transgenic PS/APP/tau. There are also lines with altered expression of neprilysin, the main degrading enzyme of Abeta and also models based on APOE. Other models are rats, chick embryo, dog, primates and cetacean, cell culture of mature hippocampic neurons and the effects of the Abeta oligomers in them (soluble toxic species). CONCLUSIONS: Experimental models in AD have supposed a key tool in order to know deeply about neurodegenerative diseases, over all AD. Besides they allow us design new therapeutic approaches.