The post-illumination pupil response of melanopsin expressing intrinsically photosensitive retinal ganglion cells in diabetes

Purpose: This study investigates the clinical utility of the melanopsin expressing intrinsically photosensitive retinal ganglion cell (ipRGC) controlled post-illumination pupil response (PIPR) as a novel technique for documenting inner retinal function in patients with Type II diabetes without diabetic retinopathy. Methods: The post-illumination pupil response (PIPR) was measured in seven patients with Type II diabetes, normal retinal nerve fiber thickness and no diabetic retinopathy. A 488 nm and 610 nm, 7.15º diameter stimulus was presented in Maxwellian view to the right eye and the left consensual pupil light reflex was recorded. Results: The group data for the blue PIPR (488 nm) identified a trend of reduced ipRGC function in patients with diabetes with no retinopathy. The transient pupil constriction was lower on average in the diabetic group. The relationship between duration of diabetes and the blue PIPR amplitude was linear, suggesting that ipRGC function decreases with increasing diabetes duration. Conclusion: This is the first report to show that the ipRGC controlled post-illumination pupil response may have clinical applications as a non-invasive technique for determining progression of inner neuroretinal changes in patients with diabetes before they are ophthalmoscopically or anatomically evident. The lower transient pupil constriction amplitude indicates that outer retinal photoreceptor inputs to the pupil light reflex may also be affected in diabetes.

Signal patterns of piston slap of a four-cylinder diesel engine

This paper presents an experimental study on the vibration signal patterns associated with a simulated piston slap test of a four-cylinder diesel engine. It is found that a simulated worn-off piston results in an increase in vibration RMS peak amplitudes associated with the major mechanical events of the corresponding cylinder (i.e., inlet and exhaust valve closing and combustion of Cylinder 1). This then led to an increase of overall vibration amplitude of the time domain statistical features such as RMS, Crest Factor, Skewness and Kurtosis in all loading conditions. The simulated worn-off piston not only increased the impact amplitude of piston slap during the engine combustion, it also produced a distinct impulse response during the air induction stroke of the cylinder attributing to an increase of lateral impact force as a result of piston reciprocating motion and the increased clearance between the worn-off piston and the cylinder. The unique signal patterns of piston slap disclosed in this paper can be utilized to assist in the development of condition monitoring tools for automated diagnosis of similar diesel engine faults in practical applications.

The effect of silicate ions on proliferation, osteogenic differentiation and cell signalling pathways (WNT and SHH) of bone marrow stromal cells

Silicon (Si) is a trace element, which plays an important role in human bone growth. Si has been incorporated into biomaterials for bone regeneration in order to improve their osteogenic potential, both in vitro and in vivo. Little is known, however, as to how Si ions elicit their biological response on bone-forming cells. The aim of this study was to investigate the effect of Si ions on the proliferation, differentiation, bone-related gene expression and cell signalling pathways of bone marrow stromal cells (BMSCs) by comparing the BMSC responses to different concentrations of NaCl and Na2SiO3, while taking into account and excluding the effect of Na ions. Our study showed that Si ions at a concentration of 0.625 mM significantly enhanced the proliferation, mineralization nodule formation, bone-related gene expression (OCN, OPN and ALP) and bone matrix proteins (ALP and OPN) of BMSCs. Furthermore, Si ions at 0.625 mM could counteract the effect of the WNT inhibitor (W.I.) cardamonin on the osteogenic genes expression, (OPN, OCN and ALP), WNT and SHH signalling pathway-related genes in BMSCs. These results suggest that Si ions by themselves play an important role in regulating the proliferation and osteogenic differentiation of BMSCs, with the involvement of WNT and SHH signalling pathways. Our study provides evidence to explain possible molecular mechanisms whereby Si ions released from Si-containing biomaterials can acquire enhanced bioactivity at desired concentration.

Human immunodeficiency virus type 1 subtype C Gag virus-like particle boost substantially improves the immune response to a subtype C gag DNA vaccine in mice

Human immunodeficiency virus type 1 (HIV-1) subtype C is the predominant HIV in southern Africa, and is the target of a number of recent vaccine candidates. It has been proposed that a heterologous prime/boost vaccination strategy may result in stronger, broader and more prolonged immune responses. Since HIV-1 Gag Pr55 polyprotein can assemble into virus-like particles (VLPs) which have been shown to induce a strong cellular immune response in animals, we showed that a typical southern African subtype C Pr55 protein expressed in insect cells via recombinant baculovirus could form VLPs. We then used the baculovirus-produced VLPs as a boost to a subtype C HIV-1 gag DNA prime vaccination in mice. This study shows that a low dose of HIV-1 subtype C Gag VLPs can significantly boost the immune response to a single subtype C gag DNA inoculation in mice. These results suggest a possible vaccination regimen for humans. © 2004 SGM.

Asylum seekers living in the community on Bridging Visa E : community sector’s response to detrimental policies

In 1997, the Australian government introduced regulations restricting work rights, income and Medicare access to asylum seekers living in the community on Bridging Visa E (BVE). These visa conditions have resulted in unacceptable hardship for asylum seekers. In response, a variety of community-based agencies have been established across Australia. This study documents and collates the experiences of some of these agencies working in Victoria. These organizations maintain a high degree of inter-agency communication and liaison, have an extensive community support network by way of volunteer work and financial assistance from philanthropic organizations and the public, and have developed successful alternative models of care for asylum seekers. However, many of the agencies have been unprepared and under-resourced for the specific legal, cultural, and health concerns common to asylum seekers on BVE. A discussion of the issues faced by the community sector in the current asylum seeker/refugee political context is presented

Achilles tendinopathy has an aberrant strain response to eccentric exercise

Purpose: Eccentric exercise has become the treatment of choice for Achilles tendinopathy. However, little is known about the acute response of tendons to eccentric exercise or the mechanisms underlying its clinical benefit. This research evaluated the sonographic characteristics and acute anteroposterior (AP) strain response of control (healthy), asymptomatic, and symptomatic Achilles tendons to eccentric exercise. Methods: Eleven male adults with unilateral midportion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Sagittal sonograms of the Achilles tendon were acquired immediately before and after completion of a common eccentric rehabilitation exercise protocol and again 24 h later. Tendon thickness, echogenicity, and AP strain were determined 40 mm proximal to the calcaneal insertion. Results: Compared with the control tendon, both the asymptomatic and symptomatic tendons were thicker (P < 0.05) and hypoechoic (P < 0.05) at baseline. All tendons decreased in thickness immediately after eccentric exercise (P < 0.05). The symptomatic tendon was characterized by a significantly lower AP strain response to eccentric exercise compared with both the asymptomatic and control tendons (P < 0.05). AP strains did not differ in the control and asymptomatic tendons. For all tendons, preexercise thickness was restored 24 h after exercise completion. Conclusions: These observations support the concept that Achilles tendinopathy is a bilateral or systemic process and structural changes associated with symptomatic tendinopathy alter fluid movement within the tendon matrix. Altered fluid movement may disrupt remodeling and homeostatic processes and represents a plausible mechanism underlying the progression of tendinopathy.

Volume-dependent response of precooling for intermittent-sprint exercise in the heat

Purpose: To assess the effects of pre-cooling volume on neuromuscular function and performance in free-paced intermittent-sprint exercise in the heat. Methods: Ten male, teamsport athletes completed four randomized trials involving an 85-min free-paced intermittentsprint exercise protocol in 33°C±33% relative humidity. Pre-cooling sessions included whole body (WB), head+hand (HH), head (H) and no cooling (CONT), applied for 20-min pre-exercise and 5-min mid exercise. Maximal voluntary contractions (MVC) were assessed pre- and postintervention and mid- and post-exercise. Exercise performance was assessed with sprint times, % decline and distances covered during free-paced bouts. Measures of core(Tc) and skin (Tsk) temperatures, heart rate, perceptual exertion and thermal stress were monitored throughout. Venous and capillary blood was analyzed for metabolite, muscle damage and inflammatory markers. Results: WB pre-cooling facilitated the maintenance of sprint times during the exercise protocol with reduced % decline (P=0.04). Mean and total hard running distances increased with pre cooling 12% compared to CONT (P<0.05), specifically, WB was 6-7% greater than HH (P=0.02) and H (P=0.001) respectively. No change was evident in mean voluntary or evoked force pre- to post-exercise with WB and HH cooling (P>0.05). WB and HH cooling reduced Tc by 0.1-0.3°C compared to other conditions (P<0.05). WB Tsk was suppressed for the entire session(P=0.001). HR responses following WB cooling were reduced(P=0.05; d=1.07) compared to CONT conditions during exercise. Conclusion: A relationship between pre-cooling volume and exercise performance seems apparent, as larger surface area coverage augmented subsequent free-paced exercise capacity, in conjunction with greater suppression of physiological load. Maintenance of MVC with pre-cooling, despite increased work output suggests the role of centrally-mediated mechanisms in exercise pacing regulation and subsequent performance.

Duration-dependant response of mixed-method pre-cooling for intermittent-sprint exercise in the heat

This study examined the effects of pre-cooling duration on performance and neuromuscular function for self-paced intermittent-sprint shuttle running in the heat. Eight male, team-sport athletes completed two 35-min bouts of intermittent-sprint shuttle running separated by a 15-min recovery on three separate occasions (33°C, 34% relative humidity). Mixed-method pre-cooling was completed for 20 min (COOL20), 10-min (COOL10) or no cooling (CONT) and reapplied for 5-min mid-exercise. Performance was assessed via sprint times, percentage decline and shuttle-running distance covered. Maximal voluntary contractions (MVC), voluntary activation (VA) and evoked twitch properties were recorded pre- and post-intervention and mid- and post-exercise. Core temperature (T c), skin temperature, heart rate, capillary blood metabolites, sweat losses, perceptual exertion and thermal stress were monitored throughout. Venous blood draws pre- and post-exercise were analyzed for muscle damage and inflammation markers. Shuttle-running distances covered were increased 5.2 ± 3.3% following COOL20 (P < 0.05), with no differences observed between COOL10 and CONT (P > 0.05). COOL20 aided in the maintenance of mid- and post-exercise MVC (P < 0.05; d > 0.80), despite no conditional differences in VA (P > 0.05). Pre-exercise T c was reduced by 0.15 ± 0.13°C with COOL20 (P < 0.05; d > 1.10), and remained lower throughout both COOL20 and COOL10 compared to CONT (P < 0.05; d > 0.80). Pre-cooling reduced sweat losses by 0.4 ± 0.3 kg (P < 0.02; d > 1.15), with COOL20 0.2 ± 0.4 kg less than COOL10 (P = 0.19; d = 1.01). Increased pre-cooling duration lowered physiological demands during exercise heat stress and facilitated the maintenance of self-paced intermittent-sprint performance in the heat. Importantly, the dose-response interaction of pre-cooling and sustained neuromuscular responses may explain the improved exercise performance in hot conditions.

Conductometric gas sensors based on nanostructured WO3 thin films

Nanostructured WO3 thin films have been prepared by thermal evaporation to detect hydrogen at low temperatures. The influence of heat treatment on the physical, chemical and electronic properties of these films has been investigated. The films were annealed at 400oC for 2 hours in air. AFM and TEM analysis revealed that the as-deposited WO3 film is high amorphous and made up of cluster of particles. Annealing at 400oC for 2 hours in air resulted in very fine grain size of the order of 5 nm and porous structure. GIXRD and Raman analysis revealed that annealing improved the crystallinity of WO3 film. Gas sensors based on annealed WO3 films have shown a high response towards various concentrations (10-10000 ppm) H2 at an operating temperature of 150oC. The improved sensing performance at low operating temperature is due to the optimum physical, chemical and electronic properties achieved in the WO3 film through annealing.

Effects of oxygen and culture system on in vitro propagation and redifferentiation of osteoarthritic human articular chondrocytes

Regenerative medicine-based approaches for the repair of damaged cartilage rely on the ability to propagate cells while promoting their chondrogenic potential. Thus, conditions for cell expansion should be optimized through careful environmental control. Appropriate oxygen tension and cell expansion substrates and controllable bioreactor systems are probably critical for expansion and subsequent tissue formation during chondrogenic differentiation. We therefore evaluated the effects of oxygen and microcarrier culture on the expansion and subsequent differentiation of human osteoarthritic chondrocytes. Freshly isolated chondrocytes were expanded on tissue culture plastic or CultiSpher-G microcarriers under hypoxic or normoxic conditions (5% or 20% oxygen partial pressure, respectively) followed by cell phenotype analysis with flow cytometry. Cells were redifferentiated in micromass pellet cultures over 4 weeks, under either hypoxia or normoxia. Chondrocytes cultured on tissue culture plastic proliferated faster, expressed higher levels of cell surface markers CD44 and CD105 and demonstrated stronger staining for proteoglycans and collagen type II in pellet cultures compared with microcarrier-cultivated cells. Pellet wet weight, glycosaminoglycan content and expression of chondrogenic genes were significantly increased in cells differentiated under hypoxia. Hypoxia-inducible factor-3alpha mRNA was up-regulated in these cultures in response to low oxygen tension. These data confirm the beneficial influence of reduced oxygen on ex vivo chondrogenesis. However, hypoxia during cell expansion and microcarrier bioreactor culture does not enhance intrinsic chondrogenic potential. Further improvements in cell culture conditions are therefore required before chondrocytes from osteoarthritic and aged patients can become a useful cell source for cartilage regeneration.

Do thermal agents affect range of movement and mechanical properties in soft tissues? A systematic review

OBJECTIVES: To examine the effect of thermal agents on the range of movement (ROM) and mechanical properties in soft tissue and to discuss their clinical relevance. DATA SOURCES: Electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE) were searched from their earliest available record up to May 2011 using Medical Subjects Headings and key words. We also undertook related articles searches and read reference lists of all incoming articles. STUDY SELECTION: Studies involving human participants describing the effects of thermal interventions on ROM and/or mechanical properties in soft tissue. Two reviewers independently screened studies against eligibility criteria. DATA EXTRACTION: Data were extracted independently by 2 review authors using a customized form. Methodologic quality was also assessed by 2 authors independently, using the Cochrane risk of bias tool. DATA SYNTHESIS: Thirty-six studies, comprising a total of 1301 healthy participants, satisfied the inclusion criteria. There was a high risk of bias across all studies. Meta-analyses were not undertaken because of clinical heterogeneity; however, effect sizes were calculated. There were conflicting data on the effect of cold on joint ROM, accessory joint movement, and passive stiffness. There was limited evidence to determine whether acute cold applications enhance the effects of stretching, and further evidence is required. There was evidence that heat increases ROM, and a combination of heat and stretching is more effective than stretching alone. CONCLUSIONS: Heat is an effective adjunct to developmental and therapeutic stretching techniques and should be the treatment of choice for enhancing ROM in a clinical or sporting setting. The effects of heat or ice on other important mechanical properties (eg, passive stiffness) remain equivocal and should be the focus of future study.

Gene expression profile of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure

BACKGROUND: Broccoli consumption has been associated with a reduced risk of prostate cancer. Isothiocyanates (ITCs) derived from glucosinolates that accumulate in broccoli are dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) derives from heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) from sprouting broccoli. While there are many studies regarding the biological activity of SF, mainly undertaken with cancerous cells, there are few studies associated with IB. METHODS: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these cells, and to quantify changes in gene expression following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. RESULTS: Global gene expression profiling identified epithelial and stromal-specific gene expression profiles. SF induced more changes in epithelial cells, whereas IB was more effective in stromal cells. Although IB and SF induced different changes in gene expression in both epithelial and stromal cells, these were associated with similar pathways, such as cell cycle and detoxification. Both ITCs increased expression of PLAGL1, a tumor suppressor gene, in stromal cells and suppressed expression of the putative tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. CONCLUSION: These data suggest that IB and SF both alter genes associated with cancer prevention, and IB should be investigated further as a potential chemopreventative agent.

INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells

Altered expression of the INT6 gene, encoding the e subunit of the translational initiation factor eIF3, occurs in human breast cancers, but how INT6 relates to carcinogenesis remains unestablished. Here, we show that INT6 is involved in the DNA damage response. INT6 was required for cell survival following γ-irradiation and G(2)-M checkpoint control. RNA interference-mediated silencing of INT6 reduced phosphorylation of the checkpoint kinases CHK1 and CHK2 after DNA damage. In addition, INT6 silencing prevented sustained accumulation of ataxia telangiectasia mutated (ATM) at DNA damage sites in cells treated with γ-radiation or the radiomimetic drug neocarzinostatin. Mechanistically, this result could be explained by interaction of INT6 with ATM, which together with INT6 was recruited to the sites of DNA damage. Finally, INT6 silencing also reduced ubiquitylation events that promote retention of repair proteins at DNA lesions. Accordingly, accumulation of the repair factor BRCA1 was defective in the absence of INT6. Our findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 and suggest that the protective action of INT6 in the onset of breast cancers relies on its involvement in the DNA damage response.

A yellow filter improves response times to low-contrast targets and traffic hazards

Purpose Anecdotal evidence suggests that some sunglass users prefer yellow tints for outdoor activities, such as driving, and research has suggested that such tints improve the apparent contrast and brightness of real-world objects. The aim of this study was to establish whether yellow filters resulted in objective improvements in performance for visual tasks relevant to driving. Methods Response times of nine young (age [mean ± SD], 31.4 ± 6.7 years) and nine older (age, [mean ± SD], 74.6 ± 4.8) adults were measured using video presentations of traffic hazards (driving hazard perception task) and a simple low-contrast grating appeared at random peripheral locations on a computer screen. Response times were compared when participants wore a yellow filter (with and without a linear polarizer) versus a neutral density filter (with and without a linear polarizer). All lens combinations were matched to have similar luminance transmittances (˜27%). Results In the driving hazard perception task, the young but not the older participants responded significantly more rapidly to hazards when wearing a yellow filter than with a luminance-matched neutral density filter (mean difference, 450 milliseconds). In the low-contrast grating task, younger participants also responded more quickly for the yellow filter condition but only when combined with a polarizer. Although response times increased with increasing stimulus eccentricity for the low-contrast grating task, for the younger participants, this slowing of response times with increased eccentricity was reduced in the presence of a yellow filter, indicating that perception of more peripheral objects may be improved by this filter combination. Conclusions Yellow filters improve response times for younger adults for visual tasks relevant to driving.