Efficacy and sustainability of natural products in COVID-19 treatment development: opportunities and challenges in using agro-industrial waste from Citrus and apple.

Natural products have been used in the treatment of illnesses throughout the history of humankind. Exploitation of bioactive compounds from natural sources can aid in the discovery of new drugs, provide the scaffold of new medicines. In the face of challenging diseases, such as the COVID-19 pandemic, for which there was no effective treatment, nature could offer insights as to novel therapeutic options for control measures. However, the environmental impact and supply chain of bioactive production must be carefully evaluated to ensure the detrimental effects will not outweigh the potential benefits gained. History has already proven that highly bioactive compounds can be rare and not suitable for medicinal exploitation; therefore, the sustainability must be accessed before expensive, time-demanding, and large trials can be initialized. A sustainable option to readily produce a phytotherapy with minimal environmental stress is the use of agro-industry wastes, a by-product produced in high quantities. In this review we evaluate the sustainability issues associated with the production of phytotherapy as a readily available tool for pandemic control.

Functional and Taxonomic Beta Diversity of Saproxylic Beetles in Mediterranean Forests: On What Factors Do They Depend?

Understanding how biodiversity is distributed across geographical and environmental gradients is a main goal of diversity sciences. However, since ecosystem processes are linked to variation in functional traits of the biota, examining functional beta diversity is particularly important. Our objective was to analyze the taxonomic and functional beta diversity patterns of saproxylic beetle assemblages in evergreen Quercus forest of Spain. We tested whether environmental or geographical distance had a greater influence on taxonomic and functional beta diversity, and if both measures of beta diversity were affected by the same environmental variables. We used 45 flight interception traps distributed in three protected areas over a 12-mo period to sample saproxylic beetles. We measured 13 environmental variables around each trap and the geographical distance between traps. For functional composition, we used 12 functional traits from four functional groups (morphological, phenological, trophic, and a surrogate of physiological). Our results showed that environmental differences between areas influenced the taxonomic and functional beta diversity components (replacement and loss/gain) but in different ways. While replacement components (higher for taxonomic composition) increased with environmental distance, the loss or gain components (higher for functional composition) remained constant, indicating that species replacement mostly involved functionally redundant species. Besides, environmental variables influencing both taxonomic and functional composition were strongly dependent on each area. In conclusion, in well-preserved Mediterranean forests, environmental filtering determines the taxonomic and functional composition of saproxylic beetle assemblages, by favoring species replacement but filtering species traits.

Lateralized cognitive functions in Parkinson's patients: A behavioral approach for the early detection of sustained attention deficits.

Parkinson's disease (PD) has been described as a disconnection syndrome. The lateralized motor onset of symptoms indicates asymmetrical dysregulation of the dopamine production in the substantia nigra, in the striatum and, in turns, a dysfunction of the basal ganglia and of the connected cortical areas. However, lateralization of cognitive symptoms is less clear, and it would be important to determine whether lateralized motor deficits are associated with cognitive impairments typically documented following damage to one specific hemisphere. We tested twenty-two PD patients at various stages of the disease on a sustained attention task, namely a multiple object tracking (MOT). This task is particularly sensitive at revealing lateralized deficits, and is often used to diagnose visual field attentional deficits in stroke patients with unilateral parietal lesions. In the present study, PD patients were asked to track four moving discs (two in the left and two in the right hemifield) amidst moving distracters. Left and right visual field tracking accuracy was psychophysically measured and compared to that of age-matched controls. Results revealed distinct behaviors: left (motor deficit) PD patients showed impaired performance in the left, while right (motor deficit) PD patients were impaired in the right hemifield. Data indicate that PD affects motor as well as attentional functions. Interestingly, performance correlated with scores on the Montreal Cognitive Assessment (MoCA) a measure of cognitive functioning. Crucially, results suggest that cognitive skills might be affected as early as motor functions, and that early evaluation might be key to predicting disease progression and planning interventions.

The effect of soil type on the extraction of insensitive high explosive constituents using four conventional methods.

Explosive contamination is commonly found at military and manufacturing sites (Hewitt et al., 2005; Clausen et al., 2004; Walsh et al., 2013). Under current environmental legislation the extent of the contamination must be characterized by soil sampling and subsequent separation of the explosive contaminants from the soil matrix by extraction to enable chemical analysis and quantification (Dean, 2009). It is essential that the extraction method can consistently recover explosive residue from a variety of soil types i.e. all materials that have not degraded or irreversibly bound to the matrix, so that any resultant risk is not underestimated. In this study, five different soil types with a range of organic content, particle size and pH, were spiked with a mixture of RDX, DNAN, NQ and NTO at 50 mg/kg and were extracted using one of four one-step extraction methods: stirring, shaking, sonication, and accelerated solvent extraction (ASE). Analysis of the extraction efficiencies of the four methods found that they were broadly successful for the extraction of all IHE constituents from all five soils (an average of 84% ±â€¯14% recovery across 80 extractions). However, soils with high organic content (Total Organic Content (TOC) ≥ 2%) were found to significantly affect extraction efficiency and reproducibility. NTO and DNAN were the least consistent in extraction efficiency with poorest recovery of NTO as low as 37% ±â€¯2%. Of the four tested methods shaking was found to be the most reproducible, though less efficient than stirring (64%-91%). ASE was found to have the most variable results for extraction of IHE constituents suggesting that ASE was the most affected by the different soil types. Therefore, it is recommended that the efficiency and reproducibility of the selected extraction method should be validated by extracting known concentrations of the IHE from the soil of interest and that any required correction factors are reported.

Investigation into the environmental fate of the combined Insensitive High Explosive constituents 2,4-dinitroanisole (DNAN), 1-nitroguanidine (NQ) and nitrotriazolone (NTO) in soil.

Contamination of military ranges by the use of explosives can lead to irreversible environmental damage, specifically to soil and groundwater. The fate and effects of traditional explosive residues are well understood, while less is known about the impact of Insensitive High Explosives (IHEs) that are currently being brought into military service. Current research has focussed on the investigation of individual constituents of IHE formulations, which may not be representative of real-world scenarios when explosive residues will be deposited together. Therefore, this study investigated the fate and transport of the combined IHE constituents 2,4-dinitroanisole (DNAN), 1-nitroguanidine (NQ) and 3-nitro-1,2,4-triazol-5-one (NTO) in two UK soil types. Static experiments ran for 9weeks to determine the fate of the combined explosive constituents in soil by monitoring the rate of degradation. Transport was examined by running soil column experiments for 5weeks, with a watering regime equivalent to the average yearly UK rainfall. Both static and soil column experiments confirmed that DNAN and NTO started to degrade within twenty-four hours in soil with high organic content, and were both completely degraded within sixty days. NQ was more stable, with 80% of the original material recovered after sixty days. The major degradation product of DNAN in the test soils was 2-amino-4-nitroanisole (2-ANAN), with trace amounts of 4-amino-2-nitroanisole. NTO was rapidly degraded in soil with high organic content, although no degradation products were identified. Results supported work from literature on the individual constituents DNAN, NQ and NTO suggesting that the three explosives in combination did not interact with each other when in soil. This study should provide a useful insight into the behaviour of three combined Insensitive High Explosive constituents for the predication of soil and water contamination during military training.

Influence of Traditional Management and Environmental Variables on Mediterranean Saproxylic Beetle Assemblages.

Mediterranean oak forests of the Iberian Peninsula host a great diversity of saproxylic beetles. For centuries, humans have carried out traditional management practices in this area, at both habitat and tree level, causing changes in forest structure. The aim of this study was to evaluate the anthropic effect of these traditional practices on saproxylic beetle diversity by measuring a set of environmental variables related to forest structure at both plot and tree level. Fauna was collected using window traps over a period of 12 mo. Multiple regression procedures showed which variables significantly affected the diversity of the studied assemblage. Our results demonstrated that the different metrics used to assess the diversity of assemblages responded variably depending on the management strategies applied and the level at which they were carried out. Certain management practices that disrupted the landscape from its natural state, such as the introduction of livestock or the local removal of particular trees, maximized species richness but, nevertheless, had a negative effect on the rest of diversity metrics analyzed. However, other practices such as pollarding, which involves the suppression of the main branch of the tree, had a positive effect on all diversity metrics evaluated as it promoted the formation of potential microhabitats for saproxylic fauna. We concluded that not all types and degrees of traditional forest management favor saproxylic beetle diversity and that different diversity metrics should be taken into consideration in future strategies for the protection and conservation of this fauna.

Hot infusions and risk of colorectal cancer in Uruguay: a case-control study.

BACKGROUND/OBJECTIVES: The evidence of possible roles for the most common hot infusions intake (tea and coffee) in the risk of colorectal cancer (CRC) needs additional data. Regarding 'mate' intake (infusion of Ilex paraguariensis herb), a previous multi-site study reported lack of association for its highest intake on CRC risk. The present study was conducted to better understand the associations between the intake of this and other infusions and CRC risk. SUBJECTS/METHODS: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals) were interviewed through a questionnaire, including socio-demographic, reproductive and lifestyle variables, and a food-frequency questionnaire of 64 items, analyzing tea, 'mate' and coffee intake (consumer status, daily intake, age at start and at quit). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated through unconditional logistic regression, adjusting for relevant potential confounders. RESULTS: Tea and coffee intake displayed significant and inverse associations with CRC risk, mainly among men (OR=0.54, 95% CI 0.38-0.76 for tea and OR=0.59, 95% CI 0.41-0.85 for coffee). Mate intake showed a significant inverse association among women (OR=0.50, 95% CI 0.33-0.77), with a marginal heterogeneity between sexes (P=0.07). Concerning age strata, tea intake displayed inverse associations in all ages, whereas 'mate' and coffee intake showed stronger inverse associations for age ⩾70, suggesting a gradient along time. CONCLUSIONS: We found evidence of different significant inverse associations for tea, 'mate' and coffee intake and CRC risk. To our knowledge, this is the first epidemiologic study reporting inverse results on 'mate' intake and CRC, which are explained by a stronger association among women.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.130.

Bacteria and Hoverflies (Diptera: Syrphidae) in Tree Hollows From the Iberian Mediterranean Forest.

Saproxylic insect communities inhabiting tree hollows in Mediterranean forests depend on a combination of physical characteristics and interactions occurring between community member species. Despite the need to preserve these organisms, little is known about their interrelationships, in particular those relationships between saproxylic insects and microbiota occurring in these microhabitats. In tree hollows of Quercus rotundifolia Lamark that hold water and contain dead leaves, abundant microbial populations can be found. Developing on them are the larvae of Mallota dusmeti Andréu, 1926 (Diptera: Syrphidae), a vulnerable species (IUCN category: Marcos-García and Quinto 2011). This study provides the first data on the microbiota living inside the gut of the larvae of M. dusmeti, as well as the microbiota in the hollow where these larvae develop. Bacteria were identified by amplification and partial sequencing of the V1-V3 regions and the complete nucleotide sequence of 16S rRNA genes. We found eight species of bacteria living in tree hollows and three species in the gut of M. dusmeti larvae: Bacillus cereus, Bacillus toyonensis, and Lysinibacillus sphaericus. The filter-feeding mechanism characteristic of M. dusmeti larvae is selective in enabling ingestion of bacteria only above 2.1 µm in diameter.

Saproxylic Beetle Assemblage Selection as Determining Factor of Species Distributional Patterns: Implications for Conservation.

The knowledge of the distributional patterns of saproxylic beetles is essential for conservation biology due to the relevance of this fauna in the maintenance of ecological processes and the endangerment of species. The complex community of saproxylic beetles is shaped by different assemblages that are composed of species linked by the microhabitats they use. We evaluate how different the species distribution patterns that are obtained can be, depending on the analyzed assemblage and to what extent these can affect conservation decisions. Beetles were sampled using hollow emergence and window traps in three protected areas of the Iberian Peninsula. Species richness, composition, and diversity turnover were analyzed for each sampling method and showed high variation depending on the analyzed assemblage. Beta diversity was clearly higher among forests for the assemblage captured using window traps. This method collects flying insects from different tree microhabitats and its captures are influenced by the forest structuring. Within forests, the assemblages captured by hollow emergence traps, which collect the fauna linked to tree hollows, showed the largest turnover of species, as they are influenced by the characteristics of each cavity. Moreover, the selection of the forest showing the highest species richness strongly depended on the studied assemblage. This study demonstrates that differences in the studied assemblages (group of species co-occurring in the same habitat) can also lead to significant differences in the identified patterns of species distribution and diversity turnover. This fact will be necessary to take into consideration when making decisions about conservation and management.

Facilitation among saproxylic insects inhabiting tree hollows in a Mediterranean forest: the case of cetonids (Coleoptera: Cetoniidae) and syrphids (Diptera: Syrphidae).

Tree hollows offer an ideal niche for saproxylic insects in mature Mediterranean forests, where Diptera and Coleoptera are the richest groups. Co-occurrence is frequently observed among many species of both groups in these microhabitats, and some of these species have been considered to facilitate the presence of other species by acting as ecosystem engineers. One of the systems that is found in Mediterranean tree hollows is formed by cetonid (Coleoptera: Cetoniidae) and syrphid (Diptera: Syrphidae) larvae. Here, cetonid larvae feed on wood and litter and produce a substrate that is easier to decompose. To assess the possible role of these larvae as facilitating agents for the saproxylic guild, we studied whether the presence of saprophagous Syrphidae inside tree hollows is associated with the activity of cetonid larvae. Furthermore, in laboratory conditions, we tested whether cetonid larvae activity can improve the development and fitness of the saprophagous syrphid species. Our results show that "cetonid activity" was the variable that best explained the presence of saprophagous syrphid species in natural conditions. Myathropa florea (L., 1758) was one of the species most influenced by this activity. The laboratory experiment gave similar results, demonstrating that an enriched substrate with Cetonia aurataeformis Curti, 1913 larval feces improves syrphid larval growth rate and fitness of adults (measured as longer wing length) of M. florea.

Molecules, wing pattern and distribution: an approach to species delimitation in the "loxurina group" (Lepidoptera: Lycaenidae: Penaincisalia).

The wide range of morphological variations in the "loxurina group" makes taxa identification difficult, and despite several reviews, serious taxonomical confusion remains. We make use of DNA data in conjunction with morphological appearance and available information on species distribution to delimit the boundaries of the "loxurina" group species previously established based on morphology. A fragment of 635 base pairs within the mtDNA gene cytochrome oxidase I (COI) was analysed for seven species of the "loxurina group". Phylogenetic relationships among the included taxa were inferred using maximum parsimony and maximum likelihood methods. Penaincisalia sigsiga (Bálint et al), P. cillutincarae (Draudt), P. atymna (Hewitson) and P. loxurina (C. Felder & R. Felder) were easily delimited as the morphological, geographic and molecular data were congruent. Penaincisalia ludovica (Bálint & Wojtusiak) and P. loxurina astillero (Johnson) represent the same entity and constitute a sub-species of P. loxurina. However, incongruence among morphological, genetic, and geographic data is shown in P. chachapoya (Bálint & Wojtusiak) and P. tegulina (Bálint et al). Our results highlight that an integrative approach is needed to clarify the taxonomy of these neotropical taxa, but more genetic and geographical studies are still required.

Molecules, wing pattern and distribution: an approach to species delimitation in the "loxurina group" (Lepidoptera: Lycaenidae: Penaincisalia)

The wide range of morphological variations in the "loxurina group" makes taxa identification difficult, and despite several reviews, serious taxonomical confusion remains. We make use of DNA data in conjunction with morphological appearance and available information on species distribution to delimit the boundaries of the "loxurina" group species previously established based on morphology. A fragment of 635 base pairs within the mtDNA gene cytochrome oxidase I (COI) was analysed for seven species of the "loxurina group". Phylogenetic relationships among the included taxa were inferred using maximum parsimony and maximum likelihood methods. Penaincisalia sigsiga (Bálint et al), P. cillutincarae (Draudt), P. atymna (Hewitson) and P. loxurina (C. Felder & R. Felder) were easily delimited as the morphological, geographic and molecular data were congruent. Penaincisalia ludovica (Bálint & Wojtusiak) and P. loxurina astillero (Johnson) represent the same entity and constitute a sub-species of P. loxurina. However, incongruence among morphological, genetic, and geographic data is shown in P. chachapoya (Bálint & Wojtusiak) and P. tegulina (Bálint et al). Our results highlight that an integrative approach is needed to clarify the taxonomy of these neotropical taxa, but more genetic and geographical studies are still required.

[Rehabilitation project and tele-monitoring of patients with mildly deteriorating cognition and their caregivers]. / Progetto di intervento riabilitativo e telesorveglianza dedicato a pazienti con deterioramento cognitive di grado lieve ed ai loro caregivers.

Dementia is a highly invalidating condition, constituting one of the major issues that health systems will face in future years. A great amount of research is focused on the looking out for effective therapies for dementia. Moreover, it is well-known that in the next thirty years the request for assistance and support services for patients will dramatically increase. It is also well-known that the perspective of institutionalization of demented patients is often source of anxiety and depression for caregivers. Telemedicine could provide an alternative option monitored by expert health operators and to caregivers the possibility to be supported in their assistance role. The project here presented entails a program of non-pharmacological treatment of cognitive and behavioural disturbances devoted to patients and caregivers, followed by a 12-months telemonitoring intervention, aimed at verifying compliance to treatments, offering constant support to caregivers and ensure patients and caregivers with a prompt access to operators of the Alzheimer Unit in case of sudden onset of health or assistance needs. It is expected that our combined cognitive-behavioural intervention devoted to patients and caregivers, followed by the 12-months telemonitoring program could produce many positive effects. In particular, we expect a slowing down of cognitive decline, a better control of behavioural disturbances and a delay in patients' institutionalization. Moreover, the accomplishment of improved information on disease and assistance options, and the reduction of caregivers' feelings of loneliness and hopelessness might engender the reduction of their anxiety and depression symptoms.

[Caregiver Need Assessment: a questionnaire for caregiver demand]. / Caregiver Need Assessment: uno strumento di analisi dei bisogni del caregiver.

UNLABELLED: Many studies have focused on the importance of the informal care provided by caregivers and on its impact in terms of worsening quality of life and increased burden. The aim of the present study is to analyze the psychometric validity and reliability of the Caregiver Needs Assessment (CNA) questionnaire, which has been built to investigate the needs (related to assistance) perceived by caregivers of severely impaired patients, particularly in the first stages of their illness. METHODS: The CNA was administered to 226 family caregivers (24.3% males) of 197 patients (50.8% males) hospitalized for neuromotor rehabilitation after a stroke, head injury, Lateral Amyotrophic Sclerosis, Parkinson or other severely impairing diseases. RESULTS: The instrument was tested on a large sample (KMO = 0.83) of heterogeneous caregivers. Explorative and confirmatory factor analysis, performed on a two subgroup random subdivision of the sample, showed the presence of two factors with good internal consistency: the factor "needs of emotional and social support" (alpha = 0.765) and the factor "needs of information and communication" (alpha = 0.742). The structural equation modeling confirms the goodness of fit of the 2-factor structure (RMSEA = 0.073; SRMR = 0.1; CFI = 0.96). We observed a positive correlation (p < 0.01) between the factor "needs of emotional and social support" of the CNA and other questionnaires aimed at assessing psychological wellbeing, and between the factor "needs of information and communication" and the factor "needs for knowledge about the disease" of the Family Strain Questionnaire, showing good convergent validity. We also observed high Pearson correlation coefficients (0.942 and 0.965) between test-retest measurements of both factors in the CNA. CONCLUSION: The statistical analysis confirms the good psychometric properties of the CNA questionnaire. For its brevity and ease in compilation the CNA is promising practical tool aimed at assessing caregivers' needs in order to personalize a programme of psychological support, to measure it's outcome and to provide comparison of the different needs in different diseases.

Effectiveness of ezetimibe in routine clinical practice. Effect on lipid profile and other laboratory parameters.

INTRODUCTION AND OBJECTIVES: Dyslipidemia is frequently related to metabolic syndrome, which carries high cardiovascular risk. Statin therapy sometimes fails to achieve the recommended plasma lipid targets. The aim of this study was to evaluate the joint effect of ezetimibe and statin on lipid profile in dyslipidemic patients not achieving target values with statins alone and to determine the action of this combination on cardiovascular risk parameters, as well as its tolerability. METHODS: We performed a descriptive prospective study in 50 consecutive hypercholesterolemic patients treated with statin alone and with poor metabolic control. Lipid profile and plasma concentrations of insulin, ferritin and homocysteine were evaluated after 3 months of combined treatment with ezetimibe. RESULTS: We found a significant reductionin low density lipoproteins (p<0.001), a mean reduction in total cholesterol (p<0.001) and triglycerides (p=0.002), as well as decreases in plasma concentrations of ferritin (p=0,016), insulin (p=0,010) and homocysteine (p<0.001) of 5%, 5% and 14%, respectively. There were no changes in either hepatic or muscular function. CONCLUSIONS: Combined treatment with ezetimibe and statin significantly improved lipid profile in poorly-controlled hypercholesterolemic patients treated with statin alone. There were no collateral effects on either hepatic or muscular parameters and there may be additional benefits on plasma levels of homocysteine, insulin and ferritin.

Computer-based cognitive intervention for dementia: preliminary results of a randomized clinical trial.

Dementia is a highly invalidating condition and, given the progressive aging of the population, one of the major issues that health systems will have to face in future years. Recently there has been an increase in the potential of diagnostic tools and pharmacological treatments for dementia; moreover, considerable interest has been expressed regarding non pharmacological interventions. However, the current evidence in support of non pharmacological treatments in patients affected by dementia still does not allow to draw definitive conclusions on what is the most effective treatment to apply, largely because of methodological difficulties and limitations of the studies so far carried out due to the complex nature of the disease. To address this need, we carried out a single blind randomized controlled study on the efficacy of computer cognitive rehabilitation in patients with mild cognitive decline. We here present preliminary data on 11 patients with diagnosis of Alzheimer's Disease (AD) and mild cognitive decline randomly assigned to treatment (a) or control (b) condition (i.e. specific vs. aspecific treatment). The specific treatment (a) consisted in a cycle of 12 individual sessions of computer exercises, while the control condition (b) consisted in sessions of semi-structured interviews with patients, conducted with the same frequency and time period as (a). Cognitive, behavioural and functional assessment was performed by an expert evaluator, blinded to the patients' group allocation. Preliminary results show a significant performance decline only in the control group at the 9-month follow-up compared to both baseline and the 3-month follow-up. Our results suggest that computer based cognitive training in patients with AD and mild cognitive decline is effective at least in delaying the continuous progression of cognitive impairment in AD.

Agrammatism: a rehabilitative programme centered on treatment of verbal inflections.

Agrammatism is a clinical syndrome characterised by the omission or substitution of bound morphemes (prefixes, inflectional and derivational suffixes) and function words (articles, prepositions, auxiliary verbs). It is a composite reality with different features involved in differing degrees in each patient. Therefore, treatment should be individually tailored and based on an accurate analysis of the specific pathological manifestations. This study describes a rehabilitative programme used in the treatment of an agrammatic patient. Inflectional morphology training was the core of the programme. For the cognitive rehabilitation of the patient AM we followed the idea that the identification of vulnerable skills should be followed by targeted interventions which constitute the phases of a complete rehabilitation programme. Results showed an improvement of AM's performance in each of the verbal abilities treated (output lexicon, phonological programming and verbal inflections). The global amelioration was also evident in the analysis of samples of spontaneous speech and/or picture descriptions in which both quantitative and qualitative improvement was observed at different steps of the rehabilitative programme and at the 1-year follow-up evaluation (after treatment maintenance). AM's aftertreatment amelioration was generalized and prolonged in time. This result even if from the clinical point of view very encouraging, from the experimental point of view constitute a problem, given that the amelioration cannot unambigously be ascribed to the treatment administered. However, our results, considering that our treatment started one-year after onset of symptoms and that the aphasic picture of AM seemed to be stable in the inter-treatment period (our treatment started six months after a post-acute period of treatment) we consider our results and the rehabilitative paradigm here applied worth of interest.

Taxonomy of Iberian Hoplia (Col., Scarabaeoidea, Hopliinae) based on mtDNA analysis.

The morphology of some Hoplia species (Scarabaeoidea: Hopliinae) is so variable that parapatric populations have often been considered different species or subspecies. In this study we analyze the nucleotide sequences of a fragment of mitochondrial gene cytochrome c oxidase subunit I (COI) of six species and two subspecies of Palaearctic Hoplia to reexamine the species limits. Based on the analysis of sequences from COI and morphological and ecological observations, we consider Hoplia freyi Baraud to be a junior synonym of Hoplia chlorophana Erichson and H. philanthus ramburi Heyden to be a junior synonym of H. philanthus philanthus (Fuessly). However, complete resolution of relationships among H. philanthus subspecies requires the addition of sequences from genes evolving faster than COI. Phylogenetic relationships among the species studied are discussed.

Gemcitabine in pre-treated advanced renal carcinoma: a feasibility study.

Eigtheen patients affected by metastatic renal cell carcinoma, 16 which were assesable, were treated with 1 g/m2 of Gemcitabine (GCB) on days 1, 8 and 15 of a 28-day treatment cycle up to a maximun of ten cycles. All patients in neoplastic progression were treated with chemo- and immunotherapy (5 FU, IL-2, IFN alpha d 13-cis-retinoic acid.) Out of the 16 assessable patients, 5/16 (31%) showed overall response (ICR, 4 PR), 5 (31%) stable disease (SD) and 6 (38%) progression of disease (PD). Toxicity was limited to WHO grades I only, primarily hematological.