Suicide, self-harm and thoughts of suicide or self-harm in infectious disease epidemics: a systematic review and meta-analysis.

AIMS: Suicide accounts for 2.2% of all years of life lost worldwide. We aimed to establish whether infectious epidemics are associated with any changes in the incidence of suicide or the period prevalence of self-harm, or thoughts of suicide or self-harm, with a secondary objective of establishing the frequency of these outcomes. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO and AMED were searched from inception to 9 September 2020. Studies of infectious epidemics reporting outcomes of (a) death by suicide, (b) self-harm or (c) thoughts of suicide or self-harm were identified. A random-effects model meta-analysis for the period prevalence of thoughts of suicide or self-harm was conducted. RESULTS: In total, 1354 studies were screened with 57 meeting eligibility criteria, of which 7 described death by suicide, 9 by self-harm, and 45 thoughts of suicide or self-harm. The observation period ranged from 1910 to 2020 and included epidemics of Spanish Flu, severe acute respiratory syndrome, human monkeypox, Ebola virus disease and coronavirus disease 2019 (COVID-19). Regarding death by suicide, data with a clear longitudinal comparison group were available for only two epidemics: SARS in Hong Kong, finding an increase in suicides among the elderly, and COVID-19 in Japan, finding no change in suicides among children and adolescents. In terms of self-harm, five studies examined emergency department attendances in epidemic and non-epidemic periods, of which four found no difference and one showed a reduction during the epidemic. In studies of thoughts of suicide or self-harm, one large survey showed a substantial increase in period prevalence compared to non-epidemic periods, but smaller studies showed no difference. As a secondary objective, a meta-analysis of thoughts of suicide and self-harm found that the pooled prevalence was 8.0% overall (95% confidence interval (CI) 5.2-12.0%; 14 820 of 99 238 cases in 24 studies) over a time period of between seven days and six months. The quality assessment found 42 studies were of high quality, nine of moderate quality and six of high quality. CONCLUSIONS: There is little robust evidence on the association of infectious epidemics with suicide, self-harm and thoughts of suicide or self-harm. There was an increase in suicides among the elderly in Hong Kong during SARS and no change in suicides among young people in Japan during COVID-19, but it is unclear how far these findings may be generalised. The development of up-to-date self-harm and suicide statistics to monitor the effect of the current pandemic is an urgent priority.

Longitudinal study on the occurrence in pigs of colistin-resistant Escherichia coli carrying mcr-1 following the cessation of use of colistin.

AIMS: In 2015, colistin-resistant Escherichia coli and Salmonella with the mcr-1 gene were isolated from a pig farm in Great Britain. Pigs were subsequently monitored over a ~20-month period for the occurrence of mcr-1-mediated colistin resistance and the risk of mcr-1 E. coli entering the food chain was assessed. METHODS AND RESULTS: Pig faeces and slurry were cultured for colistin-resistant E. coli and Salmonella, tested for the mcr-1 gene by PCR and selected isolates were further analysed. Seventy-eight per cent of faecal samples (n = 275) from pigs yielded mcr-1 E. coli after selective culture, but in positive samples only 0·2-1·3% of the total E. coli carried mcr-1. Twenty months after the initial sampling, faecal samples (n = 59) were negative for E. coli carrying mcr-1. CONCLUSIONS: The risk to public health from porcine E. coli carrying mcr-1 was assessed as very low. Twenty months after cessation of colistin use, E. coli carrying mcr-1 was not detected in pig faeces on a farm where it was previously present. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that cessation of colistin use may help over time to reduce or possibly eliminate mcr-1 E. coli on pig farms where it occurs.

Prevalence of extended-spectrum-ß-lactamase-producing Escherichia coli from pigs at slaughter in the UK in 2013.

OBJECTIVES: To determine the prevalence and types of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli occurring in pigs at slaughter in the UK in 2013. METHODS: Caecal samples from 637 pigs, sampled via a UK-wide monitoring programme in 2013, were enriched overnight in buffered peptone water, before plating to CHROMagar CTX and Oxoid Brilliance ESBL agar. Presumptive ESBL-producing E. coli from both media were tested for ESBL phenotype using MAST ESßL ID discs. Isolates with an ESBL phenotype were examined for the presence of blaCTX-M, blaOXA, blaSHV and blaTEM genes using a multiplex PCR. All blaCTX-M and blaSHV genes identified by PCR were sequenced. RESULTS: A total of 23.4% (95% CI 19.2-27.6) of pigs were positive for ESBL-producing E. coli; 22% (95% CI 17.8-26.1) of the pigs carried E. coli producing CTX-M enzymes [comprising enzyme types 1 (18.7% of pigs), 3 (0.2%), 14 (0.5%), 15 (1.4%), 27 (0.5%), 32 (0.5%) and 55 (0.3%)] and 2.2% (95% CI 0.8-3.6) of the pigs carried E. coli producing SHV-12. Five pigs carried both CTX-M- and SHV-12-producing E. coli as different isolates. There were no statistically significant differences observed between the two medium types in terms of the proportions of each CTX-M enzyme type isolated. CONCLUSIONS: In this UK study, 23.4% of pigs were found to be positive for ESBL-producing E. coli using selective culture media. The use of two different commercially available ESBL isolation media was found to improve the detection of ESBL-producing E. coli.

The effect of prosthetic torsional stiffness on the golf swing kinematics of a left and a right-sided trans-tibial amputee.

The golf swing is a biomechanically complex movement requiring three-dimensional movements at the ankle joint complex (AJC), the hips and shoulders. Trans-tibial amputees lose the natural AJC movements as many prostheses do not allow three dimensional foot movements. Torsion devices have been developed and incorporated into prostheses to facilitate internal and external transverse plane rotations. These devices can help amputees to compensate for the loss of movement and to reduce shearing stresses at the stump-socket interface. The primary aim of the present study was to investigate the effects of three torsion devices on body rotations during the golf swing. Two trans-tibial amputees (one right-sided and one left-sided) were analysed using three-dimensional video analysis at address (ADR), the top of the backswing (TBS) and at the end of the follow-through (EFT). The participants played shots with a 3-wood under three different prosthetic conditions (two with a torsion device set to different stiffness values, and one with no torsion device). The results showed that the torsion device served to improve the hip and shoulder rotations of the left-side amputee without increasing perceived stress at the stump. The torsion device had minimal effect on the hip and shoulder rotations of the right-side amputee, although perceived stress was reduced. The difference in results between the right-sided and left-sided amputees was due to the different requirements of each foot during the golf swing. The main problem faced by the right-side amputee was a loss of the sagittal plane movement of ankle joint plantarflexion at EFT, rather than the transverse plane movement.

Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist.

alpha-Conotoxins are small disulfide-constrained peptide toxins which act as antagonists at specific subtypes of nicotinic acetylcholine receptors (nACh receptors). In this study, we analyzed the structures and activities of three mutants of alpha-conotoxin ImI, a 12 amino acid peptide active at alpha7 nACh receptors, in order to gain insight into the primary and tertiary structural requirements of neuronal alpha-conotoxin specificity. NMR solution structures were determined for mutants R11E, R7L, and D5N, resulting in representative ensembles of 20 conformers with average pairwise RMSD values of 0.46, 0.52, and 0.62 A from their mean structures, respectively, for the backbone atoms N, C(alpha), and C' of residues 2-11. The R11E mutant was found to have activity near that of wild-type ImI, while R7L and D5N demonstrated activities reduced by at least two orders of magnitude. Comparison of the structures reveals a common two-loop architecture, with variations observed in backbone and side-chain dihedral angles as well as surface electrostatic potentials upon mutation. Correlation of these structures and activities with those from previously published studies emphasizes that existing hypotheses regarding the molecular determinants of alpha-conotoxin specificity are not adequate for explaining peptide activity, and suggests that more subtle features, visualized here at the atomic level, are important for receptor binding. These data, in conjunction with reported characterizations of the acetylcholine binding site, support a model of toxin activity in which a single solvent-accessible toxin side-chain anchors the complex, with supporting weak interactions determining both the efficacy and the subtype specificity of the inhibitory activity.

An interdisciplinary approach to the management of complex medical and dental conditions.

Dental and medical practice often requires an interdisciplinary approach integrating the knowledge, skills and experience of all the disciplines of dentistry, medicine and its associated fields into comprehensive treatment to maximize results. Rapid and comprehensive scientific and technological advances have made it difficult for dental and medical practitioners to keep up to date in their fields; thus, to decrease practitioner frustration and increase patient benefits, an interdisciplinary approach has become essential. This report illustrates how therapy was coordinated for a young medically compromised patient with dental phobia and significant dental problems. The latest advances in dental techniques and materials, medical technology and pharmacology are highlighted. The communication and cooperation of team members with each other and with the patient and guardians is illustrated. The astute observation by a medical practitioner in an unrelated discipline led to the improvement in the quality of life for a patient.

NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors.

Alpha-Conotoxins, peptides produced by predatory species of Conus marine snails, are potent antagonists of nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels involved in synaptic transmission. We determined the NMR solution structure of the smallest known alpha-conotoxin, ImI, a 12 amino acid peptide that binds specifically to neuronal alpha7-containing nAChRs in mammals. Calculation of the structure was based on a total of 80 upper distance constraints and 31 dihedral angle constraints resulting in 20 representative conformers with an average pairwise rmsd of 0.44 A from the mean structure for the backbone atoms N, Calpha, and C' of residues 2-11. The structure of ImI is characterized by two compact loops, defined by two disulfide bridges, which form distinct subdomains separated by a deep cleft. Two short 310-helical regions in the first loop are followed by a C-terminal beta-turn in the second. The two disulfide bridges and Ala 9 form a rigid hydrophobic core, orienting the other amino acid side chains toward the surface. Comparison of the three-dimensional structure of ImI to those of the larger, 16 amino acid alpha-conotoxins PnIA, PnIB, MII, and EpI-also specific for neuronal nAChRs-reveals remarkable similarity in local backbone conformations and relative solvent-accessible surface areas. The core scaffold is conserved in all five conotoxins, whereas the residues in solvent-exposed positions are highly variable. The second helical region, and the specific amino acids that the helix exposes to solvent, may be particularly important for binding and selectivity. This comparative analysis provides a three-dimensional structural basis for interpretation of mutagenesis data and structure-activity relationships for ImI as well other neuronal alpha-conotoxins.

Port-access cardiac surgery protocols and early outcomes.

As a new cardiac surgical procedure, port-access holds promise to significantly impact the surgical approaches for treatment of CAD. Supporting collaborative practice protocols contributes to early extubation, rapid in-hospital recovery, and shortened LOS. Discharge protocols address postoperative concerns. Early results suggest that patient recovery is shorter than the time for conventional procedures; patients are able to return to an active lifestyle that is beneficial to families, patients, and employers.

Correlation of expression of NCAM and GD3 ganglioside to motile behaviour in neoplastic glia.

Studies of developing mammalian tissues have established that certain neural cell adhesion molecules (NCAMs) may be down-regulated during the migratory phase concurrent with an increase in levels of matrix metalloproteinases. In addition, there is evidence that simple gangliosides such as GD3 are transiently present on the surface of such migratory cells. Since migration, or motility, is a prerequisite for diffuse local invasion of brain by neoplastic cells, the expression of NCAM and GD3 on brain tumour cells was studied in order to establish their possible role in the invasive process. An astrocytoma parent cell line (IPSB-18) and two morphologically distinct, cloned cell lines (clone 1 and 12) derived from it, were used in in vitro motility assays using 8 microns porosity polycarbonate filters in "Transwell" modified Boyden chambers. Immunocytochemical staining with anti-NCAM monoclonal antibodies (UJ13A and ERIC-1) and with the anti-ganglioside monoclonal antibodies LB1 (which recognises GD3) and A2B5 (which recognises a range of simple gangliosides) showed that some cells in culture from the parent line were positive for either NCAM or GD3; clone 1 was NCAM positive but GD3 negative, while clone 12 was NCAM negative but ganglioside positive. Motility assays showed that although clone 12 migrated more efficiently than either clone 1 or the parent line, this was not statistically significant. Moreover, similar assays were conducted on two further sub populations of cells which were evolved from the immunomagnetic separation of the parent cell line, IPSB-18, according to NCAM expression (i.e. NCAM positive and NCAM negative). The results indicated that the NCAM negative cells migrated more efficiently than the NCAM positive cells, in a time-dependent manner, when incubated for 4, 12 and 18 hours in Boyden chambers. These findings suggest that during the migratory phase of brain tumour invasion, NCAM expression is down-regulated whereas ganglioside expression is up-regulated.

Human wild type p53 inhibits cell proliferation and elicits dramatic morphological changes in human glioma cell lines in vitro.

A human pilocytic astrocytoma-derived cell line, a grade III astrocytoma-derived cell line, and a glioblastoma-derived cell line were transfected with the human wild-type p53 gene, in order to demonstrate the possible suppressor role of this gene in low grade as well as in high grade human astrocytomas. p53 exhibited a strong growth suppressor effect on the three cell lines studied, irrespective of the grade of malignancy of the tumours from which they originate. Furthermore, the p53 gene elicited important morphological changes in these cell lines. p53-Transfected cells displayed a flat morphology, a large cell body, and a stellate shape with long processes, characteristic of differentiated astrocytes. In addition, the growth inhibitory effect of p53 was found not to be due to induction of apoptosis. These results indicate that p53 plays a tumour suppressor role in low grade and high grade human astrocytomas and raise the possibility of the involvement of p53 in glioma cell differentiation in vitro.

Differential binding of anti-CD44 on human gliomas in vitro.

Recent studies have shown that the membrane glycoprotein, CD44, is expressed on both normal and neoplastic astrocytes. Moreover, CD44 has been shown to recognise the receptor for hyaluronic acid (HA), an extracellular matrix protein thought to be involved in tumour invasion. The present study has established, by immunocytochemical staining, that CD44 is present on the majority of cells in long and short term cultures derived from astrocytic gliomas. In glioblastoma multiforme, medulloblastoma, ependymoma and dysembryoplastic neuroepithelial tumour, however, staining is either absent or restricted to isolated cells. This differential binding suggests that HA receptor expression may be related to (a) the cell cycle and (b) local invasiveness of brain tumours.

Growth factor modulation of surface ganglioside expression in cloned neoplastic glia.

Cloned neoplastic astrocytes from a human glioma-derived cell line (IPSB-18) were grown in fetal calf serum (FCS)-supplemented culture medium in the presence of three growth factors. Basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF) induced an increase in the number of cells positive for the ganglioside-recognizing monoclonal antibody, A2B5. No such growth factor-mediated induction could be detected in cells maintained in plasma-derived serum (PDS)-supplemented medium. Small molecules, removed from PDS during dialysis, may, therefore, act synergistically with growth factors in the control of ganglioside synthesis.

Beta-adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion.

In vivo and in vitro studies of beta-adrenergic influences on GH secretion have produced apparently conflicting data in which the in vivo effect seems to be inhibitory and the in vitro effect to be stimulatory. The present studies were designed to observe the in vivo effect of isoproterenol (ISO), a beta-adrenergic agonist, on 1) GH release during a brief interval after intraatrial infusion, and 2) GH release in response to GRF infused 10 min after ISO. ISO was found to stimulate GH release in both intact and hypothalamus-lesioned animals within 2 min after infusion, but GH returned to control levels within 10 min. ISO also profoundly inhibited the release of GH in response to GRF. Pretreatment of animals with somatostatin (SRIF) antiserum prevented the inhibitory action of ISO on GRF-induced GH release. No change in peripheral levels of SRIF was detected. Also, there was no suppression of GRF-induced GH release by ISO when the treatments were applied in vitro to dispersed perifused pituitary cells. These data show that beta-adrenergic systems can stimulate a rapid but brief release of GH in vivo, and that the subsequent inhibitory action on GRF-induced GH release might be by means of SRIF release.

Influence of a prolactin- and ACTH-secreting tumour on oestrous cyclicity, the pro-oestrous surges of LH and prolactin and ovarian hypertrophy in the rat.

These studies were designed to investigate the effects of a prolactin- and ACTH-secreting tumour (7315a) on reproductive cyclicity, pro-oestrous surges of LH and prolactin and ovarian hypertrophy in the rat. Normal adult Buffalo rats, which are syngeneic to the 7315a tumour, were found to have a significant pro-oestrous prolactin surge and a relatively low-level preovulatory LH surge. Within 14 days of s.c. injection of dispersed tumour cells, a small tumour was detectable by palpation in one rat, but measurable tumours were not observed until day 18. The pro-oestrous surge of LH, but not of prolactin, was effectively suppressed by day 17. Cessation of reproductive cyclicity (anoestrus) was apparent within 19.4 +/- 1.1 days of injection of tumour cells. Removal of a single ovary showed that there was no change in ovarian weight before anoestrus in the tumour-bearing animals. Subsequent hypertrophy of the second ovary was augmented during the early stages of tumour development (days 8 and 13), and this corresponded to the unexpected finding that the gonadotrophin surges on days 8 and 13 were significantly increased when compared with controls. Ovarian hypertrophy was not significantly different from that in controls after suppression of the gonadotrophin surge (day 17). The results suggest that inhibition of the preovulatory LH surge might be a critical event in the tumour-induced cessation of reproductive cyclicity. The fact that pre-surge concentrations of prolactin did not increase substantially until the conspicuous onset of tumour prolactin secretion on day 21 indicated that the preovulatory LH surge might be inhibited by relatively low levels of tonically secreted prolactin.

Importance of "significant others" in predicting cooperation with diabetic regimen.

Patients' cooperation with their medical regimen is of prime importance in the treatment of a chronic illness such as diabetes. A psychosocial model of behavioral prediction developed by Fishbein was used to examine compliance intentions among diabetic patients. Patients' beliefs about the consequences of following their diet were identified. Surprisingly, how important following the regimen was to "significant others" in a patient's life was a stronger predictor of behavioral intention than were the patient's own beliefs.