Pedicled vascularized bone grafts compared with xenografts in the treatment of scaphoid nonunion.

INTRODUCTION: Fractures of the scaphoid account for 60-70% of all wrist bone fractures. The results of treatment in terms of bone healing vary depending on the type and location of the fracture, the time elapsed since the injury, the type of surgical treatment. Nonunion occurs in 5-15% of the cases on average. The purpose of this paper is to compare the surgical techniques and results of treating scaphoid nonunion (SNU) with osteoplastic xenografts of bovine origin or a vascularized autograft of the distal part of the dorsal radius. METHODS: We compare two groups of patients with symptomatic SNU, treated surgically with either a vascularized graft (n = 15) or a xenograft of bovine origin (n = 15). In the presurgical stage, the demographic characteristics of the patients, the time elapsed between injury and surgery, and classification of the injury (Schonberg, Herbert-Fisher, and Geissler-Slade) were recorded. One year following surgery, bone healing, total duration of the treatment, complications, the Mayo wrist score, and answers to the DASH questionnaire were analyzed. RESULTS: No statistically significant differences between the two groups of patients were observed for bone healing (86.7% vs 80%) or functional results. A highly significant difference was observed with respect to duration of the surgical intervention in favor of xenografts. CONCLUSION: The xenograft method is simple and relatively acceptable, providing good results in terms of healing and functionality.

Reaching the sustainable development goals through healthy environments: are we on track?

The adoption of the 2030 Agenda for Sustainable Development in 2015 opened new opportunities to work towards healthy environments through 'whole of government' and 'whole of society' approaches. It created a strong policy platform that acknowledges health as a result and an enabler of sustainable policies across all sectors of government. Five years into the process, an initial analysis of emerging trends indicates that, despite some encouraging developments in policy as well as overall progress in economy and technology, there remains a gap between rhetoric, ambition and reality. In particular, the monitoring system for environment and health-related sustainable development goals (SDGs) and targets requires further development; inequalities in environment and health persist and in some areas have increased; equity is not yet a central element of implementation and reporting on the achievement of the SDGs; and, most worrying of all, trends in key environmental indicators that are vital to the survival of the human species, such as those related to climate change and biodiversity, are still on an overall negative path. In summary, governments must significantly and rapidly increase action to secure the habitability and safety of planet Earth. The public health community assumes an unprecedented role in placing and maintaining health and equity at the heart of the political agenda. This demands new governance models conferring on the health sector a clear mandate and legitimacy to operate across sectors. It also requires enhancing capacities among health professionals to embrace this new level of complexity, understand the multiple links between sectoral policies and health, and successfully engage with other government sectors and stakeholders.

Influence of different biological control agents and compost on total and nitrification-driven microbial communities at rhizosphere and soil level in a lettuce - Fusarium oxysporum f. sp. lactucae pathosystem.

AIMS: The response of rhizosphere and bulk soil indigenous microbial communities focusing on nitrifiers was evaluated after the application of different biological control agents (BCAs; Bacillus, Trichoderma, Pseudomonas) and compost in controlling lettuce Fusarium wilt. METHODS AND RESULTS: Experiments were conducted 'in situ' over two lettuce cropping seasons. Total fungal, bacterial and archaeal populations and the nitrifiers were analysed using quantitative polymerase chain reaction method. The pathogen, Fusarium oxysporum forma specialis lactucae (FOL), Bacillus, Trichoderma and Pseudomonas and three antifungal genes (chiA, 2,4-diacetylphloroglucinol - phlD and HCN synthase - hcnAB genes) were also assessed. Quantitative data were corroborated with disease severity (DS), potential nitrification activity and soil chemical parameters. The application of BCAs and compost resulted in the disease reduction by as much as 69%, confirmed by significant negative correlations between Bacillus subtilis, Trichoderma and Pseudomonas sp. abundances and DS. The FOL presence in the untreated control resulted in the nitrifiers niche differentiation. CONCLUSIONS: The used treatments were efficient against Fusarium wilt and did not influence negatively the nontarget microbial communities. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of BCAs and compost appears as an effective and safe strategy to implement sustainable agricultural practices.

The clinical value of scintigraphy of neuroendocrine tumors using (99m)Tc-HYNIC-TOC.

PURPOSE: To assess the value of whole body scintigraphy using (99m)Tc-HYNIC-TOC (Tektrotyd) and with single photon emission computerized tomography (SPECT) in the detection of primary and metastatic neuroendocrine tumors (NETs). METHODS: Thirty patients with different neuroendocrine tumors, mainly gastroenteropancreatic (GEP), were investigated. Whole body scintigraphy was performed 2 h (if necessary 10 min and 24h) after i.v. administration of 740 Mbq (99m)Tc-Tektrotyd, Polatom. In cases of unclear findings obtained by whole body scintigraphy, investigation was followed by SPECT. RESULTS: From 12 patients with NETs of unknown origin, there were 10 true positive (TP), and 2 false negative (FN) findings. Diagnosis was made with SPECT in 6 patients. From 8 patients with gut carcinoids, there were 4 TP, 2 true negative (TN), one FN, and one false positive (FP) finding. Diagnosis was made with SPECT in 2 patients. From 7 patients with neuroendocrine pancreatic carcinomas there were 4 TP and 3 TN findings. Diagnosis was made with SPECT in 2 patients. From 3 patients with gastrinomas there were 2 TP findings and one TN findings. Diagnosis was made with SPECT findings in 2 patients. Sensitivity of (99m)Tc-HYNIC-TOC was 87%, specificity 86%, positive predictive value 95%, negative predictive value 67% and accuracy 87%. CONCLUSION: We concluded that scintigraphy with (99m)Tc-Tektrotyd is an useful method for diagnosis, staging and follow up of the patients with NETs.

Scintigraphic detection of colon carcinomas with iodinated monoclonal antibodies.

PURPOSE: The aim of this study was to evaluate the clinical reliability of the immunoscintigraphy with iodinated monoclonal antibodies for the detection of metastases and recurrences of colon carcinomas. METHODS: A total of 45 patients with colon carcinoma was investigated with gamma camera, after intravenous application of iodinated monoclonal antibodies. RESULTS: The sensitivity of the method was 90%, specificity 86%, positive predictive value 93%, negative predictive value 80% and accuracy 87%. There was statistically significant relationship between immunoscintigraphic and ultrasonographic (US) findings (p=0.005). Also, there was significant relationship between immunoscintigraphy and Dukes stage (p=0.019). Tumor marker levels were not significantly correlated with immunoscintigraphic findings (p<0.05). Significant difference was noted in patients with positive findings for malignancy on US and immunoscintigraphic findings (p=0.006), i.e. patients with positive findings for malignancy had more frequently immunoscintigraphic findings of malignancy. Correlation with other diagnostic procedures (rectoscopy, colonoscopy, CT) did not show significant correlations. CONCLUSION: We conclude that immunoscintigraphy can be helpful in the detection of metastases and recurrences of colon carcinomas.

Study of genotoxicity and antigenotoxicity of the Cotinus coggygria Scop. methanol extract by Drosophila melanogaster sex-linked recessive lethal test.

The genotoxic and antigenotoxic effects of Cotinus coggygria Scop. methanol extract was investigated using the Drosophila sex-linked recessive lethal (or SLRL) test. The results presented here show that the methanol extract of Cotinus coggygria in a concentration of 5% and artificial chemical agent ethyl methanesulfonate EMS (0.75 ppm) induce recessive lethal mutations on X-chromosome on Drosophila melanogaster in all broods (I, II and III). Post-treatment with lower concentration of the methanol extract of Cotinus coggygria (2%) was effective in reducing genotoxicity ofmutagen.

Mangled extremity- Modern concepts in treatment.

A mangled extremity is the most devastating limb injury and presents a challenge for the orthopedic surgeon. There are two main treatment options, reconstruction or amputation, but sometimes indications for either are not clear. There are many pro and contra arguments for both options. To make the decision easier numerous score systems have been introduced, but the final decision is based on the judgment and experience of the treating surgeon. Early extremity reconstruction appears to give better results than delayed or late reconstruction and should be the treatment of choice where possible. The goal in reconstruction of a lower extremity is to restore and maintain balance and ambulation, while restoration of an upper extremity's numerous functions is more demanding. In this paper the authors describe and suggest treatment approaches in patients with a severely mangled extremity, including assessment and treatment of all injured tissues, using defined protocols, with special attention to bone stabilization, revascularization, soft-tissue coverage and nerve reconstruction. These have a great impact on the outcome and function of the injured extremity. Rehabilitation and return to the preinjury level is slow and sometimes uncertain.

Acute drug-related mortality of people recently released from prisons.

The rate of acute drug-related mortality, or overdose deaths, among prisoners in the immediate post-release period is unacceptably high. Such incidents result from many factors, including decreased tolerance after a period of relative abstinence during imprisonment and the concurrent use of multiple drugs which, with every additional illicit drug consumed in combination with opioids, nearly doubles the risk of death from opioids. Other important factors are the lack of pre-release counselling, post-release follow-up and failure to identify those at risk. Substance dependence is a chronic disorder with high relapse rates and often requires long-term continuous treatment. The deaths are preventable and a number of interventions including opioid substitution treatment reduces the risk of overdose among opioid users after release.

Production of antibodies to Little cherry virus 1 coat protein by DNA prime and protein boost immunization.

Little cherry, an economically important disease of cherry is caused by at least two different viruses. One of these is Little cherry virus 1 (LChV-1) for the detection of which no efficient serological tools are available, so that diagnosis is based on molecular methods. In this study, different immunization strategies for producing antibodies against the viral coat protein of LChV-1 were tried, using either purified virus preparations, or bacterially expressed protein, or a DNA vector that expressed the cloned coat protein (CP) gene in vivo. Effective induction of specific antibodies to LChV-1 CP was obtained using DNA intramuscular immunization followed by a single boost with the recombinant protein. The entire coat protein sequence was cloned in a mammalian expression vector and, after being coated by an amphiphilic non-toxic reagent was delivered into rabbit. A protein boost increased the specific immune response against the virus protein. The sensitivity of this antiserum is lower if compared with that of antisera raised conventionally against other viruses, thus it requires improvements for use for diagnostic purposes.

Differences between molecular mechanisms involved in the regulation of haptoglobin gene expression during the acute phase response and dietary restriction.

Haptoglobin is a glycoprotein involved in the acute phase response. Previously we reported that haptoglobin gene expression was up-regulated during dietary restriction in young female rats. The present study aimed at determining whether chronic dietary restriction affects haptoglobin blood levels through changing levels and/or activities of IL-6-related transcription factors STAT and C/EBP in the liver as is the case during the acute phase response. To this end, we compared a female Wistar rat model of 50% 6-week-long dietary restriction with the standard laboratory model for the acute phase response induced by turpentine administration. During the turpentine-induced acute phase response, the transitory 5.4-fold increase of rat haptoglobin expression was accompanied by a prominent rise of serum IL-6 concentration and the increased binding of STAT3 and 35kD C/EBPbeta/LAP transcription factors to the haptoglobin gene hormone-responsive element. Results obtained after immunoblotting and DNA affinity chromatography (using hormone-responsive element) suggest that the stable 1.7-fold increase of serum haptoglobin level during dietary restriction was the result of increased amounts and activities of constitutive transcription factors C/EBPalpha and STAT5b, and to a smaller extent of STAT3. When dietary restriction rats were administered turpentine, a 8.7-fold increase in haptoglobin expression was followed by a considerable increase in the amount and hormone-responsive element binding activity of STAT3 but not 35kD C/EBPbeta/LAP. We concluded that haptoglobin gene up-regulation during chronic dietary restriction was regulated by different mechanisms than during the acute phase response, and that it depended on the amount(s) and activit(ies) of transcription factor(s) that characterize low-grade inflammatory conditions.

Tuberculosis-HIV co-infection: policy and epidemiology in 25 countries in the WHO European region.

OBJECTIVES: The aims of this study were to collect and review tuberculosis (TB)-HIV data for Europe and to provide an overview of current health policies addressing co-infection. METHODS: We collected reported cases of TB-HIV from the 25 most affected member states of the World Health Organization (WHO) European region. Countries were also asked whether they had implemented health policies covering collaborative TB-HIV activities and what their main achievements, obstacles and needs were in addressing TB-HIV. RESULTS: Twenty countries reported registering a total of 6925 TB-HIV cases in 2005. Among TB patients tested, 3.3% were found to be HIV-positive, up from 2.1% in 2004. The male-to-female ratio was 2.7:1. The largest percentage of co-infections were reported in people aged 25-34 years (47.8%). Recommended TB-HIV policies have been implemented in many of the countries. CONCLUSIONS: Case-finding has improved in many countries and the reported incidence of TB-HIV is increasing in the European region, particularly among young adults, although it remains low compared to other parts of the world. Strengthened coordination of existing TB and HIV services is still needed.

Optimal HIV testing and earlier care: the way forward in Europe.

The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26-27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts representing advocacy, clinical and policy areas of the HIV field, was convened in an effort to gain a common understanding on the role of HIV testing and counselling in optimizing diagnosis and the need for earlier care. Key topics discussed at the conference and described in the following articles include: current barriers to HIV testing across Europe, trends in the epidemiology of HIV in the region, problems associated with undiagnosed infection and the psychosocial barriers impacting on testing. The supplement also provides a summary of the World Health Organization's recommendations for HIV testing in Europe and an outline of an indicator disease-guided approach to HIV testing proposed by a committee of experts from the European AIDS Clinical Society (EACS). We hope that consideration of the issues discussed in this supplement will help to shift the HIV field closer towards our ultimate goal: provision of optimal HIV testing and earlier care across the whole of the European region.

Acute phase-dependent changes in the binding of rat liver nucleoproteins to the cytokine response element of the rat haptoglobin gene.

Hormones released during the acute phase reaction promote the transcriptional activation of the haptoglobin (Hp) gene and a consequent increase of Hp protein synthesis in the liver. The mechanisms underlying the alterations of basal transcription rates of eukaryotic genes are assumed to result from modulations of the binding affinities between nucleoproteins and specific DNA sequences in the enhancer and promoter elements. In order to characterize the changes in the interaction of nucleoproteins with the promoter that accompany the induction of the Hp gene, nuclear extracts from normal and inflamed livers were probed with hormone responsive element (HRE) of the rat Hp gene by gel mobility shift and Southwestern assays. Each of the three cis-acting sequences of the HRE, elements A, B, and C, recognized a distinct set of proteins. Together they conferred an additional level of specificity to the protein binding sites of the entire ABC-element. These sites were recognized by proteins in liver nuclear extracts isolated from both control and treated rats. The differences in the gel shift and Southwestern patterns of the corresponding DNA-protein complexes suggested that transcriptional activation of the Hp gene relied on changes in the concentrations and/or functional modifications of preexisting proteins rather than on the induction of new trans-acting factors.

Fetal bovine serum contains an inhibitor of interleukin-1.

The keratinocyte cell line COLO-16 constitutively produces factors with interleukin-1 (IL-1) activity including IL-1 alpha and IL-1 beta. IL-1 activity assayed by thymocyte proliferation from cell supernatants was 20-50% less if cells were maintained in media containing 10% fetal bovine serum (FBS) compared to media without serum 24 h prior to harvest. The increased IL-1 activity in supernatants from cells in serum free media was not due to increased cellular levels of IL-1 alpha or IL-1 beta mRNA. Similarly, IL-1 activity recovered from conditioned supernatants of COS cells transfected with expression vectors containing IL-1 beta cDNA was approximately 22-45% less in cells grown in 20% FBS medium compared to similar cultures grown for 3 days post transfection in 1% FBS. When serial dilutions of recombinant IL-1 were made in buffer containing 10% FBS and assayed by a thymocyte proliferation method, a 30-50% decrease in activity was observed. IL-1 activity was also measured by its ability to induce prostaglandin E2 synthesis by fibroblasts. When COS conditioned supernatants were applied to fibroblast cultures there was 30% less prostaglandin E2 activity from fibroblasts treated with COS supernatants containing 20% FBS, compared to supernatants containing 1% FBS. The inhibitor molecule was partially purified by gel filtration and found to have a molecular weight of approximately 85,000. The presence of FBS in cell-conditioned media significantly reduces the sensitivity of IL-1 detection by bioassay techniques.

Human interleukin-1 alpha is chemotactic for normal human keratinocytes.

Interleukin-1 (IL-1) has been shown to have mitogenic and chemotactic properties for a variety of cell types includes keratinocytes. These studies suggested that keratinocytes possess receptors for IL-1. In this study, the chemotactic properties of IL-1 for keratinocytes were confirmed and IL-1 receptors were demonstrated on keratinocytes using a radio receptor assay. Crosslinking studies with IL-1 alpha identified two major bands of Mr 97 kDa and 133 kDa. Thus, keratinocytes possess high affinity IL-1 receptors and respond to IL-1 by directed migration.

Regions of the haptoglobin 5' flanking gene sequence show different binding affinities to nuclear matrix proteins during the acute phase response.

The effect of the acute phase response on the affinity of binding between nuclear matrix proteins and the rat haptoglobin (Hp) gene region was examined. Nuclear matrices isolated from acute phase livers were enriched with the 5' Hp gene flanking region (-705/+159), but not with the spliced, protein-coding sequence. Reassociation experiments with isolated nuclear protein matrix spheres and end-labeled fragments I (-146/+156), II (-146/-541), and III (-541/-705) revealed that the matrix proteins displayed an increased binding potential during the acute phase response for all of the examined regions, this being most pronounced for fragment II. BAL 31 digestion of fragment II showed that the sequence element that was responsible for the increased association with nuclear matrix proteins during the acute phase response was a tract of 38 adenine bases. The DNA region established stable associations with nuclear lamin B (67 kDa, pI 5.7) in the controls, and with lamins A (69 kDa, pI 7.0), B, isoforms of lamin C (62 kDa, pI 6.55-6.95), and a 55-kDa (pI 5.9) polypeptide during the acute phase response. Sequence ABC (-165/-56), which overlaps fragments I and II and represents the Hp cis-acting element, did not bind to the non-histone nuclear matrix proteins.

HI-6 therapy and the acute phase response in the rat.

The propensity of therapeutic doses of HI-6 (50 mg/kg) in combination with atropine sulphate (17 mg/kg), antidotes used to treat organophosphate poisoning, to induce the acute phase response (APR) in the laboratory rat was examined. A single intraperitoneal injection of HI-6, either alone or with atropine, caused a rapid doubling of the plasma corticosterone concentration. However, this increase was short-lived in comparison with corticosterone kinetics during the typical, turpentine-induced APR. The elevated glucocorticosteroid concentration did not affect acute phase protein (APP) gene transcription or mRNA and protein synthesis in the livers of oxime/atropine-treated rats. On the basis of these findings, we concluded that the administered doses of HI-6 and atropine did not induce the generalised, non-specific APR.

The acute phase response of rats to soman intoxication.

The capacity of an organophosphate to elicit the acute phase response (APR) was assessed by studying the effects of acute soman intoxication on two major processes which characterize inflammation, cytokine production in macrophages and the expression of acute phase protein (APP) genes in the liver. It was established that the concentration of lymphostimulatory substances secreted by the macrophages of soman-intoxicated rats was increased to a level characteristic of the primary inflammatory reaction. Macrophage activation was followed by increased transcription rates of APP genes and the corresponding mRNA and protein synthesis in the liver. The pattern of the DNA-protein complexes obtained with nuclear extracts and the cis-element of the rat haptoglobin gene in the gel-retardation assay suggested that the molecular events which underlie the expression of APP genes of intoxicated rats are similar to those that occur during the APR. From these findings we concluded that soman intoxication was a metabolic injury which elicited the typical APR.

Multiple leiomyosarcoma of the stomach.

Leiomyosarcoma is the second most common non epithelial malignant tumor of the stomach. It is almost always a single lesion. Multiple leiomyosarcomas of the stomach are extremely rare. To our knowledge only three cases have been reported so far. We present a 40 year old female with epigastric pain, nausea, diarrhea, weight loss and melena in whom we diagnosed multiple lesions of the stomach. At operation, we found a total of 11 submucosal or subserosal lesions ranging in size from 0.5 to 6 cm in diameter localized throughout the stomach. Histological examination showed leiomyosarcoma in every lesion. Almost all the lymph nodes along curvatures had metastases. Other lymph nodes, peritoneum, liver and other organs were disease free. A total gastrectomy and Roux-en-Y esophagojejunostomy was performed. She had an uneventful recovery and has remained symptom-free so far (nine months).

Expression of C/EBP delta in rat liver during development and the acute-phase response.

Using Western analysis, C/EBP delta was established in the nuclear extract and nuclear matrix throughout rat liver development and in the adult. During the acute-phase response (APR), C/EBP delta increased in the nuclear extract but remained unchanged in the nuclear matrix of fetal and postnatal rats, whereas it increased in both the nuclear extract and nuclear matrix of the adult. The solubility partitioning of gene regulatory proteins in the nucleus is important for their functioning (Uskokovic et al. 2002). The obtained different solubility partitioning profiles of C/EBP delta suggest that its activity is regulated by different mechanisms during development and in the adult.