The dietary fatty acids α-linolenic acid (ALA) and linoleic acid (LA) selectively inhibit microglial nitric oxide production.

Alzheimer's disease (AD) is a neurodegenerative disorder without a known cure or effective treatment. Research has identified several modifiable risk factors and suggested preventative measures to reduce the risk of developing AD, including alterations in diet. Polyunsaturated fatty acids (PUFAs) have been shown to regulate inflammatory responses in the central nervous system (CNS), the main site of inflammation in AD. In the CNS, microglia are immune cells responsible for the maintenance of homeostasis. However, in AD, microglia can become adversely activated, causing them to release increased levels of cytotoxins and inflammatory mediators, including nitric oxide (NO) and monocyte-chemoattractant protein (MCP)-1. We assessed the effects of two PUFAs, α-linolenic acid (ALA) and linoleic acid (LA), on select microglial immune functions, since the effects of these dietary fatty acids on neuroimmune responses are not well characterized. In BV-2 mouse microglia activated with lipopolysaccharide (LPS), exposure to LA reduced NO secretion and inducible nitric oxide synthase (iNOS) levels, whereas exposure to ALA reduced NO without a corresponding reduction of iNOS. Neither ALA nor LA altered MCP-1 levels or cytotoxins released by THP-1 human microglia-like cells stimulated with a combination of LPS and interferon (IFN)-γ. Specific receptor antagonists were used to demonstrate that the inhibitory effect of LA on NO secretion did not depend on the free fatty acid receptor (FFAR) 1 or FFAR4. Furthermore, gas chromatography with a flame ionization detector (GC-FID) revealed that exposure to LA or ALA did not alter the fatty acid composition of BV-2 microglia. Our data indicate that regulation of select microglial immune functions by ALA and LA could be one of the mechanisms underlying the observed link between certain dietary patterns and AD, such as reduced risk of cognitive decline and dementia associated with the Mediterranean diet.

Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders.

Introduction: Adverse immune activation contributes to many central nervous system (CNS) disorders. All main CNS cell types express toll-like receptor 4 (TLR 4). This receptor is critical for a myriad of immune functions such as cytokine secretion and phagocytic activity of microglia; however, imbalances in TLR 4 activation can contribute to the progression of neurodegenerative diseases. Areas covered: We considered available evidence implicating TLR 4 activation in the following CNS pathologies: Alzheimer's disease, Parkinson's disease, ischemic stroke, traumatic brain injury, multiple sclerosis, multiple systems atrophy, and Huntington's disease. We reviewed studies reporting effects of TLR 4-specific antagonists and agonists in models of peripheral and CNS diseases from the perspective of possible future use of TLR 4 ligands in CNS disorders. Expert opinion: TLR 4-specific antagonists could suppress neuroinflammation by reducing overproduction of inflammatory mediators; however, they may interfere with protein clearance mechanisms and myelination. Agonists that specifically activate myeloid differentiation primary-response protein 88 (MyD88)-independent pathway of TLR 4 signaling could facilitate beneficial glial phagocytic activity with limited activity as inducers of proinflammatory mediators. Deciphering the disease stage-specific involvement of TLR 4 in CNS pathologies is crucial for the future clinical development of TLR 4 agonists and antagonists.

Identifying the physical and anthropometric qualities explanatory of paddling adolescents.

OBJECTIVES: This study aimed to identify the physical and/or anthropometric qualities explanatory of adolescent surf lifesavers participating in paddling activities. DESIGN: Cross-sectional observational study. METHODS: A total of 53 (14-18years) male participants were recruited and classified into two groups; paddlers (n=30; actively participating in paddling), non-paddlers (n=23; not actively participating in paddling). All participants completed a testing battery that consisted of 16 physical (isometric strength and muscular endurance) and anthropometric (height, mass, segment lengths and breadths) assessments. Binary logistic regression models and receiver operating characteristic curves were built to identify the physical and/or anthropometric qualities most explanatory of paddling status (two levels: 1=paddlers, 0=non-paddlers). RESULTS: Significant between group differences were noted for 14 of the 16 assessments (P<0.05; d=0.59-1.29). However, it was the combination of horizontal shoulder abduction isometric strength, body mass, and sitting height that provided the greatest association with paddling status (Akaike Information Criterion=47.13). This full model successfully detected 87% and 70% of the paddlers and non-paddlers, respectively, with an area under the curve of 84.2%. CONCLUSIONS: These results indicate that there are distinctive physical and anthropometric qualities that may be advantageous for prospective paddling athletes to possess. Practitioners should integrate assessments of horizontal shoulder abduction isometric strength, body mass, and sitting height, as well as their subsequent cut-off thresholds, into talent detection programs focused toward the recognition of performance potential in paddling-oriented sports.

Shoulder pain and dysfunction in young surf lifesavers.

OBJECTIVES: To determine the incidence and prevalence of significantly interrupting shoulder pain (SIP) in young surf lifesavers and to determine association with training dosage and the 'combined elevation test'. PARTICIPANTS: 54 surf lifesavers aged 10-18 from the Gold Coast, Australia. METHODS AND OUTCOME MEASURES: Retrospective survey of SIP and training dosage. Cross-sectional measures of the combined elevation test. DESIGN: Retrospective. RESULTS: 56.5% of female surf lifesavers reported a history of SIP compared to males with 48.5%. Females had a higher combined elevation score compared to males, 28.32 ± SD 8.52 cm and 26.09 ± SD 6.64 cm, respectively. Young surf lifesavers had an incidence rate of 2.1 SIP episodes per thousand hours of training, an incidence proportion of 51.9% and prevalence of 18.5%. Combined elevation had low level positive trends with training dosages and statistically significant negative correlation with board paddling sessions per week (r = -0.287, p ≤ 0.05). Those with a history of SIP had a statistically significant higher number of sessions (p = 0.008), duration (p = 0.015) and distance (p = 0.005) swimming per week. CONCLUSION: Young surf lifesavers with a history of SIP have greater swimming dosage not associated with a decreased combined elevation score. More board paddling sessions per week decreased the combined elevation score of young surf lifesavers.

Inversion of the uterus at caesarean section.

INTRODUCTION: Inversion of the uterus through the uterine incision during caesarean section is a rare event. Therapy is usually simple and maternal morbidity is low when re-inversion of the uterus can be accomplished immediately. In cases of prolonged uterine inversion thereof, haemodynamic instability and shock, often out of proportion to the degree of blood loss, have been reported as serious sequelae. CASE REPORT: We describe such a case with a prolonged inversion to re-inversion interval where the patient suffered an intraoperative cardiovascular arrest during unrepositioned uterine inversion. Reposition of the uterus led to an immediate return of the patient's vital signs and improvement of her haemodynamic status. DISCUSSION: The mechanisms of haemodynamic instability and the technical aspects of manual reduction of the inverted, heavily contracted uterus during caesarean section are discussed.

Purification and characterization of the human elongator complex.

Human Elongator complex was purified to virtual homogeneity from HeLa cell extracts. The purified factor can exist in two forms: a six-subunit complex, holo-Elongator, which has histone acetyltransferase activity directed against histone H3 and H4, and a three-subunit core form, which does not have histone acetyltransferase activity despite containing the catalytic Elp3 subunit. Elongator is a component of early elongation complexes formed in HeLa nuclear extracts and can interact directly with RNA polymerase II in solution. Several human homologues of the yeast Elongator subunits were identified as subunits of the human Elongator complex, including StIP1 (STAT-interacting protein 1) and IKAP (IKK complex-associated protein). Mutations in IKAP can result in the severe human disorder familial dysautonomia, raising the possibility that this disease might be due to compromised Elongator function and therefore could be a transcription disorder.