Psychological support during a pandemic: an intervention for hospital teams.

BACKGROUND: The COVID-19 pandemic placed unprecedented stress on healthcare professionals and resulted in teams being scattered by shielding, working from home and redeployment. The Recovery, Readjustment and Reintegration programme (R3P) was implemented and evaluated in an acute NHS hospital Trust with the aim of supporting those staff involved. AIMS: To explore the impact of offering themed reflective sessions to staff in an acute hospital and to disseminate this learning for application in other settings and future pandemics. METHODS: During the initial recovery phase of the pandemic, all Trust staff were invited to attend an R3P where themed discussions were facilitated by psychologists. Feedback was requested pre- and post-session, and a mixed-methods design was followed to gain quantitative and qualitative information. RESULTS: A total of 430 staff members attended an R3P between April 2021 and January 2022. A significant majority found attendance helpful and agreed that it had provided them with the opportunity to reflect on their own and their teams' experience of pandemic working and led them to feel more supported by their organization. CONCLUSIONS: Finding meaning in experiences through facilitated reflective discussion can help limit the negative psychological impact of working in an acute hospital during a pandemic. Staff are likely to benefit from such opportunities in any future pandemic recovery phase.

Inequalities in energy drink consumption among UK adolescents: a mixed-methods study.

OBJECTIVE: To examine energy drink consumption among adolescents in the United Kingdom (UK) and associations with deprivation and dietary inequalities. DESIGN: Quantitative dietary and demographic data from the National Diet and Nutrition Survey (NDNS) repeated cross-sectional survey were analysed using logistic regression models. Qualitative data from semi-structured interviews were analysed using inductive thematic analysis. SETTING: UK. PARTICIPANTS: Quantitative data: nationally representative sample of 2587 adolescents aged 11-18 years. Qualitative data: 20 parents, 9 teachers, and 28 adolescents from Hampshire, UK. RESULTS: NDNS data showed adolescents' consumption of energy drinks was associated with poorer dietary quality (OR 0.46 per SD; 95% CI 0.37, 0.58; p<0.001). Adolescents from more deprived areas and lower income households were more likely to consume energy drinks than those in more affluent areas and households (OR 1.40; 95%CI 1.16, 1.69; p<0.001; OR 0.98 per £1000; 95%CI, 0.96, 0.99; p<0.001 respectively). Between 2008 and 2016, energy drink consumption among adolescents living in the most deprived areas increased, but decreased among those living in the most affluent neighbourhoods (p=0.04). Qualitative data identified three themes. First, many adolescents drink energy drinks because of their friends and because the unbranded drinks are cheap. Second, energy drink consumption clusters with other unhealthy eating behaviours and adolescents don't know why energy drinks are unhealthy. Third, adolescents believe voluntary bans in retail outlets and schools do not work. CONCLUSIONS: This study supports the introduction of age-dependent legal restrictions on the sale of energy drinks which may help curb existing socio-economic disparities in adolescents' energy drink intake.

Survival of arteriovenous fistula for dialysis at different centers in the North of England.

BACKGROUND: Renal failure patients rely on their vascular access for hemodialysis. Surgery for construction of arteriovenous fistulae is provided by a range of specialists. The aim of this review was to assess the survival of arteriovenous fistulae for hemodialysis patients in different centers of Northern England. METHODS: Data was collected on 473 hemodialysis patients in the North of England. Risk factors for failure were determined for each patient (age, sex, diabetes), together with their current mode of dialysis and history of surgical access procedures. This was expressed against their duration of dialysis. The dialysis units were then compared for fistula survival using the Kaplan Meier method. RESULTS: 68.3% (323) patients were dialysed through via arteriovenous fistulae and 31.7% (150) via neck line. Overall fistula survival rates were 85.1% at 1 year, 82.5% at 2 years and 72.7% at 3 years. The best 1 year survival was 91.6% and worst 76.1%. These were 74.4% and 53.1% at 5 years and 74.4% and 29.5% at 10 years; these differences were highly statistically significant (p = 0.0033). CONCLUSION: Though graft survival is affected by many things, surgical training in access surgery is not mandatory and a review of surgical practice is urgently needed.

Identification of methicillin-resistant Staphylococcus aureus (MRSA): Comparison of a new molecular genetic test kit (GenoType MRSA) with standard diagnostic methods.

Results obtained from 188 isolates of staphylococci using standard diagnostic methods for identifying MRSA were compared with those achieved with a newly available molecular genetic test kit, the GenoType, Version 1, MRSA (Hain Lifescience GmbH, Nehren, Germany). The GenoType MRSA detects the mecA gene and, in addition, a highly specific sequence for Staphylococcus aureus (S. aureus) by polymerase chain reaction (PCR) and reverse hybridization. There was a 100% overall correlation between the results of conventional and molecular genetic testing. 143 isolates were tested positive for MRSA, 10 isolates were identified as oxacillin-sensitive Staphylococcus aureus strains (MSSA), and 35 isolates were coagulase-negative staphylococci of various species. However, five of the 143 MRSA strains yielded ambiguous results with the first line standard tests and therefore required additional testing leading to delay of definitive diagnosis. As expected, mecA could not only be detected in MRSA strains, but also in coagulase-negative staphylococci. The reliable identification as S. aureus from the same isolate is therefore an essential prerequisite for MRSA diagnosis. The GenoType MRSA fulfills this requirement by parallel detection of a S. aureus-specific sequence and the mecA gene. Molecular genetic testing with the GenoType MRSA kit needs much less time than conventional microbiological methods. Therefore genetic testing provides not only a considerable advantage with respect to reliability but also to speed.

Analysis of the CD151-alpha3beta1 integrin and CD151-tetraspanin interactions by mutagenesis.

Transmembrane proteins of the tetraspanin superfamily are associated with various integrins and modulate their function. We performed mutagenesis analysis to establish structural requirements for the interaction of CD151 with the alpha3beta1 integrin and with other tetraspanins. Using a panel of CD151/CD9 chimeras and CD151 deletion mutants we show that the minimal region, which confers stable (e.g. Triton X-100-resistant) association of the tetraspanin with alpha3beta1, maps within the large extracellular loop (LECL) of CD151 (the amino acid sequence between residues Leu(149) and Glu(213)). Furthermore, the substitution of 11 amino acids (residues 195-205) from this region for a corresponding sequence from CD9 LECL or point mutations of cysteines in the conserved CCG and PXXCC motifs abolish the interaction. The removal of the LECL CD151 does not affect the association of the protein with other tetraspanins (e.g. CD9, CD81, CD63, and wild-type CD151). On the other hand, the mutation of the CCG motif selectively prevents the homotypic CD151-CD151 interaction but does not influence the association of the mutagenized CD151 with other tetraspanins. These results demonstrate the differences in structural requirements for the heterotypic and homotypic tetraspanin-tetraspanin interactions. Various deletions involving the small extracellular loop and the first three transmembrane domains prevent surface expression of the CD151 mutants but do not affect the CD151-alpha3beta1 interaction. The CD151 deletion mutants are accumulated in the endoplasmic reticulum and redirected to the lysosomes. The assembly of the CD151-alpha3beta1 complex occurs early during the integrin biosynthesis and precedes the interaction of CD151 with other tetraspanins. Collectively, these data show that the incorporation of CD151 into the "tetraspanin web" can be controlled at various levels by different regions of the protein.

Maternal behaviors associated with smothering: a preliminary descriptive study.

OBJECTIVES: To describe maternal behavior in 15 women identified as having smothered their children. DESIGN: A descriptive study of maternal behavior and interaction with her child, using videotapes of mother and child together. These were obtained by covert video surveillance in a hospital setting. Maternal behavior was rated using an assessment schedule designed to be used with video. RESULTS: The mothers showed a range of behaviors. Three groups emerged; one whose interaction with the child resembled normal maternal behavior, a second who interacted in a hostile way, and a third who showed a paucity of interaction. CONCLUSION: These preliminary data suggest that smothering may reflect more than one type of abnormal maternal relationship or attitude towards children. This may have implications for treatment and prognosis.

Two pathways for store-mediated calcium entry in human platelets.

In human platelets and other non-excitable cell types depletion of the intracellular calcium stores promotes calcium entry across the plasma membrane. Although the mechanism of this store-mediated calcium entry remains uncertain, it has been suggested that a tyrosine phosphorylation step could be involved. In support of this hypothesis various tyrosine kinase inhibitors have been shown to reduce store-mediated calcium entry in platelets, although this inhibition is never complete. Here we investigate the properties of store-mediated calcium entry in human platelets during the time course of its activation. Our data suggest that at least two pathways may contribute to store-mediated calcium entry in these cells. An early component, activated soon after the initiation of Ca2+ store depletion, is insensitive to trivalent cations, SKF 96365 and tyrosine kinase inhibitors. This is followed by a second component which is inhibited by La3+, SKF 96365 and by tyrosine kinase inhibitors. These results suggest a role for tyrosine kinases in generating only the later stages of store-mediated calcium entry in platelets and may explain the incomplete inhibition of this pathway by inhibitors of tyrosine kinases.

A role for the actin cytoskeleton in the initiation and maintenance of store-mediated calcium entry in human platelets. Evidence for conformational coupling.

The nature of the mechanism underlying store-mediated Ca(2+) entry has been investigated in human platelets through a combination of cytoskeletal modifications. Inhibition of actin polymerization by cytochalasin D or latrunculin A had a biphasic time-dependent effect on Ca(2+) entry, showing an initial potentiation followed by inhibition of Ca(2+) entry. Moreover, addition of these agents after induction of store-mediated Ca(2+) entry inhibited the Ca(2+) influx mechanism. Jasplakinolide, which reorganizes actin filaments into a tight cortical layer adjacent to the plasma membrane, prevented activation of store-mediated Ca(2+) entry but did not modify this process after its activation. In addition, jasplakinolide prevented cytochalasin D-induced inhibition of store-mediated Ca(2+) entry. Calyculin A, an inhibitor of protein serine/threonine phosphatases 1 and 2 which activates translocation of existing F-actin to the cell periphery without inducing actin polymerization, also prevented activation of store-mediated Ca(2+) entry. Finally, inhibition of vesicular transport with brefeldin A inhibited activation of store-mediated Ca(2+) entry but did not alter this mechanism once initiated. These data suggest that store-mediated Ca(2+) entry in platelets may be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, which shows close parallels to the events mediating secretion.

Purinoceptor-evoked calcium signalling in human platelets.

ADP evokes a rise in platelet cytosolic Ca2+ concentration by stimulating Ca2+ entry and releasing Ca2+ from intracellular stores. Single cell studies indicate that the response consists of a series of spikes in cytosolic Ca2+. The release of stored Ca2+ is mediated by the generation of inositol 1,4,5-trisphosphate. Store depletion in turn leads to activation of a store-regulated Ca2+ entry pathway via a mechanism which appears to involve a protein tyrosine phosphorylation step. Preceding these events, ADP activates a receptor-operated non-selective cation channel, which mediates the entry of Ca2+ and Na+ with a latency of just a few milliseconds. Recent studies indicate that this channel is activated via a P2X1 purinoceptor at which ATP and diadenosine tetraphosphate are agonists. This receptor is distinct from that leading to the release of stored Ca2+ and to store-regulated Ca2+ entry.

Ionomycin-stimulated arachidonic acid release in human platelets: a role for protein kinase C and tyrosine phosphorylation.

Collagen (10-90 micrograms/ml) and ionomycin (1 microM; a calcium ionophore) each evoked rises in intracellular free calcium, protein kinase C activity and arachidonic acid release in human platelets, and as previously demonstrated for collagen, ionomycin (1 microM) stimulated protein tyrosine phosphorylation. However, at lower concentrations (60 and 250 nM) ionomycin selectively mobilised calcium. Ro31-8220 (a selective inhibitor of protein kinase C) inhibited (by 50%) ionomycin-stimulated arachidonic acid release. Genistein (an inhibitor of protein tyrosine kinases) also reduced by 50% ionomycin-stimulated arachidonic acid release. In combination, genistein and Ro31-8220 abolished ionomycin-stimulated arachidonic acid release. These findings show 1) that a rise in calcium is not sufficient, and 2) the activation of both protein kinase C and protein tyrosine phosphorylation is necessary, for full ionomycin-stimulated arachidonic acid release in human platelets.

Wortmannin inhibits store-mediated calcium entry and protein tyrosine phosphorylation in human platelets.

The effects of the WT on store-mediated Ca2+ entry and protein tyrosine phosphorylation were investigated in fura-2-loaded human platelets. Wortmannin (2 microM) attenuated the rise in [Ca2+]i caused by Ca2+ entry while having no effect on the mobilisation of Ca2+ from internal stores. It also reduced store-depletion-evoked protein tyrosine phosphorylation. These findings demonstrate that WT is an inhibitor of tyrosine phosphorylation and store-mediated calcium entry and provide further evidence for the involvement of a tyrosine phosphorylation step in the link between Ca2+ store depletion and Ca2+ influx in human platelets.

The effect of calcium-store depletion and refilling with various bivalent cations on tyrosine phosphorylation and Mn2+ entry in fura-2-loaded human platelets.

To investigate the possible involvement of tyrosine phosphorylation in the process of store-regulated Ca2+ entry, ionomycin (in the presence of EGTA) was used to deplete the intracellular Ca2+ stores of fura-2-loaded human platelets, and the effect of refilling with Ca2+, Ba2+ or Sr2+ evaluated. Depletion of the intracellular Ca2+ stores resulted in an increase in protein tyrosine phosporylation. This increase is reversed when the stores were refilled in Ca2+ or Sr2+, but not Ba2+. Refilling of the stores with Ca2+ or Sr2+, but not Ba2+, suppressed Mn2+ entry. These findings support the hypothesis that tyrosine phosphorylation plays a role in mediating store-regulated Ca2+ entry in human platelets and provides evidence for tyrosine phosphatase activity regulated by the Ca2+ content of the intracellular stores.

The influence of additional information, advice and support on the success of breast feeding in working class primiparas.

A sample of 38 white working class primiparas intending to breast feed were alternately assigned to either an experimental or control group during the last trimester of pregnancy. All women were visited at home antenatally for a structured interview on their attitudes towards and information on breast feeding. The experimental group were visited twice before the birth, seen within the first 5 days in hospital, and visited immediately after they returned home, to enable the provision of information, advice and support regarding breast feeding. All women were seen again at 3 months postpartum. There was a significant difference between the two groups in level of breast feeding success, and explanations for this effect are put forward in terms of the experimental intervention components.

Serotonin neurotoxins: recent advances in the mode of administration and molecular mechanism of action.

1. Slow infusion of 5,7-DHT into the left lateral ventricle of nomifensine pretreated, pentobarbitone anaesthetized rats produces moderate, asymmetric regional forebrain 5-HT depletions 24 h after the injection; rapid pulse injection of 5,7-DHT results in more extensive and almost symmetric 5-HT reductions. By the eighth day, both injection procedures cause a comparable pattern of 5-HT depletion throughout the CNS. RAdioactivity distribution patterns (following 14C-5,7-DHT) correlate with the characteristics of 5-HT depletions. The type of anaesthetic used (pentobarbitone; pentobarbitone plus ketamine; ether) has little, if any, influence on the long-term 5-HT reductions in the rat CNS. 2. In forebrain regions, near the ventricle, nomifensine does not totally protect catecholamine fibre systems when pentobarbitone is used as the anaesthetic. However, optimum selectivity is provided by a combination of DMI and nomifensine in animals anaesthetized with a combination of pentobarbitone and ketamine. 3. Reaction of 5,6- and 5,7-DHT with oxygen is essential for these drugs to act as neurotoxins. Both drugs interact with the electron transfer chain of mitochondria (at the site of complex III) resulting in accelerated formation of reactive quinoidal intermediates. Metabolism of 5,7-DHT by MAO contributes to the overall in vivo neurotoxicity of this m-substituted dihydroxytryptamine.