La lectoescritura es un aprendizaje básico y clave en la Educación Primaria y las dificultades en su aprendizaje se han relacionado con una mayor probabilidad de fracaso escolar. En España, no existen pruebas de cribado en otras lenguas oficiales distintas al español que detecten de manera temprana estas dificultades. El objetivo de este estudio fue crear y analizar las características psicométricas de una nueva prueba de cribado para la detección temprana de problemas en la lectoescritura en catalán (Prelectocat). Se llevó a cabo la prueba de cribado de lectura a un total de 459 niños de 5 años, del último curso de Educación Infantil. Esta prueba evalúa la conciencia fonológica, la correspondencia sonido-grafía, la memoria fonológica, las secuencias verbales/evocación léxico y la escritura. Los resultados muestran una buena fiabilidad y validez de constructo. Se indican valores normativos en percentiles y los puntos de corte para identificar menores con riesgo. Diversos indicadores precoces permiten detectar niños con riesgo de tener dificultades en estas áreas en la Educación Primaria. Se recomienda utilizar este tipo de pruebas como herramienta de cribado universal a los 5-6 años para iniciar una intervención temprana y así contribuir a la reducción del fracaso escolar.
Introduction. Verbal episodic memory (VEM) is often unimpaired in children with focal epilepsy undergoing left temporal lobe resections, unlike what we might expect in the adult brain. The latter findings suggest that epileptiform activity in early life disrupts memory system lateralization, leading to the development of bilateral memory representation. The present study aims to analyze whether the laterality of epilepsy is a major predictor for post-operative VEM prognosis in pediatric temporal lobe epilepsy (TLE) surgery. This research also pretends to provide evidence about the relationship of VEM performance with other relevant demographical and clinical factors such as sex, age at onset of seizures, age at surgery and duration of epilepsy, as well as to study the impact of presurgical VEM performance on postsurgical outcomes. Patients and methods. Pre-operative and one-year follow-up post-operative word-list recall scores from 25 children who underwent TLE surgery (left-sided, n = 11; right-sided, n = 14) were extracted from the Hospital Sant Joan de Deu database and were retrospectively analyzed. Results. No significant presurgical intergroup differences were found when comparing VEM scores by laterality of epilepsy (p > 0.5). Looking at the left TLE group, a high negative correlation was found between the onset age and the pre-operative long-term free recall score (rho = -0.72, p = 0.01). No significant pre- to post-operative intragroup changes were found regarding VEM performance, regardless of epilepsy laterality (left TLE group, p > 0.56; right TLE group, p > 0.12). Conclusions. The laterality of epilepsy does not show to be a significant factor in and of itself regarding presurgical VEM outcome and its prognosis one year after surgery, thus supporting the bilateral memory representation hypothesis. Furthermore, a younger age at onset of seizures seems to be related with a better pre-operative VEM performance, likely due to a more efficient reorganization of memory system induced by a greater brain plasticity at lower ages; however, this relationship has been only reported for the left-sided epilepsies in our sample.
Objective Analyzing the clinical and microbiological characteristics of coronavirus disease 2019 (COVID-19) infection in children seems essential to determine their role in the etiopathogenesis of the disease. Methods A prospective, longitudinal, and observational study, including children with severe acute respiratory syndrome coronavirus-2 infection, in the Barcelona Metropolitan Region (Spain), was performed. The recruitment pathways were: (1) children who attended a summer school and were included in an active surveillance study and (2) children who were visited in the Emergency Department of Hospital Sant Joan de Deu with symptoms. Close contacts with positive polymerase chain reaction (PCR) results were also included. The children recruited were followed up for 5 weeks. Evaluation of participants included a questionnaire for COVID-19 symptoms, nasopharyngeal swabbing for real-time PCR at 0, 7, and 14 days (weekly repeated up to week 5 if it resulted positive at 14 days), and serology testing at the recruitment and at the fifth week of follow-up. Results A total of 90 children were recruited, of which 32% were asymptomatic. Transmission was studied in 70/90 children, and in 12 cases (17%), transmission to other children or adults was observed. No clinical or epidemiological differences were found between children who transmitted and those who did not. At the end of the follow-up, 11% of nasopharyngeal PCR remained positive. The serological response was studied in 73/90 children, and 80.82% of children seroconverted. Conclusion No differences in epidemiological characteristics were found between children who transmitted and those who did not. PCR can be persistently positive for more than 5 weeks. The majority of patients who suffer from the disease produce antibodies against it.
Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020–2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 ( p < 0.01). A Basketball team showed a significant higher AR. Conclusion : Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
Several clinical trials are working on drug development for Duchenne and Becker muscular dystrophy (DMD and BMD) treatment, and, since the expected increase in dystrophin is relatively subtle, high-sensitivity quantification methods are necessary. There is also a need to quantify dystrophin to reach a definitive diagnosis in individuals with mild BMD, and in female carriers. We developed a method for the quantification of dystrophin in DMD and BMD patients using spectral confocal microscopy. It offers the possibility to capture the whole emission spectrum for any antibody, ensuring the selection of the emission peak and allowing the detection of fluorescent emissions of very low intensities. Fluorescence was evaluated first on manually selected regions of interest (ROIs), proving the usefulness of the methodology. Later, ROI selection was automated to make it operator-independent. The proposed methodology correctly classified patients according to their diagnosis, detected even minimal traces of dystrophin, and the results obtained automatically were statistically comparable to the manual ones. Thus, spectral imaging could be implemented to measure dystrophin expression and it could pave the way for detailed analysis of how its expression relates to the clinical course. Studies could be further expanded to better understand the expression of dystrophin-associated protein complexes (DAPCs).
Objective: The objective of this study was to develop a simple tool for general physicians to promptly identify and refer pediatric patients with a higher probability of having a genetic condition. Study design: This retrospective, descriptive study was conducted at a tertiary pediatric hospital's Clinical Genetics Unit from June 2019 to January 2020. We included patients under 18 years of age who visited the unit, excluding those without genetic testing. Epidemiological, clinical, and genetic variables were collected from electronic medical records. The primary outcome was the diagnosis of a genetic condition based on genetic testing. Results: Among 445 patients, 304 were included; 163 (53.6%) were male, and mean age was 7.4 years (SD 5.1 years). A genetic condition was diagnosed in 139 patients (45.7%). Using a multiple logistic regression model, five variables significantly contributed to reaching a diagnosis: suspected diagnosis at referral (OR 3.45, P < 0.001), short stature (OR 3.11, P < 0.001), global developmental delay/intellectual disability (OR 2.65, P < 0.001), dysmorphic craniofacial features (OR 1.99, P = 0.035), and multiple congenital anomalies (OR 2.54, P = 0.033). The association strength (OR) increased when these variables were paired with each other. The study's findings are presented in the form of a triangle, known as the Clinical Genetics Assessment Triangle (CGAT), which summarizes the results. A decision tree model is applied to guide clinical department referrals based on the affected sides of the triangle. Conclusions: The CGAT has the potential to enable general physicians to promptly identify pediatric patients with an increased probability of having a genetic condition.
Poor insight in schizophrenia spectrum disorders (SSD) is linked with negative outcomes. This single-centre, assessor-blind, parallel-group 1-year follow-up randomised controlled trial (RCT) tested whether metacognitive training (MCT) (compared to psychoeducation) may improve insight and outcomes in outpatients with SSD assessed: at baseline (T0); after treatment (T1) and at 1-year follow-up (T2). Insight (primary outcome) was measured with (i) the Schedule for Assessment of Insight-Expanded version- (SAI-E), including illness recognition (IR), symptom relabelling (SR), treatment compliance (TC) and total insight scores (TIS); and (ii) the Beck Cognitive Insight Scale (BCIS). Between-group comparisons were nonsignificant, while within the MCT group (but not within controls) there was a significant medium effect size for improved TIS at T2 ( d = 0.67, P = 0.02). Secondary outcomes included cognitive measures: Jumping to Conclusions (JTC), Theory of Mind (ToM), plus symptom severity and functioning. Compared to psychoeducation, MCT improved the PANSS excitement ( d = 1.21, P = 0.01) and depressed ( d = 0.76, P = 0.05) factors at T2; and a JTC task both at T1 ( P = 0.016) and at T2 ( P = 0.031). Participants in this RCT receiving MCT showed improved insight at 1-year follow-up, which was associated with better mood and reduced JTC cognitive bias. In this pilot study, no significant benefits on insight of MCT over psychoeducation were detected, which may have been due to insufficient power.
Objectives Ventilator-associated pneumonia (VAP) is the second most common healthcare-associated infection in children. The aim of this study was to determine the risk factors for VAP in children and to create a risk score for developing VAP (RISVAP score). Study design It was a prospective observational study, including children who required mechanical ventilation (MV), registered in the multicentre ENVIN-HELICS database from 2014 to 2019. The regression coefficients of each independent risk factor for VAP were used to create the RISVAP score. Each factor scored 0 if it was absent, or, if it was present, an assigned value from 1 to 7, according to the regression coefficient. Results A total of 3798 patients were included, 97(2.5%) developing VAP. The independent risk factors for VAP were: female (odds ratio [OR]: 1.642, p = 0.024), MV > 4 days (OR: 26.79, p < 0.001), length in pediatric intensive care unit > 7 days (OR: 11.74, p < 0.001), and previous colonisation (OR: 4.18, p < 0.001). The RISVAP was calculated for each patient as the sum of all the independent risk factors. Three risk groups were obtained: low (0-5 points), intermediate (6-12 points), and high risk for VAP (13-16 points). The area under the curve for the final score was 0.905 (95%confidence interval: 0.888-0.923, p < 0.001). Conclusions The RISVAP is the first risk score for VAP in pediatric populations. Using this predictive score, might be helpful to detect vulnerable patients and therefore implement preventative strategies.
AIM:To study neurotransmitter status in children with early epileptic and developmental and epileptic encephalopathy (DEE) and to explore the clinical response to dopaminergic and serotoninergic therapies in a group of patients.METHOD:Two hundred and five patients (111 males [54.1.%] and 94 females [45.9%], mean age 10 months at the onset of epilepsy [SD 1 year 1 month], range 0-3 year) with epileptic encephalopathy/DEE were recruited, including those with West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, myoclonic encephalopathy in non-progressive disorders, infantile spasms, Doose syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and those unclassified. Cerebrospinal fluid (CSF) neurotransmitter studies and patients' medical records were reviewed. Additionally, we present clinical data of 10 patients with low CSF neurotransmitter levels who received dopaminergic/serotoninergic treatments.RESULTS:Abnormal neurotransmitter values were identified in 68 (33%) patients. 5-Hydroxyindoleacetic acid (5-HIAA) deficit was the most prevalent alteration (91%). Low CSF 5-HIAA levels were significantly higher in 1- to 3-year-old children. A negative significant correlation was found between 5-HIAA levels and epilepsy duration before CSF study (Spearman's ρ=-0.191, p=0.007). Abnormalities in deep grey matter were associated with low levels of CSF homovanillic acid and 5-HIAA. Ten patients with low CSF neurotransmitter levels received dopamine and/or serotonin therapies. Six of them showed initial decrease of seizure frequency and severity and maintained improvement in some neurodevelopmental skills.INTERPRETATION:A considerable number of patients showed neurotransmitter abnormalities. Age at seizure onset and duration of epilepsy before CSF study were the principal factors related to neurotransmitter depletion. Early monoamine supplementation would seem advisable as a neuroprotective strategy.WHAT THIS PAPER ADDS:5-Hydroxyindoleacetic acid homeostasis is especially vulnerable in patients with epileptic encephalopathy/developmental and epileptic encephalopathy. Age of seizure onset and duration of epilepsy are determinants of neurotransmitter depletion.
Hormonal changes have been proposed as an etiological factor of stress urinary incontinence (SUI) during pregnancy. Our main objective was to demonstrate the role of hormones in SUI development during pregnancy and postpartum. A prospective longitudinal study was designed. Primiparous women without previous urinary incontinence symptoms were included. Symptoms and Quality of Life (QoL) Questionnaires, physical examinations, and hormone concentration (progesterone, estradiol, and relaxin) were collected twice during pregnancy and three times during postpartum. Logistic regression models, with Wald’s forward variable selection method, were used. Prevalence of SUI was 11% in the first trimester, 50% in the third trimester, and 16.4% at 6 months postpartum. The risk of developing SUI throughout pregnancy is higher in women with higher progesterone concentration in the first trimester (OR 1.38, 95% CI 1.06–1.81, p < 0.05) and it is lower in women with stronger pelvic floor muscles in the first trimester (OR 0.35, 95% CI 0.17–0.72, p < 0.05). When occurred during pregnancy, SUI has a 14-fold higher risk of persistence 6 months after birth. In addition, the severity of these symptoms is also an independent risk factor for SUI persistence at 6 months postpartum (OR 1.41, 95% CI 1.15–1.73, p < 0.05). Quality of Life was affected for pregnant women with SUI symptoms. SUI is a highly prevalent condition during pregnancy, affecting the QoL of women in many areas. Higher concentration of progesterone can play a role in SUI development during pregnancy. The presence and severity of SUI during pregnancy are risk factors for the persistence of symptoms 6 months postpartum. Sustaining an optimal pelvic floor muscle strength could prevent SUI during pregnancy.
BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.
A protective effect has traditionally been attributed to estrogen in psychotic disorders. The aim of this study was to investigate cumulative lifetime estrogen by assessing the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and the age of menarche, measuring their effects on symptoms, cognition, social cognition, and metacognition. As it was not possible to directly measure cumulative estrogen levels over the lifetime of a patient, the study sample was composed of 42 women with first-episode psychosis; estrogen levels were inferred by the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and menarche. All patients were assessed with a battery of questionnaires using the BDI, PSYRATS, PANSS, STROOP, TAVEC, WSCT, IPSAQ, and BCIS questionnaires. The results related to menstrual cycle length showed a relationship with memory; specifically, shorter cycles with semantic strategies (p = 0.046) and longer cycles with serial strategies in the short term (p = 0.005) as well as in the long term (p = 0.031). The results also showed a relationship with perseverative errors (p = 0.035) and self-certainty (p = 0.049). Only personalized bias (p = 0.030) was found to be significant in relation to the age at menarche. When analyzing the differences in years of difference between the age at menarche and the onset of psychotic symptoms, the results indicated lower scores in women with a smaller difference between both events in memory (short-term (p = 0.050), long-term (p = 0.024), intrusions (p = 0.013), and recognition (p = 0.043)) and non-perseverative errors (p = 0.024). No relationship was found between symptoms and menstrual characteristics. The investigatory outcomes seem to indicate a relationship between estrogen cumulative effects and the memory domain. More in-depth investigations in the field are necessary in order to improve personalized treatment in women with psychosis.
BACKGROUND:Family clusters offer a good opportunity to study viral transmission in a stable setting. We aimed to analyze the specific role of children in transmission of SARS-CoV-2 within households. METHODS:A prospective, longitudinal, observational study, including children with documented acute SARS-CoV-2 infection attending 22 summer-schools in Barcelona, Spain, was performed. Moreover, other patients and families coming from other school-like environments that voluntarily accessed the study were also studied. A longitudinal follow-up (5 weeks) of the family clusters was conducted to determine whether the children considered to be primary cases were able to transmit the virus to other family members. The household reproduction number (Re*) and the secondary attack rate (SAR) were calculated. RESULTS:1905 children from the summer schools were screened for SARS-CoV-2 infection and 22 (1.15%) tested positive. Moreover, 32 additional children accessed the study voluntarily. Of these, 37 children and their 26 households were studied completely. In half of the cases (13/26), the primary case was considered to be a child and secondary transmission to other members of the household was observed in 3/13, with a SAR of 14.2% and a Re* of 0.46. Conversely, the SAR of adult primary cases was 72.2% including the kids that gave rise to the contact tracing study, and 61.5% without them, and the estimated Re* was 2.6. In 4/13 of the paediatric primary cases (30.0%), nasopharyngeal PCR was persistently positive > 1 week after diagnosis, and 3/4 of these children infected another family member (p<0.01). CONCLUSIONS:Children may not be the main drivers of the infection in household transmission clusters in the study population. A prolonged positive PCR could be associated with higher transmissibility.
The authors regret that the Fig. 1 was incorrect in the originally published manuscript. The correct Fig. 1 is as follows: Fig. 1. Proposed decision-tree algorithm for administration of nusinersen. The online version of the paper has been updated and now has the correct figure. The authors would like to apologise for any inconvenience caused. Pediatric SMA patients with complex spinal anatomy: Implementation and evaluation of a decision-tree algorithm for administration of nusinersenEuropean Journal of Paediatric NeurologyVol. 31PreviewThe approval of nusinersen for the treatment of spinal muscular atrophy (SMA) has significantly changed the natural history of the disease. Nevertheless, scoliosis secondary to axial muscle weakness occurs at some point in most of patients with SMA and a conventional posterior interlaminar approach for intrathecal administration of nusinersen can be particularly challenging to perform in patients with severe scoliosis and/or previous spine fusion surgeries. We developed a protocol for the administration of nusinersen in pediatric patients, which includes a decision-tree algorithm that categorizes patients according to the estimated technical difficulty for the intrathecal administration. Full-Text PDF
Introduction: In this study, we aimed at quantifying placental concentrations of 22 chemical elements in small fetuses (SGA) as compared with normally grown fetuses (AGA), and to assess the relationship with Doppler markers of placental function. Methods: Prospective cohort study, including 71 SGA fetuses (estimated fetal weight < 10th percentile) and 96 AGA fetuses (estimated fetal weight > 10th percentile), recruited in the third trimester of gestation. The placental concentration of 22 chemical elements was determined by inductively coupled plasma optical emission spectrophotometer (ICP-OES, ICAP 6500 Duo Thermo): aluminum (Al), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cobalt (Co), chrome (Cr), copper (Cu), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), phosphorus (P), lead (Pb), rubidium (Rb), sulfur (S), strontium (Sr), titanium (Ti), thallium (Tl), antimony (Sb), selenium (Se), and zinc (Zn). Placental function was assessed by measuring the following fetal-maternal parameters: Uterine artery Pulsatility Index (UtA PI), Umbilical artery Pulsatility Index (UA PI) and Middle Cerebral artery Pulsatility Index (MCA PI). The association between the chemical elements concentration and study group and the association with Doppler measures were evaluated. Results: SGA was associated with significantly (p < 0.05) lower concentrations of Al (AGA 21.14 vs SGA 0.51 mg/kg), Cr (AGA 0.17 vs SGA 0.12 mg/kg), Cu (AGA 0.89 vs SGA 0.81 mg/kg), Mg (AGA 0.007 vs SGA 0.006 g/100g), Mn (AGA 0.60 vs SGA 0.47 mg/kg), Rb (AGA 1.68 vs SGA 1.47 mg/kg), Se (AGA 0.02 vs SGA 0.01 mg/kg), Ti (AGA 0.75 vs SGA 0.05 mg/kg) and Zn (AGA 9.04 vs SGA 8.22 mg/kg). Lower placental concentrations of Al, Cr, Mn, Se, Ti were associated with abnormal UtA, UA and MCA Doppler. Discussion: Lower placental concentrations of Al, Cr, Cu, Mn, Rb, Se, Ti and Zn are associated with SGA fetuses and abnormal fetal-maternal Doppler results. Additional studies are required to further understand how chemical elements affect fetal growth and potentially find strategies to prevent SGA.
Objective To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness. Methods This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD. Results We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation. Conclusion This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.
Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.