Disorders of Blood Pressure Regulation—Role of Catecholamine Biosynthesis,Release, and Metabolism

Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension. This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments.     

Use of antibiotic prophylaxis in elective inguinal hernia repair in adults in London and south-east England: a cross-sectional survey

Purpose

Evidence regarding whether or not antibiotic prophylaxis is beneficial in preventing post-operative surgical site infection in adult inguinal hernia repair is conflicting. A recent Cochrane review based on 17 randomised trials did not reach a conclusion on this subject. This study aimed to describe the current practice and determine whether clinical equipoise is prevalent.

Methods

Surgeons in training were recruited to administer the Survey of Hernia Antibiotic Prophylaxis usE survey to consultant-level general surgeons in London and the south-east of England on their practices and beliefs regarding antibiotic prophylaxis in adult elective inguinal hernia repair. Local prophylaxis guidelines for the participating hospital sites were also determined.

Results

The study was conducted at 34 different sites and received completed surveys from 229 out of a possible 245 surgeons, a 93 % response rate. Overall, a large majority of hospital guidelines (22/28) and surgeons’ personal beliefs (192/229, 84 %) supported the use of single-dose pre-operative intravenous antibiotic prophylaxis in inguinal hernia repair, although there was considerable variation in the regimens in use. The most widely used regimen was intravenous co-amoxiclav (1.2 g). Less than half of surgeons were adherent to their own hospital antibiotic guidelines for this procedure, although many incorrectly believed that they were following these.

Conclusion

In the south-east of England, there is a strong majority of surgical opinion in favour of the use of antibiotic prophylaxis in this procedure. It is therefore likely to be extremely difficult to conduct further randomised studies in the UK to support or refute the effectiveness of prophylaxis in this commonly performed procedure.     

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

We report a British family with young-onset Parkinson’s disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation. Post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes in addition to the caudate, putamen, globus pallidus and amygdala. There was severe loss of pigmentation in the substantia nigra and pallor of the locus coeruleus. Neuronal loss was most marked in frontal and temporal cortices, hippocampal CA2/3 subregions, substantia nigra, locus coeruleus and dorsal motor nucleus of the vagus. The cellular pathology included widespread and frequent neuronal α-synuclein immunoreactive inclusions of variable morphology and oligodendroglial inclusions similar to the glial cytoplasmic inclusions of multiple system atrophy (MSA). Both inclusion types were ubiquitin and p62 positive and were labelled with phosphorylation-dependent anti-α-synuclein antibodies In addition, TDP-43 immunoreactive inclusions were observed in limbic regions and in the striatum. Together the data show clinical and neuropathological similarities to both the A53T SNCA mutation and multiplication cases. The cellular neuropathological features of this case share some characteristics of both PD and MSA with additional unique striatal and neocortical pathology. Greater understanding of the disease mechanism underlying the G51D mutation could aid in understanding of α-synuclein biology and its impact on disease phenotype.     

The Short Attachment to Pets Scale (SAPS) for Children and Young People: Development,Psychometric Qualities and Demographic and Health Associations

This study describes the development of the SAPS and investigates its reliability and validity within the context of the Health Behaviour in School-Aged Children Survey (HBSC) which gathered data on representative samples of school pupils aged 11, 13 and 15 in Scotland and England. In the development of SAPS, following a comprehensive review of the literature, two small-scale empirical studies were carried out (one qualitative and one quantitative). Regarding the validation process, the reliability and validity of the SAPS was assessed in a sub-sample (n?=?7159) of pupils who completed the HBSC survey and were identified as owning pets. Factor analysis resulted in a one-factor solution (explaining 67.78 % of the variance); Cronbach’s alpha for the scale was 0.894. The item-total correlation ranged from 0.368 to 0.784. A linear model showed that attachment to pets was associated with age (being 11 or 13 years old), being a girl, white ethnicity, and considering a pet as one’s own. SAPS scores were also positively associated with quality of life. The total variance in SAPS explained by these variables was 15.7 %. Effect sizes of associations were medium (age, considering a pet as one’s own) and small (ethnicity, age, gender, quality of life). The study concludes that SAPS is a coherent and psychometrically sound measure. It is associated with a range of demographic variables and quality of life, which confirms its utility as a new succinct measure of children’s and young people’s attachment to pets for use in health and social science research.     

Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance

Expression of a polysaccharide capsule is required for the full pathogenicity of many mucosal pathogens such as Streptococcus pneumoniae. Although capsule allows for evasion of opsonization and subsequent phagocytosis during invasive infection, its role during mucosal colonization, the organism's commensal state, remains unknown. Using a mouse model, we demonstrate that unencapsulated mutants remain capable of nasal colonization but at a reduced density and duration compared to those of their encapsulated parent strains. This deficit in colonization was not due to increased susceptibility to opsonophagocytic clearance involving complement, antibody, or the influx of Ly-6G-positive cells, including neutrophils seen during carriage. Rather, unencapsulated mutants remain agglutinated within lumenal mucus and, thus, are less likely to transit to the epithelial surface where stable colonization occurs. Studies of in vitro binding to immobilized human airway mucus confirmed the inhibitory effect of encapsulation. Likewise, pneumococcal variants expressing larger amounts of negatively charged capsule per cell were less likely to adhere to surfaces coated with human mucus and more likely to evade initial clearance in vivo. Removal of negatively charged sialic acid residues by pretreatment of mucus with neuraminidase diminished the antiadhesive effect of encapsulation. This suggests that the inhibitory effect of encapsulation on mucus binding may be mediated by electrostatic repulsion and offers an explanation for the predominance of anionic polysaccharides among the diverse array of unique capsule types. In conclusion, our findings demonstrate that capsule confers an advantage to mucosal pathogens distinct from its role in inhibition of opsonophagocytosis--escape from entrapment in lumenal mucus.     

Influence of delayed CSF storage on concentrations of phospho-tau protein (181), total tau protein and beta-amyloid (1-42)

It is generally accepted that cerebrospinal fluid (CSF) biomarkers such as tau protein, phosphorylated tau protein (threonine 181) and beta-amyloid (1-42) can facilitate early and differential diagnosis of Alzheimer's disease (AD). Since the respective concentrations can only be measured in a number of specialized centers, time to CSF specimen work-up has been considered as crucial for the stability of the respective biomarkers. When shipping of CSF samples is needed for biomarker measurement and immediate freezing of samples is not available, an overnight delay of up to 24h frequently occurs. Therefore, we investigated the potential impact of a 24h delayed freezing on CSF biomarker concentrations and compared it to 2h storage (room temperature, 20 degrees C) and an immediate freezing. First, storage at room temperature for 2h had only marginal, non-significant effects on the concentrations of CSF total tau protein and phospho-tau protein (181) compared to immediate freezing. Second, storage at room temperature for 24h did not significantly affect total tau protein or phospho-tau protein but beta-amyloid (1-42) concentrations which increased significantly compared to the samples frozen immediately. These results indicate that CSF samples for the evaluation of total tau and phospho-tau protein may be kept at room temperature for up to 24h whereas CSF samples for beta-amyloid (1-42) need to be frozen immediately.     

Exploring Antipsychotic Prescribing Behaviors for Nursing Home Residents With Dementia: A Qualitative Study

Objectives

Caution is advised when prescribing antipsychotics to people with dementia. This study explored the determinants of appropriate, evidence-based antipsychotic prescribing behaviors for nursing home residents with dementia, with a view to informing future quality improvement efforts and behavior change interventions.