The acute tryptophan depletion (ATD) technique has been used extensively to study the effect of low serotonin in the human brain. This review assesses the validity of a number of published criticisms ...of the technique and a number of previously unpublished potential criticisms. The conclusion is that ATD can provide useful information when results are assessed in conjunction with results obtained using other techniques. The best-established conclusion is that low serotonin function after tryptophan depletion lowers mood in some people. However, this does not mean that other variables, altered after tryptophan depletion, are necessarily related to low serotonin. Each aspect of brain function has to be assessed separately. Furthermore, a negative tryptophan depletion study does not mean that low serotonin cannot influence the variable studied. This review suggests gaps in knowledge that need to be filled and guidelines for carrying out ATD studies.
The fourth factor that could play a role in raising brain serotonin is diet. According to some evidence, tryptophan, which increases brain serotonin in humans as in experimental animals, 69 is an ...effective antidepressant in mild-to-moderate depression.67,70 Further, in healthy people with high trait irritability, it increases agreeableness, decreases quarrelsomeness and improves mood.34 However, whether tryptophan should be considered primarily as a drug or a dietary component is a matter of some dispute.
Background
Although large series from national joint registries may accurately reflect indications for revision TKAs, they may lack the granularity to detect the true incidence and relative ...importance of such indications, especially periprosthetic joint infections (PJI).
Questions/purposes
Using a combination of individual chart review supplemented with New Zealand Joint Registry data, we asked: (1) What is the cumulative incidence of revision TKA? (2) What are the common indications for revising a contemporary primary TKA? (3) Do revision TKA indications differ at various followup times after primary TKA?
Methods
We identified 11,134 primary TKAs performed between 2000 and 2015 in three tertiary referral hospitals. The New Zealand Joint Registry and individual patient chart review were used to identify 357 patients undergoing subsequent revision surgery or any reoperation for PJI. All clinical records, radiographs, and laboratory results were reviewed to identify the primary revision reason. The cumulative incidence of each revision reason was calculated using a competing risk estimator.
Results
The cumulative incidence for revision TKA at 15 years followup was 6.1% (95% CI, 5.1%–7.1%). The two most-common revision reasons at 15 years followup were PJI followed by aseptic loosening. The risk of revision or reoperation for PJI was 2.0% (95% CI, 1.7%–2.3%) and aseptic loosening was 1.2% (95% CI, 0.7%–1.6%). Approximately half of the revision TKAs secondary to PJI occurred within 2 years of the index TKA (95% CI, 0.8%–1.2%), whereas half of the revision TKAs secondary to aseptic loosening occurred 8 years after the index TKA (95% CI, 0.4%–0.7%).
Conclusions
In this large cohort of patients with comprehensive followup of revision procedures, PJI was the dominant reason for failure during the first 15 years after primary TKA. Aseptic loosening became more important with longer followup. Efforts to improve outcome after primary TKA should focus on these areas, particularly prevention of PJI.
Level of Evidence
Level III, therapeutic study.
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Acute tryptophan depletion (ATD) studies indicate that low serotonin can lower mood and also increase aggression, although results vary somewhat between studies with similar participants. Lowering of ...mood after ATD is related to the susceptibility of the study participants to clinical depression, and some participants show no effect on mood. This indicates that low serotonin can contribute to lowered mood, but cannot—by itself—cause lowered mood, unless other unknown systems interact with serotonin to lower mood. Studies using tryptophan supplementation demonstrate that increased serotonin can decrease quarrelsomeness and increase agreeableness in everyday life. Social interactions that are more agreeable and less quarrelsome are associated with better mood. Thus, serotonin may have direct effects on mood, but may also be able to influence mood through changes in social behaviour. The increased agreeableness and decreased quarrelsomeness resulting from increases in serotonin will help foster congenial relations with others and should help to increase social support. As social support and social isolation have an important relationship with both physical and mental health, more research is needed on the implications of the ability of serotonin to modulate social behaviour for the regulation of mood, and for future physical and mental health.
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Recent research indicates that suicide rates are elevated in those living at higher altitudes in both the United States and South Korea. A possible mechanism that was proposed is metabolic stress ...associated with hypoxia. This commentary discusses these results, and also the association between elevated suicide rates and other conditions associated with hypoxia (smoking, chronic obstructive pulmonary disease and asthma). Tryptophan hydroxylase may not normally be saturated with oxygen, so mild hypoxia would decrease serotonin synthesis. Low brain serotonin is known to be associated with suicide. Thus, the commentary proposes and discusses the hypothesis that decreased brain serotonin synthesis associated with hypoxia is a mechanism that may contribute to suicide in conditions causing hypoxia. Finally the commentary proposes various studies that could test aspects of this hypothesis.
Comprising three parts, this book is a companion volume to The Boggart: Folklore, History, Place-Names and Dialect. Part one, ‘Boggart Ephemera’, is a selection of about 40,000 words of ...nineteenth-century boggart writing (particularly material that is difficult to find in libraries). Part two presents a catalogue of ‘Boggart Names’ (place-names and personal names, totalling over 10,000 words). Finally, part three contains the entire ‘Boggart Census’ – a compendium of ground-breaking grassroots research. This census includes more than a thousand responses, totalling some 80,000 words, from older respondents in the north-west of England, to the question: ‘What is a boggart?’ The Boggart Sourcebook will be of interest to folklorists, historians and dialect scholars. It provides the three corpora on which the innovative monograph, The Boggart, is based.
Somatostatin is an endogeneous cyclic tetradecapeptide hormone that exerts multiple biological activities via five ubiquitously distributed receptor subtypes. Classified as a broad inhibitory ...neuropeptide, somatostatin has anti-secretory, anti-proliferative and anti-angiogenic effects. The clinical use of native somatostatin is limited by a very short half-life (1 to 3min) and the broad spectrum of biological responses. Thus stable, receptor-selective agonists have been developed. The majority of these somatostatin therapeutic agonists bind strongly to two of the five receptor subtypes, although recently an agonist of wider affinity has been introduced. Somatostatin agonists are established in the treatment of acromegaly with recently approved indications in the therapy of neuroendocrine tumours. Potential therapeutic uses for somatostatin analogues include diabetic complications like retinopathy, nephropathy and obesity, due to inhibition of IGF-1, VEGF together with insulin secretion and effects upon the renin-angiotensin-aldosterone system. Wider uses in anti-neoplastic therapy may also be considered and recent studies have further revealed anti-inflammatory and anti-nociceptive effects. This review provides a comprehensive, current view of the biological functions of somatostatin and potential therapeutic uses, informed by the wide range of pharmacological advances reported since the last published review in 2004 by P. Dasgupta. The pharmacology of somatostatin receptors is explained, the current uses of somatostatin agonists are discussed, and the potential future of therapeutic applications is explored.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Trypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; ...later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.
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•T. brucei parasites accumulate in the adipose tissue early after mouse infection•Adipose tissue forms (ATFs) can replicate and are capable of infecting naive mice•ATFs are transcriptionally distinct and upregulate genes for fatty acid metabolism•ATFs can actively uptake exogenous myristate and form β-oxidation intermediates
Trypanosoma brucei is found in the bloodstream and interstitial compartment of several organs in the mammalian host. Trindade et al. uncover the adipose tissue as a major extravascular parasite niche. Extensive remodeling of parasite gene expression in this lipid-rich environment includes upregulation of fatty acid β-oxidation enzymes, suggestive of a functional adaptation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Anterior cruciate ligament injuries cause significant morbidity, and may be increasing in incidence as participation in high‐risk sports increases. The aim of this study is to investigate ...the incidence of anterior cruciate ligament reconstruction (ACLR) surgery in New Zealand, and to analyse changes over time in demographic subgroups.
Method
Data were sourced from the Accident Compensation Corporation. Data relating to primary ACLRs performed from 2009 to 2016 were evaluated (n = 20 751). Baseline population estimates were obtained from national census data to calculate the incidence, and results were compared to previous data from 2000 to 2005 (n = 7375).
Results
The annual incidence of ACLR for 2009–2016 was 58.2 per 100 000 person‐years and was greater in males than in females (72.2 and 44.9, respectively). This represents a 58% increase when compared with the period 2000–2005 (36.9 per 100 000). The greatest increase was seen in females aged 15–19 years, with the incidence increasing by 120% in the last decade, compared with 53% in females aged 20–24 years. The percentage of injuries caused by sports changed from 65% over 2000–2005 to 76% over 2009–2016, with netball, rugby and football accounting for the highest number of injuries.
Conclusion
The incidence of ACLR procedures has increased markedly in New Zealand, and this increase was most pronounced in females aged 15–19 years. A greater proportion of procedures are now due to sport‐related injuries.
We found a 120% increase in the incidence of anterior cruciate ligament reconstruction surgery in young females in New Zealand from 2000–2005 to 2013–2016. A higher proportion of anterior cruciate ligament reconstruction in New Zealand are now due to sport‐related causes, particularly netball, rugby and football. Injury prevention strategies should target these high‐risk groups, especially young females.
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