Does proprioception contribute to the sense of verticality?

The representation of the vertical can be assessed by measuring the visual, tactile or perception of the postural vertical (PV). It is well accepted that visceral graviceptors and Golgi tendon receptors contribute to perception of the PV, whereas the role of muscular proprioception (Ia muscle spindles) remains to be clarified. The objective of this study was to analyze whether or not muscular proprioception contributes to the representation of verticality. We hypothesized that the modulation of proprioception by appropriate tendinomuscular vibration may tilt the PV. We present two experiments that explore this hypothesis. PV was firstly measured in the pitch plane in twelve healthy subjects in two conditions: baseline and vibration of both Achilles tendons during six minutes, according to a counterbalanced presentation. PV orientation (mean) and dispersion (standard deviation) were calculated on the six measurements per condition. Vibration of the Achilles tendons induced a systematic backward tilt of PV (2.7° ± 0.8° on average; P < 10⁻³), and no significant changes regarding PV dispersion. A clear post-effect was found for PV orientation in subjects who started the experiment with the condition vibration on. The possibility that PV could also be modulated by a much shorter duration of vibration (less than 8 s of vibration) was analyzed in a second experiment using a similar general procedure but a simplified experimental plane in other subjects. Again a backward PV tilt was induced by the vibration, but with a magnitude lower than that found in the first experiment, and with no post-effect. Since body geometry was unchanged, these two studies mean that proprioception contributes to the representation of the vertical. In conclusion, this study brings new insights to our understanding of the sense of verticality and contributes to the interpretation of backward falls induced by vibration. The induced backward fall is partly due to alignment of the erect posture with a backward-tilted referential of verticality.     

Does the bronchial circulation contribute to congestion in heart failure?

Pulmonary congestion is a hallmark feature of heart failure and is a major reason for hospital admissions in this patient population. Heart failure patients often demonstrate restrictive and obstructive pulmonary function abnormalities; however, the mechanisms of these changes remain controversial. It has been suggested that the bronchial circulation may play an important role in the development of these pulmonary abnormalities and in the symptoms associated with pulmonary congestion.Congestion may occur in the bronchial circulation from either a marked increase in flow or an increase in blood volume but with a reduction in flow due to high cardiac filling pressures and high pulmonary vascular pressures (a stasis like condition). Either may lead to thickened bronchial mucosal and submucosal tissues and reduced airway compliance resulting in airway obstruction and restriction and a lack of airway distensibility. These structural changes may contribute to “cardiac asthma” and dyspnea, characteristic features common in HF patients. Thus the bronchial circulation may be a potential target for therapeutic interventions.The aim of this paper is to review factors governing the control of the bronchial circulation, how bronchial vascular conductance may change with HF and to pose arguments, both supporting and in opposition to the bronchial circulation contributing to congestion and altered pulmonary function in HF. We ultimately hypothesize that the engorgement of the bronchial circulatory bed may play a role in pulmonary function abnormalities that occur in HF patients and contribute to symptoms such as orthopnea and exertional dyspnea.     

Does the social environment contribute to asthma?

The impact of the social environment on asthma has recently begun to receive increasing attention. This article reviews the current literature to investigate the impact of the social environment at three levels-the neighborhood level, the peer level, and the family level-and to explore pathways through which the social environment "gets under the skin" to impact asthma onset and morbidity. Research to date suggests that adverse social conditions at the neighborhood and family levels impact asthma morbidity through direct effects on physiologic systems as well as by altering health behaviors. The impact on asthma of social networks, such as friendships, is less clear and will need to be investigated further. Future research will need to take into account the impact of the social environment to develop more comprehensive models of asthma pathogenesis.     

Does sexual violence contribute to elevated rates of anxiety and depression in females?

BACKGROUND: It is well documented that females have higher rates of internalizing disorders (anxiety, depression) than males. It is also well known that females have higher exposure to childhood sexual abuse and sexual assault. Recently, it has been proposed that the higher levels of internalizing disorders in females may be caused by their greater exposure to sexual violence. METHOD: Data were gathered as part of the Christchurch Health and Development Study. In this study a cohort of 1265 children born in Christchurch, New Zealand, in 1977 have been studied from birth to age 21 years. The measures collected included: major depression and anxiety, childhood sexual abuse and adolescent sexual assault. RESULTS: Findings confirmed the established conclusion that internalizing disorders are over twice as common in females than males (ORs 2.2-2.7). In addition, it was found that females were exposed to higher rates of sexual violence than males (ORs 5.1-8.4). Statistical control for gender related differences in exposure to sexual violence reduced the associations between gender and anxiety and depression. Nonetheless, even after such control, gender was significantly (P < 0.0001) related to both anxiety (OR = 1.8; 95% CI, 1.3-2.4) and depression (OR = 1.9; 95% CI, 1.4-2.3). CONCLUSIONS: Greater female exposure to sexual violence may be a factor that contributes to greater female susceptibility to internalizing disorders. However, even after adjustment for gender differences in exposure to sexual violence it is clear that a substantial relationship between gender and internalizing disorder persists.     

Does SV40 infection contribute to the development of human cancers?

A large number of recent studies have reported the detection of simian virus 40 (SV40) nucleotide sequences in a number of unrelated human cancers which include paediatric and adult brain tumours, pleural mesotheliomas, bronchopulmonary carcinomas and osteosarcomas. Most of the data have been gathered by the use of PCR assays. These observations imply that SV40 is circulating in human communities by person-to-person transmission and that the virus is capable of wide dissemination in the infected individual. These claims must be regarded with skepticism for a variety of reasons. There are several inconsistencies in the reported data; for example, there is a wide variation (0-23%) in the frequency of SV40 sequences in normal tissues. The results of PCR assays have been difficult to confirm by less error-prone and independent assays and the relationship of the virus to the tumour cell is not characterised. The SV40 sequences reported from humans are essentially identical to those of wild-type SV40; it is difficult to conceive that a highly species-specific polyomavirus like SV40 would cross the species barrier, become a human infection, and acquire pathogenic potential for the new host without significant adaptive change in its genome. The available evidence, although not extensive, does not indicate that SV40 is circulating in human communities. It is premature to discuss or speculate on the potential role of SV40 in the development of human cancer until the presence of SV40 in cancers and in human communities is established unequivocally, the risk factors for SV40 infection are elucidated, and the effect of SV40 exposure on the development of specific cancers is examined in the context of other known risk factors for those cancers.     

Does the vestibular system contribute to head direction cell activity in the rat?

Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.     

Does response selection contribute to inhibition of return?

Inhibition of return (IOR) means delayed responses for targets at a cued compared to targets at an uncued location. It is assumed to reflect delayed reallocation of attention toward a previously attended location. Besides an attentional mechanism, IOR could also be due to a cue‐evoked inhibition to respond toward a cued target. In the present study, IOR with simple, compatible, and incompatible choice responses was compared and tracked by means of event‐related EEG activity. IOR was amplified with simple responses but did not differ between compatible and incompatible responses. Attention‐related ERP correlates were constant across cue target onset asynchronies as were, in part, behavioral effects. Early, rather sensory ERP components varied with time, reflecting sensory or attentional interaction of cue and target processing. None of these effects varied with response requirements, indicating that response selection does not contribute to IOR in manual choice response tasks.     

Does the perceived neighborhood reputation contribute to neighborhood differences in social trust and residential wellbeing?

The authors used a mixed methods approach to examine if the reputation of a housing area has bearing on residential wellbeing and social trust in three pairs of socioeconomically contrasting neighborhoods in a Swedish urban municipality. Multilevel logistic regression analyses were performed to examine associations between area reputation and residential wellbeing and social trust, controlling for the random effect of neighborhood and individual level sociodemographic factors. Qualitative data were analyzed to identify mechanisms of how neighborhood reputations were established. The housing area reputation was found to be strongly associated with wellbeing and social trust. The area reputation also seemed to be a determinant of position in the local social structure; residents were found to position themselves in a rank order. The results suggest that area reputation is an important and probably underestimated dimension in the development of residential wellbeing and social trust in housing. © 2010 Wiley Periodicals, Inc.     

Does nitric oxide generation contribute to the mechanism of remote ischemic preconditioning?

The protective effect of local or remote ischemic preconditioning (IPC) on subsequent 40-min ischemic and 120-min reperfusion myocardial damage was investigated. Preconditioned rats underwent one cycle of myocardial ischemia/reperfusion consisting of 5-min ischemia produced as a left coronary artery (LCA) occlusion and 5 min of reperfusion. Remote IPC was produced as 15 min of small intestinal ischemia with 15 min of reperfusion as well as 30 min of limb ischemia with 15 min of reperfusion. A marked protective action was afforded by both IPC protocols with a more significant effect of local (classic) ischemic preconditioning. Since the protective effect of remote IPC was not abolished by nitric oxide (NO) synthase inhibition with Nω-nitro- -arginine ( -NNA) it is concluded that NO generation may not be involved in the mechanism of remote IPC.     

Does endotoxin contribute to aseptic loosening of orthopedic implants?

Aseptic loosening of orthopedic implants caused by wear particles is a major clinical problem. This review examines the hypothesis that bacterial endotoxin contributes to aseptic loosening. Clinical findings support this hypothesis: bacterial biofilms exist on many implants from patients with aseptic loosening and antibiotics in bone cement reduce the rate of aseptic loosening. Three approaches were used to demonstrate that adherent endotoxin increases bioactivity of titanium particles. These experiments measured cytokine production and osteoclast differentiation in vitro and murine calvarial osteolysis in vivo. First, removal of >99.9% of the adherent endotoxin from titanium particles significantly ablates their biological activity. Second, adding lipopolysaccharide back to these "endotoxin-free" particles restores their biological activity. Third, cells or mice that are genetically hyporesponsive to endotoxin are significantly less responsive to titanium particles than are wild-type controls. Other investigators have confirmed and extended these results to include virtually all orthopedically relevant types of particles, including authentic titanium alloy particles retrieved from patients with loosening. Our recent studies suggest that adherent endotoxin on orthopedic implants may also inhibit initial osseointegration of the implants. Taken together, these studies suggest that bacterial endotoxin may have a significant role in induction of aseptic loosening.     

Could visible light contribute to the development of leukaemia and other cancers in children?

This paper suggests to rigorously test the hypothesis that there are causal links between visible light and the development of leukaemia and other cancers in children. Light can be considered as a candidate risk factor because it suppresses melatonin biosynthesis which may play a role in a series of anticancer defences. Indeed, melatonin may offer some protection against all "hallmarks of cancer" [i.e., self-sufficiency in growth signals; insensitivity to growth-inhibitory signals; evasion of programmed cell death (apoptosis); limitless replicative potential; sustained angiogenesis; tissue invasion and metastasis] recently suggested by Hanahan and Weinberg. Already ongoing investigations into the possible nexus of light, endocrine systems and the development of cancers will be further fueled by recent insights into photoreception and -- transduction, including the discovery of "novel" photoreceptors in the eye. Among a variety of different photosensory tasks, these receptors constitute crucial gates for light information from the environment which is employed for the temporal organization of our physiology and it has been proposed that chronodisruption, i.e., a significant disturbance of the coordination and thus order of biological rhythms, could contribute to the development of cancers. With regard to public health, the pervasive exposures to light -- at work and in homes -- imply that visible radiation could be a strong risk factor defined epidemiologically as a causal contributor to disease in a large proportion of cases. Importantly, if light were to be corroborated as a contributor to cancers in children, it would be amenable to manipulations with the perspective of reducing inherent risks significantly. In fact, it could be much easier -- and much more effective -- to reevaluate and modify lighting systems than to manipulate other possible determinants of the chronic processes of cancer such as genetic, nutritional or lifestyle factors.     

Does environmental replication contribute to Bacillus anthracis spore persistence and infectivity in soil?

Bacillus anthracis is the zoonotic causal agent of anthrax. Its infectious form is the spore, which can persist in soil. Herbivores usually acquire the disease from grazing in spore-contaminated sites. There are two schools of thought regarding B. anthracis activities in soil. One contends the bacteria are obligate animal parasites and soil-based spores remain inert until taken up by another animal host. Others contend that spores can germinate in soil and the bacteria replicate and re-sporulate to maintain and/or increase spore numbers. This review discusses whether soil replication of B. anthracis is an important part of its life cycle.     

Does postprandial storage of triglycerides in endothelial cells contribute to the endothelial dysfunction associated with insulin resistance and fatty diets?

Insulin resistance syndrome is associated with endothelial dysfunction characterized by decreased nitric oxide bioactivity and subnormal endothelium-dependent vasodilation. Excessive exposure to free fatty acids (FFAs) is thought to mediate this dysfunction, at least in part, since free fatty acid overexposure, both in vivo and in vitro, decreases the capacity of endothelial cells to generate bioactive nitric oxide. Yet this endothelial dysfunction tends to correlate, not with fasting FFA levels, but with poor insulin suppressibility of FFA flux postprandially. I propose that triglycerides are synthesized and stored in endothelial cells during the postprandial period, when FFAs and insulin are jointly elevated, and that this triglyceride pool serves as a source of FFA overexposure postabsorptively--thus accounting for the endothelial dysfunction associated with insulin resistance syndrome and the role of excessive postprandial FFA flux in its induction. Since a substantial proportion of postprandial FFA flux derives, not from adipocytes, but from the fat provided by meals, these considerations may help to rationalize the documented clinical utility of very-low-fat diets for management of coronary disease.     

Does high load of oxidants in human semen contribute to male factor infertility?

Basal generation of reactive oxygen species (ROS) was essential for male reproductive function, whereas high ROS levels may be linked to low quality of sperm and male infertility. We examined the associations between ROS levels in whole ejaculates and sperm quality among 1092 male factor infertility (MFI) patients and 50 donors with normal semen characteristics. ROS levels were significantly positively correlated with abnormal morphology rate, head defect, and sperm deformity index. Further, we investigated whether seminal plasma from MFI patients with high ROS levels affects sperm motility from donors with normal semen characteristics. After cross-culturing fresh human sperm from donors possessing normal semen characteristics with seminal plasma from infertitle men, sperm motility was measured at different ROS levels. Seminal plasma from MFI patients significantly reduced motility of sperm and the reduction rate increased with increasing ROS levels in seminal plasma. On the other hand, we found MFI patients with the ROS levels in the lowest 25th percentile had similar ROS levels to donors with normal semen characteristics. Collectively, our observations lead to the hypothesis that oxidative stress plays a critical role in the development of MFI among those with high ROS levels, but not those with low ROS levels.     

Does excessive daytime sleepiness contribute to explaining the association between obesity and ADHD symptoms?

Recent studies suggest a significant association between obesity and attention-deficit/hyperactivity disorder (ADHD). The factors underlying this newly described comorbidity are still unclear and unexplored. In the present article, we propose that excessive daytime sleepiness (EDS) contributes to explaining the association between ADHD and obesity. The background for this hypothesis comes from studies on the association between ADHD and EDS, as well as from investigations on EDS in obese individuals. Available studies suggest that ADHD behaviours are significantly associated with EDS. Moreover, increasing evidence indicates that obesity is significantly associated with EDS independently of sleep-disordered breathing (SDB) or any other sleep disorders. Given the relationship between EDS and ADHD behaviors, we hypothesize that the higher than expected rates of EDS in obese individuals contribute to explaining the association between obesity and ADHD behaviors. We further speculate on the role of the brain derived neurotrophic factor (BDNF) and other molecules such as the proinflammatory cytokines IL-6 and TNF-alpha. Our hypothesis generates potentially relevant clinical and therapeutic implications. From a clinical standpoint, it may suggest to systematically look for ADHD symptoms (including hyperactivity and impulsivity) in obese patients described as sleepy. With regard to the therapeutic implications, we suggest that wake-promoting agents with anorexigenic effect, such as mazindol, might be particularly indicated for the treatment of ADHD symptoms in obese patients, since they might address both ADHD symptoms and weight reduction. In conclusion, considering the burden that ADHD adds to obesity, we believe that further studies on the comorbidity between obesity and ADHD are necessary. Research on the role of EDS might allow advancements in this field, suggesting a more effective management and, ultimately, a better quality of life of patients with both obesity and ADHD.     

Does dopaminergic reward system contribute to explaining comorbidity obesity and ADHD?

Some recent studies have reported a strong link between obesity and attention-deficit/hyperactivity disorder (ADHD). However, to date, the factors underlying this newly described comorbidity are still unclear and unexplored. In the present article, we proposed that the dopamine system and implicate dopamine genes contribute to explaining the association between ADHD and obesity. The background for this hypothesis comes from studies on the association between ADHD and dopamine, as well as from investigations on dopamine in obese individuals. There is strong evidence that indicate catecholamines dopamine is very important in the pathophysiology of ADHD, as well as in the mechanism of therapeutic action of stimulant drugs. Furthermore, increasing evidence indicated that dopaminergic reward system is significantly associated with obesity. With regard to the therapeutic implications, recent studies indicate that methylphenidate (MPH) - a drug widely used for ADHD reduced overall energy intake with a selective reduction in dietary fat. Findings are consistent with a reward deficiency model of obesity whereby low brain dopamine predicts overeating and obesity, and administering agents that increase dopamine results in reduced feeding behavior. Given the above background, we hypothesize that the increased prevalence of ADHD in obese individual could be explained by the imbalance of dopaminergic reward system.     

Does s-methyl methanethiosulfonate trap the thiol-disulfide state of proteins?

S-Methyl methanethiosulfonate (MMTS) is a reagent used to trap the natural thiol-disulfide state of the proteins. The efficiency of trapping mixed disulfides in vivo has been found to be higher for MMTS than for the more commonly used N-ethylmaleimide. MMTS has also been used for studying protein S-nitrosylation and the role of catalytic and structural cysteines on enzyme activities. However, the treatment of a protein with MMTS can potentially generate additional protein disulfide bonds. These results indicate that in vitro MMTS is able to form both intramolecular and intermolecular protein disulfide bonds in addition to dithiomethane adducts.