Teaching Frailty to Medical Residents: A Needs Assessment Among Geriatrics Faculty.

BACKGROUND: Knowledge of frailty is essential for meeting the Accreditation Council for Graduate Medical Education core competencies for US trainees. The UK General Medical Council requires that frailty be included in undergraduate and graduate medical education curricula. Trainees are expected to appropriately modify care plans and help make patient-centered decisions, while incorporating diagnostic uncertainty, such as frailty, in older adults. Little is known about current needs for frailty instruction in graduate medical education in the US and beyond. OBJECTIVE: We sought to capture faculty perceptions on how frailty should be defined and identified, and what aspects and level of detail should be taught to residents. DESIGN: The authors developed a 4-item short response questionnaire, and faculty had the option to respond via electronic survey or via semi-structured interviews. SETTING AND SUBJECTS: Respondents included 24 fellowship-trained geriatricians based at 6 different academic medical centers in a single urban metropolitan area. METHODS: An invitation to participate in either an electronic survey or semi-structured virtual interview was e-mailed to 30 geriatricians affiliated with an academic multi-campus Geriatric Medicine fellowship. Responses were transcribed and coded independently by two authors. RESULTS: Responses were received from 24 geriatricians via a combination of digital questionnaires (n=18) and semi-structured online interviews (n=6), for a response rate of 80%. Responses revealed significant diversity of opinion on how to define and identify frailty and how these concepts should be taught. CONCLUSIONS: As frailty is increasingly incorporated into clinical practice, consensus is needed on how to define and teach frailty to residents.

Was adenine the first purine?

Oligomerization of HCN (1 molar) in the presence of added formaldehyde (0.5 molar) produced an order of magnitude more 8-hydroxymethyladenine than adenine or any other biologically significant purine. This result suggests that on the prebiotic Earth, nucleoside analogs may have been synthesized directly in more complex mixtures of HCN with other aldehydes.

Template-directed synthesis of novel, nucleic acid-like structures.

In studying the origins of life, it is important to examine reactions of substrate mixtures that could plausibly have accumulated on the primitive earth. Nucleoside diphosphates would probably have been synthesized along with the standard nucleotides under prebiotic conditions. For these reasons, the template-directed reactions of activated derivatives of these diphosphates, alone or mixed with activated nucleotides, were investigated. An activated derivative of deoxyguanosine 3',5'-diphosphate condensed efficiently on a polycytidylate template to give oligonucleotide analogues in which each 3',5'-phosphodiester bond was replaced by a pyrophosphate linkage. Oligomers were formed even in the absence of a template, but much more slowly. Template-directed condensation occurred also with an analogous deoxyadenosine derivative on polyuridylic acid and with an analogous acycloguanosine derivative on polycytidylic acid.

Purines and pyrimidines in sediments from lake erie.

Quantitative analyses of purines and pyrimidines in sequential sections of cores from the central and eastern basins of Lake Erie show steeply increasing concentrations in the youngest sediments. This may be related to increased loading of nutrients and recent cultural eutrophication of the lake. The purine and pyrimidine distributions suggest the operation of a specific degradative process for uracil at an extremely early stage in, or prior to, sediment formation.

Template-directed oligomerization catalyzed by a polynucleotide analog.

A pyrophosphate-linked analog of polycytidylic acid has been synthesized and shown to catalyze the oligomerization of the complementary monomer 2'-deoxyguanosine 3',5'-bisphosphoimidazolide. Analogs of polynucleotides are of interest in studies of the origins of life as possible precursors of the first RNA molecules. These results demonstrate that such molecules are capable of serving as templates for further synthesis.

Prebiotic evolution: selecting for homochirality before RNA.

Recent results show that the self-assembly of long homochiral oligomers of a nucleotide analogue can be achieved by ligation of short oligomers of chirally mixed composition. Do these results show how the RNA world might have arisen?

Origin of life. The origin of macromolecular chirality.

Do recent results obtained with "peptide nucleic acids" offer an explanation for the origin of biological chirality?

Did minerals perform prebiotic combinatorial chemistry?

It has long been suspected that mineral surfaces may have been important in prebiotic chemistry. The recent demonstrations of extended oligomerization of nucleotides, amino acids and carbohydrates on mineral surfaces add support to the potential prebiotic importance of minerals, but leave a number of questions unanswered.

Axonal transport and axonal processing of low molecular weight proteins from the abdominal ganglion of Aplysia.

Axonal transport of proteins in nerves of the abdominal ganglion of Aplysia was observed after a 2 h incubation of the ganglion in tritiated amino acids. The transported proteins migrate as a series of discrete peaks, all apparently moving at a rate of 3 mm/h. This process is sensitive to both colchicine and vinblastine, the former agent reducing the amount of transported material without affecting the transport rate. The molecular weight distribution of the transported proteins, as revealed by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS), is basically unchanged for up to 20 h after labeling. Low molecular weight species (less than or equal to 18,000 daltons) make up 10-20% of the transported protein and appear to be enriched in leucine. These proteins undergo proteolytic cleavage during transport, eventually reaching a molecular weight of 3000 daltons or lower. It is suggested that these data reflect the axonal transport and processing of neurosecretory peptides synthesized by identifiable neurons of the ganglion.

The RNA World and its origins.

The theory of the "RNA World" states that the first molecular systems to display the properties of self-replication and evolution were RNA molecules. The origin of life not only depended crucially upon this event, but RNA molecules can even be viewed as the first "living" things. In recent years this theory has gained ascendancy over competing ideas and is now largely accepted by biologists as the most satisfactory explanation for the origin of life. The reasons for this development will be reviewed and the problem of the origin of the first RNA molecules will be discussed.

Prebiotic photosynthetic reactions.

Historically, numerous attempts have been made to mimic - by means of inorganic model reactions - the photosynthetic fixation of CO2 by green plants. The literature in this field is strewn with claims and counter-claims. Two factors have led us to reexamine this subject: firstly; doubts concerning the highly reducing model for the atmosphere of the primitive Earth and secondly; recent results which demonstrate that photoreductive fixation is feasable on a suitable catalytic surface, for both CO2 and N2. The latter observation is of particular interest due to the well-known susceptibility of NH3 to photolytic destruction. Our review of the literature leads us to suggest that similar processes would have been plausible for the primitive Earth and could have been prebiotic precursors to an early development of CO2-fixing autotrophs.

Synthesis of uracil and thymine under simulated prebiotic conditions.

Evaporation and mild heating of solutions of beta-alanine and urea in the presence of clay minerals leads to the formation of 5,6-dihydrouracil (DHU). Ultraviolet irradiation of DHU in the presence of clay minerals and water vapor leads to the synthesis of uracil. Addition of acetate to this system results in the synthesis of thymine. The entire pathway could plausibly occur in pools subject to cycles of dehydration and rehydration and would result in the formation of significant concentrations of uracil and thymine from indisputably prebiotic materials.

Prebiotic adenine synthesis via HCN oligomerization in ice.

Adenine is produced (after hydrolysis) when 0.01 M solutions of HCN are adjusted to pH 9.2 with NH4OH and are frozen at -2 degrees C for 60-100 days. The addition of glycolonitrile (the cyanohydrin of formaldehyde) increases the yield of adenine under these conditions by about five-fold. These results confirm and extend an earlier suggestion that purine synthesis on the prebiotic Earth might have occurred in frozen, dilute solutions of HCN.

Nucleic acid analogues and the origins of replication.

Recent interest in the properties of "nucleic acid-like structures" has been stimulated by difficulties encountered in the synthesis and nonenzymatic oligomerization of nucleotides. However, none of the newly proposed monomers has yet been synthesized in a plausibly prebiotic manner. Arguments are presented that analogues based on 8-hydroxymethyladenine and 5-hydroxymethyluracil are promising candidates for primitive nucleotide precursors.

Minimal requirements for molecular information transfer.

The information transfer properties of nucleic acids are largely due to the properties of the bases themselves, for which it would appear evolution has selected a highly favorable set of molecules. In aqueous solution, it is possible that this task can only be carried out efficiently by heterocyclic, condensed-ring structures fairly similar to the purines and pyrimidines. Alterations in backbone structure, however, whether in the mode of linkage or in the nature of the sugar residue, are much less critical. Such alternatives could have played a role in the emergence of life on Earth and should be considered likely in extraterrestrial environments. The possible existence of low-efficiency, information transfer systems based on other structures entirely (proteins, clay minerals, etc), remains an interesting speculation for which no evidence is presently available.