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Biomedical subjects

John R Williams

Publications and source records attributed to John R Williams.

At least 19 recordsLinked to original sources
PubMed2026

The investigation of human cerebrospinal fluid exosome in spinal cord injury.

Spinal cord injury (SCI) leads to severe neurological and functional impairments, yet reliable biomarkers for assessing injury severity and predicting recovery remain limited. Cerebrospinal fluid (CSF) is in direct contact with the central nervous system and provides a valuable source for detecting molecular changes after SCI. Although exosomal microRNAs (miRNAs) and proteins are increasingly recognized as mediators of intercellular communication, the role of human CSF exosomes in SCI has not been systematically investigated. To identify exosome-based biomarkers and potential therapeutic targets, we analyzed CSF and serum exosomes from patients with acute SCI using RNA sequencing and proteomic profiling. Weighted gene co-expression network analysis identified 6 gene modules significantly associated with injury severity and neurological recovery at 3 months. Proteomic analysis revealed a 5-protein panel that distinguished complete from incomplete SCI and a 4-protein panel that predicted neurological improvement. Additionally, 15 CSF-specific and 9 serum-specific exosomal miRNAs were identified independent of injury severity. Among 10 tested miRNAs associated with neurological recovery, 7 regulated astrocyte proliferation, and 6 promoted neurite extension and synapse formation. Overall, this study provides a comprehensive characterization of CSF exosomal miRNAs and proteins in human SCI and identifies molecular signatures associated with injury severity and recovery.

Humans↗
PubMed2006

Synthesis of the aglycone of the shark repellent pavoninin-4 using remote functionalization.

[reaction: see text] The aglycone of shark repellent pavoninin-4, (25R)-5alpha-cholestan-3alpha,15alpha,26-triol 26-acetate 1a, was synthesized from (25R)-cholest-5-en-3beta,26-diol 4 (26-hydroxycholesterol) in eight steps in 18% overall yield. Breslow's remote functionalization strategy was used as a key step to introduce the C-15alpha alcohol on a steroid D ring. An efficient synthesis of the 26-hydroxycholesterol from the 16beta hydroxyl steroid, (25R)-cholest-5-ene-3beta,16beta,26-triol (3a), is also reported.

Aminoglycosides↗
PubMed2006

The physician's role in the protection of human research subjects.

Responsibility for the protection of human research subjects is shared by investigators, research ethics committees, sponsors/funders, research institutions, governments and, the focus of this article, physicians who enrol patients in clinical trials. The article describes the general principles of the patient-physician relationship that should regulate the participation of physicians in clinical trials and proposes guidelines for determining when and how such participation should proceed. The guidelines deal with the following stages of the trial: when first considering participation, when deciding whether to enrol patients, when asking patients to participate, when the trial is underway and when it is completed.

Clinical Trials as Topic↗
PubMed2005

Synthesis of the shark repellent pavoninin-4.

[reaction: see text] The first synthesis of the shark repellent pavoninin-4, 3, was achieved in 12 steps with 21% overall yield from diosgenin, 8. Key reactions involve an efficient synthesis of the C-15alpha hydroxyl steroid from a C-16beta hydroxyl steroid by an unexpected 1,2-transposition strategy, a stereospecific glycosylation of a hindered C-15alpha alcohol using glycosyl fluoride as a glycosyl donor and a highly chemoselective acetylation of the C-26 primary alcohol by catalytic transesterification.

Aminoglycosides↗
PubMed2005

The pre-vaccination regional epidemiological landscape of measles in Italy: contact patterns, effort needed for eradication, and comparison with other regions of Europe.

BACKGROUND: Strong regional heterogeneity and generally sub-optimal rates of measles vaccination in Italy have, to date, hampered attainment of WHO targets for measles elimination, and have generated the need for the new Italian National Measles Elimination Plan. Crucial to success of the plan is the identification of intervention priorities based upon a clear picture of the regional epidemiology of measles derived from the use of data to estimate basic parameters. Previous estimates of measles force of infection for Italy have appeared anomalously low. It has been argued elsewhere that this results from Italian selective under-reporting by age of cases and that the true measles force of infection in Italy is probably similar to that of other European countries. A deeper examination of the evidence for this conjecture is undertaken in the present paper. METHODS: Using monthly regional case notifications data from 1949 to the start of vaccination in 1976 and notifications by age from 1971-76, summary equilibrium parameters (force of infection (FOI), basic reproductive ratio (R0) and critical vaccination coverage (pc)) are calculated for each region and for each of 5 plausible contact patterns. An analysis of the spectra of incidence profiles is also carried out. Finally a transmission dynamics model is employed to explore the correspondence between projections using different estimates of force of infection and data on seroprevalence in Italy. RESULTS: FOI estimates are lower than comparable European FOIs and there is substantial regional heterogeneity in basic reproductive ratios; certain patterns of contact matrices are demonstrated to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer, and compared with England & Wales there appears to be little synchronisation between regions. Modelling results suggest that the lower FOI estimated from corrected aggregate national data matches serological data more closely than that estimated from typical European data. CONCLUSION: Results suggest forces of infection in Italy, though everywhere remaining below the typical European level, are historically higher in the South where currently vaccination coverage is lowest. There appears to be little evidence to support the suggestion that a higher true force of infection is masked by age bias in reporting.

Journal Article↗
PubMed2005

Outcome following Bankart repair for shoulder instability 1998-2002 using a subjective patient based shoulder questionnaire (Oxford).

Bankart repair for shoulder instability has been performed by the senior author since 1998. We employ a modification of the technique as described by Rowe et al., using suture anchors but without a coracoid osteotomy. If inferior instability was present this procedure was combined with a capsular shift. We performed a retrospective case note review and postal questionnaire incorporating the Oxford Instability Score (OIS) on all patients. Fifty Bankart repairs were performed in the study period, three patients had further dislocations and three patients had ongoing symptoms of instability. Response rate to the questionnaire was 62%. Mean OIS following primary stabilisation was 21.7 (possible scores from 12-excellent to 60-poor). OIS following Bankart stabilisation of the shoulder has not been previously reported. These results compare favourably to original scores published by Dawson et al. (1999) who included both patients treated by surgery or physiotherapy.

Adult↗
PubMed2005

The ethics activities of the World Medical Association.

Since its formation in 1947, the World Medical Association (WMA) has been a leading voice in international medical ethics. The WMA's principal ethics activity over the years has been policy development on a wide variety of issues in medical research, medical practice and health care delivery. With the establishment of a dedicated Ethics Unit in 2003, the WMA's ethics activities have intensified in the areas of liaison, outreach and product development. Initial priorities for the Ethics Unit have been the review of paragraph 30 of the Declaration of Helsinki, the expansion of the Ethics Unit section of the WMA website and the development of an ethics manual for medical students everywhere.

Ethics, Medical↗
PubMed2005

Medical ethics in contemporary clinical practice.

This review article describes and analyzes ethical issues in medical practice, particularly those issues encountered by physicians in their relationships with their patients. These relationships often involve ethical conflicts between 2 or more interests, which physicians need to recognize and resolve. The article deals with 4 topics in clinical practice in which ethical conflicts occur: physicians' duty of confidentiality in a digital environment, their responsibilities for dealing with abuses of the human rights of patients, their role in clinical research, and their relationships with commercial enterprises. The ethical policies of the World Medical Association provide the basis for determining appropriate physician conduct on these matters. The article concludes with reflections on the need for international standards of medical ethics.

Confidentiality↗
PubMed2005

Unesco's proposed Declaration on Bioethics and Human Rights - a bland compromise.

The latest (June 2005) draft of UNESCO's proposed Universal Declaration on Bioethics and Human Rights is a major disappointment. The committee of government 'experts' that produced it made sure that it would not introduce any new obligations for States, and so the document simply restates existing agreements and lists desirable goals without specifying how they can be achieved. This article focuses on the shortcomings of the document as it would apply to health care. These shortcomings are evident in the document's scope, aims and principles. The conclusion is that if UNESCO still thinks that such a declaration is needed, it should produce either an ethical document addressed to individuals and groups, which would be primarily educational in nature, or a legal document addressed to States, which should not have the word 'ethics' in its title.

Advisory Committees↗
PubMed2004

Realistic population dynamics in epidemiological models: the impact of population decline on the dynamics of childhood infectious diseases. Measles in Italy as an example.

Most contributions in the field of mathematical modelling of childhood infectious diseases transmission dynamics have focused on stationary or exponentially growing populations. In this paper an epidemiological model with realistic demography is used to investigate the impact of the non-equilibrium conditions typical of the transition to sustained below replacement fertility (BRF) recently observed in a number of western countries, upon the transmission dynamics of measles. The results depend on the manner we model the relation between the (changing) age distribution of the population and contacts. Under some circumstances the transitional ageing phase typical of BRF populations might complexly interact with epidemiological variables leading to (i) a substantial reduction in the amount of vaccination effort required for eliminating the disease; (ii) a significant magnification of the perverse impact of vaccination in terms of the burden of severe age related morbidity.

Adolescent↗
PubMed2004

Ageing populations and childhood infections: the potential impact on epidemic patterns and morbidity.

BACKGROUND: Population decline, arising from below replacement fertility and possibly giving rise to substantial changes in age distribution, is a feature of many industrialized developed countries; Italy is one of the most notable European examples. The potential influence of this phenomenon on prevalence of chronic non-infectious disease is well known, but little attention to date has been paid to the impact on severe disease due to childhood infections in those cases where control is insufficient to achieve elimination. METHODS: A transmission dynamics model incorporating realistic demography is used to investigate the possible impact of population decline and ageing and suboptimal vaccination uptake on the age distribution of incidence of measles infection and of consequent mortality. Data from Italy is used to parameterize the model. RESULTS: Population ageing in the absence of vaccination is shown to reduce per capita incidence of infection but also to increase average and upper quartile ages at infection. The effect is substantially enhanced by significantly suboptimal vaccination uptake, when disease-induced mortality has, for a period, the potential to exceed that in the absence of vaccination. CONCLUSIONS: Although a substantially increased burden from chronic non-infectious disease has frequently been proposed as a consequence of population decline, there is also potential for an increase in morbidity and mortality from measles and other childhood infectious diseases, particularly where vaccine uptake is substantially below the optimum. Rubella is highlighted as a particular cause for concern. This work also has implications for less-developed countries.

Adolescent↗
PubMed2004

Synthesis and intramolecular reactions of trans-cyclohexyl-1,2-bisacrylate.

Photocycloaddition of dimethyl cyclobut-1-ene-1,2-dicarboxylate (1) with cyclohexene (7) afforded two photoadducts 8 and 9 in 44% and 28% yields, respectively. Spontaneous thermal isomerization of 8 gave (4Z,10Z)-dimethyl cyclodeca-4,10-diene-1,4-dicarboxylate (10), which subsequently isomerized to produce trans-1,2-cyclohexanebis-alpha-acrylic acid dimethyl ester 11. Hydride reduction of the bisacrylate 11 gave the trans-octahydro-1H-inden-2-ols 12a and 15 via a novel, stereoselective, intramolecular reaction. Reaction of the bisacrylate 11 with methyllithium afforded the bis-tertiary alcohol 16. In contrast, lithium dimethylcuprate reacted with the bisacrylate 11 to give the trans-hexahydro-1H-inden-2-one 17 in high yield via a novel, stereoselective, intramolecular reaction.

Acrylates↗
PubMed2004

Alpha-hydroxylation at C-15 and C-16 in cholesterol: synthesis of (25R)-5alpha-cholesta-3beta,15alpha,26-triol and (25R)-5alpha-cholesta-3beta,16alpha,26-triol from diosgenin.

[reaction: see text] (25R)-5alpha-cholesta-3beta,16alpha,26-triol 7b and (25R)-5alpha-cholesta-3beta,15alpha,26-triol 10b were synthesized, via (25R)-5alpha-cholesta-3beta,16beta,26-triol 5a, from diosgenin 3 in 52% yield over six steps and 47% yield over eight steps, respectively. An efficient method for inversion of a C-16beta hydroxyl to the C-16alpha position and a short method for transposition of a C-16beta hydroxyl to the C-15alpha position via the unexpected beta-reduction of a C-15 ketone in a steroid are reported.

Cholesterol↗
PubMed2004

Isolation and synthesis of shark-repelling saponins.

Saponins are complex compounds that are composed of a saccharide attached to a steroid or triterpene. They are natural surfactants, or detergents. Several important biological effects have been ascribed to saponins. They have been isolated from a great number of terrestrial plants. In the animal kingdom they are found in most sea cucumbers and starfish, whereas they are found only rarely in alcyonarians, gorgonians, sponges, and as shark-repelling compounds in fish. The present review deals with the isolation and some syntheses of the shark-repelling saponins mosesins-1 to -5 and pavoninins-1 to -6 obtained from the fish species Pardachirus.

Animals↗