Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.

Effects of mass casualty incidents on anxiety, depression, and post-traumatic stress disorder among doctors and nurses: a systematic review.

OBJECTIVES: Doctors and nurses suffer different mental health conditions following traumatic incidents. We systematically synthesized existing evidence on the prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) and their associated risk factors among doctors and nurses following mass casualty incidents (MCIs). STUDY DESIGN: Systematic review. METHODS: Seven databases were searched (2010-2022) with peer-reviewed articles in English using the predefined keywords. Two reviewers screened the titles, abstracts, and full texts using the eligibility criteria and extracted data independently. We used the National Institutes of Health Quality Assessment Tools (NIH-QAT) and the Critical Appraisal Skills Programme checklist (CASP) to measure the quality appraisal of the included studies. RESULTS: A total of 5170 articles were retrieved, and 2512 articles were assessed by title and abstract (53 were eligible for full-text review). Finally, we included 19 studies. Most were assessed as of fair quality with a considerable risk of bias. PTSD was the highest-reported mental health condition. Nurses reported higher mental conditions, particularly PTSD. Two sets of risk factors (personal and workplace) are associated with anxiety, depression, and PTSD were found. CONCLUSIONS: MCIs have a significant impact on the mental health outcomes of emergency health workers. Preventive measures should be designed considering the high-risk group, personal, and organizational risk factors of mental health outcomes.

Hospital surge capacity preparedness in disasters and emergencies: a systematic review.

BACKGROUND: Adequate and effective emergency preparedness for hospital surge capacity is a prerequisite to ensuring standard healthcare services for disaster victims. This study aimed to identify, review, and synthesize the preparedness activities for and the barriers to hospital surge capacity in disasters and emergencies. METHODS: We systematically searched seven databases (PubMed, MEDLINE, CINAHL, Scopus, Embase, Ovid, and PsycINFO). We included all English peer-reviewed studies published in January 2016 and July 2022 on surge capacity preparedness in hospital settings. Two independent researchers screened titles and abstracts, reviewed the full texts, and conducted data extractions using CADIMA software. We assessed the rigor of the included studies using the NIH quality assessment tools for quantitative studies, the Noyes et al. guidelines for qualitative studies, and the MMAT tool for mixed methods studies and summarized findings using the narrative synthesis method. We also used PRISMA reporting guidelines. RESULTS: From the 2560 studies identified, we finally include 13 peer-reviewed studies: 10 quantitative, one qualitative, and two mixed methods. Five studies were done in the USA, three in Iran (n = 3), and the remaining in Australia, Pakistan, Sweden, Taiwan, and Tanzania. The study identified various ways to increase hospital surge capacity preparedness in all four domains (staff, stuff, space, and system); among them, the use of the Hospital Medical Surge Preparedness Index and the Surge Simulation Tool for surge planning was noteworthy. Moreover, nine studies (69%) recognized several barriers to hospital surge capacity preparedness. CONCLUSION: The review provides synthesized evidence of contemporary literature on strategies for and barriers to hospital surge capacity preparedness. Despite the risk of selection bias due to the omission of gray literature, the study findings could help hospital authorities, public health workers, and policymakers to develop effective plans and programs for improving hospital surge capacity preparedness with actions, such as enhancing coordination, new or adapted flows of patients, disaster planning implementation, or the development of specific tools for surge capacity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360332.

Application of metasurface-enhanced infra-red spectroscopy to distinguish between normal and cancerous cell types.

Fourier transform infrared (FTIR) spectra of biological cells can reveal clinically important information about cells' composition, including their normal or cancerous status. The recently emerged diagnostic technique of spectral cytopathology (SCP) combines FTIR with multivariate statistical analysis to detect cell abnormalities, differentiate between cell types, and monitor disease progression. We demonstrate a new variant of SCP, a metasurface-enhanced infrared reflection spectroscopic cytopathology (MEIRSC) that utilises judiciously designed plasmonic metasurfaces to localize and enhance the evanescent field near the cell's membrane, and to carry out spectroscopic interrogations of the cells attached to the metasurface using reflected infrared light. Our findings indicate that the MEIRSC approach enables us to differentiate between normal and cancerous human colon cells. The sensitivity of MEIRSC is such that a very small (about 50 nm deep) portion of the cell can yield valuable diagnostic information.

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.

RATIONALE: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. OBJECTIVE: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. METHODS: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. MEASUREMENTS: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. RESULTS: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. CONCLUSIONS: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Decreased RARß expression induces abundant inflammation and cervical precancerous lesions.

It is well known that vitamin A and its receptors protect against cancer development and that Retinoid Acid Receptor ß (RARß) is epigenetically silenced during tumoral progression. Cervical Cancer (CC) has been causally linked to high risk human papillomavirus (HR-HPV) infection. However, host factors are important in determining the outcome of persistent HR-HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Increasing evidence suggests that low diet in vitamin A and their receptors participate in the development of CC. The aim of this study has been to investigate the effects of abated RARß expression in the development of cervical premalignant lesions in 4 month-old conditional mice (RARß(L-/L-)). Results demonstrated the development of spontaneous squamous metaplasia, inflammatory infiltrate, enhanced mitotic activity, loss of cell differentiation, as well as decreased apoptosis and p16(INK4a) protein levels in RARß(L-/L-) mice cervix. All these changes are hallmarks of moderate dysplasia. Importantly, our results suggest that the low expression of RARß, may induce the down regulation of p16(INK4a), chronic inflammation and decreased apoptosis and may be involved in vulnerability to HR-HPV and early stage cervical carcinogenesis.

Inferior alveolar nerve trajectory, mental foramen location and incidence of mental nerve anterior loop.

OBJECTIVES: Injury of the inferior alveolar nerve (IAN) is a serious intraoperative complication that may occur during routine surgical procedures, such as dental implant placement or extraction of impacted teeth. Thus, the purpose of this study was to analyze the trajectory of the mandibular canal (MC), the location of the mental foramen (MF) and the presence and extension of an anterior loop of the mental nerve (AL). STUDY DESIGN: In this cross-sectional study, a total of 348 CBCTs were analyzed. Distances from MC to the surface of the basal, medial and lateral cortical of the mandible were measured at the level of the second molar, first molar and second premolar. Location of the MF relative to the apices of the premolars, as well as incidence and anterior extent of the AL were also determined. RESULTS: Significant and clinically relevant correlations were found between the position of the MC in women, which was located more caudal (r=-0.219, p=0.007; r=-0.276, p<0.001; right and left, respectively) and lateral (r=-0.274, p=0.001; r=-0.285, p<0.001; right and left, respectively), particularly at the level of the premolars. Additionally, the presence (r=-0.181, p=0.001; r=-0.163, p=0.002; right and left, respectively) and anterior extension (r=-0.180, p=0.009; r=-0.285, p=0.05; right and left, respectively) of the AL was found to be inversely correlated with the age of the patient. CONCLUSIONS: This analysis of a Caucasian population has found that the older the patient, the lower the incidence of the loop and the shorter its anterior extension.

Glycerol supplementation enhances the protective effect of dietary FloraMax-B11 against Salmonella Enteritidis colonization in neonate broiler chickens.

Two independent trials were conducted in the present study to evaluate the effect of 5% glycerol supplementation combined with dietary FloraMax-B11 (FM) against Salmonella Enteritidis colonization in neonate broiler chickens. In each trial, 60 chicks were randomly assigned into 4 groups. Group 1 received a control diet. Group 2 received a control diet supplemented with 5% glycerol. Group 3 received a control diet supplemented with FM, and group 4 received a control diet supplemented with 5% glycerol and FM. At placement, chickens were challenged with Salmonella Enteritidis at 10(4) cfu/bird. In each trial, 12 chicks were humanely killed 72 h postchallenge, respectively, for Salmonella Enteritidis colonization. Supplementation of 5% glycerol or FM by themselves, showed no significant effect on Salmonella Enteritidis recovery or incidence when compared with control nontreated chickens in both trials. However, no detectable Salmonella Enteritidis was observed in the chickens that received the supplementation of 5% glycerol combined with FM in both trials. Further studies are in progress in older birds to substantiate these findings.

Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006-2010.

INTRODUCTION: Global developmental delay (GDD) and intellectual disability (ID) are common reasons for consultation in paediatric neurology. Results from aetiological evaluations of children with GDD/ID vary greatly, and consequently, there is no universal consensus regarding which studies should be performed. MATERIAL AND METHOD: We review our experience with determining aetiological diagnoses for children with GDD/ID who were monitored by the paediatric neurology unit over the 5-year period between 2006 and 2010. RESULTS: During the study period, 995 children with GDD/ID were monitored. An aetiological diagnosis was established for 309 patients (31%), but not in 686 (69%), despite completing numerous tests. A genetic cause was identified in 142 cases (46% of the total aetiologies established), broken down as 118 cases of genetic encephalopathy and 24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile spasms/West syndrome, or visual deficit, but more difficult in cases of autism spectrum disorders. Genetic studies provide an increasing number of aetiological diagnoses, and they are also becoming the first step in diagnostic studies. Array CGH (microarray-based comparative genomic hybridisation) is the genetic test with the highest diagnostic yield in children with unexplained GDD/ID. DISCUSSION: The cost-effectiveness of complementary studies seems to be low if there are no clinically suspected entities. However, even in the absence of treatment, aetiological diagnosis is always important in order to provide genetic counselling and possible prenatal diagnosis, resolve family (and doctors') queries, and halt further diagnostic studies.

The effect of single-file reciprocating systems on Substance P and Calcitonin gene-related peptide expression in human periodontal ligament.

AIM: To quantify the effect of two single-file reciprocating root canal preparation systems on Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament (PDL). METHODOLOGY: Forty PDL samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 20 of these premolars were divided equally in two groups, and then, root canals were prepared using one of two different single-file systems: WaveOne and Reciproc. Ten premolars were prepared with hand files and served as a positive control group. The remaining 10 premolars where extracted without treatment and served as a negative control group. All PDL samples were processed, and SP and CGRP were measured by radioimmunoassay. RESULTS: Greater SP and CGRP expression were found in the hand instrumentation group (1.220 pmol SP and 0.084 pmol CGRP per mg of PDL), followed by the WaveOne group (0.908 pmol SP and 0.046 pmol CGRP per mg of PDL) and the Reciproc group (0.511 pmol SP and 0.022 pmol CGRP per mg of PDL). The lower SP and CGRP values were associated with the intact control group (0.453 pmol SP and 0.018 pmol CGRP per mg of PDL). The Kruskal-Wallis test revealed significant differences between groups (P < 0.001). Post hoc Tukey HSD tests revealed significant differences in SP and CGRP expression between intact teeth in the control group and all the other groups (P < 0.001) except with the Reciproc group (P = 0.165 and P = 0.42 for SP and CGRP, respectively). Hand instrumentation was associated with significant differences with all the other groups (P < 0.001). Differences between the WaveOne and Reciproc groups were also significant (P < 0.001). CONCLUSION: Substance P and CGRP expression in PDL cells increased when teeth were prepared with WaveOne as well as with hand instrumentation. Reciproc maintained SP and CGRP levels in line with the negative control group.

P450-aromatase mRNA is expressed in the corpus luteum (CL) of the non-pregnant sheep and goat: the expression of the enzyme is present throughout pregnancy in the goat CL.

In most mammals, the corpus luteum (CL) and placenta are the major sources of progesterone. The goat pregnancy depends on the presence of CL after mid-gestation, while sheep pregnancy does not. The expression and distribution of P450-aromatase (P450-Aro) mRNA throughout gestation has not been investigated in the goat CL and partially in the sheep CL. The present research was designed to characterize the expression of P450-Aro mRNA in small ruminant CL with emphasis in the goat. For this purpose, ovaries from Criollo goats and Pelibuey sheeps were analysed using in situ reverse transcription-polymerase chain reaction (RT-PCR) for the histological detection of P450-Aro transcripts. In addition, P450-Aro expression was determined by in vitro RT-PCR. In situ RT-PCR studies showed that the goat and sheep CL were rich in cells positive for P450-Aro mRNA. We have also found in vitro RT-PCR expression of P450-Aro mRNA in goat CL at 1, 3 and 4 months of gestation. This study shows that the goat CL expresses P450-Aro mRNA along gestation, suggesting that this structure is capable to produce oestrogens up to the end of gestation.

Singlet molecular oxygen quenching by the antioxidant dimethylmethoxy chromanol in solution and in ex vivo porcine skin.

Singlet-oxygen is a non-radical reactive oxygen species believed to play a major role in many photooxidation processes in connection with diverse photo-biological processes such as skin ageing or photocarcinogenesis. Dimethylmethoxy chromanol (3,4-dihydro-6-hydroxy-2,2-dimethyl-7-methoxy-1(2H)-benzopyran) is a potent antioxidant used in cosmetic and pharmaceutical formulations. We have assessed the singlet oxygen quenching ability of dimethylmethoxy chromanol, by monitoring the near-IR phosphorescence of singlet-oxygen in solution and in ex vivo porcine skin samples. Dimethylmethoxy chromanol quenches singlet oxygen with a rate constant of (1.3 ± 0.1) × 108 M⁻¹ s⁻¹ in solution. Consistent with this, a clear reduction in the singlet oxygen lifetime and emission intensity was observed when ex vivo porcine skin samples were treated with dimethylmethoxy chromanol.

[Survival of out-hospital cardiac arrests attended by a mobile intensive care unit in Asturias (Spain) in 2010]. / Supervivencia de las paradas cardiacas extrahospitalarias atendidas por una unidad de vigilancia intensiva móvil de Asturias en 2010.

OBJECTIVE: To evaluate attendance timings, out- and in-hospital characteristics, and survival of cardiac arrests attended by an advanced life support unit in Asturias (Spain) in 2010. Factors related to survival upon admission and at discharge were also analyzed. DESIGN: A retrospective, observational trial was carried out involving a cohort of out-hospital cardiac arrests (OHCA) occurring between 1 January 2010 and 31 December 2010, with one year of follow-up from OHCA. SETTING: Health Care Area IV of the Principality of Asturias, with a population of 342,020 in 2010. PATIENTS: All patients with OHCA and attended by an advanced life support unit were considered. MAIN VARIABLES: Demographic data, the etiology of cardiac arrest, bystander cardiopulmonary resuscitation (CPR), attendance timings and survival upon admission, at discharge and after one year. RESULTS: A total of 177 OHCA were included. Of these, 120 underwent CPR by the advanced life support team. Sixty-six of these cases (55%) were caused by presumed heart disease. A total of 63 patients (52.5%) recovered spontaneous circulation, and 51 (42.5%) maintained circulation upon admission to hospital. Thirteen patients (10.8%) were discharged alive. After one year, 11 patients were still alive (9.2%) - 9 of them (7.5%) with a Cerebral Performance Category (CPC) score of 1. Ventricular fibrillation and short attendance timings were related to increased survival. CONCLUSIONS: The survival rate upon admission was better than in other series and similar at discharge. Initial rhythm and attendance timings were related. Public automated external defibrillators (AED) were not used, and bystander CPR was infrequent.

Inhibition of Retinoic Acid Signaling in Proximal Tubular Epithelial cells Protects against Acute Kidney Injury by Enhancing Kim-1-dependent Efferocytosis.

Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development, but in the adult kidney is restricted to occasional collecting duct epithelial cells. We now show there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI), and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protects against experimental AKI but is associated with increased expression of the PTEC injury marker, Kim-1. However, Kim-1 is also expressed by de-differentiated, proliferating PTECs, and protects against injury by increasing apoptotic cell clearance, or efferocytosis. We show that the protective effect of inhibiting PTEC RAR signaling is mediated by increased Kim-1 dependent efferocytosis, and that this is associated with de-differentiation, proliferation, and metabolic reprogramming of PTECs. These data demonstrate a novel functional role that reactivation of RAR signaling plays in regulating PTEC differentiation and function in human and experimental AKI.

Assessing discards in an illegal small-scale fishery using fisher-led reporting.

About a third of all marine fish in the world are caught in Small-Scale Fisheries (SSF). SSF are increasingly recognised as essential for food security and livelihoods for vulnerable and economically fragile communities globally. Although individual SSF vessels are usually perceived as having little impact on the ecosystem, the cumulative impact of gear type and number of vessels may be substantial. Bottom trawling is a common fishing method that can greatly influence the marine ecosystem by damaging the seafloor and generating high levels of discards. However, appropriate sampling coverage using on-board observer programmes to collect these data from SSF are rare, as they are expensive and pose logistical constraints. A mobile App was used to assess whether self-reporting by fishers could provide reliable fine-scale information on fishing effort and discards over time in an illegal shrimp trawling fishery in northern Peru. Maps depicting the spatial distribution of trawling effort and the proportion of discards from observers and fishers were compared using the Similarity in Means (SIM) Index, which ranges from 0 when spatial patterns differ completely to 1 when spatial patterns are very similar. High levels of agreement between spatio-temporal patterns of effort (SIM Index = 0.81) and discards (0.96) were found between fisher and observer maps. Moreover, far greater spatial coverage was accomplished by fishers, suggesting that self-reporting via an App represents a useful approach to collect reliable fisheries data as an initial step for effective monitoring and management of these fisheries. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-022-09708-9.

A novel mutation in the ZNF462 gene c.3306dup; p.(Gln1103Thrfs*10) is associated to Weiss-Kruszka syndrome. A case report.

BACKGROUND: Weiss-Kruszka syndrome (WSKA) is a rare disorder caused by mutations in the ZNF462 gene or deletion of 9p31.2 chromosome region, involving ZNF462. The prevalence of WSKA is unknown as only 24 affected individuals have been described. This syndrome should be suspected in individuals presenting mild global developmental delay and common craniofacial abnormalities. CASE PRESENTATION: We presented a case of an infant, 3 years and 4-month life who presented pondostatural and psychomotor retardation, generalized hypotonia with hypermobility, bilateral palpebral ptosis, epicanthal folds, and poorly expressive facies as the main clinical features. These characteristics lead to the realization of genetics studies that resulted in the identification of a novel mutation c.3306dup; p.(Gln1103Thrfs*10) in ZNF462. CONCLUSIONS: WSKA should be suspected in individuals presenting mild global developmental delay, ptosis, downslanting palpebral fissures, exaggerated Cupid's Bow, arched eyebrows, epicanthal folds and short upturned nose with a bulbous tip. Hypertrophy of the ventricular septum and severe OSA were described in our patient and should be considered in future reviews of the disease. This case is added to the reduced number of publications previously reported regarding WSKA and contributes to understanding the genetic characteristics, clinical features, and diagnosis of this syndrome.Abbreviations: WSKA: Weiss-Kruszka syndrome; CP: craniofacial perimeter; WES: whole-exome sequencing; RSV: respiratory syncytial virus; OSA: obstructive sleep apnoea; ACMG: American College of Medical Genetics and Genomics.

Coping with uncertainty: breeding adjustments to an unpredictable environment in an opportunistic raptor.

No environment is truly constant in time. As a result, animals have evolved multiple adjustments to cope with such fluctuations. However, the allocation of effort to costly activities that imply long-term commitments, such as breeding, may be extremely challenging when future resources change constantly and unpredictably, a context that has received little investigation. To fill this gap, we studied the breeding response by a wetland-dependent raptor, the black kite Milvus migrans, to within and between-years fluctuations in resource availability (inundation levels). The breeding performance of the population was decomposed into reproductive components expressed in a sequence of successive tasks along the breeding cycle (e.g. timing of laying, clutch size, hatching success, brood reduction). Variation in each component was related to resource levels observed at different key dates of the season in order to test whether and when population-level reproduction was adjusted to available resources. Along a 22-year time-series, inundation levels fluctuated unpredictably within and among years, and mostly affected the later components of kites' reproduction, such as hatching success and the incidence of brood reduction, which were the main determinants of the population yearly breeding output. Results were consistent with multiple adjustments to cope with uncertainty. As the season progressed and resources became easier to assess, a bet-hedging waiting strategy based on a conservatively small, invariant and asynchronous clutch gave way to real-time resource-tracking mechanisms mediated by progressive adjustments to current prey availability, so that population-level breeding rates were determined and tuned to resources rather late in the season. Such adjustments were the likely outcome of the interaction between parental tactics and environmental constraints. Behavioural flexibility, such as dietary opportunism, probably promoted further resistance to resource oscillations. Given that all ecosystems show some degree of unpredictability, resource-tracking adjustments, such as the ones depicted here, are likely to be commonplace in most communities.

Probable interaction between trazodone and carbamazepine.

The need to maintain long-term treatment of chronic pathologies makes the appearance of interactions possible when such therapies incorporate other drugs to deal with the aggravation of the same or other intercurrent pathologies. A case is presented in which the addition of trazodone to a chronic treatment with carbamazepine (CBZ) is associated with symptoms typical for intoxication by this antiepileptic, accompanied by a raised serum concentration. When the trazodone was suspended, these symptoms lessened and the concentration of CBZ decreased progressively, suggesting a probable interaction between the 2 drugs.

Prenatal encephalopathies of unknown origin. Our 19-years experience. To what extent must genetic and biochemical studies be carried out?

INTRODUCTION: We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages. MATERIAL AND METHODS: We analysed our 19 year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin. RESULTS: The 19 year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them. DISCUSSION: Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs.