RESUMEN

BACKGROUND: Delirium is an underdiagnosed clinical syndrome typified by an acute alteration of mental state. It is an important problem in critical care and intensive care units (ICU) due to its high prevalence and its association with adverse outcomes. Delirium is a very distressing condition for patients, with a huge impact on their well-being. Diagnosis of delirium in the critical care setting is challenging. This is especially true for patients who are mechanically ventilated and are therefore unable to engage in a verbal interview. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a tool specifically designed to assess for delirium in the context of ICU patients, including those on mechanical ventilation. CAM-ICU can be administered by non-specialists to give a dichotomous delirium present/absent result. OBJECTIVES: To determine the diagnostic accuracy of the CAM-ICU for the diagnosis of delirium in adult patients in critical care units. SEARCH METHODS: We searched MEDLINE (Ovid SP, 1946 to 8 July 2022), Embase (Ovid SP, 1982 to 8 July 2022), Web of Science Core Collection (ISI Web of Knowledge, 1945 to 8 July 2022), PsycINFO (Ovid SP, 1806 to 8 July 2022), and LILACS (BIREME, 1982 to 8 July 2022). We checked the reference lists of included studies and other resources for additional potentially relevant studies. We also searched the Health Technology Assessment database, the Cochrane Library, Aggressive Research Intelligence Facility database, WHO ICTRP, ClinicalTrials.gov, and websites of scientific associations to access any annual meetings and abstracts of conference proceedings in the field. SELECTION CRITERIA: We included diagnostic studies enrolling adult ICU patients assessed using the CAM-ICU tool, regardless of language or publication status and reporting sufficient data on delirium diagnosis for the construction of 2 x 2 tables. Eligible studies evaluated the diagnostic performance of the CAM-ICU versus a clinical reference standard based on any iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria applied by a clinical expert. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and collated study data. We assessed the methodological quality of studies using the QUADAS-2 tool. We used two univariate fixed-effect or random-effects models to determine summary estimates of sensitivity and specificity. We performed sensitivity analyses that excluded studies considered to be at high risk of bias and high concerns in applicability, due mainly to the target population included (e.g. patients with traumatic brain injury). We also investigated potential sources of heterogeneity, assessing the effect of reference standard diagnosis and proportion of patients ventilated. MAIN RESULTS: We included 25 studies (2817 participants). The mean age of participants ranged from 48 to 69 years; 15 of the studies included critical care units admitting mixed populations (e.g. medical, trauma, surgery patients). The percentage of patients receiving mechanical ventilation ranged from 11.8% to 100%. The prevalence of delirium in the studies included ranged from 12.5% to 83.9%. Presence of delirium was determined by the application of DSM-IV criteria in 13 out of 25 included studies. We assessed 13 studies as at low risk of bias and low applicability concerns for all QUADAS-2 domains. The most common issue of concern was flow and timing of the tests, followed by patient selection. Overall, we estimated a pooled sensitivity of 0.78 (95% confidence interval (CI) 0.72 to 0.83) and a pooled specificity of 0.95 (95% CI 0.92 to 0.97). Sensitivity analysis restricted to studies at low risk of bias and without any applicability concerns (n = 13 studies) gave similar summary accuracy indices (sensitivity 0.80 (95% CI 0.72 to 0.86), specificity 0.95 (95% CI 0.93 to 0.97)). Subgroup analyses based on diagnostic assessment found summary estimates of sensitivity and specificity for studies using DSM-IV of 0.79 (95% CI 0.72 to 0.85) and 0.94 (95% CI 0.90 to 0.96). For studies that used DSM-5 criteria, summary estimates of sensitivity and specificity were 0.75 (95% CI 0.67 to 0.82) and 0.98 (95% CI 0.95 to 0.99). DSM criteria had no significant effect on sensitivity (P = 0.421), but the specificity for detection of delirium was higher when DSM-5 criteria were used (P = 0.024). The relative specificity comparing DSM-5 versus DSM-IV criteria was 1.05 (95% CI 1.02 to 1.08). Summary estimates of sensitivity and specificity for studies recruiting < 100% of patients with mechanical ventilation were 0.81 (95% CI 0.75 to 0.85) and 0.95 (95% CI 0.91 to 0.98). For studies that exclusively recruited patients with mechanical ventilation, summary estimates of sensitivity and specificity were 0.91 (95% CI 0.76 to 0.97) and 0.98 (95% CI 0.92 to 0.99). Although there was a suggestion of differential performance of CAM-ICU in ventilated patients, the differences were not significant in sensitivity (P = 0.316) or in specificity (P = 0.493). AUTHORS' CONCLUSIONS: The CAM-ICU tool may have a role in the early identification of delirium, in adult patients hospitalized in intensive care units, including those on mechanical ventilation, when non-specialized, properly trained clinical personnel apply the CAM-ICU. The test is most useful for exclusion of delirium. The test may miss a proportion of patients with incident delirium, therefore in situations where detection of all delirium cases is desirable, it may be best to repeat the test or combine CAM-ICU with another assessment. Future studies should compare different screening tests proposed for bedside assessment of delirium, as this approach will reveal which tool yields superior accuracy. In addition, future studies should consider and report the flow and timing of the tests and clearly report key characteristics related to patient selection. Finally, future research should focus on the impact of CAM-ICU screening on patient outcomes.

Asunto(s)

Delirio , Unidades de Cuidados Intensivos , Adulto , Humanos , Persona de Mediana Edad , Anciano , Sensibilidad y Especificidad , Delirio/diagnóstico , Cuidados Críticos

RESUMEN

The top-down and indirect effects of insects on plant communities depend on patterns of host use, which are often poorly documented, particularly in species-rich tropical forests. At Barro Colorado Island, Panama, we compiled the first food web quantifying trophic interactions between the majority of co-occurring woody plant species and their internally feeding insect seed predators. Our study is based on more than 200 000 fruits representing 478 plant species, associated with 369 insect species. Insect host-specificity was remarkably high: only 20% of seed predator species were associated with more than one plant species, while each tree species experienced seed predation from a median of two insect species. Phylogeny, but not plant traits, explained patterns of seed predator attack. These data suggest that seed predators are unlikely to mediate indirect interactions such as apparent competition between plant species, but are consistent with their proposed contribution to maintaining plant diversity via the Janzen-Connell mechanism.

Asunto(s)

Cadena Alimentaria , Bosques , Insectos , Clima Tropical , Animales , Biodiversidad , Panamá , Filogenia , Semillas

RESUMEN

Vanilla is an orchid of economic importance widely cultivated in tropical regions and native to Mexico. We sampled three species of Vanilla (V. planifolia, V. pompona, and V. insignis) in different crop systems. We studied the effect of crop system on the abundance, type of fungi, and quality of pelotons found in the roots using light and electron microscopy and direct sequencing of mycorrhizal structures. Fungi were identified directly from pelotons obtained from terrestrial roots of vanilla plants in the flowering stage. Root samples were collected from plants in crop systems located in the Totonacapan area in Mexico (states of Puebla and Veracruz). DNA was extracted directly from 40 pelotons and amplified using ITS rRNA sequencing. Peloton-like structures were observed, presenting a combination of active pelotons characterized by abundant hyphal coils and pelotons in various stages of degradation. The most active pelotons were observed in crop systems throughout living tutors (host tree) in comparison with roots collected from dead or artificial tutors. Fungi identified directly from pelotons included Scleroderma areolatum, a common ectomycorrhizal fungus that has not been reported as a mycorrhizal symbiont in orchids. Direct amplification of pelotons also yielded common plant pathogens, including Fusarium and Pyrenophora seminiperda, especially in those sites with low colonization rates, and where large numbers of degraded pelotons were observed. This research reports for the first time the potential colonization of Vanilla by Scleroderma, as a putative orchid mycorrhizal symbiont in four sites in Mexico and the influence of crop system on mycorrhizal colonization on this orchid.

Asunto(s)

Basidiomycota/fisiología , Micorrizas/fisiología , Vanilla/microbiología , Basidiomycota/clasificación , Productos Agrícolas , ADN de Hongos/genética , ADN Intergénico/genética , México , Micorrizas/clasificación , Filogenia , Análisis de Secuencia de ADN

Asunto(s)

Carnitina O-Palmitoiltransferasa/genética , Indígenas Norteamericanos/genética , Infecciones/enzimología , Infecciones/genética , Humanos

RESUMEN

We have bred a Pkd1 floxed allele with a nestin-Cre expressing line to generate cystic mice with preserved glomerular filtration rate to address the pathogenesis of complex autosomal dominant polycystic kidney disease (ADPKD) phenotypes. Hypertension affects about 60% of these patients before loss of renal function, leading to significant morbimortality. Cystic mice were hypertensive at 5 and 13 weeks of age, a phenotype not seen in noncystic controls and Pkd1-haploinsufficient animals that do not develop renal cysts. Fractional sodium excretion was reduced in cystic mice at these ages. Angiotensinogen gene expression was higher in cystic than noncystic kidneys at 18 weeks, while ACE and the AT1 receptor were expressed in renal cyst epithelia. Cystic animals displayed increased renal cAMP, cell proliferation, and apoptosis. At 24 weeks, mean arterial pressure and fractional sodium excretion did not significantly differ between the cystic and noncystic groups, whereas cardiac mass increased in cystic mice. Renal concentrating deficit is also an early finding in ADPKD. Maximum urine osmolality and urine nitrite excretion were reduced in 10-13- and 24-week-old cystic mice, deficits not found in haploinsufficient and noncystic controls. A trend of higher plasma vasopressin was observed in cystic mice. Thus, cyst growth most probably plays a central role in early-stage ADPKD-associated hypertension, with activation of the intrarenal renin-angiotensin system as a key mechanism. Cyst expansion is also likely essential for the development of the concentrating deficit in this disease. Our findings are consistent with areas of reduced perfusion in the kidneys of patients with ADPKD.

Asunto(s)

Presión Arterial , Proliferación Celular , Hipertensión/etiología , Capacidad de Concentración Renal , Riñón/metabolismo , Riñón Poliquístico Autosómico Dominante/complicaciones , Canales Catiónicos TRPP/deficiencia , Animales , Apoptosis , Presión Arterial/genética , Biomarcadores/sangre , Biomarcadores/orina , Proliferación Celular/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación de la Expresión Génica , Genotipo , Tasa de Filtración Glomerular , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Riñón/patología , Riñón/fisiopatología , Capacidad de Concentración Renal/genética , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Sistema Renina-Angiotensina , Canales Catiónicos TRPP/genética , Factores de Tiempo

RESUMEN

SUMMARY: We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors. INTRODUCTION: The aim of this study is to assess the prevalence and correlates of AAC in a sample of 278 Afro-Caribbean men (mean age 56) and to test for a largely unexplored association between cortical and trabecular vBMD with AAC prevalence. METHODS: Men were recruited consecutively as part of an ongoing prospective cohort study of body composition in men aged 40+. For this analysis, AAC was assessed by computed tomography of the abdomen from L3 to S1. Aortic calcium was scored using the Agatston method, and prevalence was defined as a score ≥10 to rule out false positives. Men also had BMD assessed using peripheral quantitative computed tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and tibia. RESULTS: Abdominal aortic calcification was present in 68.3 % of the men. Significant independent predictors of AAC prevalence were increased age, increased BMI, hypertension, and current smoking. Age was the strongest predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased odds of having AAC (P < 0.0001). A one SD greater cortical, but not trabecular, vBMD was associated with a significant decreased odds of AAC prevalence independent of other traditional risk factors (OR 0.65; 95 % CI 0.45-0.92). CONCLUSIONS: Cortical vBMD is inversely associated with AAC presence. This finding suggests that there may be shared physiology between cortical bone compartment remodeling and vascular calcification.

Asunto(s)

Enfermedades de la Aorta/fisiopatología , Densidad Ósea/fisiología , Calcificación Vascular/fisiopatología , Adulto , Anciano , Aorta Abdominal , Enfermedades de la Aorta/etnología , Población Negra/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodos , Trinidad y Tobago/epidemiología , Calcificación Vascular/etnología

RESUMEN

The Salar Grande in the Coastal Range of Northern Chile is a fossil evaporitic basin filled with almost pure halite (95% NaCl average). It is assumed that the basin has not received input of brines since the Pliocene (5.3 to 1.8 million years). Below 1 m the halite has remained undissolved since this time, whereas the upper layer has been dissolved and recrystallized by dripping fogs and occasional rainfall. We compared the archaeal community at different depths using both nested PCR and cultivation. The upper 10 cm of halite crust contained diverse haloarchaeal species, including several from new genera, but their provenance is unknown. For samples deeper in the core, a new and rigorous procedure for chemically sterilizing the surface of single halite crystals was developed. These halite crystals contained only species of the genus Halobacterium (Hbt.). Halobacterium salinarum-like sequences were detected by PCR, and evidence that they were from ancient DNA include: comparison with numerous negative controls; detection of 16S rRNA sequence differences in non-conserved regions, indicating genuine evolutionary mutations rather than PCR-cloning artefacts; independent isolation of Hbt. salinarum from ancient halite; and diverse mechanisms possessed by this species for minimizing radiation damage and thus enhancing its potential for long-term survival. Haloarchaea related to Hbt. noricense were obtained from enrichment cultures from ≈ 0.4 and 15.4 m depth. We investigated Hbt. noricense strain A1 and found that when trapped inside halite crystals its recovery was as rapid after 27 months of entombment as at day 0, faring much better than other extreme halophiles. A biogeographical investigation showed that Hbt. noricense-like organisms were: commonly found in surface-sterilized ancient halite, associated with salt mines, in halite crusts, and, despite a much more intense search, only rarely detected in surface environments. We conclude that some Halobacterium species are specialists at long-term survival in halite.

Asunto(s)

Archaea/clasificación , Archaea/fisiología , Biodiversidad , Microbiología Ambiental , Sales (Química) , Archaea/genética , Técnicas Bacteriológicas , Chile , Halobacterium/clasificación , Halobacterium/genética , Halococcus/genética , Halococcus/fisiología , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética

RESUMEN

Animals communicating socially are expected to produce signals that are conspicuous within the habitats in which they live. The particular way in which a species adapts to its environment will depend on its ancestral condition and evolutionary history. At this point, it is unclear how properties of the environment and historical factors interact to shape communication. Tropical Anolis lizards advertise territorial ownership using visual displays in habitats where visual motion or "noise" from windblown vegetation poses an acute problem for the detection of display movements. We studied eight Anolis species that live in similar noise environments but belong to separate island radiations with divergent evolutionary histories. We found that species on Puerto Rico displayed at times when their signals were more likely to be detected by neighboring males and females (during periods of low noise). In contrast, species on Jamaica displayed irrespective of the level of environmental motion, apparently because these species have a display that is effective in a range of viewing conditions. Our findings appear to reflect a case of species originating from different evolutionary starting points evolving different signal strategies for effective communication in noisy environments.

Asunto(s)

Comunicación Animal , Lagartos/fisiología , Adaptación Fisiológica , Animales , Ecosistema , Femenino , Jamaica , Masculino , Filogenia , Puerto Rico , Detección de Señal Psicológica , Especificidad de la Especie , Territorialidad , Percepción Visual

RESUMEN

A key hypothesis explaining the existence of dawn and dusk choruses in acoustically communicating animals centers on the need to advertise continued territorial occupancy after and before a period of nocturnal inactivity. If this hypothesis is correct, it follows that similar dawn and dusk choruses should occur in territorial animals exploiting other signal modalities. Adult male Anolis lizards defend territories by using elaborate head-bobbing displays and extensions of a throat fan or dewlap. Males are inactive at night and return to their territories at dawn, remaining there until dusk. I quantified the production of visual displays as a function of time of day for four species on the island of Jamaica: Anolis lineatopus, Anolis sagrei, Anolis grahami, and Anolis opalinus. All exhibited dawn and/or dusk peaks in display behavior. These patterns have remarkable parallels with the dawn and dusk choruses reported for many acoustically communicating animals.

Asunto(s)

Lagartos/fisiología , Territorialidad , Animales , Jamaica , Masculino , Tiempo

RESUMEN

Uma linha do tempo do trabalho de Skinner em comportamento verbal deve ter como ponto de partida o princípio de sua carreira científica. Já em sua tese, Skinner estabeleceu o modelo conceitual de sua Teoria do Comportamento. Ele desenvolveu seu trabalho experimental dentro deste modelo e dependeu de resultados de pesquisa para ajustar e modificar a sua teoria. Ao mesmo tempo, ele deu início a tentativas de interpretação do comportamento verbal de acordo com suas formulações teóricas e com base nas relações operantes descobertas em laboratório. Os trabalhos em relações mediadas e não mediadas permeiam toda sua carreira. Lenta e indutivamente ele descobriu as relações verbais básicas durante um período de vinte e cinco anos de empenho.

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A time line of Skinner’s work on verbal behavior must start at the very beginning of his scientific career. Skinner laid down the conceptual framework of his Theory of Behavior as early as his thesis. He developed his experimental work within this framework, and depended on research results to adjust and modify his theory. At the same time, he initiated efforts to interpret verbal behavior within his theoretical formulations and upon the operant relations he discovered in the laboratory. Work on both mediated and nonmediated relations entwined throughout his career. He discovered the basic verbal relations slowly and inductively over a twenty-five year span of effort.

RESUMEN

Uma linha do tempo do trabalho de Skinner em comportamento verbal deve ter como ponto de partida o princípio de sua carreira científica. Já em sua tese, Skinner estabeleceu o modelo conceitual de sua Teoria do Comportamento. Ele desenvolveu seu trabalho experimental dentro deste modelo e dependeu de resultados de pesquisa para ajustar e modificar a sua teoria. Ao mesmo tempo, ele deu início a tentativas de interpretação do comportamento verbal de acordo com suas formulações teóricas e com base nas relações operantes descobertas em laboratório. Os trabalhos em relações mediadas e não mediadas permeiam toda sua carreira. Lenta e indutivamente ele descobriu as relações verbais básicas durante um período de vinte e cinco anos de empenho.(AU)

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A time line of Skinner’s work on verbal behavior must start at the very beginning of his scientific career. Skinner laid down the conceptual framework of his Theory of Behavior as early as his thesis. He developed his experimental work within this framework, and depended on research results to adjust and modify his theory. At the same time, he initiated efforts to interpret verbal behavior within his theoretical formulations and upon the operant relations he discovered in the laboratory. Work on both mediated and nonmediated relations entwined throughout his career. He discovered the basic verbal relations slowly and inductively over a twenty-five year span of effort.(AU)

Asunto(s)

Historia , Behaviorismo

RESUMEN

In general, leaf wetness duration (LWD) is a key parameter influencing plant disease epidemiology, since it provides the free water required by pathogens to infect foliar tissue. LWD is used as an input in many disease warning systems, which help growers to decide the best time to spray their crops against diseases. Since there is no observation standard either for sensor or exposure, LWD measurement is often problematic. To assess the performance of electronic sensors, LWD measurements obtained with painted cylindrical and flat plate sensors were compared under different field conditions in Elora, Ontario, Canada, and in Piracicaba, São Paulo, Brazil. The sensors were tested in four different crop environments--mowed turfgrass, maize, soybean, and tomatoes--during the summer of 2003 and 2004 in Elora and during the winter of 2005 in Piracicaba. Flat plate sensors were deployed facing north and at 45 degrees to horizontal, and cylindrical sensors were deployed horizontally. At the turfgrass site, both sensors were installed 30 cm above the ground, while at the crop fields, the sensors were installed at the top and inside the canopy (except for maize, with a sensor only at the top). Considering the flat plate sensor as a reference (Sentelhas et al. Operational exposure of leaf wetness sensors. Agric For Meteorol 126:59-72, 2004a), the results in the more humid climate at Elora showed that the cylindrical sensor overestimated LWD by 1.1-4.2 h, depending on the crop and canopy position. The main cause of the overestimation was the accumulation of big water drops along the bottom of the cylindrical sensors, which required much more energy and, consequently, time to evaporate. The overall difference between sensors when evaporating wetness formed during the night was around 1.6 h. Cylindrical sensors also detected wetness earlier than did flat plates--around 0.6 h. Agreement between plate and cylinder sensors was much better in the drier climate at Piracicaba. These results allow us to caution that cylindrical sensors may overestimate wetness for operational LWD measurements in humid climates and that the effect of other protocols for angling or positioning this sensor should be investigated for different crops.

Asunto(s)

Clima , Hojas de la Planta/química , Agricultura , Brasil , Electrónica/instrumentación , Solanum lycopersicum/química , Conceptos Meteorológicos , Ontario , Enfermedades de las Plantas , Poaceae/química , Glycine max/química , Agua/análisis , Zea mays/química

RESUMEN

During the last decade, sensitive techniques for detecting DNA have been successfully applied to archaeological and other samples that were a few hundred to a few thousand years old. Nevertheless, there is still controversy and doubt over claims of exceptionally ancient DNA. Additional accounts stretching back nearly a century suggest that microorganisms may survive over geological time in evaporite deposits. There is, however, often doubt over the age relationship between evaporite formation and the incorporation of microorganisms. Here, we have used petrographic and geochemical techniques (laser ablation microprobe inductively coupled plasma mass spectrometry) to verify the estimated geological age of halite (NaCl) evaporite samples. Fragments of 16S ribosomal RNA genes were detected by polymerase chain reaction amplification of DNA extracted from halite samples ranging in age from 11 to 425 Myr (millions of years). Haloarchaeal 16S rDNA amplicons were present in one sample (11 16 Myr), whereas other samples (65 425 Myr) yielded only bacterial 16S rDNA amplicons. Terminal restriction fragment length polymorphism analyses indicate complex and different populations of microorganisms or their free DNA in ancient halites of different ages.

Asunto(s)

ADN Ribosómico/aislamiento & purificación , Fósiles , Sedimentos Geológicos/microbiología , ARN Ribosómico 16S/aislamiento & purificación , Cloruro de Sodio , Brasil , ADN de Archaea/genética , ADN de Archaea/aislamiento & purificación , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , ADN Ribosómico/genética , Michigan , Datos de Secuencia Molecular , Filogenia , Polonia , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , ARN Ribosómico 16S/genética , Tailandia , Factores de Tiempo

RESUMEN

The CLN6 gene that causes variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), a recessively inherited neurodegenerative disease that features blindness, seizures, and cognitive decline, maps to 15q21-23. We have used multiallele markers spanning this approximately 4-Mb candidate interval to reveal a core haplotype, shared in Costa Rican families with vLINCL but not in a Venezuelan kindred, that highlighted a region likely to contain the CLN6 defect. Systematic comparison of genes from the minimal region uncovered a novel candidate, FLJ20561, that exhibited DNA sequence changes specific to the different disease chromosomes: a G-->T transversion in exon 3, introducing a stop codon on the Costa Rican haplotype, and a codon deletion in exon 5, eliminating a conserved tyrosine residue on the Venezuelan chromosome. Furthermore, sequencing of the murine homologue in the nclf mouse, which manifests recessive NCL-like disease, disclosed a third lesion-an extra base pair in exon 4, producing a frameshift truncation on the nclf chromosome. Thus, the novel approximately 36-kD CLN6-gene product augments an intriguing set of unrelated membrane-spanning proteins, whose deficiency causes NCL in mouse and man.

Asunto(s)

Proteínas de la Membrana/genética , Mutación/genética , Lipofuscinosis Ceroideas Neuronales/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 15/genética , Costa Rica , Análisis Mutacional de ADN , Exones/genética , Femenino , Eliminación de Gen , Frecuencia de los Genes/genética , Haplotipos/genética , Humanos , Masculino , Proteínas de la Membrana/química , Proteínas de la Membrana/deficiencia , Ratones , Datos de Secuencia Molecular , Linaje , Polimorfismo Genético/genética , ARN Mensajero/análisis , ARN Mensajero/genética , Alineación de Secuencia , Venezuela