Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Individual placement and support focusing on employment and education for young people at clinical high risk of psychosis: A feasibility study.

OBJECTIVE: This study aimed to assess the feasibility of implementing Individual Placement and Support (IPS) with a focus on educational and employment goals, within a clinical service for the early detection of individuals at clinical high risk (CHR) of psychosis. METHOD: Between June 2019 and April 2021, participants were recruited and received up to 6 (± 2) months support. Primary outcome: Enrolled participants, attended sessions, and disengagement rates were analyzed to assess feasibility. SECONDARY OUTCOMES: Enrollment in mainstream education or/and employment, hours spent working or/and studying, salary, level of functioning, and self-efficacy at baseline and follow-up were compared. RESULTS: Thirty-one participants were recruited, 13 of whom were remotely recruited after the first COVID-19 lockdown. Dropout rates were relatively low (16.1%), and 26 participants (83.9%) completed the program. Each participant received on average nine sessions (M = 9.65; SD = 4.92). Secondary outcomes: At follow-up, 73.1% participants were employed, working on average more hours per week, t(25) = -2.725; p = .012, and were earning significantly more money, t(25) = -3.702; p = .001, compared to baseline. Gains in educational outcomes were less clear. Global Assessment of Functioning, t = 248.50; p = .001, and Social Occupational Functioning, t(25) = -3.273; p = .003, were significantly higher at 6-month follow-up compared to baseline. No differences were found in participants' self-efficacy. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings indicate that research procedures are appropriate and that IPS implementation within a CHR clinical team is feasible. Secondary outcomes also suggest that IPS may be a beneficial intervention for young people at CHR. A longer follow-up might be needed to assess its impact on educational outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Insights on metal pollution of a Patagonia watershed: A case study in the lower course of the Negro river, Argentina.

This study evaluated the occurrence and distribution of largely known pollutants (Ag, Cd, Cu, Cr, Hg, Ni, Pb, Pd, and Zn), as well as emerging ones (Li, and V) in the water dissolved fraction, suspended particulate matter, and surface sediments from the lower course of the Negro River, Argentina. There are scarce preceding data on inorganic pollution in the entire watershed and, in the case of the emerging pollutants, there are almost no studies performed worldwide. Sampling was conducted in 2019 at six sampling sites, three of them mostly river dominated and the rest under marine domain. The samples were subjected to an acid digestion in a microwave digester, and analyzed using an Inductively Coupled Plasma Atomic Emission Spectrometer. Results: revealed that Cu, Li, V, and Zn were always on the top four of the highest average metal concentrations in water and sediment fractions. The pollution assessment indicated that the watershed might be exposed to anthropogenic pollution, as over 60% of Cu and Zn, and over 85% of Hg in water dissolved samples from the marine dominated sites were above the maximum recommended values from guidelines. The multivariate analyses characterized the watershed into two clusters, with metals in the sediment fraction mainly contributing to the uppermost sites. Indeed, sedimentary Cu and Zn background enrichment indices pointed out a moderate pollution of the river dominated sites. This study highlights the relevance of an integrative approach in metal pollution evaluation, as the results denoted a progressive deterioration of the watershed, affecting the water quality of the lower course of the Negro River and its adjacent coastal zone. Overall, these results contribute to a more complete evaluation of the potential to fulfill the Sustainable Development Goals, with implications for future treatment strategies to enhance the environmental quality of the area.

Water quality analysis based on phytoplankton and metal indices: a case study in the Sauce Grande River Basin (Argentina).

The increasing landscape alterations due to anthropogenic activities is of global concern since it affects aquatic ecosystems, often resulting in compromise of the ecological integrity and the water quality. In this sense, the evaluation, monitoring, and prediction of the aquatic ecosystem quality becomes an important research subject. This study presents the first integrated water quality assessment of the Sauce Grande River Basin, in Argentina, based on the spatial distribution of the phytoplankton community, the physicochemical parameters, and the metal concentrations (Cd, Cu, Cr, Fe, Mn, Ni, Pb, and Zn) found in the particulate fraction. According to the trophic indices and the phytoplankton abundance, composition, and diversity, the water quality showed significant deterioration in the lower basin after the Sauce Grande lake. The trophic state index indicated that water was oligotrophic in over 75% of the sampling sites, increasing downstream, where two sites were characterized as mesotrophic, and one described as hypertrophic. The phytoplankton community was dominated by diatoms in zones with low anthropogenic impact and conductivity, whereas high densities of Euglenophyta, Chlorophyta, and Cyanobacteria were found in the middle-lower basin, associated with higher organic matter and eutrophication. The conductivity, turbidity, and most metal concentrations also increased towards the downstream area, even exceeding recommended levels for the metals Cu, Cr, Mn, and Pb in the middle and lower reaches of the basin (Cu: 3.5 µg L-1; Cr: 2.4 µg L-1; Pb: 1.2 µg L-1; Mn 170 µg L-1). This study generates a database for the water quality of the Sauce Grande River Basin and sets an example of how the water quality varies along a basin that crosses different topographic environments, land covers, and anthropogenic influences.

The positive climate impact of the Mediterranean diet and current divergence of Mediterranean countries towards less climate sustainable food consumption patterns.

The Mediterranean diet (MD) is a world-renowned healthy dietary pattern. In the present study we analyse the climate sustainability of the MD and the greenhouse gas emissions (EGHG) associated with current dietary patterns in Mediterranean and non-Mediterranean EU countries, focusing on the major deviations from the MD health and environmental targets in Mediterranean countries. The EGHG associated with dietary patterns were calculated for seven Mediterranean countries (Cyprus, Croatia, Greece, Italy, Portugal, Spain and Malta, referred to as 7MED) and the other 21 countries in the EU 28 (referred to as 21OTHER), using 2017 as the reference year. A new harmonised compilation of 3449 carbon footprint values of food commodities, based on a standardised methodology to extract information and assign optimal footprint values and uncertainties to food items, was used to estimate EGHG of food consumption. Our findings show that the EGHG associated with the ideal MD pattern, 2.3 kg CO2equivalents (CO2eq) capita-1 d-1, are in line with planetary GHG climate targets, though GHG emissions associated with food consumption in Mediterranean countries strongly diverged from the ideal MD. Both MED and 21OTHER countries were found to have comparable dietary associated EGHG (4.46 and 4.03 kg CO2eq capita-1 d-1 respectively), almost double that expected from a sustainable dietary pattern. The primary factor of dietary divergence in 7MED countries was found to be meat overconsumption, which contributed to 60% of the EGHG daily excess (1.8 kg of CO2eq capita-1 d-1).

Sexual Desire and Body Image. Gender Differences and Correlations before and during COVID-19 Lockdown.

Recent literature has extensively examined sexual behavior during lockdown due to COVID-19. However, there are no recent studies that have considered the relationship between body image quality, sexual arousability, and sexual anxiety. The present study has two main objectives: (1) to examine gender differences in bodily and sexual experience; and (2) the comparison of bodily and sexual experience, before and during the COVID-19 lockdown. A total of 301 adult subjects (161 women and 140 men) aged between 16 and 73 years (Mean = 37.4; S.D. = 10.3) participated in the study. Data on biographical information were collected via an online panel. The Body Uneasiness Test (BUT) and the Sexual Arousability Inventory (SAI) were used for the assessment. Univariate ANOVA showed worse scores for women, compared with men, in terms of body image avoidance, depersonalization, overall severity of body image quality, sexual arousability, and sexual anxiety dimensions. When compared against time, only women showed significant correlations between the function of sexual arousal and all parameters concerning body image alteration. Interestingly, these correlations were weak and sporadic before lockdown, but strong and numerous during lockdown. This finding suggests that the impact of COVID-19 restrictions affected the female population more, with a profound repercussion on self-image and sexual and mental well-being.

Synthetic microfibers and tyre wear particles pollution in aquatic systems: Relevance and mitigation strategies.

Evidence shows that the majority of aquatic field microplastics (MPs) could be microfibers (MFs) which can be originated directly from massive sources such as textile production and shedding from garments, agricultural textiles and clothes washing. In addition, wear and tear of tyres (TRWPs) emerges as a stealthy major source of micro and nanoplastics, commonly under-sampled/detected in the field. In order to compile the current knowledge in regards to these two major MPs sources, concentrations of concern in aquatic environments, their distribution, bulk emission rates and water mitigation strategies were systematically reviewed. Most of the aquatic field studies presented MFs values above 50%. MPs concentrations varied from 0.3 to 8925 particles m-3 in lakes, from 0.69 to 8.7 × 106 particles m-3 in streams and rivers, from 0.16 to 192000 particles m-3 estuaries, and from 0 to 4600 particles m-3 in the ocean. Textiles at every stage of production, use and disposal are the major source of synthetic MFs to water. Laundry estimates showed an averaged release up to 279972 tons year-1 (high washing frequency) from which 123000 tons would annually flow through untreated effluents to rivers, streams, lakes or directly to the ocean. TRWPs in the aquatic environments showed concentrations up to 179 mg L-1 (SPM) in runoff river sediments and up to 480 mg g-1 in highway runoff sediments. Even though average TRWR emission is of 0.95 kg year-1 per capita (10 nm- 500 µm) there is a general scarcity of information about their aquatic environmental levels probably due to no-availability or inadequate methods of detection. The revision of strategies to mitigate the delivering of MFs and TRWP into water streams illustrated the importance of domestic laundry retention devices, Waste Water Treatment Plants (WWTP) with at least a secondary treatment and stormwater and road-runoff collectors quality improvement devices.

Continental microplastics: Presence, features, and environmental transport pathways.

Microplastics (MPs) are ubiquitous contaminants of great concern for the environment. MPs' presence and concentration in the air, soil, marine, and freshwater environments have been reported as a matter of priority in recent years. This review addresses the current knowledge of the main pathways of MPs in air, soil, and freshwater reservoirs in order to provide an integrated understanding of their behaviors in the continental environment. Therefore, MPs' occurrence (as particle counts), sources, and how their features as shape, size, polymer composition, and density could influence their transport and final sink were discussed. Wind resuspension and atmospheric fallout, groundwater migration, runoff from catchments, and water flow from rivers and effluents were pointed as the principal pathways. MPs' size, shape, polymer composition, and density interact with environmental variables as soil structure and composition, precipitation, wind, relative humidity, water temperature, and salinity. Sampling designs for MPs research should further consider soil characteristics, climate variability and extreme events, time lag and grasshopper effects, morphological and hydrological features of aquatic systems, and water currents, among others. Furthermore, long-term monitoring and lab experiments are still needed to understand MPs' behavior in the environment. This information will provide a unified understanding of the continental MPs pathways, including the key main findings, knowledge gaps, and future challenges to understand this emerging contaminant.

Assessing threats, regulations, and strategies to abate plastic pollution in LAC beaches during COVID-19 pandemic.

Plastic use and production have dramatically increased globally over the past 65 years with the improvement of life quality by the daily use of plastic products. Still, around 50% of the plastic produced is disposable products that generate substantial waste. Several reports pointed out the adverse effects of plastic litter in coastal environments in recent years, emphasizing single-use plastics (SUP). In this manner, Latin America and the Caribbean (LAC) coastal environments are highly vulnerable due to wastewater treatment facilities scarcity and poor plastic waste management strategies. Since COVID-19 pandemic, the single-use plastic waste/person rate is expected to rise due to the use of personal protective equipment and SUP as health care measures. Based on literature research and the review of plastic waste regulations, this paper will assess the main COVID-19 plastic pollution threats and LAC beaches' regulations to suggest possible measures to abate this problem. The main findings suggest that unifying the ongoing fragmented and overlapped policies is key to abate plastic pollution, including plastic industry regulations and circular economies. In addition, increasing public risk perception about plastic pollution is critical to reducing plastic waste generation. Research advances in the adverse effects of plastic debris could improve the public's perception of plastic pollution risk, pushing forward global marine plastic governance.

First evidence of microplastics in nine lakes across Patagonia (South America).

Microplastics (MPs) on lakes have been reported mainly from Europe, Asia, and North America. Then, this study aimed to address the quantification and identification of MPs in nine lakes from the Argentine Patagonian Region. Blue colored fibers were dominant, with a size range between 0.2 and <0.4 mm. The mean MPs concentration was 0.9 ± 0.6 MPs m-3, suggesting a low pollution state when compared to other worldwide lakes. Raman microscopy analysis showed a predominance of Indigo Blue Polyethylene terephthalate (PET) particles. The upper-gradient runoff from urban settlements, textiles, and fisheries were identified as the main MPs sources and levels positively correlated with the higher area, shallower depth, and with an end-position in the watershed. These findings fill a gap in the geographical distribution knowledge, setting a baseline that emphasizes the need for better treatment of urban and fisheries wastes in continental lakes.

Microplastics integrating the zooplanktonic fraction in a saline lake of Argentina: influence of water management.

This study address for the first time in Argentina and the South American continent the effect of water management on the presence of microplastics (MPs) in a shallow lake, assessing their contribution to the zooplankton fraction. Water samples were collected in the lake and its principal affluent, an irrigation channel, from winter 2018 to summer 2019 with a zooplankton net (47 µm). MPs were present in all analyzed samples, with a dominance of fibers, black color, and ≤ 1000 µm range size. MPs concentration was maximum during summer at the lake (180 MPs m-3) while during spring (140 MPs m-3) at the channel. Rotifers and cyclopoids dominated the zooplanktonic fraction at both sites which range sizes (< 200 to 600 µm) included most of the size range found for MPs (50-950 µm). According to our results, the MPs found represents a potential risk for the first levels of the food web. In the lake, the concentration of MPs concerning total zooplankton abundance was higher when the channel was closed. Nevertheless, when the channel was open, the higher concentration in summer matches with the increase of tourism and an extraordinary rainfall. Our results suggest that while the runoff of agro-industrial waste regulates the MPs concentration in the channel, its water management, the touristic activities, and the runoff of MPs from nearby urban settlements regulate the concentration of MPs in the lake. These findings emphasize the need for better treatment of urban and agro-industrial waste that develops near continental aquatic systems, mainly in those where tourism activities are frequent and treatment facilities scarce.

Fat Grafting for Treatment of Facial Burns and Burn Scars.

This article presents the authors' experience with the use of fat grafting via the Coleman technique, for the adjuvant treatment of facial burn wounds and their sequelae. It demonstrates the regenerative effects of fat injected under the wound and/or the scar as well as of fat delivered to the debrided surface of the wound and to the surface of the scar after laser treatment or microneedling.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

Valorization of Rhizoclonium sp. algae via pyrolysis and catalytic pyrolysis.

The valorization of Rhizoclonium sp. algae through pyrolysis for obtaining bio-oils is studied in this work. The reaction is carried out at 400°C, at high contact time. The bio-oil has a practical yield of 35% and is rich in phytol. Besides, it is simpler than the corresponding to lignocellulosic biomass due to the absence of phenolic compounds. This property leads to a bio-oil relatively stable to storage. In addition, heterogeneous catalysts (Al-Fe/MCM-41, SBA-15 and Cu/SBA-15), in contact with algae during pyrolysis, are analyzed. The general trend is that the catalysts decrease the concentration of fatty alcohols and other high molecular weight products, since their mild acidity sites promote degradation reactions. Thus, the amount of light products increases upon the use of the catalysts. Particularly, acetol concentration in the bio-oils obtained from the catalytic pyrolysis with SBA-15 and Cu/SBA-15 is notably high.

Autism spectrum disorders and intestinal microbiota.

Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder-not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesize that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD.

Fat grafting for treatment of burns, burn scars, and other difficult wounds.

This article presents the authors' 3-year experience with the use of fat grafting, via the Coleman technique, for the adjuvant treatment of burn wounds, venous ulcers, diabetic ulcers, and burn scars. It demonstrates the regenerative effects of fat injected under the scar, and of fat injected under the wound, in the periphery of the wound, and within a bone fracture line or space, and of fat deposited over the wound.

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders.

Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytes - especially in children - have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation.

Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells.

The pharmacological potential of curcumin (CURC) is severely restricted because of its low water solubility/absorption, short half-life and poor bioavailability. To overcome these issues, CURC-loaded nanoparticles (NPs) were produced by a double emulsion technique. In particular, NPs were made up of an amphiphilic blend of poloxamers and PLGA to confer stealth properties to the NPs to take advantage of the enhanced permeability and retention (EPR) effect. Different surface properties of NPs made up of bare PLGA and PLGA/poloxamer blend were confirmed by the different interactions of these NPs with serum proteins and also by their ability to be internalized by mesothelioma cell line. The uptake of PLGA/poloxamer NPs induces a persistent block in G0/G1 phase of the cell cycle up to 72 h, thus overcoming the drug tolerance phenomenon, normally evidenced with free CURC.

Salivary Microbiota Associated with Immunoglobulin A Nephropathy.

This study aimed at investigating the salivary microbiota of 28 patients affected by immunoglobulin A nephropathy (IgAN). Fourteen healthy volunteers (HC) were used as control. Compared to HC, the number of some cultivable bacteria groups (e.g., total anaerobes) significantly (P < 0.05) decreased in the salivary samples of IgAN patients. Total bacteria from salivary samples of IgAN patients and HC subjects were analyzed by pyrosequencing of 16S rRNA gene. Paired t test showed no significant (P > 0.05) differences of alpha-diversity parameters (OTU, ACE, Chao1, and Shannon index) between the salivary samples of HC and IgAN patients. The difference for the community structure was further analyzed using three phylogeny-based beta-diversity measures. Compared to HC, the ratio between Firmicutes/Proteobacteria markedly decreased in IgAN patients. Gemella haemolysins, Granulicatella adiacens, and Veillonella parvula were positively associated (P < 0.05) with HC. Within the phylum Bacteroidetes, Prevotella species (Prevotella nigrescens, Prevotella intermedia, Prevotella pallens, and Prevotella salivae) were the highest in HC. The only exception was for Prevotella aurantiaca. Compared to HC, the percentage of abundance of some species, belonging to Pasteurellaceae family (e.g., Haemophylus parainfluenzae), increased in IgAN patients. Fusobacteriaceae (Fusobacterium) and Corynebacterium sp. also differed between the salivary samples of HC and IgAN patients.

Combined anticancer therapies: an overview of the latest applications.

Tumor resistance and low drug efficacy prompt to investigate new therapeutic strategies that have high efficacy and low toxicity, especially for cancers with poor prognosis. This goal has been recently achieved using particular pharmaceutical combination or nanotechnologies to specifically deliver drugs at the tumor site. Novel combined treatments employ either naturally active ingredients or drugs already intended for other uses, with the aim to increase cell sensitivity to therapy and reduce drug toxicity. Combined treatments usually improve the overall therapeutic efficacy of the single drug. Drug-drug interactions allow synergistic effects. Several evidences indicate that synergy can be affected by drug-drug ratio and drug administration order. Therapeutic efficacy can be enhanced through drug entrapment in nanocarriers that allow a site-specific targeting, resulting in a build-up of the drug in the tumor with a significant toxicity reduction. Several studies investigated combined entrapment of two or more drugs each one characterized by different mechanisms of action. These nanosystems improve synergistic efficacy and could be a device to resolve toxicity and multi-drug resistance. Nano-encapsulation of anticancer agents by targeting specific tumor tissues significantly optimizes drug bioavailability, biocompatibility and therapeutic efficacy. The efficacy of these formulations results from receptor-mediated endocytosis and prolonged circulation time. Drug encapsulation also allows using limited final concentration while avoiding its activity within the blood circulation. In this review we report recent findings about novel combined treatment focusing on synergistic effects and mechanisms of action. We will also overview the latest drug delivery system and their therapeutic benefits in cancer treatment.