Current Trends and Future Directions in Urban Social Prescribing.

PURPOSE OF REVIEW: Social prescribing (SP) is defined as a non-medical community referral program to support well-being and health. This review explores the current evidence about the effectiveness of SP. RECENT FINDINGS: This review examined existing SP models that have been or are being tested to connect people to these opportunities through direct and indirect referral schemes. The review identified a fifth model that facilitates a group-based approach used to mental well-being and resilience. While the development of SP largely originates from the UK, the global interest in SP has increased, with over 31 nations reporting elements of SP. The main goal of SP is to better integrate care between the traditional medical setting and resources available in the community and voluntary sectors. Although this review found widespread optimism around SP, there remain concerns about its effectiveness and demands for high-quality evaluations to strengthen the evidence base for SP.

Spatial Analysis and Lead-Risk Assessment of Philadelphia, USA.

Childhood lead poisoning is an issue that continues to plague major U.S. cities. Despite efforts by the Philadelphia Department of Public Health to curtail systemic childhood lead poisoning, children continue to be identified with elevated blood lead levels. The persistence of elevated blood lead levels in children is concerning because lead poisoning has been linked to decreases in academic achievement and IQ, with associated repercussions for entire communities. This paper reports the results of an analysis of the spatial distribution of houses with lead paint (i.e., pre-1978), demolitions, and occurrence of historic smelters, in West and North Philadelphia, relative to elevated blood lead level data, to determine which lead sources act as primary lead-risk factors. The presence of lead paint in homes and the number of demolitions of older properties were found to have the highest correlations to elevated blood lead levels for children in Philadelphia. Using lead-risk factors including lead paint, housing code violations, demolitions, and owner-occupied housing units, a lead-risk assessment was performed at the census tract level to identify future soil sampling sites and high-risk neighborhoods in Philadelphia. These sites of high risk for lead exposure, and in particular the census tracts 175 and 172, should be prioritized for lead poisoning prevention initiatives.

Commissural communication allows mouse intergeniculate leaflet and ventral lateral geniculate neurons to encode interocular differences in irradiance.

KEY POINTS: Unlike other visual thalamic regions, the intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) possess extensive reciprocal commissural connections, the functions of which are unknown. Using electrophysiological approaches, it is shown that commissural projecting IGL/vLGN cells are primarily activated by light increments to the contralateral eye while cells receiving commissural input typically exhibit antagonistic binocular responses. Across antagonistic cells, the nature of the commissural input (excitatory or inhibitory) corresponds to the presence of ipsilateral ON or OFF visual responses and in both cases antagonistic responses disappear following inactivation of the contralateral thalamus. The steady state firing rates of antagonistic cells uniquely encode interocular differences in irradiance. There is a pivotal role for IGL/vLGN commissural signalling in generating new sensory properties that are potentially useful for the proposed contributions of these nuclei to visuomotor/vestibular and circadian control. ABSTRACT: The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) are portions of the visual thalamus implicated in circadian and visuomotor/vestibular control. A defining feature of IGL/vLGN organisation is the presence of extensive reciprocal commissural connections, the functions of which are at present unknown. Here we use a combination of multielectrode recording, electrical microstimulation, thalamic inactivation and a range of visual stimuli in mice to address this deficit. Our data indicate that, like most IGL/vLGN cells, those that project commissurally primarily convey contralateral ON visual signals while most IGL/vLGN neurons that receive this input exhibit antagonistic binocular responses (i.e. excitatory responses driven by one eye and inhibitory responses driven by the other), enabling them to encode interocular differences in irradiance. We also confirm that this property derives from commissural input since, following inactivation of the contralateral visual thalamus, these cells instead display monocular contralateral-driven ON responses. Our data thereby reveal a fundamental role for commissural signalling in generating new visual response properties at the level of the visual thalamus.

SpyRings Declassified: A Blueprint for Using Isopeptide-Mediated Cyclization to Enhance Enzyme Thermal Resilience.

Enzymes often have marginal stability, with unfolding typically leading to irreversible denaturation. This sensitivity is a major barrier, both for de novo enzyme development and for expanding enzyme impact beyond the laboratory. Seeking an approach to enhance resilience to denaturation that could be applied to a range of different enzymes, we developed SpyRing cyclization. SpyRings contain genetically encoded SpyTag (13 amino acids) on the N-terminus and SpyCatcher (12kDa) on the C-terminus of the enzyme, so that the Spy partners spontaneously react together through an irreversible isopeptide bond. SpyRing cyclization gave major increases in thermal resilience, including on a model for enzyme evolution, ß-lactamase, and an industrially important enzyme in agriculture and nutrition, phytase. We outline the SpyRing rationale, including comparison of SpyRing cyclization to other cyclization strategies. The cloning strategy is presented for the simple insertion of enzyme genes for recombinant expression. We discuss structure-based approaches to select suitable enzyme cyclization targets. Approaches to evaluate the cyclization reaction and its effect on enzyme resilience are described. We also highlight the use of differential scanning calorimetry to understand how SpyRing cyclization promotes enzyme refolding. Efficiently searching sequence space will continue to be important for enzyme improvement, but the SpyRing platform may be a valuable rational adjunct for conferring resilience.

The quantity of naturally processed peptides stably bound by HLA-A*0201 is significantly reduced in the absence of tapasin.

Tapasin plays a critical role in promoting peptide binding by major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum. In its absence, cell surface expression of most allotypes is significantly reduced. Two exceptions are HLA-A*0201 and HLA-B*2705. In this study, the repertoire of peptides bound endogenously by these allotypes in the absence of tapasin was examined and stability of the HLA class I/peptide complexes assessed. Similar quantities of peptides were recovered from B*2705 complexes expressed in the absence and presence of tapasin and the composition of the peptide pools were not radically different. However, the stability of B*2705 molecules expressed at the surface of tapasin-deficient cells was found to be reduced which suggests there are subtle changes to the peptide repertoire. The impact of the absence of tapasin was more dramatic for A*0201. Although equivalent levels of cell surface A*0201 are expressed in the presence and absence of tapasin, very little A*0201 glycoprotein was recovered from tapasin-deficient cells suggesting the complexes readily dissociate. Consistent with reduced stability, A*0201 complexes were found to be rapidly lost from the surface of tapasin-deficient cells. Analysis of the small quantity of endogenously bound peptides recovered from A*0201 expressed in the absence of tapasin revealed a complex mixture typical of A*0201 molecules expressed in normal cells. Therefore these molecules are unable to exploit the alternative supply of TAP-independent A*0201-binding peptides present in the endoplasmic reticulum. Loading of A*0201 with peptides from both TAP-dependent and TAP-independent sources is significantly compromised without tapasin.

Are intravenous cannulae still being misused?

We have surveyed the use of intravenous cannulae (IVC) in a district general hospital. Of 354 patients interviewed on various wards, 125 (35.3%) had IVC in situ. The wrist was the commonest location for the cannulae (41.6%). An indication for cannula insertion was present in the majority (93.7%) of patients. Cannulae were left in situ even after their use had ceased, most commonly on wards for the elderly, and on these wards complications were more common. Other wards had specific IVC documentation, which resulted in fewer complications. Cannulae should be used for specific indications and should be reviewed daily for the development of complications and the need for their continued presence.

The quality of hospital discharge: a survey of discharge arrangements for the over-65s.

A three-phase study comprising semi-structured interviews with patients and/or their carers, follow-up postal questionnaires, and a postal survey of the views of professionals involved in the discharge of participating patients was conducted to assess the quality of arrangements for patients over 65 years of age, discharged from hospitals in Chester and Ellesmere Port in the United Kingdom. A large majority of patients (80%) felt they had been adequately consulted about arrangements for their discharge, but less than 2% of health and social care professionals considered all discharges satisfactory. This apparent disparity between patient and professional views may be explained by low levels of expectation among patients in this aspect of their care and their reluctance to express views which they fear may compromise future care. Continuing difficulties with interprofessional communication and liaison suggest that further attention to discharge management is required if improvements are to be effected.

Evaluation of 201Tl SPET myocardial perfusion imaging in the detection of coronary artery disease after orthotopic heart transplantation.

Accelerated coronary artery disease is a common complication following orthotopic cardiac transplantation. The relationship between acute rejection and accelerated coronary artery disease remains unclear. While thallium-201 (201Tl) imaging has been advocated in the diagnosis of post-transplant coronary arteriopathy, other investigators have found little role for this technique in the evaluation of such patients. We undertook a retrospective review of 13 stress/rest (10 exercise, 2 dobutamine, 1 dipyridamole) and 2 rest/rest 201Tl single photon emission tomographic (SPET) imaging studies performed in seven patients post-cardiac transplantation (mean duration post transplantation = 2.5 years). Four of these patients had serial studies with an average interval between studies of 8.3 months (range 3-14 months). Coronary angiography was performed within 12 months of each 201Tl study (mean = 4.2 months). Using the coronary angiographic diagnostic criterion of > or = 50% stenosis in one or more vessels, one or more fixed or reversible segmental defects were found on 201Tl imaging with a sensitivity of 78% and specificity of 33%. When the angiographic criterion of > 70% stenosis in one or more vessels was used the sensitivity increased to 100%, and where reversible segments were diagnostic the sensitivity was 67% and the specificity range from 42 to 58%. Although based on a small sample of patients, these results suggest that use of appropriate test methods and interpretive criteria may improve the utility of 201Tl SPET myocardial imaging in the diagnosis of coronary artery disease in cardiac transplant patients. Limited specificity may reflect associated pathological processes in these patients, including rejection, oedema and focal inflammation.

Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute.

OBJECTIVE: After an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (LCMV) infections among the institute's employees and to identify risk factors for infection. DESIGN: Retrospective cohort study. SETTING: A US cancer research institute. PARTICIPANTS: Eighty-two of 90 institute employees. MAIN OUTCOME MEASURES: Serum LCMV antibodies. RESULTS: Seven workers (9%) with definite LCMV infection (LCMV IgG antibody titer greater than or equal to 16) and one worker (1%) with probable infection (IgG titer = 8) were identified (10% overall seroprevalence). All infected employees handled animals or animal tissues and were more likely than other animal handlers to have worked with nude mice (Mus musculus) (P less than .02). Among the 31 employees who worked with nude mice at the institute, infected workers were more likely to clean the cages of nude mice (P much less than .001), change their bedding (P less than .01), and change their water (P less than .001). The institute had been injecting nude mice with LCMV-infected tumor cell lines and had recently increased the nude mouse population and the duration of experiments. These changes would have increased the LCMV burden at the facility and were temporally associated with the cluster of LCMV infections in employees. CONCLUSIONS: This LCMV outbreak, the first reported since 1974, is the first associated with nude mice. It illustrates the ongoing hazard LCMV poses in research laboratories. Since the symptoms of LCMV infection can be nonspecific, clinicians should consider this diagnosis in ill patients who report laboratory rodent exposure.

Identification using 1H NMR spectroscopy of slowly exchanging amide hydrogens of hen lysozyme in solution.

Resonances of over 20 of the most slowly exchanging amide hydrogens have been identified and assigned in the 1H NMR spectrum of hen lysozyme. This was achieved by combining information about spin-spin coupling patterns with nuclear Overhauser enhancement measurements. A computer-based search program was used to permit the assumptions and constraints in this procedure to be closely defined and to reveal possible ambiguities. In addition, experimental values of coupling constants were compared with values calculated on the basis of the torsion angles found in the crystal structure. The close correlation between these gave further confidence in the assignment procedures and provided information concerning the nature of fluctuations about the average solution structure. The very slowly exchanging amide hydrogens are largely buried in alpha-helical and beta-sheet regions of the protein structure.