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).

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.

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.

Occupational mechanical exposures and reoperation after first-time inguinal hernia repair: a prognosis study in a male cohort.

PURPOSE: The aim of this study was to evaluate exposure-response relationships between occupational mechanical exposures and risk of reoperation after inguinal hernia repair. METHODS: Using register information, we identified all men born in Denmark 1938-1988, who had their first inguinal hernia repair 1998-2008, and who were 18-65 years old and active in the labour market at the time of surgery. The Danish Hernia Database provided information on repairs and reoperations. We used registered occupational codes and a job exposure matrix based on experts' ratings to estimate total load lifted per day, frequency of heavy lifting, and number of hours per day spent standing/walking. We also obtained register information on sickness absence. Multivariable Cox regression analysis was used. RESULTS: The cohort comprised 34,822 patients. We did not reveal exposure-response relationships between occupational mechanical exposures and the hazard ratio (HR) of reoperation. The percentage of patients with >2 weeks of sickness absence within 8 weeks after surgery increased with total load lifted per day from 15 to 53%. Longer sickness absence was associated with an increased HR of reoperation, but within strata of sickness absence, we found no increase in the HR of reoperation with increasing exposures. CONCLUSION: We did not find indications that the HR of reoperation was related to occupational mechanical exposures, even after accounting for a potential protective effect of sickness absence. Hence, the exposure-related prolonged duration of sickness absence could not be explained by exposure-related complications that led to reoperation.

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel ß3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.

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.

MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells.

When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle proteins like c-myc, continuing tumor cell growth depends on cap-independent translation, which is mediated by internal ribosome entry sites (IRESes) located in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. In a RAP-resistant MM cell lines as well as a resistant primary MM specimen, co-exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP-induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors.

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.

Computer use and ulnar neuropathy: results from a case-referent study.

We aimed to evaluate associations between vocational computer use and 1) ulnar neuropathy, and 2) ulnar neuropathy- like symptoms as distinguished by electroneurography. We identified all patients aged 18-65 years, examined at the Department of Neurophysiology on suspicion of ulnar neuropathy, 2001-2007. We mailed a questionnaire to 546 patients with ulnar neuropathy, 633 patients with ulnar neuropathy-like symptoms, and three community referents per case, matched on sex, age, and primary care centre. From a Job Exposure Matrix we extracted estimates of daily hours of computer use. The analysis was performed by conditional logistic regression.There were a negative association between daily hours of computer use and the two outcomes of interest. Participants who reported their elbow to be in contact with their working table for 2 hours or more during the workday had an elevated risk for ulnar neuropathy (OR=2.16, 95 % CI; 1.06-4.44).The two outcomes were not associated with daily hours of computer use. Findings suggested specific effects of pressure on the elbow, and might be an explanation for the overweight of left-sided outcomes in this primarily right-handed group. Preventive efforts would then be straightforward by providing appropriate arm support for the left arm and elbow.

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.

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.

Boerhaave's syndrome - rapidly evolving pleural effusion; a radiographic clue.

Boerhaave's syndrome is the rare and often fatal condition of spontaneous esophageal rupture. Meckler's triad of vomiting, pain and subcutaneous emphysema are characteristic features of Boerhaave's syndrome. When these symptoms are absent, diagnosis is frequently late and often occurs as the result of incidental investigation. This contributes to the observed high morbidity and mortality. Unless specifically considered in the differential diagnosis, this rare disease is frequently overlooked. The authors described the case of a patient in whom the diagnosis was made several days following presentation by observing that a large pleural effusion had evolved rapidly on chest radiographs. This uncommon radiological sign has relatively few causes and prompted a review of the history and diagnosis, followed by the initiation of additional investigations that confirmed Boerhaave's syndrome.

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.

Feto-placental adaptations to maternal obesity in the baboon.

Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.