Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

The impact of a total knee arthroplasty on jaw movements,upper body posture,plantar pressure distribution,and postural control

ABSTRACT

Objective: The purpose of this study was to examine the influence of a total knee arthroplasty (TKA) on linked cranial and caudal structures.

Methods: Thirty-five (14f/21m) subjects participated in this study: 15 subjects (9f, 6m) pre- and post- TKA and a control group of 20 subjects (5f, 15m). The measurements included: jaw condyle position and movement, back scan, plantar pressure distribution, and body sway.

Results: There were no significant differences in electronic position analysis of the jaw; however, the protrusion of the TKA group improved (p = 0.001). The test group had a more anteriorly inclined thoracic spine and a less pronounced lumbar lordosis. Before and after surgery, the body sway in the test group was larger.

Conclusion: The TKA affected most prominently the static mechanisms of the postural control and the spine position. The trajectories of the mandible during protrusion also changed slightly.     

Mechanismen der arteriellen Restenose und Therapieansätze zur Prävention

Both vascular surgery and endovascular interventions traumatise the arterial wall, especially the endothelium. The vessel responds with neointimal hyperplasia and/or constrictive remodelling, and this is still the limiting factor in curative interventions. Stent placement prevents constrictive remodelling but is the main trigger for in-stent restenosis. Hyperproliferation of neointimal tissue is the main response to arterial thrombosis, local inflammation or medio-intimal injury such as occurs, for example, after balloon dilatation in the region of arterial anastomoses or of a thrombectomy (Fogarty-manoeuvre). At present, research on prevention of restenosis is focused on inhibiting neointimal hyperproliferation by using drug-eluting stents, and especially sirolimus- or paclitaxel-eluting stents. In addition, further experimental research work is in progress, with the aim of esablishing new treatment regimens and solving the problem of neointimal formation, thrombosis and constrictive remodelling. These include both local and systemic pharmacological therapy, brachy- and laser therapy, and many genetic treatment options, some of which are currently the subjects of experimental studies and early-stage clinical trials. Gene therapy seems like a promising way of preventing restenosis, but has not yet been tested in clinical trials. In the near future, selective, simultaneous, and perhaps even polyphasic regulation for gene silencing of two or more genes involved in the development of restenosis could improve the long-term patency rate.     

Effects of capsaicin in temporomandibular joint arthritis in rats

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P- (SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.     

Aconitum in Traditional Chinese Medicine-A valuable drug or an unpredictable risk?

Aconitum species have been used in China as an essential drug in Traditional Chinese Medicine (TCM) for 2000 years. Reviewing the clinical application of Aconitum, their pharmacological effects, toxicity and detoxifying measures, herb–herb interactions, clinical taboos, famous herbal formulas, traditional and current herbal processing methods based upon a wide range of literature investigations serve as a case study to explore the multidisciplinary implications of botanicals used in TCM. The toxicological risk of improper usage of Aconitum remains very high, especially in countries like China, India and Japan. The toxicity of Aconitum mainly derives from the diester diterpene alkaloids (DDAs) including aconitine (AC), mesaconitine (MA) and hypaconitine (HA). They can be decomposed into less or non-toxic derivatives through Chinese traditional processing methods (Paozhi), which play an essential role in detoxification. Using Paozhi, the three main forms of processed aconite – Yanfuzi, Heishunpian and Baifupian – can be obtained (CPCommission, 2005). Moreover, some new processing techniques have been developed in China such as pressure-steaming. The current development of fingerprint assays, in particular HPLC, has set a good basis to conduct an appropriate quality control for TCM crude herbs and their ready-made products. Therefore, a stipulation for a maximum level of DDA content of Aconitum is highly desirable in order to guarantee the clinical safety and its low toxicity in decoctions. Newly developed HPLC methods have made the accurate and simultaneous determination and quantification of DDA content interesting.     

Regional distribution of somatostatin binding sites in the human hypothalamus: a quantitative autoradiographic study.

Using in vitro quantitative autoradiography and [125I]Tyr0-D-Trp8SRIF 14 as radioligand, we characterized the detailed distribution of somatostatin binding sites in human hypothalamus of both infants and adults. Guanosine triphosphate pretreatment, before incubation, allowed us to detect higher [125I]Tyr0-D-Trp8SRIF 14 binding site densities in hypothalamic structures such as preoptic and anterior hypothalamic areas and ventromedial and dorsomedial nuclei. In contrast, guanosine triphosphate was without effect in the other hypothalamic regions. The regional effects of guanosine triphosphate pretreatment were not different in infant and adult hypothalamus. Scatchard analysis showed that in a guanosine triphosphate-sensitive region (preoptic area) and a guanosine triphosphate-insensitive area (infundibular nucleus), [125I]Tyr0-D-Trp8SRIF 14 bound to a single class of binding sites. Affinities were similar in both regions, not modified by guanosine triphosphate pretreatment and not different in the adult (1.5 +/- 1.2 nM vs 3.2 +/- 2.1 nM for preoptic area and infundibular nucleus, respectively) and infant (0.9 +/- 0.5 nM vs 2.4 +/- 1.7 nM for preoptic area and infundibular nucleus). [125I]Tyr0-D-Trp8SRIF 14 binding sites were widely distributed in the anterior, mediobasal and posterior hypothalamus. Somatostatin 28 was twice as potent as somatostatin 14 to displace [125I]Tyr0-D-Trp8SRIF 14 binding in the preoptic area and infundibular nucleus. However, IC50s were 30 times lower in the preoptic area as compared with the infundibular nucleus. In adult as well as in infant, high densities were found mainly in the diagonal band of Broca, preoptic area and infundibular nucleus. Intermediate densities were localized in the anterior hypothalamic area, ventromedial, dorsomedial and lateral mammillary nuclei. The dorsal hypothalamic area, the paraventricular and medial mammillary nuclei displayed low but measurable densities. The only marked difference in the distribution of [125I]Tyr0-D-Trp8SRIF 14 binding sites in adult vs infant was observed in the medial and tuberal nuclei where the concentrations were seven-fold higher in adult hypothalamus.     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Renal tubular epithelial cells express osteonectin in vivo and in vitro.

Osteonectin (SPARC, culture shock protein, BM-40) is a widely distributed glycoprotein which binds calcium and several extracellular matrix proteins, including interstitial collagens and thrombospondin, but whose physiologic role remains undefined. In the present studies, we have demonstrated that immunoreactive osteonectin is present in the distal cortical tubule and medullary tubules of murine kidney. We surveyed the renal epithelial cell lines LLC-PK1, MDCK, and OK for the expression of mRNA encoding osteonectin. We found that osteonectin mRNA is expressed by LLC-PK1 and OK cells but not by MDCK cells, as well as by adult kidney from several species. Calcitonin and vasopressin, agents which increase cAMP in these cells, were found to decrease steady-state osteonectin mRNA concentrations. We found that LLC-PK1 cells produced osteonectin protein, that the protein was localized to intracellular granules, and that the protein bound hydroxyapatite in vitro. Pulse-chase analysis revealed that osteonectin was secreted from the cell layer to the medium after a lag time of four to six hours and was secreted preferentially from the basolateral domain of the cell. The preferential secretion of the calcium-binding protein osteonectin from the renal epithelial cell is consistent with several possible functions, including a structural extracellular matrix protein, a participant in transepithelial ion transport, and an inhibitor of extracellular calcification.