Nanomedicines: From Bench to Bedside and Beyond

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients.     

Development of a shoulder-mounted robot for MRI-guided needle placement: phantom study

Purpose

This paper presents new quantitative data on a signal-to-noise ratio (SNR) study, distortion study, and targeting accuracy phantom study for our patient-mounted robot (called Arthrobot). Arthrobot was developed as an MRI-guided needle placement device for diagnostic and interventional procedures such as arthrography.

Methods

We present the robot design and inverse kinematics. Quantitative assessment results for SNR and distortion study are also reported. A respiratory motion study was conducted to evaluate the shoulder mounting method. A phantom study was conducted to investigate end-to-end targeting accuracy. Combined error considering targeting accuracy, respiratory motion, and structure deformation is also reported.

Results

The SNR study showed that the SNR changes only 2% when the unpowered robot was placed on top of a standard water phantom. The distortion study showed that the maximum distortion from the ground truth was 2.57%. The average error associated with respiratory motion was 1.32 mm with standard deviation of 1.38 mm. Results of gel phantom targeting studies indicate average needle placement error of 1.64 mm, with a standard deviation of 0.90 mm.

Conclusions

Noise and distortion of the MR images were not significant, and image quality in the presence of the robot was satisfactory for MRI-guided targeting. Combined average total error, adding mounting stability errors and structure deformation errors to targeting error, is estimated to be 3.4 mm with a standard deviation of 1.65 mm. In clinical practice, needle placement accuracy under 5 mm is considered sufficient for successful joint injection during shoulder arthrography. Therefore, for the intended clinical procedure, these results indicate that Arthrobot has sufficient positioning accuracy.

     

Revealing the WEDM Process Parameters for the Machining of Pure and Heat-Treated Titanium (Ti-6Al-4V) Alloy

Ti-6Al-4V is an alloy that has a high strength-to-weight ratio. It is known as an alpha-beta titanium alloy with excellent corrosion resistance. This alloy has a wide range of applications, e.g., in the aerospace and biomedical industries. Examples of alpha stabilizers are aluminum, oxygen, nitrogen, and carbon, which are added to titanium. Examples of beta stabilizers are titanium–iron, titanium–chromium, and titanium–manganese. Despite the exceptional properties, the processing of this titanium alloy is challenging when using conventional methods as it is quite a hard and tough material. Nonconventional methods are required to create intricate and complex geometries, which are difficult with the traditional methods. The present study focused on machining Ti-6Al-4V using wire electrical discharge machining (WEDM) and conducting numerous experiments to establish the machining parameters. The optimal setting of the machining parameters was predicted using a multiresponse optimization technique. Experiments were planned using the response surface methodology (RSM) technique and analysis of variance (ANOVA) was used to determine the significance and contribution of the input parameters to changes in the output characteristics (cutting speed and surface roughness). The cutting speed obtained during the processing of the annealed titanium alloy using WEDM was quite large as compared to the cutting speed obtained in the case of processing the pure, quenched, and hardened titanium alloys using WEDM. The maximum cutting speed obtained while processing the annealed titanium alloy was 1.75 mm/min.     

In-Vitro Analysis of FeMn-Si Smart Biodegradable Alloy

Special materials are required in many applications to fulfill specific medical or industrial necessities. Biodegradable metallic materials present many attractive properties, especially mechanical ones correlated with good biocompatibility with vivant bodies. A biodegradable iron-based material was realized through electric arc-melting and induction furnace homogenization. The new chemical composition obtained presented a special property named SME (shape memory effect) based on the martensite transformation. Preliminary results about this special biodegradable material with a new chemical composition were realized for the chemical composition and structural and thermal characterization. Corrosion resistance was evaluated in Ringer’s solution through immersion tests for 1, 3, and 7 days, the solution pH was measured in time for 3 days with values for each minute, and electro-corrosion was measured using a potentiostat and a three electrode cell. The mass loss of the samples during immersion and electro-corrosion was evaluated and the surface condition was studied by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). SME was highlighted with differential scanning calorimetry (DSC). The results confirm the possibility of a memory effect of the materials in the wrought case and a generalized corrosion (Tafel and cyclic potentiometry and EIS) with the formation of iron oxides and a corrosion rate favorable for applications that require a longer implantation period.     

Fluoride Treatment and In Vitro Corrosion Behavior of Mg-Nd-Y-Zn-Zr Alloys Type

Fluoride conversion coatings on Mg present many advantages, among which one can find the reduction of the corrosion rate under “in vivo” or “in vitro” conditions and the promotion of the calcium phosphate deposition. Moreover, the fluoride ions released from MgF₂ do not present cytotoxic effects and inhibit the biofilm formation, and thus these treated alloys are very suitable for cardiovascular stents and biodegradable orthopedic implants. In this paper, the biodegradation behavior of four new magnesium biodegradable alloys that have been developed in the laboratory conditions, before and after surface modifications by fluoride conversion (and sandblasting) coatings, are analyzed. We performed structural and surface analysis (XRD, SEM, contact angle) before and after applying different surface treatments. Furthermore, we studied the electrochemical behavior and biodegradation of all experimental samples after immersion test performed in NaCl solution. For a better evaluation, we also used LM and SEM for evaluation of the corroded samples after immersion test. The results showed an improved corrosion resistance for HF treated alloy in the NaCl solution. The chemical composition, uniformity, thickness and stability of the layers generated on the surface of the alloys significantly influence their corrosion behavior. Our study reveals that HF treatment is a beneficial way to improve the biofunctional properties required for the studied magnesium alloys to be used as biomaterials for manufacturing the orthopedic implants.     

Antiepileptic drugs in posttraumatic stress disorder

Antiepileptic drugs might be effective in the treatment of patients with Posttraumatic Stress Disorder, a condition with unmet pharmacologic needs. We review the literature on the efficacy and tolerability of antiepileptic drugs in Posttraumatic Stress Disorder, both case reports and open studies, as well as controlled studies if available. The results of the studies will be presented together with their methodological limitations (e.g., open trials, use of additional medications, and lack of use of standardized scales for Posttraumatic Stress Disorder). The effects of antiepileptic drugs on kindling, a suggested pathogenesis for Posttraumatic Stress Disorder are overviewed, and suggestions for further research are raised.     

Kleptomania: comorbid psychiatric diagnosis in patients and their families

OBJECTIVES: Kleptomania, defined by DSM-IV as the inability to resist the impulse to steal objects which are not needed for personal use or for their monetary value, may reflect a form of obsessive-compulsive spectrum disorder and/or affective spectrum disorder. METHODS: Twenty-one kleptomanic patients and 57 first-degree relatives completed a semistructured DSM-IV-based interview and questionnaires. Questionnaires are: the HDRS-17 (the Hamilton Rating Scale for Depression), the HARS (Hamilton Rating Scale for Anxiety), the Y-BOCS (Yale-Brown Obsessive Compulsive Scale), the YMRS (Young Mania Rating Scale). The two groups were compared to demographically matched normal controls (n = 64). RESULTS: We found a high prevalence of affective and anxiety disorders in our sample of kleptomanic patients and their first-degree relatives. In addition, the scores on the HDRS, HARS, and Y-BOCS were significantly higher in the study group than in the control group. CONCLUSIONS: Our finding of a high prevalence of psychiatric comorbidity in kleptomanic patients could lead to the development of new treatment strategies for this disorder. Furthermore, the pattern of psychiatric disorders seen in the first-degree relatives can lead to new insights about the nosology and etiopathology of kleptomania.