Long COVID and return to work: a qualitative study.

BACKGROUND: The COVID-19 pandemic has given rise to an increasing number of patients with 'long COVID'. Long COVID is the persistence of symptoms for weeks or months after an infection by SARS-CoV-2. It often impacts on the professional life of affected people. AIMS: The aim of this study is to understand the experiences and needs of people with long COVID in relation to their return to work. METHODS: A qualitative study, combining individual interviews and online forum discussions, was performed early 2021, as part of a larger mixed method study on the needs of long COVID patients in Belgium. RESULTS: One hundred and thirty-four people participated in the study. Participants described various clinical symptoms precluding their return to work. They also face sceptical reactions from employers and colleagues and a lack of support from the social welfare system to facilitate their return to work. These barriers have various impacts, including psychological ones, likely to compromise the professional future of long COVID patients. CONCLUSIONS: While the analysis of patients' experiences shows variation in long COVID patients' experiences with return to work, it may help occupational physicians and healthcare practitioners to better take up their crucial role in the return to work of long COVID patients, including raising employers' and colleagues' awareness of the specific difficulties related to long COVID.

[Somatic care in psychiatry : barriers perceived by patients and health professionals]. / Soins de santé somatiques en psychiatrie : barrières perçues par les patients et les professionnels de la santé.

Disparities in access to, use of and delivery of somatic health care contribute to widening gaps in morbidity and mortality between psychiatric patients and the general population. We conducted a qualitative semi-structured interview study with psychiatric patients and health professionals from different psychiatric care settings to understand these poor physical health outcomes. Optimal somatic follow-up of patients with severe mental illness seems to be hampered by (1) provider-related elements (attitude, training, experiences); (2) organisational aspects (equipment, infrastructure, staff, pharmacy, communication networks); (3) psychiatric patient-related elements and (4) financial barriers.There is an urgent need for integrated somatic and psychiatric health care systems and for cultural change. Psychiatrists and somatic health care providers continue to view the mental and physical health of their patients as mutually exclusive responsibilities. A range of system changes will improve the quality of somatic health care for these vulnerable patients.

Les disparités dans l'accès, l'utilisation et la prestation des soins de santé somatiques contribuent à creuser les écarts de morbidité et mortalité entre patients psychiatriques et la population générale. Nous avons mené une étude qualitative par entretiens semi-structurés auprès de patients psychiatriques et de professionnels de santé de différents lieux de soins psychiatriques afin de comprendre ces mauvais résultats en matière de santé physique. Le suivi somatique optimal des patients atteints d'une maladie mentale sévère semble entravé par des éléments : (1) liés aux prestataires de soins (attitude, formation, expériences); (2) en relation avec des aspects organisationnels (équipement, infrastructure, personnel, pharmacie, réseaux de communication); (3) inhérents aux caractéristiques des patients psychiatriques et (4) représentés par des obstacles financiers. Il est urgent de mettre en place des systèmes de soins de santé somatiques et psychiatriques intégrés et d'entamer un changement culturel. Les psychiatres et les prestataires de soins somatiques continuent de considérer la santé mentale et la santé physique de leurs patients comme des responsabilités mutuellement exclusives. Un changement de paradigme tendant vers une meilleure intégration permettra d'améliorer la qualité des soins de santé somatiques pour ces patients vulnérables.

[Anterior cruciate ligament injury in adults : Diagnostics and treatment]. / Verletzung des vorderen Kreuzbandes beim Erwachsenen : Diagnostik und Therapie.

The anterior cruciate ligament (ACL) together with the posterior cruciate ligament is the central stabilizer of the knee. It stabilizes the tibia against increased anterior translation and internal rotation. With an incidence of 46/100,000 ACL tears are among the most common sports injuries in Germany. New prevention programs can reduce the risk of ACL injuries. Surgical treatment is recommended for young and athletic patients as it can also reduce the risk of further relevant injuries of the meniscus and cartilage. The standard of surgical treatment in Germany is the ACL reconstruction with an autologous tendon graft. In selected cases, the preservation of the ACL by arthroscopic refixation shows good results. Instead of the previously used purely time-based rehabilitation, function-based criteria are increasingly being included in the aftercare.

Multidisciplinary work in oncology: Population-based analysis for seven invasive tumours.

The concept of multidisciplinary team meetings (MDTs) in cancer care is endorsed internationally, but its uptake varies considerably. In Belgium, MDT meetings were financially recognised in 2003 to encourage healthcare professionals to join their knowledge and competences to improve the quality and coordination of cancer care. This study aimed to evaluate for seven cancer types diagnosed between 2004 and 2011, the practices of MDT meetings in Belgium by means of population-based administrative databases. Results show a clear increase over time in the proportion of individual patients discussed at MDT meetings. Although this evolution may be partly explained by the legal implementation of several financial initiatives to stimulate MDT meetings, it also suggests an increase in specialists' awareness of the importance of such meetings. Nevertheless, there is still room for improvement, for specific cancer types as well as for certain subgroups such as older patients. From the specialists' point of view, reducing the administrative burden and time these meetings demand may entail a greater participation to MDT meetings. Further research is needed to identify the barriers to discuss more patients at MDT meetings and to elucidate the impact of MDT meetings on the quality of cancer care.

[Operative treatment of cartilage lesions]. / Operative Therapie von Knorpelschäden.

Cartilage damage is often associated with pain, reduced quality of life and decreased physical performance. In addition, even small cartilage lesions can lead to osteoarthritis. Since young active people are particularly affected, the correct treatment of cartilage damage plays an important role. Operative treatment includes bone marrow-stimulating procedures with or without a matrix, cell-based procedures and osteochondral graft transplantation. The choice of the best procedure depends on the localization, the size and the extent of the cartilage damage. In addition, especially in the treatment of cartilage damage to the lower limbs, the leg axis and loading relationships should be taken into account and possibly treated as well as additional joint instabilities. The following article gives an overview of the available surgical treatment possibilities as well as the correct indications and implementation. It also gives a brief projection of possible further treatment options associated with stem cells.

[Breast cancer screening : a tool for informed decision making]. / Dépistage du cancer du sein : un outil pour aider les femmes à prendre une décision éclairée.

INTRODUCTION: Our population has an intuitive approach of the screening and is mostly enthusiastic to participate. The related inquiries on breast cancer screening shows that most women misunderstood this advantages as well as disadvantages. Consequently, the Kenniscentrum (Brussels) started a study in order to present those in neutral messages. METHODOLOGY: This aims allowing women to make an informed decision. These messages are obviously based on the best methodologies applied on Belgian data. The content of these messages is especially based on the IPDAS criteria (international Patient Decision Aid Standards). RESULTS: Three visual graphical presentations including these messages were designed for four age brackets (40-49 y.,50-59 y.,60-69 y., 70-79 y.). The first visual presents the burden of breast cancer among other causes of death. The second is related to the impact of screening or no screening on detection and on mortality, this one computed over the ten years after the screening. The third visual shows consequences (positive or negative result, eventual additional investigations needed) of each mammography at short or mid-term. DISCUSSION: This tool can be used in the context of informed decision or shared decision making. This tool is in the public domain and can be downloaded, in French or Dutch, on KCE (https://kce.fgov.be, tab breast).

INTRODUCTION: Notre population a une approche intuitive du dépistage et se montre la plupart du temps enthousiaste à l'idée de se faire dépister. Les enquêtes effectuées auprès des femmes témoignant d'une méconnaissance tant des avantages que des désavantages du dépistage du cancer du sein, le Centre fédéral d'Expertise des Soins de Santé (KCE, Bruxelles) a entrepris une étude ayant pour objectif de présenter ceux-ci sous forme de messages neutres. Méthodologie : Cette étude a pour objectif de permettre aux femmes de prendre une décision éclairée. Ces messages sont basés sur les meilleures méthodologies appliquées aux données belges. Le développement du contenu des messages est notamment inspiré des critères IPDAS (International Patient Decision Aid Standards). Résultats : Trois présentations visuelles intégrant ces messages ont été élaborées pour quatre tranches d'âge (40-49 ans, 50-59 ans, 60-69 ans, 70- 79 ans). Le premier visuel présente le poids du cancer du sein parmi les autres causes de mortalité. Le deuxième visuel illustre les conséquences du dépistage ou du non-dépistage sur la détection du cancer et sur la mortalité, celle-ci étant calculée pour la période des dix années qui suivent le dépistage. Le troisième visuel illustre les conséquences (examen positif ou négatif, examens complémentaires éventuels) de chaque mammographie à court ou moyen terme. DISCUSSION: Cet outil est utilisable dans le cadre d'une prise de décision éclairée, tout comme dans celui d'une décision médicale partagée. Il est dans le domaine public et téléchargeable en français et en néerlandais sur le site du KCE (https:// kce.fgov.be, onglet sein).

Alignment does not influence cartilage T2 in asymptomatic knee joints.

PURPOSE: To investigate whether the static knee alignment affects articular cartilage ultrastructures when measured using T2 relaxation among asymptomatic subjects. METHODS: Both knee joints (n = 96) of 48 asymptomatic volunteers (26 females, 22 males; 25.4 ± 1.7 years; no history of major knee trauma or surgery) were evaluated clinically (Lysholm, Tegner) and by MRI (hip-knee-ankle angle, standard knee protocol, T2 mapping). Group (n = 4) division was as follows: neutral (<1° varus/valgus), mild varus (2°-4° varus), severe varus (>4° varus) and valgus (2°-4° valgus) deformity with n = 12 subjects/group; n = 24 knees/group. Regions of interest (ROI) for T2 assessment were placed within full-thickness cartilage across the whole joint surface and were divided respecting compartmental as well as functional joint anatomy. RESULTS: Leg alignment was 0.7° ± 0.5° varus among neutral, 3.0° ± 0.6° varus among mild varus, 5.0° ± 1.1° varus among severe varus and 2.5° ± 0.7° valgus among valgus group subjects and thus significantly different. No differences between the groups emerged from clinical measures. No morphological pathology was detected in any knee joint. Global T2 values (42.3 ± 2.3; 37.7-47.9 ms) of ROIs placed within every knee joint per subject were not different between alignment groups or between genders, respectively. CONCLUSION: Static frontal plane leg malalignment does not affect cartilage ultrastructure among young, asymptomatic individuals as measured by T2 quantitative imaging. LEVEL OF EVIDENCE: Cross-sectional study, Level II-III.

Age does not influence the clinical outcome after high tibial osteotomy.

PURPOSE: Valgus high tibial osteotomy (HTO) is an established procedure for the medial gonarthrosis. In several studies, many negative influencing factors were evaluated. However, until now, the factor "age" was examined only insufficiently. The aim of our study was to evaluate the factor age in predicting the functional outcome after HTO, and we hypothesized that valgus HTO leads to equal results in the treatment of varus osteoarthritis independent of the patient's age. METHODS: We could generate 13 pairs of patients with a median age at operation of 57 (55-63) years (group A) versus patients 15 years younger with a median age of 42 (39-47) years (group B). The patients were matched according to the following criteria: age, gender, operation/osteosynthesis method, body mass index, same additional operations, and follow-up time. Evaluation of the patients was done by use of the Tegner and Lysholm score and visual analogue scale (VAS) as well as by subjective satisfaction of the patients. RESULTS: The Lysholm score showed a significant improvement in group A from 41 (SD ± 12.3) to 65 (SD ± 23.8) points (p = 0.01) and in group B from 33 (SD ± 16.7) to 70 (SD ± 31.8) points (p = 0.007). Moreover, the VAS decreased significantly in group A from 77 (SD ± 15.3) to 36 (SD ± 21.3) points (p = 0.003) and in group B from 73 (SD ± 22.7) to 41 (SD ± 33.7) points (p = 0.02). However, there was no significant difference for both groups regarding the activity of the patients evaluated by the Tegner score (group A: preop.: 5 (1-9), follow-up: 3.5 (1-6); group B: preop.: 6 (3-9), follow-up: 4 (2-7)). Furthermore, there was no significant difference between both groups in view of the Lysholm, Tegner and VAS. CONCLUSION: Valgus high tibial osteotomy is an effective procedure for the treatment of medial gonarthrosis independent of the patient's age. As a consequence, the age of the patient does not have to be taken into consideration for the indication of high tibial osteotomy. LEVEL OF EVIDENCE: III.

In vitro antiviral activity of Brazilian plants (Maytenus ilicifolia and Aniba rosaeodora) against bovine herpesvirus type 5 and avian metapneumovirus.

CONTEXT: Medicinal plants are well known for their use in traditional folk medicine as treatments for many diseases including infectious diseases. OBJECTIVE: Six Brazilian medicinal plant species were subjected to an antiviral screening bioassay to investigate and evaluate their biological activities against five viruses: bovine herpesvirus type 5 (BHV-5), avian metapneumovirus (aMPV), murine hepatitis virus type 3, porcine parvovirus and bovine respiratory syncytial virus. MATERIALS AND METHODS: The antiviral activity was determined by a titration technique that depends on the ability of plant extract dilutions (25 or 2.5 µg/mL) to inhibit the viral induced cytopathic effect and the extracts' inhibition percentage (IP). RESULTS: Two medicinal plant species showed potential antiviral activity. The Aniba rosaeodora Ducke (Lauraceae) extract had the best results, with 90% inhibition of viral growth at 2.5 µg/mL when the extract was added during the replication period of the aMPV infection cycle. The Maytenus ilicifolia (Schrad.) Planch. (Celastraceae) extracts at a concentration of 2.5 µg/mL exhibited antiviral activity during the attachment phase of BHV-5 (IP = 100%). DISCUSSION AND CONCLUSION: The biomonitored fractionation of the active extracts from M. ilicifolia and A. rosaeodora could be a potential tool for identifying their active compounds and determining the exact mechanism of action.

[Fractures of tibial shaft and tibial head in winter sports]. / Tibiakopf- und Tibiaschaftfrakturen im Wintersport.

BACKGROUND: Injuries in alpine skiing often affect the lower extremities, in particular the knee joint and lower leg. In addition to conventional radiological diagnostics, CT and, in the case of fractures of the knee joint area, MRI also play an important role. In the case of tibial head fractures, especially if there has been a dislocation mechanism, there is an increased risk of vascular and nerve injuries. Lower leg fractures are predestined for the development of a compartment syndrome. For these reasons, an exact survey of the vascular-nerve status and a monitoring of the soft tissues should be carried out. THERAPY: In the further therapy, whether conservative or surgical, the soft tissue situation must also be included in the planning. In the case of tibial head fractures in particular, the choice of the right approach is essential for a good result in surgical therapy. Angle-stable plate osteosynthesis and screw osteosynthesis play the most important role as osteosynthesis methods in the knee joint area. In the case of fractures in the shaft area, medullary nail osteosynthesis or angle-stable plate systems are primarily used. In the case of severely compromised soft tissue or unstable situations, it may be necessary to apply an external fixator first. The initiated therapy should enable functional follow-up treatment as early as possible. PREVENTION: Good physical fitness, driving-specific training, but also good core stabilization have a preventative effect against injuries. In addition, the correct material coordination between ski boot, binding and ski is important for accident prevention.

Pathophysiology and mechanism of long COVID: a comprehensive review.

BACKGROUND: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as "long COVID", and it was defined more recently as "Post COVID-19 condition" by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic. AIM: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID. METHOD: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation. RESULTS: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far. CONCLUSION: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGESLong-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins.

Thyroid-stimulating immunoglobulins (TSI) are a functional biomarker of Graves' disease (GD). To develop a novel TSI bioassay, a cell line (MC4-CHO-Luc) was bio-engineered to constitutively express a chimeric TSH receptor (TSHR) and constructed with a cyclic adenosine monophosphate (cAMP)-dependent luciferase reporter gene that enables TSI quantification. Data presented as percentage of specimen-to-reference ratio (SRR%) were obtained from 271 patients with various autoimmune and thyroid diseases and 180 controls. Sensitivity of 96% and specificity of 99% for untreated GD were attained by receiver operating characteristic analysis, area under the curve 0·989, 95% confidence interval 0·969-0·999, P = 0·0001. Precision testing of manufactured reagents of high, medium, low and negative SRR% gave a percentage of coefficient-of-variation of 11·5%, 12·8%, 14·5% and 15·7%, respectively. There was no observed interference by haemoglobin, lipids and bilirubin and no non-specific stimulation by various hormones at and above physiological concentrations. TSI levels from GD patients without (SRR% 406 ± 134, mean ± standard deviation) or under anti-thyroid treatment (173 ± 147) were higher (P < 0·0001) compared with TSI levels of patients with Hashimoto's thyroiditis (51 ± 37), autoimmune diseases without GD (24 ± 10), thyroid nodules (30 ± 26) and controls (35 ± 18). The bioassay showed greater sensitivity when compared with anti-TSHR binding assays. In conclusion, the TSI-Mc4 bioassay measures the functional biomarker accurately in GD with a standardized protocol and could improve substantially the diagnosis of autoimmune diseases involving TSHR autoantibodies.

Resistance of MHC class I-deficient mice to experimental systemic lupus erythematosus.

Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal antibody to DNA that bears a common idiotype (16/6Id). These mice generate antibodies to 16/6Id, antibodies to DNA, and antibodies directed against nuclear antigens. Subsequently, manifestations of SLE develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. In contrast, after immunization with 16/6Id, mice lacking major histocompatibility complex (MHC) class I molecules generated antibodies to 16/6Id but did not generate antibodies to DNA or to nuclear antigen. Furthermore, they did not develop any of the above clinical manifestations. These results reveal an unexpected function of MHC class I in the induction of autoimmune SLE.

Thyroid gangliosides with high affinity for thyrotropin: potential role in thyroid regulation.

Thyroid cell membranes contain a multiplicity of gangliosides, some of which inhibit thyrotropin binding to thyroid membranes. The most potent inhibitor is a ganglioside which is present in only trace amounts and appears to have a novel structure. Thyroid gangliosides may play a role in relaying the hormonal message to the thyroid cell.

Defect in conversion of procollagen to collagen in a form of Ehlers-Danlos syndrome.

Three patients with a form of the Ehlers-Danlos syndrome, a generalized disorder of connective tissue, have detectable amounts of procollagen in extracts of their skin and tendon. The activity of procollagen peptidase, the enzyme that converts procollagen to collagen, is reduced in cultures of fibroblasts. The clinical manifestations of this syndrome may be related to impaired enzymatic conversion of procollagen to collagen. Cultures of skin fibroblasts from these patients have an increased rate of synthesis of collagenous protein (collagen and procollagen), possibly related to the inability of these cells to convert procollagen to collagen.

Thyroglobulin repression of thyroid transcription factor 1 (TTF-1) gene expression is mediated by decreased DNA binding of nuclear factor I proteins which control constitutive TTF-1 expression.

Follicular thyroglobulin (TG) selectively suppresses the expression of thyroid-restricted transcription factors, thereby altering the expression of thyroid-specific proteins. In this study, we investigated the molecular mechanism by which TG suppresses the prototypic thyroid-restricted transcription factor, thyroid transcription factor 1 (TTF-1), in rat FRTL-5 thyrocytes. We show that the region between bp -264 and -153 on the TTF-1 promoter contains two nuclear factor I (NFI) elements whose function is involved in TG-mediated suppression. Thus, NFI binding to these elements is critical for constitutive expression of TTF-1; TG decreases NFI binding to the NFI elements in association with TG repression. NFI is a family of transcription factors that is ubiquitously expressed and contributes to constitutive and cell-specific gene expression. In contrast to the contribution of NFI proteins to constitutive gene expression in other systems, we demonstrate that follicular TG transcriptionally represses all NFI RNAs (NFI-A, -B, -C, and -X) in association with decreased NFI binding and that the RNA levels decrease as early as 4 h after TG treatment. Although TG treatment for 48 h results in a decrease in NFI protein-DNA complexes measured in DNA mobility shift assays, NFI proteins are still detectable by Western analysis. We show, however, that the binding of all NFI proteins is redox regulated. Thus, diamide treatment of nuclear extracts strongly reduces the binding of NFI proteins, and the addition of higher concentrations of dithiothreitol to nuclear extracts from TG-treated cells restores NFI-DNA binding to levels in extracts from untreated cells. We conclude that NFI binding to two NFI elements, at bp -264 to -153, positively regulates TTF-1 expression and controls constitutive TTF-1 levels. TG mediates the repression of TTF-1 gene expression by decreasing NFI RNA and protein levels, as well as by altering the binding activity of NFI, which is redox controlled.

Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells.

Thyroid transcription factor 1 (TTF-1) was identified for its critical role in thyroid-specific gene expression; its level in the thyroid is regulated by thyrotropin-increased cyclic AMP levels. TTF-1 was subsequently found in lung tissue, where it regulates surfactant expression, and in certain neural tissues, where its function is unknown. Ligands or signals regulating TTF-1 levels in lung or neural tissue are unknown. We recently identified TTF-1 in rat parafollicular C cells and parathyroid cells. In this report, we show that TTF-1 is present in the parafollicular C cells of multiple species and that it interacts with specific elements on the 5'-flanking regions of the extracellular Ca2+-sensing receptor (CaSR), calmodulin, and calcitonin genes in C cells. When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased. The changes in TTF-1 inversely alter CaSR gene and calcitonin gene expression. We show, therefore, that TTF-1 is a Ca2+-modulated transcription factor that coordinately regulates the activity of genes critical for Ca2+ homeostasis by parafollicular C cells. We hypothesize that TTF-1 similarly coordinates Ca2+-dependent gene expression in all cells in which TTF-1 and the CaSR are expressed, i. e., parathyroid cells, neural cells in the anterior pituitary or hippocampus, and keratinocytes.

Styryl lactones and their derivatives: biological activities, mechanisms of action and potential leads for drug design.

Nature is an inexhaustible source of natural compounds with interesting biological activities. In general, natural products are an important source of new compounds with a variety of structural arrangements and singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess interesting biological properties, in particular antiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to be specific against cancer cells since insignificant effects of these compounds on normal cells are reported. A large body of evidence suggests that the antiproliferative activity of styryl lactones is associated with the induction of apoptosis in target cells. In the first part of this review we discuss the biological activities of styryl lactones focusing on cancer cells, the causal agent of Chagas' disease and the vectors for yellow fever and human lymphatic filariasis. Stru described in detail for ninety styryl lactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well as immunosuppressive and inflammatory processes. Overall, understanding how these compounds exert their activities in biological system is essential for future development and application of styryl lactones for human health.

Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells.

Increased major histocompatibility complex (MHC) class I gene expression in nonimmune cell 'target tissues' involved in organ-specific diseases may be important in the pathogenesis of autoimmune diseases. This possibility in part evolves from studies of cultured thyrocytes where properties appear relevant to the development of thyroid autoimmune disease. In FRTL-5 rat thyroid cells in continuous culture, hormones and growth factors that regulate cell growth and function specifically decrease MHC class I gene expression. We hypothesized that this could reflect a mechanism to preserve self-tolerance and prevent autoimmune disease. The mechanisms of action of some of these hormones, namely TSH and hydrocortisone, have been already characterized. In this report, we show that IGF-I transcriptionally downregulates MHC class I gene expression and that its action is similar to that of insulin. The two hormones have a complex effect on the promoter of the MHC class I gene, PD1. In fact, they decrease the full promoter activity, but upregulate the activity of deleted mutants that have lost an upstream, tissue-specific regulatory region but still retain the enhancer A region. We show that insulin/IGF-I promotes the interactions of the p50/p65 subunits of NF-kappaB and AP-1 family members with these two regions, and that the tissue-specific region acts as a dominant silencer element on insulin/IGF-I regulation of promoter activity. These observations may be important to understand how MHC class I gene transcription is regulated in the cells.

Overexpression and overactivation of Akt in thyroid carcinoma.

Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequently identified. We hypothesized that Akt overactivation could be a common finding in sporadic thyroid cancer and might be important in thyroid cancer biology. We examined thyroid cancer cells lines and benign and malignant thyroid tissue for total Akt activation and isoform-specific Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability. In human thyroid tissue, increased levels of phosphorylated total Akt were identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt levels were higher in five of six cancers, including three of three follicular cancers. These data suggest that Akt activation may play a role in the pathogenesis or progression of sporadic thyroid cancer.