Temporal factors in violence related injuries--An 11 year trend analysis of violence-related injuries from a Swiss Emergency Department

Injury from interpersonal violence is a major social and medical problem in the industrialized world. Little is known about the trends in prevalence and injury pattern or about the demographic characteristics of the patients involved.

The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells

The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

A high-resolution soil erosion risk map of Switzerland as strategic policy support system

Soil erosion models and soil erosion risk maps are often used as indicators to assess potential soil erosion in order to assist policy decisions. This paper shows the scientific basis of the soil erosion risk map of Switzerland and its application in policy and practice. Linking a USLE/RUSLE-based model approach (AVErosion) founded on multiple flow algorithms and the unit contributing area concept with an extremely precise and high-resolution digital terrain model (2 m × 2 m grid) using GIS allows for a realistic assessment of the potential soil erosion risk, on single plots, i.e. uniform and comprehensive for the agricultural area of Switzerland (862,579 ha in the valley area and the lower mountain regions). The national or small-scale soil erosion prognosis has thus reached a level heretofore possible only in smaller catchment areas or single plots. Validation was carried out using soil loss data from soil erosion damage mappings in the field from long-term monitoring in different test areas. 45% of the evaluated agricultural area of Switzerland was classified as low potential erosion risk, 12% as moderate potential erosion risk, and 43% as high potential erosion risk. However, many of the areas classified as high potential erosion risk are located at the transition from valley to mountain zone, where many areas are used as permanent grassland, which drastically lowers their current erosion risk. The present soil erosion risk map serves on the one hand to identify and prioritise the high-erosion risk areas, and on the other hand to promote awareness amongst farmers and authorities. It was published on the internet and will be made available to the authorities in digital form. It is intended as a tool for simplifying and standardising enforcement of the legal framework for soil erosion prevention in Switzerland. The work therefore provides a successful example of cooperation between science, policy and practice.

Association of a large lateral extension of the acromion with rotator cuff tears

BACKGROUND: Factors predisposing to tearing of the rotator cuff are poorly understood. We have observed that the acromion of patients with a rotator cuff tear very often appears large on anteroposterior radiographs or during surgery. The purpose of this study was to quantify the lateral extension of the acromion in patients with a full-thickness rotator cuff tear and in patients with an intact rotator cuff. METHODS: The lateral extension of the acromion was assessed on true anteroposterior radiographs made with the arm in neutral rotation. The distance from the glenoid plane to the lateral border of the acromion was divided by the distance from the glenoid plane to the lateral aspect of the humeral head to calculate the acromion index. This index was determined in a group of 102 patients (average age, 65.0 years) with a proven full-thickness rotator cuff tear, in an age and gender-matched group of forty-seven patients (average age, 63.7 years) with osteoarthritis of the shoulder and an intact rotator cuff, and in an age and gender-matched control group of seventy volunteers (average age, 64.4 years) with an intact rotator cuff as demonstrated by ultrasonography. RESULTS: The average acromion index (and standard deviation) was 0.73 +/- 0.06 in the shoulders with a full-thickness tear, 0.60 +/- 0.08 in those with osteoarthritis and an intact rotator cuff, and 0.64 +/- 0.06 in the asymptomatic, normal shoulders with an intact rotator cuff. The difference between the index in the shoulders with a full-thickness supraspinatus tear and the index in those with an intact rotator cuff was highly significant (p < 0.0001). CONCLUSIONS: A large lateral extension of the acromion appears to be associated with full-thickness tearing of the rotator cuff.

Lesser tuberosity osteotomy for total shoulder arthroplasty. Surgical technique

BACKGROUND: Recent studies have suggested that tenotomy and repair of the subscapularis tendon carried out for anterior approaches to the shoulder can be followed by failure of the tendon repair and by changes resulting in permanent loss of subscapularis function. We hypothesized that release of the subscapularis with use of a superficial osteotomy of the lesser tuberosity followed by repair of the two opposing bone surfaces would lead to consistent bone-to-bone healing, which would be possible to monitor radiographically, and would lead to satisfactory clinical and structural outcomes. METHODS: Thirty-nine shoulders in thirty-six consecutive patients who, at an average age of fifty-seven years, had undergone total shoulder replacement through an anterior approach involving an osteotomy of the lesser tuberosity were evaluated at an average of thirty-nine months. Assessment included a standardized interview and physical examination, scoring according to the system described by Constant and Murley, and imaging with conventional radiography and computed tomography to assess healing of the osteotomy site and changes in the subscapularis. RESULTS: The osteotomized tuberosity fragment healed in an anatomical position in all shoulders, and no cuff tendon ruptures were observed. At the time of follow-up, thirty-three (89%) of thirty-seven shoulders evaluated with a belly-press test had a negative result and twenty-seven (75%) of thirty-six shoulders evaluated with a lift-off test had an unequivocally normal result. Fatty infiltration of the subscapularis muscle increased after the operation (p < 0.0001) and was at least stage two in eleven (32%) of thirty-four shoulders. The fatty infiltration had progressed by one stage in eight (24%) of the thirty-four shoulders, by two stages in five shoulders (15%), and by three stages in two shoulders (6%). CONCLUSIONS: Osteotomy of the lesser tuberosity provides an easy anterior approach for total shoulder replacement and is followed by consistent bone-to-bone healing, which can be monitored, and good subscapularis function. In the presence of documented anatomical healing of the osteotomy site, postoperative fatty infiltration of the subscapularis muscle remains unexplained and needs to be investigated further as it is associated with a poorer clinical outcome.

Malignant melanoma and bone resorption

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51-) differentiated into osteoclasts (CD14-/CD51+) in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-alpha and interleukin (IL)-1alpha. RT-PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively.

Prediction of first coronary events with the Framingham score: a systematic review

BACKGROUND: Uncertainty exists about the performance of the Framingham risk score when applied in different populations. OBJECTIVE: We assessed calibration of the Framingham risk score (ie, relationship between predicted and observed coronary event rates) in US and non-US populations free of cardiovascular disease. METHODS: We reviewed studies that evaluated the performance of the Framingham risk score to predict first coronary events in a validation cohort, as identified by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005). Two reviewers independently assessed 1496 studies for eligibility, extracted data, and performed quality assessment using predefined forms. RESULTS: We included 25 validation cohorts of different population groups (n = 128,000) in our main analysis. Calibration varied over a wide range from under- to overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7 cohorts (n = 18658) from the United States, Australia, and New Zealand was well calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The estimated population risks for first coronary events were strongly associated (goodness of fit: R2 = 0.84) and in good agreement with observed risks (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European cohorts (n = 109499), the corresponding figures indicated close association (R2 = 0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk score was well calibrated on the intercept for both population clusters. CONCLUSION: The Framingham score is well calibrated to predict first coronary events in populations from the United States, Australia, and New Zealand. Overestimation of absolute risk in European cohorts requires recalibration procedures.

[The study of apoptosis factors released from laser injured cartilage inducing apoptosis of chondrocyte]

OBJECTIVE: To explore the role of pro-apoptotic signals following tissue injury and how these may promote a progression of further cell death. METHODS: Laser treated porcine articular cartilage disks were maintained in culture media. The collected media at various time periods (3, 6, 9, 12, 24 and 48 h), was called treated conditioned media (TCM). Non-laser treated cartilage disks were used to create control conditioned media (CCM). Each disk was subsequently maintained for 28 days and used in confocal microscopic assessment to document the progression of the damaged area. Isolated porcine chondrocytes were cultured in monolayer, and were exposed to TCM, CCM or normal culture medium (NM). As a positive inducer of apoptosis, the monolayer cells were exposed to UV radiation for 10 min and cultured in NM. Following 24 h exposure, the cells were harvested and stained with the appropriate combination of fluorescent dyes and processed via flow cytometry. RESULTS: All cultured cells exposed to TCM displayed a caspase-3 positive subpopulation, a loss of CMXRos, and with a reduced or lost NO signal. CCM exposure signals were comparable to the NM treatments with all having retained CMXRos, NO and without evidence of caspase-3 activity. UV treatment also induced a reduction in NO, but both CMXRos and caspase-3 positive, representing an earlier stage of apoptosis and suggesting that the mode of cell death via UV and TCM exposure are via different processes. The investigation of a dose (100%, 50%, 25% and 12.5%) and time (0.5, 1, 3, 9, 12 h) response to TCM exhibited that all treatments observed an increase in caspase-3 positive cells and a reduction in NO and CMXRos. CONCLUSION: The usefulness of FCM can be used in the study of cell viability and apoptosis. Such a system may be useful in the study of mechanisms of disease such as osteoarthritis, thus may be of practical use for the pharmaceutical industry for screening associated drugs.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.

Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function

In protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.