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Managers of health in livestock systems are asked to shift from a curative approach to a more preventive approach. This change requires sociological and technical reconfiguration and raises the issue of how changes are implemented by farmers and their technical support ecosystem (advisors, trainers, veterinarians). Here, we report work conducted in western France by an Agricultural European Innovation Partnership Operational Group bringing together animal scientists and sociologists to advance knowledge on animal health in a range of livestock sectors, i.e. dairy cattle, beef cattle, small ruminants (sheep, goats), poultry and pigs. In this study, our aim was to answer this question: what are the Informational Resources (I.R.) that farmers use to promote animal health of their herds? First, we used a survey to characterize 129 I.R. used by advisors, then, we used statistical analysis to classify these I.R. into six clusters. Second, we organized eight focus-group sessions that involved a total of 50 farmers from across all livestock sectors to find out how they mobilize the I.R. and what they see as important for animal health monitoring practice. Finally, we performed individual interviews with 42 farmers to expand the data captured in the collective focus groups. Results showed that farmers and advisors have a broad and diverse range of I.R. to help monitor animal health. We identified six clusters of I.R.: regulatory tools, periodic reports, tools for farmer-led monitoring, tools and indicators for national reference datasets, slaughterhouse and laboratory indicators, and training delivered to farmers. During focus group, livestock farmers identified some of their I.R. within these clusters but they also cited other daily routines that help them monitor animal health that were not cited by advisors. We found that farmers mainly use sensory indicators (typically smell, sight, touch) in their daily practice whereas advisors mainly use relatively sophisticated retrospective monitoring tools. Farmers also cited the importance of indicators that can rapidly objectify any change in animal condition, behavior, or health. This work finds a split in the distribution of animal health management roles, with farmers implementing daily checks whereas advisors run periodic health surveillance, thus revealing differentiated roles and needs between farmers and their advisors.
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Indústria de Laticínios , Fazendeiros , Bovinos , Ovinos , Animais , Suínos , Humanos , Indústria de Laticínios/métodos , Ecossistema , Estudos Retrospectivos , Cabras , GadoRESUMO
Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteína 1 Associada a ECH Semelhante a Kelch , Consenso , Fator 2 Relacionado a NF-E2 , Análise por ConglomeradosRESUMO
INTRODUCTION: Fournier's gangrene is a potentially fatal emergency condition, supported by an infection of perineal and perianal region, characterized by necrotizing fasciitis with a rapid spread to fascial planes. FG, usually due to compromised host, may be sustained by many microbial pathogens. CASE REPORT: A 66-year-old man, with a history of uncontrolled type 2 diabetes, obesity with BMI 38, chronic kidney failure and chronic heart failure, was admitted to the Emergency Department with a large area of necrosis involving the perineal and perianal regions. DISCUSSION: Fournier's gangrene is favoured by hypertension, obesity, chronic alcoholism, renal and heart failure. Generally, Fournier's gangrene needs other procedures in addition to wound debridement such as colostomy, cystostomy, or orchiectomy. CONCLUSION: We report a case of FG found as complication in a patient with uncontrolled type 2 diabetes, treated with effective combination therapy with surgical debridement and antibiotics infusion.
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INTRODUCTION: Since its inception, laparoscopic surgery has evolved and new techniques have been developed due to technological advances. This requires a different and more complex skill set in comparison with open surgery. Reduced working hours, less training time and patient safety factors demand that such skills need to be achieved outside the operating theatre environment. Several studies have been published and have determined the effectiveness of virtual reality training. We aimed to compare virtual reality training with the traditional apprenticeship method of training and determine whether it can supplement or replace the traditional apprenticeship model. We also aimed to perform a meta-analysis of the literature and develop conclusions with respect to the benefits achieved by adding virtual reality training on a regular basis to surgical training programmes. METHODS: A literature search was carried out on PubMed, MEDLINE, EMBASE and Google Scholar academic search engines using the MESH terms 'randomised controlled trials', 'virtual reality', 'laparoscopy', 'surgical education' and 'surgical training'. All randomised controlled trials published to January 2018 comparing virtual reality training to apprenticeship training were included. Data were collected on improved dexterity, operative performance and operating times. Each outcome was calculated with 95% confidence intervals and with intention-to-treat analysis; 24 randomised controlled trials were analysed. FINDINGS: Meta-analytical data were extracted for time, path length, instrument handling, tissue handling, error scores and objective structure assessment of technical skills scoring. There was significant improvement in individual trainee skill in all meta-analyses (p < 0.0002). CONCLUSION: This meta-analysis shows that virtual reality not only improves efficiency in the trainee's surgical practice but also improves quality with reduced error rates and improved tissue handling.
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Estágio Clínico , Laparoscopia/educação , Realidade Virtual , Estágio Clínico/métodos , HumanosRESUMO
Resistive switching (RS) devices based on self-assembled nanowires (NWs) and nanorods (NRs) represent a fascinating alternative to conventional devices with thin film structure. The high surface-to-volume ratio may indeed provide the possibility of modulating their functionalities through surface effects. However, devices based on NWs usually suffer from low resistive switching performances in terms of operating voltages, endurance and retention capabilities. In this work, we report on the resistive switching behaviour of ZnO NW arrays, grown by hydrothermal synthesis, that exhibit stable, bipolar resistive switching characterized by SET/RESET voltages lower than 3 V, endurance higher than 1100 cycles and resistance state retention of more than 105 s. The physical mechanism underlying these RS performances can be ascribed to nanoionic processes involving the formation/rupture of conductive paths assisted by oxygen-related species in the ZnO active layer. The reported results represent, to the best of our knowledge, the best resistive switching performances observed in ZnO NW arrays in terms of endurance and retention.
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BACKGROUND: Reconstruction of posttraumatic bone defects represents a difficult challenge. The induced membrane technique is an effective two-stage procedure for bone defect reconstruction. To overcome the problems of autologous bone grafting, different graft substitutes have been investigated. The aim of the present study is to evaluate our clinical experience in reconstruction of critical posttraumatic bone defects using an induced membrane technique based on a combination of autologous graft and allograft (cancellous bone) enriched with platelet-rich plasma (PRP) and bone marrow concentrate aspirate (BMCA). MATERIALS AND METHODS: Between 2009 and 2014, we reconstructed 18 posttraumatic bone defects in 16 patients. Their average length was 6.4 cm (range 1.6-13.2 cm). The defect location was the femur in nine cases (50%), the tibia in eight (44%) cases, and the humerus in one (6%) case. In all cases, we used a combination of autologous and cancellous allograft graft enriched with PRP and BMCA. Bone fixation was achieved using intramedullary nailing in 2 cases (11%), plating in 15 cases (66%), and external fixation in 1 case (6%). RESULTS: Both clinical and radiographic union were achieved in 13 (72%) cases (13 patients). Five (28%) cases (four patients) developed nonunion. Nonunion was observed in two of eight (25%) tibial defects and in three (33%) of nine femoral defects (ns). Three of 4 (75%) double defects had delayed union, whereas 2 of 14 (14%) single defects did not heal (p = 0.016). The average length of the 13 defects that united was 6 cm (range 1.6-11.8 cm), while the length of the 5 defects that did not unite was 10.3 cm (range 6-13.2 cm) (p = 0.009). CONCLUSIONS: In this series using an induced membrane technique based on a combination of autograft and allograft enriched with BMCA and PRP, the healing rate was lower than in other series where autologous bone graft alone was employed. Nonunion was more frequent in longer and double defects. Further research aimed at developing effective alternative options to autogenous cancellous bone graft is desirable. LEVEL OF EVIDENCE: III.
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Transplante Ósseo/métodos , Fêmur/lesões , Fixação Interna de Fraturas/métodos , Procedimentos de Cirurgia Plástica/métodos , Plasma Rico em Plaquetas , Tíbia/lesões , Cicatrização , Adulto , Idoso , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Awareness of healthcare-associated infections (HAIs) and antimicrobial use in long-term care facilities (LTCFs) is increasing. In 2017, the third national point prevalence survey (PPS) was conducted in Italy as part of the third 'Healthcare-Associated Infections in European Long-Term Care Facilities' (HALT3) study. AIM: To report the results of HALT3 and analyse the resident population of LTCFs, implementation of good practices, prevalence of infections and antimicrobial use. METHODS: The survey was designed as a PPS, carried out from April to June 2017. All residents who lived full-time in the institution were included. All facilities were asked to complete an institutional questionnaire, a ward list for all residents, and a resident questionnaire for those residents presenting with signs/symptoms of active infection and/or receiving an antimicrobial agent. FINDINGS: In total, 418 facilities took part in the study; 24,132 residents were eligible, and most were aged >85 years, disoriented and incontinent. The prevalence of HAIs was 3.9%, and 50% of the institutions reported that they had a professional trained in infection control on their staff. Only 26.4% of infections were confirmed by a microbiological sample, and 26.9% of the isolated micro-organisms were resistant to at least one antimicrobial class. In total, 1022 residents received at least one antimicrobial agent, and cephalosporins were prescribed most commonly. CONCLUSION: The number of infection control and antimicrobial stewardship measures implemented was found to be considerably higher in this study compared with previous studies. This could lead to a reduction in the prevalence of HAIs, antimicrobial use and antimicrobial resistance. Further studies are needed to monitor these aspects.
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Anti-Infecciosos/uso terapêutico , Infecção Hospitalar/epidemiologia , Uso de Medicamentos/estatística & dados numéricos , Assistência de Longa Duração/métodos , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos/métodos , Feminino , Humanos , Controle de Infecções/métodos , Itália/epidemiologia , Masculino , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The decision to resort to living donor transplantation determines a particular condition characterized by a strong mental and emotional anguish, both for the patients and their families. The purpose of the study was to correlate the relational dynamics between donor-recipient, donor/recipient couple with the health team, and the family support perceived by the couple with the quality of life 6 months before transplant and 12 months after transplant and compare the data between the 2 time points after participating in the psychotherapy program of counseling about behavioral change. PATIENTS AND METHODS: Twenty-seven donor and recipient pairs consented to participate. The quality of life was studied through the Complete Form Health Survey (SF-36). All subjects completed a questionnaire that investigated the 3 types of fundamental relationships (donor-recipient, donor/recipient with the health team, and family support perceived by the couple). All participants were involved in an 18-month psychotherapy program in the pre- and post-transplant phase. RESULTS: The quality of the donor-recipient relationship significantly positively influences the subjective perception of psychophysical well-being before and after transplant. Post-transplant family support is crucial in ensuring a good perception of psychological and emotional health in donors and recipients. The relationship with the health team is important in ensuring a good perception of psychophysical health only in recipients after transplant. CONCLUSIONS: This study suggests that patients should be assisted by a multidisciplinary health care team and receive continuous support from relatives during the post-transplant adaptation process. This facilitates the donor and recipient postoperative quality of life.
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Transplante de Rim/psicologia , Doadores Vivos/psicologia , Qualidade de Vida/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Apoio Social , Inquéritos e QuestionáriosRESUMO
Resistive switching (RS) devices are considered as the most promising alternative to conventional random access memories. They interestingly offer effective properties in terms of device scalability, low power-consumption, fast read/write operations, high endurance and state retention. Moreover, neuromorphic circuits and synapse-like devices are envisaged with RS modeled as memristors, opening the route toward beyond-Von Neumann computing architectures and intelligent systems. This work investigates how the RS properties of zinc oxide thin films are related to both sputtering deposition process and device configuration, i.e. valence change memory and electrochemical metallization memory (ECM). Different devices, with an oxide thickness ranging from 50-250 nm, are fabricated and deeply characterized. The electrical characterization evidences that, differently from typical nanoscale amorphous oxides employed for resistive RAMs (HfO x , WO x , etc), sub-micrometric thicknesses of polycrystalline ZnO layers with ECM configuration are needed to achieve the most reliable devices. The obtained results are deeply discussed, correlating the RS mechanism to material nanostructure.
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INTRODUCTION: Amyloid goiter is due to the deposition of amyloid in the thyroid, resulting with enlargement of the gland and compressive symptoms. CASE: We herein present a case of a 45-year-old male patient who complained of a big swelling in the neck. Ultrasound showed an enlarged thyroid gland with mediastinal involvement. The multinodular appearance was consistent with the diagnosis of multinodular goiter. He had a history of multiple myeloma but no sign of systemic amyloidosis. DISCUSSION: Thyroid gland was removed and the histopathological examination revealed a diffuse deposition of amyloid associated with metaplastic lipomatosis of the stroma. CONCLUSIONS: The treatment of choice in patients with amyloid goiter is total thyroidectomy to solve compression symptoms.
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Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including pain transmission via selective activation of a specific receptor named NOP. The aim of this study was the investigation of the antinociceptive properties of NOP agonists and their interaction with opioids in the trigeminal territory. The orofacial formalin (OFF) test in mice was used to investigate the antinociceptive potential associated to the activation of NOP and opioid receptors. Mice subjected to OFF test displayed the typical biphasic nociceptive response and sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1-1mgkg-1) and morphine (0.1-10mgkg-1) elicited dose dependent antinociceptive effects in the OFF with the alkaloid showing larger effects; the isobologram analysis of their actions demonstrated an additive type of interaction. The mixed NOP/opioid receptor agonist cebranopadol elicited potent (0.01-0.1mgkg-1) and robust antinociceptive effects. In the investigated dose range, all drugs did not modify the motor performance of the mice in the rotarod test. Collectively the results of this study demonstrated that selective NOP agonists and particularly mixed NOP/opioid agonists are worthy of development as innovative drugs to treat painful conditions of the trigeminal territory.
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Imidazóis/farmacologia , Indóis/farmacologia , Morfina/farmacologia , Receptores Opioides/agonistas , Compostos de Espiro/farmacologia , Analgésicos/farmacologia , Animais , Animais não Endogâmicos , Masculino , Camundongos , Camundongos Knockout , Dor/tratamento farmacológico , Medição da Dor , Teste de Desempenho do Rota-Rod , Receptor de NociceptinaRESUMO
INTRODUCTION: Myopericytoma is a rare tumor of deep soft tissues, originating from pericytes and characterized by numerous thin walled blood vessels. CASE REPORT: We report a case of myopericytoma found at the level of the second toe of the right foot.A patient came to the Endocrinology Surgery Department of Catania Polyclinic because of a presence of a small swelling in the plantar region, between the 2nd and 3rd toe of the right foot. At the anatomopathological examination, the escalated lesion showed a neoformation of 0.6 cm in diameter, well circumscribed, capsulated, with myopericytoma diagnosis. DISCUSSION: Its histopathological appearance is similar to myofibromatic lesions from glomic and angiomyoma tumors. It is a rare tumor that affects all ages with a peak after 50 years 3. The most frequent localization is at the lower extremities, particularly in soft subcutaneous tissues, but can rarely occur in other sites. CONCLUSION: At the anatomopathological evaluation, the immunohistochemical examination for the correct formulation of the diagnosis is essential and an adequate surgical excision is important.
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Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 µM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1-10 µM result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium.
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Neoplasias da Mama/patologia , Movimento Celular , AMP Cíclico/metabolismo , Células Endoteliais/patologia , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2/metabolismo , Transdução de Sinais , Trifosfato de Adenosina/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Humanos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacosRESUMO
The use of TiO2 nanotube (NT) arrays as templates for hydrothermal conversion of one-dimensional barium titanate (BaTiO3) structures is considered a promising synthesis approach, even though the formation mechanisms are not yet fully understood. Herein we report a nanostructural study by means of XRD and (HR)TEM of high aspect ratio TiO2-NTs hydrothermally converted into BaTiO3. The nanostructure shows two different and well-defined regions: at the top the conversion involves complete dissolution of NTs and subsequent precipitation of BaTiO3 crystals by homogeneous nucleation, followed by the growth of dendritic structures by aggregation and oriented attachment mechanisms. Instead, at the bottom, the low liquid/solid ratio, due to the limited amount of Ba solution that infiltrates the NTs, leads to the rapid crystallization of such a solution into BaTiO3, thus allowing the NTs to act as a template for the formation of highly oriented one-dimensional nanostructures. The in-depth analysis of the structural transformations that take place during the formation of the rod-like arrays of BaTiO3 could help elucidate the conversion mechanism, thus paving the way for the optimization of the synthesis process in view of new applications in energy harvesting devices, where easy and low temperature processing, controlled composition, morphology and functional properties are required.
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Patients with Hydrocephalus are usually treated by diverting the excess Cerebrospinal Fluid (CSF) to other parts of the body using shunts. More than 40 percentage of shunts implanted fail within the first two years. Obstruction in the shunts is one of the major causes of failure (45 percent) and the detection of obstruction reduces the complexity of the revision surgery. This paper describes a proposed wireless monitoring system for clog detection and flow measurement in shunts. A prototype was built using multiple pressure sensors along the shunt catheters for sensing the location of clog and flow rate. Regular monitoring of flow rates can be used to adjust the valve in the shunt to prevent over drainage or under drainage of CSF. The accuracy of the flow measurement is more than 90 percent.
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Hidrocefalia , Derivações do Líquido Cefalorraquidiano , Computadores , Humanos , Próteses e Implantes , ReoperaçãoRESUMO
Liver receptor homolog-1 (LRH-1, NR5A2) is an orphan nuclear receptor that has an essential role in cancer progression, notably in breast cancer. Although its role in promoting cancer cell proliferation and migration is well documented, the molecular basis is not completely established. Here, we report that LRH-1 inhibition affects two- and three-dimensional cell proliferation of different types of breast cancer cells, including estrogen receptor α (ERα)-positive and triple-negative cells. This phenotype is accompanied by the upregulation of the cyclin-dependent kinase inhibitor CDKN1A (aka p21(CIP1/WAF1)) in a p53-independent manner. Chromatin immunoprecipitation analysis shows that LRH-1 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at -62 kb from its transcriptional start sites, allowing repression of CDKN1A transcription. LRH-1 or FOXA1 depletion induces CDKN1A upregulation by removing histone deacetylase 2 from the promoter and distal regulatory elements and permitting histone acetylation in these regions. Analysis of breast cancer samples reveals that a high LRH-1 level is inversely correlated with CDKN1A expression in breast cancer patients and is associated with poor prognosis. This study reveals a novel mechanism of control of cell proliferation by LRH-1 regulating CDKN1A transcription in breast cancer cells, independent of ERα and p53 status. Targeting LRH-1 may provide an attractive prospect for treatment of tumors that are resistant to hormonal and targeted therapy.
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Neoplasias da Mama/patologia , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica , Receptores Citoplasmáticos e Nucleares/fisiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Receptor alfa de Estrogênio/análise , Feminino , Fator 3-alfa Nuclear de Hepatócito/fisiologia , Histona Desacetilase 2/fisiologia , Humanos , Proteína Supressora de Tumor p53/fisiologiaRESUMO
Dengue is a major international public health concern and impacts one-third of the world's population. No specific vaccine and treatment are available for this vector-borne disease. There are four similar but distinct serotypes of dengue viruses (DENV). Infection with one serotype affords life-long immunity to that serotype but only temporary partial immunity, or cross immunity (CI), to others. This increases the risk of developing lethal complications upon re-infection, mainly because of the effect of antibody-dependent enhancement (ADE). There have been multiple studies of the dynamic behavior created by the interplay of ADE and CI using mathematical models. However, models in the literature seldom capture the vector population, which we consider important because combating the mosquito vector is the only way to contain dengue transmission in the absence of vaccines. We therefore propose two differential-equation models of dengue fever (DF) with different levels of complexity and details. Our results support the need for ADE to explain the complexity of the epidemiological data.
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Aedes/imunologia , Anticorpos Antivirais/imunologia , Dengue/imunologia , Dengue/transmissão , Insetos Vetores/imunologia , Modelos Imunológicos , Aedes/virologia , Animais , Reações Cruzadas/imunologia , Dengue/epidemiologia , Humanos , Dinâmica PopulacionalRESUMO
In this paper a forward solver software for the time domain and the CW domain based on the Born approximation for simulating the effect of small localized fluorophores embedded in a non-fluorescent biological tissue is proposed. The fluorescence emission is treated with a mathematical model that describes the migration of photons from the source to the fluorophore and of emitted fluorescent photons from the fluorophore to the detector for all those geometries for which Green's functions are available. Subroutines written in FORTRAN that can be used for calculating the fluorescent signal for the infinite medium and for the slab are provided with a linked file. With these subroutines, quantities such as reflectance, transmittance, and fluence rate can be calculated.
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Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn(2+), Ni(2+), Cu(2+), and the biologically relevant Mg(2+) and Zn(2+) efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.Interestingly, metal ion complexation dramatically affects ligand-stabilising effects on G-quadruplex, the melting temperature of the folded structure being increased up to 30 degrees C at ligand concentrations as low as 1 microM in the presence of Ni(2+) and Cu(2+). In addition, the test complexes were able to induce G-4 formation from essentially unfolded G-rich sequences even in the absence of K(+) ions as shown by gel shift and circular dichroism experiments. In line with their G-4 stabilising properties bis-Phen complexes are effective inhibitors of telomerase activity, Ni(II) complexes being effective in the sub-micromolar range. This is combined with lack of unselective DNA-damaging activity and short-term cellular toxicity, which makes the novel compounds (above all their Ni(II) complexes) interesting antiproliferative drug leads.