Reducing Shoulder Complaints in Employees with High Occupational Shoulder Exposures: A Cluster-Randomised Controlled Study (The Shoulder-Café Study).

PURPOSE: To evaluate if a group-based Shoulder-Café intervention could reduce shoulder complaints more effectively than an individual-based control intervention in employees with shoulder complaints and high occupational shoulder exposures. METHODS: A cluster-randomised controlled study of 109 participants from 60 companies in Central Denmark Region. Companies were randomised and allocated to either Shoulder-Café or control intervention. Participants in both interventions received a pamphlet on home-based shoulder exercises and a pamphlet with general information on reducing occupational shoulder exposures. They also had their occupational shoulder exposures assessed. Shoulder-Café participants additionally received three café-meetings with casual discussion, clinical shoulder evaluation, education about shoulder anatomy and occupational shoulder exposures, supervised exercises, workplace-oriented counselling, and an optional workplace visit. The primary outcome measure was the Oxford Shoulder Score (OSS) at 6-month follow-up. Secondary outcome measures were the OSS at 12 months, Fear-Avoidance Beliefs Questionnaire - Physical Activity at 6 and 12 months, and Patients' Global Impression of Change at 6 months. The study also included seven supplementary outcome measures. RESULTS: Both groups improved from baseline to 6 months with respect to the primary outcome (P < 0.01). No group differences were found for the primary outcome (mean difference (MD) [95% confidence interval]: 0.3 [- 1.6; 2.2]) or secondary outcomes. The supplementary outcomes "felt informed about handling shoulder complaints" and "felt informed about reducing occupational exposures" at 6 months, and "Patients' Global Impression of Change" and "overall satisfaction" at 12 months favoured the Shoulder-Café intervention. CONCLUSION: The Shoulder-Café intervention did not reduce shoulder complaints more effectively than the control intervention. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov on 19 May 2017 (ID: NCT03159910).

Observational study investigating tooth extraction and the shortened dental arch approach.

The shortened dental arch (SDA) provides a cost-effective dentition, considering the population is ageing and retaining teeth for longer. The aims were to observe the reasons and sites of tooth extraction and assess the functional dentition over 15 years in dental practice. Subjects were recruited who required permanent tooth extractions between 2000 and 2015. The reasons for extractions were chosen from twelve extraction codes. Data were also collected for demographics, tooth position, root treated teeth and functional pairs remaining. Patient-centred factors on reasons for tooth extraction and comments on chewing ability and aesthetics following extractions were recorded. Nine hundred and fifty-one teeth were extracted in 900 patients. The mean age was 60 years (SD 20, SE 7, 95% CI 46, 74). Reasons for extraction were periodontal disease (n = 361, 38%), periapical infection (n = 288, 34%) or tooth and tooth-root fractures (15%). Extractions included 201 (21%) second molars, 179 (19%) first molars, 152 (16%) second premolars, 95 (10%) first incisors, 86 (9%) second incisors, 76 (8%) canines and 67 (7%) first premolars. Following extractions, median functional pairs were 12, interquartile range (IQR) 19-7. Individuals with ≥10 functional pairs including anterior teeth (60%, n = 571) had no complaints with chewing ability or aesthetics. They did not require additional prostheses. Periodontal disease and periapical infection were the main causes for the extraction. First and second molars followed by second premolars were the most commonly extracted teeth. This study supports the SDA in creating a cost effective, functional dentition in an aging population, provided remaining teeth and restorations are preserved/maintained, oral health is promoted, and anterior aesthetic tooth replacement is ensured.

Cross-neutralization studies with salmonid alphavirus subtype 1-6 strains: results with sera from experimental studies and natural infections.

The serological reactivity between strains of each of the six currently genetically defined subtypes of salmonid alphavirus (SAV) was examined by comparison of homologous and heterologous virus neutralization titres on sera from experimentally infected fish. With the exception of the level of SAV subtype 6 neutralization by heterologous sera, good cross-neutralization was detected between all subtypes, albeit with variation in geometric mean titres when each subtype-specific serum set was tested against the panel of virus subtypes. A similar pattern was evident with field sera, except that heterologous neutralization of the SAV6 strain was more evident. In only 23% of available pairwise comparisons was the homologous titre recorded with an experimentally derived serum fourfold or greater than the heterologous titre, and in only two instances was this difference demonstrated in both directions. No virus strains consistently met the old serology-based criteria (Sub-committee on Inter-relationships Among Catalogued Alphaviruses) to be considered separate subtypes within an alphavirus species. Only when testing with an SAV subtype-2-specific monoclonal antibody was a major difference between homologous and heterologous neutralization capacity evident. These results provide new direct or indirect information in terms of SAV classification, vaccine efficacy and the selection and validation of reagents for serological and immunological diagnostic purposes.

Time trends in surgery for non-traumatic shoulder disorders and postoperative risk of permanent work disability: a nationwide cohort study.

OBJECTIVES: Three previous randomized controlled trials found no overall difference in the effect of surgery compared with non-surgical treatment including exercise for patients with non-traumatic shoulder disorders. We assessed Danish temporal trends in the incidence of surgery for rotator cuff-related shoulder disorders, frozen shoulder, and osteoarthritis (OA) of the acromioclavicular (AC) joint, and the subsequent risk of permanent work disability. METHODS: Based on registers, we calculated annual incidence rates for the Danish population aged 18-63 years between 1996 and 2008. For a cohort of 19 264 first-time shoulder-operated patients who were in the labour market on admission, we used Cox proportional hazards models to assess risk of permanent work disability within 2 years after surgery. RESULTS: The annual incidence increased from 3.5 to 14.8 per 10 000, and 9.8% of the patients became permanently work disabled. No time trend was observed in this percentage. Formal education level was an important prognostic factor. Using 'higher or medium-level education' as a reference, the hazard ratio (HR) was 1.5 [95% confidence interval (CI) 1.3-1.8] for 'vocational education and training' and 2.0 (95% CI 1.8-2.3) for 'low education level'. For 'missing information on education', the HR was 0.7 (95% CI 0.6-0.9). CONCLUSIONS: We found a fourfold increase in surgery rates and a substantial risk of postoperative permanent work disability that remained constant over time. The risk was related to education level. These findings suggest that indications for surgery may need to be revisited and that attention should be given to supporting return to work, especially for blue-collar workers.

The influence of dietary ß-glucan, PAMP exposure and Aeromonas salmonicida on apoptosis modulation in common carp (Cyprinus carpio).

The association between ß-glucan (MacroGard®) supplemented feed and apoptosis in immune-related organs of common carp (Cyprinus carpio) was studied using fluorescence microscopy and real-time PCR. In addition the effect of Aeromonas salmonicida, LPS and Poly(I:C) injections on this relationship was evaluated. Whilst acridine orange staining revealed that apoptosis levels were independent of MacroGard® and LPS/Poly(I:C) administration or their combination, it was shown that injection with A. salmonicida increased the percentage of apoptotic cells irrespective of the feeding regime. It was apparent that in all the treatments gene expression profiles displayed organ and time dependency. For example no effect was observed at 7 days of MacroGard® administration while 25 days of feeding led to increased iNOS expression and differential up-regulation of anti- or pro-apoptotic genes depending on organ. This may indicate differences in NO sensitivity. MacroGard® also led to an elevation of pro- as well as anti-apoptotic genes in LPS or Poly(I:C) injected fish, while LPS/Poly(I:C) alone had little effect. A. salmonicida caused enhanced iNOS expression and it is possible that the type of apoptosis pathway induced is organ dependent as Caspase 9 is induced in mid-gut but not in pronephros. These results indicate that MacroGard® feeding alone or in combination with other pathogenic factors did not induce significant apoptosis in immune organs.

Inguinal hernia repair among men: development and validation of a preoperative risk score for persistent postoperative pain.

PURPOSE: Persistent postoperative pain (PPP) is a prevalent complication after inguinal hernia repair. The aim of this study was to develop and validate a preoperative risk score for PPP. METHODS: We developed the risk score based on a cohort of 2,508 Danish men, who answered a questionnaire six months after inguinal hernia repair performed 2015-2016. PPP was defined as a numerical rating scale score ≥ 2 during activity six months postoperatively. Logistic regression analyses were undertaken to determine statistically significant predictors of PPP. Univariable analysis selected potential predictors with a p value ≤ 0.20, and a subsequent multivariable model was built using backward elimination with a criterion of p value < 0.10. We created a risk score based on the ß coefficients of the multivariable model. The risk score was validated internally using Hosmer-Lemeshow goodness of fit test, calibration belt test, and receiver operating characteristic curve analyses with 95% confidence intervals based on the bootstrap analysis. External validation was performed in a cohort of 293 men recruited preoperatively. RESULTS: Predictors of PPP were age 18-49 and 50-59 (versus ≥ 60) years (p < 0.001), total load lifted > 1,000 kg/day (p = 0.001), working in a bent-over position > 1 h/day (p < 0.001), leisure-time physical activity < 2 h/week (p = 0.009), increasing body mass index (per unit) (p < 0.003), and repair of recurrent hernia (p = 0.001).The preoperative risk score predicted risks of 6-61% in the development population. The model showed good internal and external validity. CONCLUSION: The results suggest that the risk of PPP after inguinal hernia repair can be predicted using a preoperative risk score.

Combinatorial chemoprevention of intestinal neoplasia.

A combination of two drugs afforded remarkable protection from intestinal neoplasia in APC(Min/+) mice, a murine model of human familial adenomatous polyposis (FAP). One of the drugs was sulindac, a prototypical non-steroidal anti-inflammatory drug with established chemopreventative activity. The second drug was EKI-569, a newly developed, irreversible inhibitor of the epidermal growth factor receptor kinase. Although 100% of the untreated APC(Min/+) mice developed approximately 20 polyps, nearly half the mice treated with these two agents developed no polyps at all. These results suggest a powerful strategy for the chemoprevention of human colonic neoplasia.

Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination.

Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark for the use of DNA vaccine technology for the production of protective immune responses.

A comparative study of marine salmonid alphavirus subtypes 1-6 using an experimental cohabitation challenge model.

A comparative challenge study of six marine isolates representing subtypes 1-6 of salmonid alphavirus (salmon pancreas disease virus, Genus Alphavirus, Family Togaviridae) was conducted in Atlantic salmon in a fresh water cohabitation trial. Histopathological lesions typical of pancreas disease were observed with all subtypes, and virus was re-isolated from serum of cohabitant fish in each case. Using a virus neutralization (VN) test neutralizing salmonid alphavirus (SAV) subtype 1 strain F93-125, VN antibodies were detected in all challenge groups, consistent with serological cross-reactivity between these subtypes. Using real-time RT-PCR, SAV RNA was detected in heart tissue from 2 to 3 weeks post-challenge (wpc) in all cohabitant groups excluding controls. The results obtained suggested differences in the dynamics of infection between strains of SAV and potentially between subtypes. Results for SAV subtypes 1 and 3 suggested essentially synchronous infection of cohabitant fish. These two study groups also had the highest virus load in heart tissue as measured by quantitative RT-PCR and also had the most extensive histopathological changes. In contrast, results for SAV subtypes 2 and 6 strains were consistent with asynchronous infection in the cohabitant fish and were characterized by slow spread, low virus loads and mild histopathological changes. The SAV subtype 4 and 5 strains occupied an intermediate position in this regard. Despite the use of concentration procedures, it was not possible to detect SAV RNA in water samples from selected study tanks. However, testing of faeces from the SAV subtypes 1, 3 and 6 challenge groups found positive signals in each beginning at 1-3 wpc and remaining detectable for a further 2-3 weeks. Parallel testing of mucus samples found these became positive at 2-3 wpc and remained positive for a further 1-3 weeks. These results demonstrate for the first time that shedding and transmission of virus may occur by both these routes and suggest that dispersal in these matrices should be included in any disease transmission models.

Selection of strongly immunogenic "tum-" variants from tumors at high frequency using 5-azacytidine.

Highly immunogenic "tum-" (non-tumorigenic in normal syngeneic hosts) clonal variants can be selected from a variety of poorly immunogenic and highly tumorigenic mouse cell lines at very high frequencies (e.g., greater than 80%) after treatment in vitro with chemical mutagens such as ethyl methanesulfonate (EMS) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We herein demonstrate that the same result can be obtained with the poorly mutagenic cytidine analogue, 5-azacytidine, a strong DNA hypomethylating agent. 5-Azacytidine and EMS were equally and comparably effective, or ineffective, in inducing tum- variants from three different highly tumorigenic mouse cell lines. Like mutagen-induced tum- variants, those obtained after 5-azacytidine treatment generated usually strong cytolytic T lymphocyte (CTL) responses in vitro, and could grow in immunosuppressed (nude mouse) hosts. However, pretreatment of the tumor cell lines with 5-azacytidine did not cause significant increases in mutations at several independent drug-resistant gene loci, whereas EMS did. It is known that treatment of cells with 5-azacytidine can induce transcriptional activation of "silent" genes through a reduction of DNA 5-methylcytosine content, a process that can also be effected by mutagenic DNA alkylating agents such as EMS and MNNG. We therefore hypothesize that an "epigenetic" mechanism (DNA hypomethylation) leading to activation and expression of genes coding for potential tumor antigens is involved in the generation at high frequency of tum- variants after "mutagen" treatment. The implications of these findings to mechanisms of tumor progression and the generation of tumor heterogeneity are discussed.

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.

Responses of alkaline phosphatase activity to phosphorus stress in Daphnia magna.

We examined how alkaline phosphatase (AP) activity within the bodies and in the materials released by the crustacean Daphnia magna responds to variable algal food phosphorus (P)-content. We found that Daphnia eating P-poor food (C:P approximately 700) had significantly higher AP activity in their bodies on a mass-specific basis compared with individuals eating P-rich food (C:P approximately 100). This dietary P effect on AP activity was not altered by Daphnia starvation but was partially related to differences in the P concentration of animal body homogenates. By contrast, poor P-nutrition of Daphnia lowered AP activity in released materials compared with that measured from their P-sufficient conspecifics. Moreover, AP activity in Daphnia release was lowest in animals consuming P-poor food for longer time periods. Our results support the hypothesis that AP activity increases inside P-limited Daphnia as a mechanism to increase P-acquisition and retention from ingested algae in these nutritionally stressed animals. The lower level of AP activity present in the water of P-deprived animals could reflect a change from largely free to membrane-bound AP isotypes in the digestive tracts of P-starved animals or a decrease in the shedding of membrane-anchored AP from their intestinal lining. These results supplement accumulating evidence that P-poor algal food reduces the dietary mineral P available to Daphnia. In addition, animal body AP activity measurements, with some refinement, may prove useful as an in situ indicator of P-stress in aquatic consumers.

Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors.

Colorectal (CR) tumors are usually curable if detected before metastasis. Because genetic alterations are associated with the development of these tumors, mutant genes may be found in the stool of individuals with CR neoplasms. The stools of nine patients whose tumors contained mutations of K-ras were analyzed. In eight of the nine cases, the ras mutations were detectable in DNA purified from the stool. These patients included those with benign and malignant neoplasms from proximal and distal colonic epithelium. Thus, colorectal tumors can be detected by a noninvasive method based on the molecular pathogenesis of the disease.

Identification of p53 gene mutations in bladder cancers and urine samples.

Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene products. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.

Fetal blood sampling in baboons (Papio spp.): important procedural aspects and literature review.

BACKGROUND: The baboons (Papio cynocephalus) have similarities with human placentation and fetal development. Fetal blood sampling allows investigators to assess fetal condition at a specific point in gestation as well as transplacental transfer of medications. Unfortunately, assessing fetal status during gestation has been difficult and fetal instrumentation associated with high rate of pregnancy loss. Our objectives are to describe the technique of ultrasound guided cordocentesis (UGC) in baboons, report post-procedural outcomes, and review existing publications. METHODS: This is a procedural paper describing the technique of UGC in baboons. After confirming pregnancy and gestational age via ultrasound, animals participating in approved research protocols that required fetal assessment underwent UGC. RESULTS: We successfully performed UGC in four animals (five samples) using this technique. Animals were sampled in the second and third trimesters with fetal blood sampling achieved by sampling a free cord loop, placental cord insertion site or the intrahepatic umbilical vein. All procedures were without complication and these animals delivered at term. CONCLUSIONS: Ultrasound guided fetal umbilical cord venipuncture is a useful and safe technique to sample the fetal circulation with minimal risk to the fetus or mother. We believe this technique could be used for repeated fetal venous blood sampling in the baboons.

AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and VEGF expression in multiple myeloma cells.

We recently demonstrated that the mammalian target of rapamycin (mTOR) inhibitor, CCI-779, curtailed the growth of a subcutaneous challenge of multiple myeloma (MM) cells in immunodeficient mice. This antitumor effect was associated with prevention of cell proliferation, induction of apoptosis and inhibition of angiogenesis. Interestingly, myeloma tumors with heightened AKT activation were particularly sensitive to a CCI-779-induced antitumor response. To investigate whether part of the differential sensitivity was due to an AKT-regulated effect on angiogenesis, we compared the effects of mTOR inhibitors against isogenic MM cell lines that only differ by their degree of AKT activity. In this model, heightened AKT activity significantly sensitized MM cells to the following inhibitory effects of mTOR inhibition: angiogenesis in vivo, vascular endothelial growth factor (VEGF) expression in vitro and in vivo and VEGF translation (but not transcription). Assessment of p70S6 kinase activity indicated that rapamycin induced comparable mTOR inhibition in both cell lines suggesting that an adverse effect on VEGF cap-dependent translation would be comparable. Internal ribosome entry site (IRES)-mediated cap-independent translation is a salvage pathway for protein expression when mTOR is inhibited, so we analyzed a possible regulatory role of AKT on VEGF IRES activity. We found that elevated AKT activity inhibited VEGF IRES function. These results support a mechanism whereby AKT prevents VEGF IRES activity in myeloma cells during mTOR inhibition resulting in a more complete abrogation of VEGF translation, and ultimately, angiogenesis.

Effects of dietary cholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men.

The individual effects of dietary cholesterol and fat saturation on plasma lipoprotein concentrations were determined in an ethnically diverse population of normolipidemic young men (52 Caucasian, 32 non-Caucasian). The experimental diets contained approximately 200 or 600 mg/d of cholesterol, 36-38% of calories as fat, and high or low proportions of saturated and polyunsaturated fat (polyunsaturated/saturated fat ratio approximately 0.8 vs 0.3). At the lower cholesterol intake, the high saturated fat diet had only a modest effect on LDL cholesterol in Caucasians (+ 6 mg/dl-1) and none in non-Caucasians. 600 mg cholesterol with high saturated fat led to a substantial mean increase in LDL cholesterol, which was significantly greater in Caucasian than in non-Caucasian subjects (+ 31 mg/dl vs 16 mg/dl, P < 0.005). 600 mg cholesterol with increased polyunsaturated fat gave a mean LDL increase of 16 mg/dl, lower than found when the same high cholesterol intake was coupled with increased saturated fat. Variation in cholesterol rather than the proportions of saturated and polyunsaturated fat had the most influence on LDL-cholesterol levels. Among non-Caucasians it was the only significant factor.

Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity.

Detection of new ligand-defective mutations of apolipoprotein B (apoB) will enable identification of sequences involved in binding to the LDL receptor. Genomic DNA from patients attending a lipid clinic was screened by single-strand conformation polymorphism analysis for novel mutations in the putative LDL receptor-binding domain of apoB-100. A 46-yr-old woman of Celtic and Native American ancestry with primary hypercholesterolemia (total cholesterol [TC] 343 mg/dl; LDL cholesterol [LDL-C] 241 mg/dl) and pronounced peripheral vascular disease was found to be heterozygous for a novel Arg3531-->Cys mutation, caused by a C-->T transition at nucleotide 10800. One unrelated 59-yr-old man of Italian ancestry was found with the same mutation after screening 1,560 individuals. He had coronary heart disease, a TC of 310 mg/dl, and an LDL-C of 212 mg/dl. A total of eight individuals were found with the defect in the families of the two patients. They had an age- and sex-adjusted TC of 240 +/- 14 mg/dl and LDL-C of 169 +/- 10 mg/dl. This compares with eight unaffected family members with age- and sex-adjusted TC of 185 +/- 12 mg/dl and LDL-C of 124 +/- 12 mg/dl. In a dual-label fibroblast binding assay, LDL from the eight subjects with the mutation had an affinity for the LDL receptor that was 63% that of control LDL. LDL from eight unaffected family members had an affinity of 91%. By way of comparison, LDL from six patients heterozygous for the Arg3500-->Gln mutation had an affinity of 36%. The percentage mass ratio of the defective Cys3531 LDL to normal LDL was 59:41, as determined using the mAb MB19 and dynamic laser light scattering. Thus, the defective LDL had accumulated in the plasma of these patients. Using this mass ratio, it was calculated that the defective Cys3531 LDL particles bound with 27% of normal affinity. Deduced haplotypes using 10 apoB gene markers showed the Arg3531-->Cys alleles to be different in the two kindreds and indicates that the mutations arose independently. The Arg3531-->Cys mutation is the second reported cause of familial ligand-defective apoB.

Risk factors for hand-wrist disorders in repetitive work.

OBJECTIVES: To identify the risk of hand-wrist disorders related to repetitive movements, use of hand force and wrist position in repetitive monotonous work. METHODS: Using questionnaires and physical examinations, the prevalence and incidence of hand-wrist pain and possible extensor tendonitis (wrist pain and palpation tenderness) were determined in 3123 employees in 19 industrial settings. With the use of questionnaires and video recordings of homogenous work tasks number of wrist movements, hand force requirements and wrist position were analysed as risk factors for hand-wrist disorders, controlling for potential personal and psychosocial confounders. All participants were re-examined three times during a follow-up period of three years. RESULTS: Force but not repetition and position was related to hand-wrist pain and possible tendonitis in the baseline analyses showing an exposure-response pattern. Odds ratios for the risk of hand pain was 1.7 (95% CI 1.3 to 2.2) and for possible tendonitis 1.9 (95% CI 1.1 to 3.3). There was no significant interaction between the ergonomic factors. In the follow-up analyses force remained a risk factor for hand pain (OR 1.4, 95% CI 1.1 to 1.8) and for possible tendonitis (OR 2.9, 95% CI 1.3 to 6.8). Repetition was also a risk factor for the onset of hand-wrist pain (OR 1.6, 95% CI 1.2 to 2.3). CONCLUSIONS: Increasing levels of force were associated with prevalent and incident hand-wrist pain and possible extensor tendonitis. The results for repetition were less consistent. Working with the hand in a non-neutral position could not be identified as a risk factor.