The Use of Dermal Substitute in the Treatment of Burns as a Complication of Type 2 Diabetes Mellitus and Diabetic Foot Syndrome.

Diabetic Foot Syndrome is a complex and challenging clinical condition associated with high risk of mortality and lower limb amputation. The distal lesions represent the epiphenomenon of this syndrome and request a multidisciplinary care and an appropriate therapeutic path to ensure their healing. This case report describes the management of burns in a patient with type 2 diabetes mellitus, end stage renal disease and Diabetic Foot Syndrome. The lesions were treated with autologous epidermal skin graft until healing. Products that stimulate or replace extracellular matrix, which has a central role in wound healing, can be consider in the treatment of burns and offer a simpler and less disabling reconstructive possibility for the patient.

Low-Cost Hyperspectral Imaging to Detect Drought Stress in High-Throughput Phenotyping.

Recent developments in low-cost imaging hyperspectral cameras have opened up new possibilities for high-throughput phenotyping (HTP), allowing for high-resolution spectral data to be obtained in the visible and near-infrared spectral range. This study presents, for the first time, the integration of a low-cost hyperspectral camera Senop HSC-2 into an HTP platform to evaluate the drought stress resistance and physiological response of four tomato genotypes (770P, 990P, Red Setter and Torremaggiore) during two cycles of well-watered and deficit irrigation. Over 120 gigabytes of hyperspectral data were collected, and an innovative segmentation method able to reduce the hyperspectral dataset by 85.5% was developed and applied. A hyperspectral index (H-index) based on the red-edge slope was selected, and its ability to discriminate stress conditions was compared with three optical indices (OIs) obtained by the HTP platform. The analysis of variance (ANOVA) applied to the OIs and H-index revealed the better capacity of the H-index to describe the dynamic of drought stress trend compared to OIs, especially in the first stress and recovery phases. Selected OIs were instead capable of describing structural changes during plant growth. Finally, the OIs and H-index results have revealed a higher susceptibility to drought stress in 770P and 990P than Red Setter and Torremaggiore genotypes.

Photodynamic Topical Antimicrobial Therapy for Infected Diabetic Foot Ulcers in Patients With Diabetes: A Case Series.

Diabetic foot ulcers (DFUs) are common, complex, costly complications, associated with frequent recurrences and increased morbidity and mortality. DFUs can be prevented and their healing can be mostly influenced by appropriately and aggressively managing any infection, but the role of antiseptic therapies in reducing healing time lacks sufficient evidence. Several therapeutic interventions have been developed based on the principles of photomedicine to overcome the issue of poor drug circulation in infected areas, with the aim of killing microbial agents while leaving the surrounding host cells unharmed. Such techniques use absorption of photons by specific chromophores. Among these, RLP068 is a tetracationic Zn(II) phthalocyanine derivative activated by exposure to red light, used as a topical treatment for superficial bacterial and fungal infections. The photoactivation of RLP068 results in the production of singlet oxygen and other reactive oxygen species, able to affect a range of cellular targets, including cell membrane and/or wall, cytoplasm, and cellular components, resulting in a rapid, broad range, bactericidal and fungicidal effect. The phase IIa study showed that photoactivated RPL068 is capable of inducing a dose-dependent reduction in total and pathogen microbial load in infected diabetic foot ulcers. In this article, a case series of 22 DFU treated with photoactivated RLP068 at 5 different centers in Italy is presented. Considering microbial agents reduction, ulcer healing facilitation, healing rate (9 DFUs out of 22), and amputation rate (only 1 case over 22), the decrease in the cost of DFU seems to be a point in favor of RLP068 and its cost-effectiveness.

Sustainable Bioactive Packaging Based on Thermoplastic Starch and Microalgae.

This study combines the use of corn starch and Tetradesmus obliquus microalgae for the production of antioxidant starch films as flexible packaging material. Starch was plasticized with glycerol and blended with 1 w% polyallylamine chosen as an agent to modify the film physical properties. The addition of polyallylamine improved film water stability and water vapor transmission rate as well as mechanical stiffness and tenacity. The dried Tetradesmus obliquus microalgae, which showed an EC50 value of 2.8 mg/mg DPPH (2.2-Diphenyl-1-picrylhydrazyl radical), was then used as antioxidant filler. The addition of microalgae provided the films with good antioxidant activity, which increased with microalgae content increasing. To our knowledge, this is the first study reporting the development of sustainable bioactive packaging films composed of almost 100% starch, and follows the European union's goals on plastics strategy concerning the promotion of bio-based, compostable plastics and the setting up of approaches to prevent food waste with a simple plastic packaging.

Native Arbuscular Mycorrhizal Fungi Characterization from Saline Lands in Arid Oases, Northwest China.

Arbuscular mycorrhizal fungi (AMF) colonize land plants in almost every ecosystem, even in extreme conditions, such as saline soils. In the present work, we report the mycorrhizal capacity of rhizosphere soils collected in the dry desert region of the Minqin Oasis, located in the northwest of China (Gansu province), which is characterized by several halophytes. Lycium spp. and Peganum nigellastrum were used as trap plants in a greenhouse experiment to identify autochthonous AMF associated with the halophytes' rhizospheres. Morphological observations showed the typical AMF structures inside roots. Twenty-six molecularly distinct AMF taxa were recovered from soil and root DNA. The taxonomical diversity mirrors the several AMF adapted to extreme environmental conditions, such as the saline soil of central China. Knowledge of the AMF associated with halophytes may contribute to select specific fungal isolates to set up agriculture strategies for protecting non-halophyte crop plants in saline soils.

Do halophytes and glycophytes differ in their interactions with arbuscular mycorrhizal fungi under salt stress? A meta-analysis.

BACKGROUND: Halophytes are better than glycophytes at employing mechanisms to avoid salt injury, but both types of plants can undergo damage due to high soil salinity. Arbuscular mycorrhizal fungi (AMF) can mitigate the damage from salt stress in both halophytes and glycophytes by enhancing salt tolerance and improving energy efficiency. However, variations in mycorrhizal symbiotic efficiency between halophytes and glycophytes were still poorly understood. Therefore, we evaluated the magnitude of AMF effects on plant growth and determined the mechanisms that regulate the growth response of halophytes and glycophytes by performing a meta-analysis of 916 studies (from 182 publications). RESULTS: Arbuscular mycorrhizal fungi significantly enhance biomass accumulation, osmolytes synthesis (soluble sugar and soluble protein), nutrients acquisition (nitrogen, phosphorus, and potassium ion), antioxidant enzyme activities (superoxide dismutase and catalase), and photosynthetic capacity (chlorophyll and carotenoid contents, photosynthetic rate, stomatal conductance, and transpiration rate). AMF also substantially decreased sodium ion acquisition and malondialdehyde levels in both halophytes and glycophytes under salt stress conditions. Mycorrhizal halophytes deploy inorganic ions (potassium and calcium ions) and limited organic osmolytes (proline and soluble sugar) to achieve energy-efficient osmotic adjustment and further promote biomass accumulation. Mycorrhizal glycophytes depend on the combined actions of soluble sugar accumulation, nutrients acquisition, sodium ion exclusion, superoxide dismutase elevation, and chlorophyll synthesis to achieve biomass accumulation. CONCLUSIONS: Arbuscular mycorrhizal fungi inoculation is complementary to plant function under salt stress conditions, not only facilitating energy acquisition but also redistributing energy from stress defence to growth. Glycophytes are more dependent on AMF symbiosis than halophytes under salt stress conditions.

Continuous Movement Monitoring of Daily Living Activities for Prevention of Diabetic Foot Ulcer: A Review of Literature.

Lower extremity ulcers represent the most ominous, feared, and costly complications of diabetes mellitus. The aim of this review is to highlight the role of daily life physical activities (PAs) and continuous movement monitoring (CMM) in the prevention of foot ulcers. Peripheral neuropathy and peripheral vascular disease are the main causes of foot ulceration and contribute, in turn, to the development of additional risk factors such as foot deformities and/or joint and muscular alterations. Moreover, a deficit of balance, posture abnormalities, followed by gait alterations, increases the risk of ulceration. PA can play a key role in the management of patients with diabetes and in the prevention of ulcers; however, even if it has been reported that some of these risk factors significantly improve after a few weeks of exercise therapy (ET), the real preventive role of ET has not yet been demonstrated. These uncertain results can occur due to some limitations in the management of the same relationship between PA and diabetic foot prevention. Technological advances during the last years enable timely management of overall daily PA. The use of these modern technologies and devices allows CMM assessment and description of daily PA even in the long term. The data collected from these devices can be used to properly manage patients' PA and thus contribute to the prevention of foot ulcers.

Tapentadol Prolonged Release Reduces the Severe Chronic Ischaemic Pain and Improves the Quality of Life in Patients with Type 2 Diabetes.

This study has been performed in diabetic type 2 patients with pain due to peripheral artery disease (PAD) in order to evaluate the efficacy and tolerability of tapentadol prolonged release (PR). Methods. 25 patients with type 2 diabetes (13 F and 12 M) were admitted in the study. The evaluation of the analgesic efficacy of tapentadol PR was based on both the assessment of the intensity of the pain (NRS scale from 0 to 10) and the nature of the pain (DN4 questionnaire) and on assessment of the patient's quality of life and state of health (SF-12 Health Survey). Study duration was 3 months: a baseline visit and follow-up included visits after 1 week, 1 month, 2 months, and 3 months. Results. At the beginning of the study, the mean intensity of the pain was 7.88 ± 1.17 on the NRS scale and at visit 2 it reduced in a statistically significant way; at the end of the treatment with tapentadol PR, the mean intensity was 2.84 points on the NRS scale. Conclusion. In type 2 diabetic patients with chronic severe pain due to PAD, tapentadol PR reduced pain intensity, improving the quality of life.

Hospitalization for Charcot neuroarthropathy in diabetes: A population study in Italy.

AIMS: To provide data on hospitalization and incidence rates of Charcot neuroarthropathy (CN) and its relation to lower limbs' amputations/revascularizations in population with diabetes of Italy as well as of one of its regions (Tuscany). METHODS: Hospitalizations with CN diagnosis (codes ICD-9-CM: 7130, 7135, 7138) have been recorded in people with diabetes over years 2003-2013 in Italy and 2008-2015 in Tuscany. Amputations, peripheral vascular disease, revascularizations and infections were likewise evaluated. RESULTS: Between 2003 and 2013 CN hospitalizations were very infrequent in Italy ranging between 14×100,000 and 11×100,000 patients with diabetes. In Tuscany they declined to a minimum of 7×100,000 patients in 2015, after a previous increase to a maximum of 22×100,000 (p=NS for both). Yearly CN incidence remained constant in Italy, declining in Tuscany to a minimum of 3.4×100,000 diabetic patients in 2015 (p=0.047). CN patients were younger and with longer length of hospital stay than those with non-Charcot diabetic foot (p<0.05 for both). Amputation and infection rates were manifold higher in CN patients than in those with non-Charcot diabetic foot, while the revascularization rate was similar in both. CONCLUSIONS: Over last decade, in Italy and Tuscany yearly CN incidence and hospitalization rates concerned only a small percentage of patients, remaining constant over years and declining in Tuscany in the last couple of years. CN was significantly associated to younger age, longer hospital stay and greater risk of amputations and infections while the need of revascularization was similar to that of non-Charcot diabetic foot.

Pilot study investigating the prognostic significance of thymidine phosphorylase expression in patients with metastatic breast cancer: a single institution retrospective analysis.

BACKGROUND: The thymidine phosphorylase (TP) enzyme is expressed in higher levels in cancer tissue when compared with normal tissue. It is involved in the intratumoral activation of widely prescribed pyrimidine-derived antimetabolites such as 5'-deoxy-5-fluorouridine and capecitabine (Xeloda(®)). The purpose of this study was to determine the clinical correlation between TP expression in tumor tissue and the clinical outcome of capecitabine-based therapy in patients with locally advanced (stage III) or metastatic breast cancer (stage IV). METHODS: The following variables were analyzed as potential determinants of benefit from a capecitabine-based therapy: TP expression, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor-2 status, and Ki67 status. This was accomplished by immunohistochemical analysis of paraffin-embedded cancer tissues from 18 patients with breast cancer treated with at least one cycle of capecitabine. Clinical outcome was measured as time to progression. RESULTS: TP staining intensities in both the invasive and in situ components in patients with lobular and ductal carcinomas were reported. Higher levels of TP in the invasive component were expressed in ER-negative tumors when compared with ER-positive tumors (P<0.05). The ER-positive group expressing lower levels of TP had a median time to progression of 13 months compared with the ER-negative group expressing higher levels of TP which had a median time to progression of 7.5 months (P=0.14). CONCLUSION: Patients with ER-positive tumors expressing lower levels of TP exhibit a longer time to progression when compared with patients with ER-negative tumors. Consequently, tumor TP expression does not seem to predict the outcome of capecitabine-based chemotherapy.

The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer.

AIMS: Evaluation of how ankle joint mobility (AJM) can be useful in the identification of patients with diabetes at risk of foot ulcer (FU). METHODS: Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87 patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects. Patients with diabetes were followed up for diagnosis of FU over the next 8 years and subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2) and those who had history of first ulceration detected by the 8th year of the evaluation period (7 type 2). RESULTS: Aging and diabetes caused a significant reduction in mobility of each of the movements investigated (p<0.001), whereas after adjusting for the confounding effect of age, diabetes specifically reduced plantar flexion (p<0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups (p<0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). CONCLUSIONS: Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk.

Custom-made orthesis and shoes in a structured follow-up program reduces the incidence of neuropathic ulcers in high-risk diabetic foot patients.

OBJECTIVE: The objective of this study was to assess the impact of a structured follow-up program on the incidence of diabetic foot ulceration (DFU) in high-risk diabetic patients. RESEARCH DESIGN AND METHODS: A total of 1874 diabetic patients referred to the Diabetic Foot Unit of the University of Pisa were ranked based on the ulcerative risk score proposed by the International Consensus on Diabetic Foot. Out of 334 patients (17.8%) with a score ≥2, 298 accepted to participate in this prospective trial and were randomized into 2 groups: group A, which received standard treatment, and group B, in which the patients received, as a part of a structured prevention program, custom-made orthesis and shoes. Incidence of new DFUs was observed for no less than 1 year and in a subset of patients after 3 and 5 years, respectively. Incidence of new DFUs and recurrences were considered as primary endpoints to establish the effectiveness of the program; costs were also compared. RESULTS: Among the patients enrolled in this follow-up analysis, 46% had neuropathy and deformities, 20% had previous ulceration, 25% had previous minor amputation, and 9% had neuro-osteoarthropathy. During the first 12-month follow-up, 11.5% of patients in group B developed a DFU compared with 38.6% in group A (P < .0001). In the extended follow-up, the cumulative incidence of ulcer in group B compared with group A was 17.6% versus 61% (P < .0001) after 3 years and 23.5% versus 72% (P < .0001) after 5 years, respectively. The net balance at the end of the follow-up was highly in favor of the prevention program, with a saving of more than €100 000 per year. CONCLUSIONS: The implementation of a structured follow-up with the use of orthesis and shoes can reduce the incidence of DFU in diabetic patients who are at high ulcerative risk and its related costs.

Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients.

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.

Microbiology at first visit of moderate-to-severe diabetic foot infection with antimicrobial activity and a survey of quinolone monotherapy.

Samples from 1295 patients with diabetic foot infection were evaluated; 4332 samples were collected with an average of 3.3 samples per patient. Fifty-seven percent of patients had a 2B ulcer and 23% had a 3B ulcer according to Texas University Classification. In 64.2% of samples collected at first visit an etiologic agent was identified. About 40% of the positive samples were polymicrobial. Gram positive bacteria were more frequently isolated (52.6%), Staphylococcus aureus was the most frequently isolated single agent (29.9%) and MRSA was 22% of S. aureus. Enterococcus spp., mainly Enterococcus faecalis, were 9.9%, all vancomycin susceptible except 2 isolates. Streptococci were 4.6%, more than 60% Streptococcus agalactiae. Gram negative rods were 40.6%, with enterobacteria 23.5% and Pseudomonas aeruginosa 10.3%. Anaerobes were only 0.3%, probably due to culture methods applied in our laboratory. Cotrimoxazole, rifampin and doxycycline were still active against S. aureus. ESBL producers, among enterobacteria, were 10%, mainly Escherichia coli and Proteus spp. Only colistin had a rate of susceptibility against P. aeruginosa above 90%. Levofloxacin had the best clinical activity with respect to the other quinolones, but when it failed, selected more resistant strains with respect to moxifloxacin among S. aureus and with respect to ciprofloxacin among P. aeruginosa.

Use of nanotechnology-designed footsock in the management of preulcerative conditions in the diabetic foot: results of a single, blind randomized study.

The Difoprev system constituted by a sock loaded with nanocapsules containing a hydrating agent in the diabetic foot is tested. A total of 30 neuropathic outpatients with foot anhydrosis were randomized into group A, treated with the application of the sock with the nanocapsules, and group B wearing only the socks without the nanocapsules. Patients were blindly evaluated with a clinical score, hygrometry, transepidermal water loss, skin temperature, and skin hardness at baseline and after 6 weeks. No difference between the groups emerged at baseline. Although group B showed no changes at the end of the treatment, group A significantly (P< .05) improved in all the parameters evaluated. No adverse events were recorded in both groups during the study. The use of hydrating agents carried by nanocapsules-loaded socks is safe and effective for the neuropathic diabetic foot.

Clinical outcomes of wide postsurgical lesions in the infected diabetic foot managed with 2 different local treatment regimes compared using a quasi-experimental study design: a preliminary communication.

The safety and efficacy of a novel superoxidized solution (Dermacyn Wound Care [DWC], Oculus Innovative Sciences, Petaluma, Calif) was evaluated for the treatment of wide postsurgical infected ulcers of the diabetic foot. A group (group A, n = 18) of patients with diabetes mellitus who had postsurgical lesions > 5 cm(2) without ischemia or infection were recruited consecutively and treated with DWC-saturated dressings. These dressings were renewed once daily and were compared with a group of patients that had been previously treated with diluted povidone iodine (group B, n = 15) using a quasi-experimental study design. Both sets of patients also received standard systemic antibiotic therapy, as per the practice in this center, and local surgical debridement. Patients had weekly assessments until wounds had re-epithelialized completely. Patients in group A had statistically significant shorter healing time and duration of antibiotic therapy and a higher healing rate at 6 months compared with those in group B (p < .01). Recurrence of infection, requirement for debridement procedures, and requirement for minor amputations were significantly less frequent during follow-up in group A patients (p < .05) when compared with those in group B. These preliminary data suggest that DWC used as a wound dressing together with other local and systemic therapies may have a role in reducing healing time as well as complications in patients with diabetes who have postsurgical lesions of the diabetic foot. These data propose the need for a robust controlled study of DWC-saturated dressings to explore its full potential.

An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast.

OBJECTIVE: This study was designed to test the safety, effectiveness, and costs of off-loading with a novel, off-the-shelf irremovable device in the management of diabetic foot ulceration (DFU). RESEARCH DESIGN AND METHODS: We prospectively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic outpatients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up, number and severity of adverse events, healing time, costs and applicability of the device, and patients' satisfaction between those randomly assigned to total contact casting (TCC; group A) or to the Optima Diab walker (group B). Deep or infected ulcers were excluded. RESULTS: No difference between groups A and B was observed in healing rates at 12 weeks (95 vs. 85%), healing time (6.5 +/- 4.4 vs. 6.7 +/- 3.4 weeks), and number of adverse events (six versus four). Treatment was significantly less expensive in group B, which showed a mean reduction of costs of 78% compared with group A (P < 0.001). Practicability was more favorable in group B, with a reduction of 77 and 58% of the time required for application and removal of the devices, respectively (P < 0.001). Patients' satisfaction with the treatment was higher in group B (P < 0.01). CONCLUSIONS: The Optima Diab walker is as safe and effective as TCC in the management of DFU, but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot.

Mesoscopic and microscopic investigation on poly(vinyl alcohol) hydrogels in the presence of sodium decylsulfate.

The structure of poly(vinyl alcohol) (PVA) hydrogels formed as a result of freeze/thaw treatments of aqueous solutions of the polymer (11 wt % PVA) in the freshly prepared state is analyzed through the combined use of small (SANS) and ultrasmall (USANS) angle neutron scattering techniques. The structure of these hydrogels may be described in terms of polymer rich regions, with dimensions of the order of 1-2 microm, dispersed in a water rich phase, forming two bicontinuous phases. The PVA chains in the polymer rich phase form a network where the cross-linking points are mainly crystalline aggregates of PVA having average dimensions of approximately 45 A. The structural organization of freeze/thaw PVA hydrogel membranes does not change either after rehydration of dried gels or in the presence of a tensile force. Finally, addition of surfactant micelles inside the gel provides a formulation with both hydrophobic and hydrophilic regions, which demonstrates the potential of the system for drug delivery. Both SANS and EPR measurements show that sodium decylsulfate (C10OS) micelles do not significantly interact with the PVA gel. Variation of the gel structure by the number of freeze/thaw cycles should modulate the rate of release of an active constituent, for example, in a dermal patch.

Characterization of antisense oligonucleotides comprising 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (FANA): specificity, potency, and duration of activity.

Antisense oligonucleotides (AON) are being developed for a wide array of therapeutic applications. Significant improvements in their serum stability, target affinity, and safety profile have been achieved with the development of chemically modified oligonucleotides. Here, we compared 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (FANA)-containing AONs with phosphorothioate oligodeoxynucleotides (PS-DNA), 2'-O-methyl-RNA/DNA chimeras and short interfering RNAs (siRNA) with respect to their target knockdown efficacy, duration of action and resistance to nuclease degradation. Results show that two different configurations of FANA/DNA chimeras (altimers and gapmers) were found to have potent antisense activity. Specific target inhibition was observed with both FANA configurations with an estimated EC50 value comparable to that of an siRNA but 20-to 100-fold lower than the other commonly used AONs. Moreover, the FANA/DNA chimeras showed increased serum stability that was correlated with sustained antisense activity for up to 4 days. Taken together, these results indicate that chimeric FANA/DNA AONs are promising new tools for therapeutic gene silencing when increased potency and duration of action are required.

Improvements in siRNA properties mediated by 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (FANA).

RNA interference (RNAi) has emerged recently as an efficient mechanism for specific gene silencing. Short double-stranded small interfering RNAs (siRNAs) are now widely used for cellular or drug target validation; however, their use for silencing clinically relevant genes in a therapeutic setting remains problematic because of their unfavourable metabolic stability and pharmacokinetic properties. To address some of these concerns, we have investigated the properties of siRNA modified with 2'-deoxy-2'-fluoro-beta-d-arabinonucleotide units (araF-N or FANA units). Here we provide evidence that these modified siRNAs are compatible with the intracellular RNAi machinery and can mediate specific degradation of target mRNA. We also show that the incorporation of FANA units into siRNA duplexes increases activity and substantially enhances serum stability of the siRNA. A fully modified sense 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (FANA) strand when hybridized to an antisense RNA (i.e. FANA/RNA hybrid) was shown to be 4-fold more potent and had longer half-life in serum (approximately 6 h) compared with an unmodified siRNA (<15 min). While incorporation of FANA units is well tolerated throughout the sense strand of the duplex, modifications can also be included at the 5' or 3' ends of the antisense strand, in striking contrast to other commonly used chemical modifications. Taken together, these results offer preliminary evidence of the therapeutic potential of FANA modified siRNAs.