Vitamin D binding protein gene polymorphisms are associated with lower plasma 25-hydroxy-cholecalciferol concentrations in Ethiopian lactating women.

Ethiopian women have been reported to have low plasma 25-hydroxy-cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect vitamin D status in this population. In this study (Clinical Trial NCT02210884), we hypothesized that polymorphisms in the vitamin D binding protein (VDBP) gene (rs7041, rs4588) are associated with reduced plasma 25(OH)D concentrations in Ethiopian women. Lactating Ethiopian women (n = 110) were randomly assigned to weekly administration of vitamin D3 (15,000 IU) or a placebo. Plasma 25(OH)D was measured at baseline (within 2 weeks of delivery, before supplementation) and at 3, 6, and 12 months after delivery. Associations between VDBP polymorphism status for rs7041 and rs4588 and plasma 25(OH)D were determined by analysis of variance and multiple linear and logistic regressions. Multiple linear regression with maternal age as a covariate revealed that rs7041 is associated with reduced plasma 25(OH)D (P = .021) and more risk alleles at rs7041 and rs4588 are associated with reduced plasma 25(OH)D (P = .017). Logistic regression models for vitamin D insufficiency showed that additional risk alleles for rs7041 and rs4588 are associated with increased odds ratios (OR = 1.66; 95% CI, 1.10-2.62; P = .019) for plasma 25(OH)D below 40 nmol/L. Supplementation increased plasma 25(OH)D at 3 months in women with fewer risk alleles and across all genotypes at 6 and 12 months. VDBP polymorphisms may contribute to vitamin D insufficiency in Ethiopian lactating women. Furthermore, VDBP polymorphisms may blunt short-term responses to vitamin D supplementation and require longer periods of intervention.

Pollen performance decreases with plant age for outcrosser but not selfer: evidence for cost of male performance.

PREMISE: Declines in reproductive capabilities with increasing age are common across the tree of life. However, in plants, mating system traits have rarely been tested for signs of senescence. Since reproduction is often resource limited, we might expect outcrossing and selfing taxa to allocate these resources differently, especially as a plant ages. Compared with selfers, outcrossers are expected to produce showy, rewarding flowers that attract pollinators and high-quality pollen that can successfully compete for ovules. Yet, this resource-intensive strategy of outcrossers may result in declines in floral allocation and pollen performance metrics, relative to selfers. METHODS: To explore age-related changes in reproduction, we measured flower size and pollen germinability over the flowering period for multiple populations of an annual sister species pair, Collinsia linearis (outcrosser) and C. rattanii (selfer), in a growth chamber experiment. RESULTS: We found that flower size decreased significantly with age in both species. The outcrosser expressed a significant and dramatic (88%) decline in pollen germinability with age, while the selfer's pollen germinability decline was non-significant and low (17%). CONCLUSIONS: Our results support the idea that the higher total cost of reproduction in outcrossers can deplete available resources more rapidly than in selfers, manifesting as a decline in male performance with plant age.

Phylogeny of the Australian Solanum dioicum group using seven nuclear genes, with consideration of Symon's fruit and seed dispersal hypotheses.

The dioecious and andromonoecious Solanum taxa (the "S. dioicum group") of the Australian Monsoon Tropics have been the subject of phylogenetic and taxonomic study for decades, yet much of their basic biology is still unknown. This is especially true for plant-animal interactions, including the influence of fruit form and calyx morphology on seed dispersal. We combine field/greenhouse observations and specimen-based study with phylogenetic analysis of seven nuclear regions obtained via a microfluidic PCR-based enrichment strategy and high-throughput sequencing, and present the first species-tree hypothesis for the S. dioicum group. Our results suggest that epizoochorous trample burr seed dispersal (strongly linked to calyx accrescence) is far more common among Australian Solanum than previously thought and support the hypothesis that the combination of large fleshy fruits and endozoochorous dispersal represents a reversal in this study group. The general lack of direct evidence related to biotic dispersal (epizoochorous or endozoochorous) may be a function of declines and/or extinctions of vertebrate dispersers. Because of this, some taxa might now rely on secondary dispersal mechanisms (e.g. shakers, tumbleweeds, rafting) as a means to maintain current populations and establish new ones.

Enhancing wastewater remediation by drinking water treatment residual-augmented floating treatment wetlands.

In this study, the involvement of aluminum-based drinking water treatment residual (DWTR) as substrate in floating treatment wetland (FTW) to enhance its treatment performance was firstly proposed and trialed. A laboratory scale DWTR-FTW fed with synthetic wastewater containing COD, nitrogen (N), phosphorus (P) and mineral salts was operated in three stages of unplanted (1-30 days), planted (31-60 days) and aerated (61-135 days) modes. The results showed that the average removal rates of COD, total nitrogen (TN), total phosphorus (TP) in stage 3 were 88%, 85%, and 90.2%, respectively, indicating the outstanding purification performance of DWTR-FTW in comparison of traditional FTWs. The embedded DWTR enriches the biomass and robustly adsorbs P, while aeration supplies sufficient dissolved oxygen for the microorganism. The results revealed that 7.022 g P was accumulated in DWTR, which is 400 times higher than that in sediment and plants during the experimental period, reflecting that DWTR adsorption is the major P removal pathway in DWTR-FTW. Overall, DWTR-FTW could significantly remove pollutants, especially P, and provide an alternative pathway to enhance purification performance of FTW.

Tamsulosin attenuates abdominal aortic aneurysm growth.

BACKGROUND: Tamsulosin, an α1A-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to abdominal aortic aneurysm. The goal of this study was to investigate the effect of tamsulosin on abdominal aortic aneurysm pathogenesis. METHODS: Abdominal aortic aneurysms were induced in WT C57BL/6 male mice (n = 9-18/group), using an established topical elastase abdominal aortic aneurysm model. Osmotic pumps were implanted in mice 5 days before operation to create the model, administering either low dose (0.125 µg/day tamsulosin), high dose (0.250µg/day tamsulosin), or vehicle treatments with and without topical application of elastase. Blood pressures were measured preoperatively and on postoperative days 0, 3, 7, and 14. On postoperative day 14, aortic diameter was measured before harvest. Sample aortas were prepared for histology and cytokine analysis. RESULTS: Measurements of systolic blood pressure did not differ between groups. Mice treated with the low dose of tamsulosin and with the high dose of tamsulosin showed decreased aortic diameter compared with vehicle-treated control (93% ± 24 versus 94% ± 30 versus 132% ± 24, respectively; P = .0003, P = .0003). Cytokine analysis demonstrated downregulation of pro-inflammatory cytokines in both treatment groups compared with the control (P < .05). Histology exhibited preservation of elastin in both low- and high-dose tamsulosin-treated groups (P = .0041 and P = .0018, respectively). CONCLUSION: Tamsulosin attenuates abdominal aortic aneurysm formation with increased preservation of elastin and decreased production of pro-inflammatory cytokines. Further studies are necessary to elucidate the mechanism by which tamsulosin attenuates abdominal aortic aneurysm pathogenesis.

Acute ingestion of neuromuscular enhancement supplements do not improve power output, work capacity, and cognition.

BACKGROUND: Improving motor unit recruitment and function is trainable and positively affects performance. Evidence suggests that supplementation of choline, uridine, and docosahexaenoic acid (DHA) may also enhance neuromuscular function. The purpose of this study was to assess the influence of acute ingestion of these supplements on anaerobic exercise performance and cognition. METHODS: Twenty college-aged trained males (21.2±1.4 years, 181.2±6.1 cm, 94.4±20.5 kg, and 15.9±6.6% body fat) received the supplements (SUPP: 500 mg alpha glycerophosphocholine [AGPC], 250 mg uridine-5'-monophosphate, and 1500 mg DHA) or a placebo (PLA) in a randomized cross-over study design. All participants completed one familiarization and two experimental testing sessions, consisting of a warm up, vertical jump assessment, 61-kg bench press rep max, and completion of the ImPACT neural cognition test. In the two testing sessions, participants received, in random order, either the SUPP or a PLA, 90 minutes before testing. RESULTS: There was no significant difference between SUPP and PLA on exercise performance or neural cognition (P>0.05). CONCLUSIONS: The results of this study indicated no benefit from acute ingestion of a DHA, uridine, and choline supplement versus a placebo on anaerobic performance or cognition. It is likely that acute ingestion of these supplements did not provide the necessary elements to increase acetylcholine concentration or number of dendritic spines, rather ingestion for a longer time period and subsequent days may provide a benefit.

Conservative Care of Pediatric Acquired Torticollis: A Report of 2 Cases.

OBJECTIVE: The purpose of this case report is to describe the conservative management of 2 cases of acquired torticollis in children under 3 years of age. CLINICAL FEATURES: Both patients awoke with painful, stiff, twisted necks the day after play in a bouncy house. Range of motion was limited, and hypertonic muscles were palpated. Their neurologic and physical evaluation was consistent with a diagnosis of acquired torticollis of musculoskeletal origin. INTERVENTION AND OUTCOMES: Both children were treated with chiropractic care that consisted of light myofascial release, use of an Activator instrument, and home stretching. Patients improved in pain and range of motion immediately posttreatment and returned to normal ranges in 1 or 2 visits. CONCLUSION: Chiropractic care provided relief for these 2 young patients with acquired torticollis.

Salicylate improves macrophage cholesterol homeostasis via activation of Ampk.

Atherosclerosis stems from imbalances in lipid metabolism and leads to maladaptive inflammatory responses. The AMP-activated protein kinase (Ampk) is a highly conserved serine/threonine kinase that regulates many aspects of lipid and energy metabolism, although its specific role in controlling macrophage cholesterol homeostasis remains unclear. We sought to address this question by testing the effects of direct Ampk activators in primary bone marrow-derived macrophages from Ampk ß1-deficient (ß1(-/-)) mice. Macrophages from Ampk ß1(-/-) mice had enhanced lipogenic capacity and diminished cholesterol efflux, although cholesterol uptake was unaffected. Direct activation of Ampk ß1 via salicylate (the unacetylated form of aspirin) or A-769662 (a small molecule activator), decreased the synthesis of FAs and sterols in WT but not Ampk ß1(-/-) macrophages. In lipid-laden macrophages, Ampk activation decreased cholesterol content (foam cell formation) and increased cholesterol efflux to HDL and apoA-I, effects that occurred in an Ampk ß1-dependent manner. Increased cholesterol efflux was also associated with increased gene expression of the ATP binding cassette transporters, Abcg1 and Abca1. Moreover, in vivo reverse cholesterol transport was suppressed in mice that received Ampk ß1(-/-) macrophages compared with the WT control. Our data highlight the therapeutic potential of targeting macrophage Ampk with new or existing drugs for the possible reduction in foam cell formation during the early stages of atherosclerosis.

Large, binge-type meals of high fat diet change feeding behaviour and entrain food anticipatory activity in mice.

Male C57BL/6 mice fed ad libitum on control diet but allowed access to a palatable high fat diet (HFD) for 2 h a day during the mid-dark phase rapidly adapt their feeding behaviour and can consume nearly 80% of their daily caloric intake during this 2 h-scheduled feed. We assessed food intake microstructure and meal pattern, and locomotor activity and rearing as markers of food anticipatory activity (FAA). Schedule fed mice reduced their caloric intake from control diet during the first hours of the dark phase but not during the 3-h period immediately preceding the scheduled feed. Large meal/binge-like eating behaviour during the 2-h scheduled feed was characterised by increases in both meal number and meal size. Rearing was increased during the 2-h period running up to scheduled feeding while locomotor activity started to increase 1 h before, indicating that schedule-fed mice display FAA. Meal number and physical activity changes were sustained when HFD was withheld during the anticipated scheduled feeding period, and mice immediately binged when HFD was represented after a week of this "withdrawal" period. These findings provide important context to our previous studies suggesting that energy balance systems in the hypothalamus are not responsible for driving these large, binge-type meals. Evidence of FAA in HFD dark phase schedule-fed mice implicates anticipatory processes in binge eating that do not involve immediately preceding hypophagia or regulatory homeostatic signalling.

VL: a further case of erroneous recollection.

We report a single-case study of a female patient (VL) who exhibited frequent episodes of erroneous recollections triggered by everyday events. Based on neuropsychological testing, VL was classified as suffering from mild to moderate dementia (MMSE=18) and was given a diagnosis of probable Alzheimer׳s disease. Her memory functions were uniformly impaired but her verbal abilities were generally well preserved. A structural MRI scan showed extensive areas of gray matter atrophy particularly in frontal and medial-temporal (MTL) areas. Results of experimental recognition tests showed that VL had very high false alarm rates on tests using pictures, faces and auditory stimuli, but lower false alarm rates on verbal tests. We provide a speculative account of her erroneous recollections in terms of her MTL and frontal pathology. In outline, we suggest that owing to binding failures in MTL regions, VL׳s recognition processes were forced to rely on earlier than normal stages of analysis. Environmental features on a given recognition trial may have combined with fragments persisting from previous trials resulting in erroneous feelings of familiarity and of recollection that were not discounted or edited out, due to her impaired frontal processes.

Resources required for processing ambiguous complex features in vision and audition are modality specific.

Processing multiple complex features to create cohesive representations of objects is an essential aspect of both the visual and auditory systems. It is currently unclear whether these processes are entirely modality specific or whether there are amodal processes that contribute to complex object processing in both vision and audition. We investigated this using a dual-stream target detection task in which two concurrent streams of novel visual or auditory stimuli were presented. We manipulated the degree to which each stream taxed processing conjunctions of complex features. In two experiments, we found that concurrent visual tasks that both taxed conjunctive processing strongly interfered with each other but that concurrent auditory and visual tasks that both taxed conjunctive processing did not. These results suggest that resources for processing conjunctions of complex features within vision and audition are modality specific.

Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner.

We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects the autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2µg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reductions in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggest that hypothalamic PACAP signaling plays a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.

Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2.

AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice. Because male mice are not obese, the current study examined their metabolic phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. RESULTS: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated ß-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Optimising the management of primary breast cancer in older women - a report of a multi-disciplinary study day.

PURPOSE: The objectives of the study day were to (i) develop an in-depth understanding around the biology and treatment options; (ii) explore the specific physical and psychosocial needs and consideration including patients perspective; and (iii) gain insight into the development of a dedicated, holistic and multi-disciplinary clinic service and the importance of supporting research, for older women with primary breast cancer. DESIGN: The format included presentations (with lectures from external and local faculty, and short research papers from Nottingham) with a number of interactive discussions, and sharing of patients' experience. RESULTS: Four sessions were held covering (i) pathological features, (ii) role of radiotherapy and adjuvant chemotherapy, (iii) role of surgery, geriatric assessment and quality of life issues, and (iv) challenges in running research trials. CONCLUSIONS: A dedicated and joint team approach is required to improve clinical service and support research, in order to optimise the management of primary breast cancer in older women.

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study.

BACKGROUND: Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. AIM: To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. METHODS: Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. RESULTS: Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. CONCLUSION: In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

Is surgery always indicated in older women with breast cancer?

Although surgery has long been considered the main form of curative treatment for breast cancer, its use in older women may not always be indicated. Whilst surgery has been shown to provide superior local control for breast cancer, there is conflicting evidence on whether surgery offers a significant improvement on overall survival in these patients. The more indolent tumour biology commonly seen in older women with breast cancer, coupled with competing causes of death may alter the goals of treatment. The differing needs of older patients should be thoroughly assessed to consider their comorbidities, functional status and quality of life. A comprehensive geriatric assessment and quality of life assessment could identify pretreatment risk factors and guide clinical decision making, improving morbidity and prognosis. Alternatives to surgery include primary endocrine therapy and primary radiotherapy. Further research is required to identify different patient or tumour factors which can be used to individualize treatment for breast cancer in older women and to develop holistic assessment tools which take into account their individual quality of life, geriatric syndromes and functional needs. A dedicated multidisciplinary-led clinic may provide a suitable platform for the assessment, review and management of this distinctive set of patients.

Efficacy of a whole-body vibration intervention on functional performance of community-dwelling older adults.

OBJECTIVE: The objective of this study was to investigate efficacy of a whole-body vibration (WBV) intervention on functional performance of community-dwelling older adults. DESIGN: The study was designed as a randomized controlled trial. SETTING: The setting was in community centers. SUBJECTS: There were 37 total subjects (21 women and 16 men) (age 69 +/- 8 years; mean +/- standard deviation). INTERVENTION: Participants were randomized to a WBV intervention (INT) group and control (CON) group. Whole-body vibration was administered for five 1-minute bouts per session, 3 days per week, for 6 weeks. The CON group was asked not to commence any form of physical training. OUTCOME MEASURES: Functional performance was measured with the timed-up-and-go-test (TUG) and sit-to-stand-test (STS). RESULTS: After WBV, TUG and STS time was less for INT than CON (INT, TUG 7.6 +/- 0.3 seconds, STS 11.9 +/- 2.0 seconds; CON, TUG 8.6 +/- 0.9, STS 13.5 +/- 1.1 seconds; p < 0.05). Within INT, TUG improved 0.9 +/- 0.4 seconds; p = 0.01 and STS improved 3.0 +/- 0.9 seconds; p = 0.05). CONCLUSIONS: The efficacy of this WBV intervention was established. Functional performance improvement after WBV may be attributed to a number of biological mechanisms that remain speculative. Further research is required to mechanistically understand the effects of WBV on older adults.

The influence of respiratory muscle training upon intermittent exercise performance.

The purpose of this study was to determine the effect of respiratory muscle training (RMT) on intermittent exercise performance, respiratory muscle strength (PI (max)), respiratory muscle fatigue (RMF), and dyspnea in soccer athletes. Collegiate soccer athletes (20 male, 7 female) were randomly divided into either a RMT or control condition during off-season conditioning. The RMT group performed a 30RM protocol (10 times weekly) for 5 weeks using a commercially-available training device, while the controls received no RMT. Performance was evaluated utilizing Level 1 of the Yo-Yo Intermittent Recovery Test (IRT) and dyspnea was assessed during and immediately following the IRT. RMF was quantified within 2 minutes (RMF2) and 10 minutes (RMF10) after completing the IRT. Following training, the RMT group significantly increased IRT performance by 216.6 +/- 231.0 meters (p = .008) while the 49.2 +/- 75.1 meter increase observed in the controls was not significant. PI (max) in the RMT group increased from 138.1 +/- 19.6 to 165.3 +/- 23.5 cmH (2)O (p < .001), with no significant change observed in the controls. RMT did not significantly affect RMF or dyspnea. In conclusion, RMT improved intermittent exercise performance in these soccer athletes. The mechanisms by which RMT improves performance warrant further study.

Formation and characterization of fluid lipid bilayers on alumina.

Fluid lipid bilayers were deposited on alumina substrates with the use of bubble collapse deposition (BCD). Previous studies using vesicle rupture have required the use of charged lipids or surface functionalization to induce bilayer formation on alumina, but these modifications are not necessary with BCD. Photobleaching experiments reveal that the diffusion coefficient of POPC on alumina is 0.6 microm (2)/s, which is much lower than the 1.4-2.0 microm (2)/s reported on silica. Systematically accounting for roughness, immobile regions and membrane viscosity shows that pinning sites account for about half of this drop in diffusivity. The remainder of the difference is attributed to a more tightly bound water state on the alumina surface, which induces a larger drag on the bilayer.