Validity of the Dictionary of Occupational Titles for Assessing Upper Extremity Work Demands

Objectives: The Dictionary of Occupational Titles (DOT) is used in vocational rehabilitation to guide decisions about the ability of a person with activity limitations to perform activities at work. The DOT has categorized physical work demands in five categories. The validity of this categorization is unknown. Aim of this study was to investigate whether the DOT could be used validly to guide decisions for patients with injuries to the upper extremities. Four hypotheses were tested. Methods: A database including 701 healthy workers was used. All subjects filled out the Dutch Musculoskeletal Questionnaire, from which an Upper Extremity Work Demands score (UEWD) was derived. First, relation between the DOT-categories and UEWD-score was analysed using Spearman correlations. Second, variance of the UEWD-score in occupational groups was tested by visually inspecting boxplots and assessing kurtosis of the distribution. Third, it was investigated whether occupations classified in one DOT-category, could significantly differ on UEWD-scores. Fourth, it was investigated whether occupations in different DOT-categories could have similar UEWD-scores using Mann Whitney U-tests (MWU). Results: Relation between the DOT-categories and the UEWD-score was weak (r(sp) = 0.40; p < .01). Overlap between categories was found. Kurtosis exceeded +/- 1.0 in 3 occupational groups, indicating large variance. UEWD-scores were significantly different within one DOT-category (MWU = 1.500; p < .001). UEWD scores between DOT-categories were not significantly different (MWU = 203.000; p = .49). Conclusion: All four hypotheses could not be rejected. The DOT appears to be invalid for assessing upper extremity work demands

Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz in treatment naive HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2011-2012

Background: Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients. Methods: A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load <40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal, skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians. Results: Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42 patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant increase (172 cells/mm3) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of the percentage of cardiovascular risk. Conclusions: The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary ARV drugs. Trial registration: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202. Registered 19 November 2015.This research was made possible by contribution from the Corporación de Lucha Contra el SIDA, Cali-Colombia, and Comité para el Desarrollo de la Investigación (CODI), Universidad de Antioquia, Medellín, Colombia. In addition, Humax Pharmaceutical S.A. provided the antiretroviral drugs

Identification of Mammalian Protein Quality Control Factors by High-Throughput Cellular Imaging

Protein Quality Control (PQC) pathways are essential to maintain the equilibrium between protein folding and the clearance of misfolded proteins. In order to discover novel human PQC factors, we developed a high-content, high-throughput cell-based assay to assess PQC activity. The assay is based on a fluorescently tagged, temperature sensitive PQC substrate and measures its degradation relative to a temperature insensitive internal control. In a targeted screen of 1591 siRNA genes involved in the Ubiquitin-Proteasome System (UPS) we identified 25 of the 33 genes encoding for 26S proteasome subunits and discovered several novel PQC factors. An unbiased genome-wide siRNA screen revealed the protein translation machinery, and in particular the EIF3 translation initiation complex, as a novel key modulator of misfolded protein stability. These results represent a comprehensive unbiased survey of human PQC components and establish an experimental tool for the discovery of genes that are required for the degradation of misfolded proteins under conditions of proteotoxic stress

Ecological phytochemistry of Cerrado (Brazilian savanna) plants

The Cerrado (the Brazilian savanna) is one of the vegetation formations of great biodiversity in Brazil and it has experienced strong deforestation and fragmentation. The Cerrado must contain at least 12,000 higher plant species.We discuss the ecological relevance of phytochemical studies carried out on plants from the Cerrado, including examples of phytotoxicity, antifungal, insecticidal and antibacterial activities. The results have been classified according to activity and plant family. The most active compounds have been highlighted and other activities are discussed. A large number of complex biochemical interactions occur in this system. However, only a small fraction of the species has been studied from the phytochemical viewpoint to identify the metabolites responsible for these interactions

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature

Salivary Gland Disorders and Diseases

Saliva plays an important role in maintaining healthy oral mucosa and teeth as well as oral function by continually covering and lubricating the oral tissues. Salivary gland dysfunction designates decreased saliva flow rate (salivary gland hypofunction), increased saliva flow rate (sialorrhea or hypersalivation), and changed saliva composition. Xerostomia (the subjective feeling of oral dryness) is often associated with salivary gland hypofunction and may severely affect nutritional intake, social interaction and quality of life. Local or systemic disorders and diseases are common causes of compromised saliva secretion. Some of these are related to gland pathology or to the pathophysiological conditions of the host, whereas others affect the gland innervation or are an iatrogenic result of treatment of a disease (e.g., radiation therapy for head and neck cancer, side effects of medications). In general, many patients suffering from diseases that influence salivary gland function also undergo treatments that may impair saliva secretion and/or induce xerostomia as an adverse effect. Consequently, it can be difficult to distinguish what can be attributed to the disease per se or what can be induced by treatment (e.g., medication intake). Thus, a thorough diagnostic workup and early diagnosis of salivary gland dysfunction are crucial to provide appropriate evidence-based treatment of salivary gland dysfunction to prevent oral sequelae and to initiate individualized alleviating management strategies of xerostomia.</p

Impairment and employment issues after nerve repair in the hand and forearm

Purpose. To evaluate retrospectively subjective impairments, experienced disabilities, job and leisure restrictions and job changes in patients at least 2 years after repair of a peripheral nerve injury in the forearm, wrist or hand. Methods. Between January 1997 and January 2000, 125 patients were treated surgically for a peripheral nerve injury in the hand and forearm at the Department of Plastic Surgery of a University Hospital. Sixty-one patients met the inclusion criteria. Using a questionnaire the ability to return to work (RTW), the possible consequences on Activities of Daily Life (ADL) and Instrumental Activities of Daily Life (IADL), job, hobby and housekeeping related disabilities and subjective pain were assessed. Results. Forty of the 61 included patients returned the questionnaire. As a result of the injury, seven patients (19%) were not able to return to their own job and eight patients (20%) needed to quit or change their hobbies. Mean Time Off Work (TOW) was significantly longer (p = 0.024) in non-digital nerve lesions (21.4 weeks) as compared to digital nerve lesions (9.5 weeks). Conclusions. From this study it was concluded that digital nerve lesions have little consequence on the ability to return to work and the time off work. However, the patients' hobbies are significantly affected. At least 2 years after the injury, the effects on ADL and IADL are minor