Theranostics - a sure cure for cancer after 100 years?

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field.

Using Machine Learning and Silver Nanoparticle-Based Surface-Enhanced Raman Spectroscopy for Classification of Cardiovascular Disease Biomarkers.

Characterizing complex biofluids using surface-enhanced Raman spectroscopy (SERS) coupled with machine learning (ML) has been proposed as a powerful tool for point-of-care detection of clinical disease. ML is well-suited to categorizing otherwise uninterpretable, patient-derived SERS spectra that contain a multitude of low concentration, disease-specific molecular biomarkers among a dense spectral background of biological molecules. However, ML can generate false, non-generalizable models when data sets used for model training are inadequate. It is thus critical to determine how different SERS experimental methodologies and workflow parameters can potentially impact ML disease classification of clinical samples. In this study, a label-free, broadband, Ag nanoparticle-based SERS platform was coupled with ML to assess simulated clinical samples for cardiovascular disease (CVD), containing randomized combinations of five key CVD biomarkers at clinically relevant concentrations in serum. Raman spectra obtained at 532, 633, and 785 nm from up to 300 unique samples were classified into physiological and pathological categories using two standard ML models. Label-free SERS and ML could correctly classify randomized CVD samples with high accuracies of up to 90.0% at 532 nm using as few as 200 training samples. Spectra obtained at 532 nm produced the highest accuracies with no significant increase achieved using multiwavelength SERS. Sample preparation and measurement methodologies (e.g., different SERS substrate lots, sample volumes, sample sizes, and known variations in randomization and experimental handling) were shown to strongly influence the ML classification and could artificially increase classification accuracies by as much as 27%. This detailed investigation into the proper application of ML techniques for CVD classification can lead to improved data set acquisition required for the SERS community, such that ML on labeled and robust SERS data sets can be practically applied for future point-of-care testing in patients.

A prospective investigation of impacts of comorbid attention deficit hyperactivity disorder (ADHD) on clinical features and long-term treatment response in adult patients with obsessive-compulsive disorder (OCD).

BACKGROUND: A close association between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents has been investigated in previous studies. However, few studies examined the relationship between lifetime comorbidity of ADHD and OCD in adults. Therefore, we sought to investigate the clinical and psychopathological features related to comorbid ADHD in Japanese adult patients with OCD. METHODS: We assessed lifetime comorbidity of ADHD in 93 adult Japanese patients with OCD. Additionally, we used the Japanese version of Conners' Adult ADHD Rating Scales to assess the characteristics and severity of ADHD in each participant. According to the results, we excluded OCD patients that did not have ADHD but who exhibited elevated levels of ADHD traits. We compared OCD patients with ADHD (ADHD+ group) and those without ADHD or its trait (ADHD- group) in terms of background profiles and clinical features, such as OCD symptomatology and psychometric test results. Additionally, the 6-month treatment outcome was compared prospectively between groups. RESULTS: Of the 93 OCD participants, the prevalence of lifetime comorbidity of ADHD was estimated as 16.1%. Compared with the ADHD- group, participants in the ADHD+ group had an earlier age of onset of OCD, higher frequencies of hoarding symptoms, higher levels of depressive and anxiety symptoms and lower quality of life, more elevated levels of impulsivity, and higher rates of substance or behavioral addiction and major depression. Finally, the mean improvement rate on the Yale-Brown Obsessive Compulsive Scale after 6 months of standardized OCD treatment in the ADHD+ group (16.1%) was significantly lower than that in the ADHD- group (44.6%). CONCLUSION: The lifetime comorbidity of ADHD is likely to exert a significant effect on clinical features and treatment outcome in adult patients with OCD. It is important to consider that underlying ADHD pathology may function as a facilitator for increased severity of global clinical features and treatment refractory conditions in OCD patients. Further studies are required to examine treatment strategies for such patients.

Capsule robot pose and mechanism state detection in ultrasound using attention-based hierarchical deep learning.

Ingestible robotic capsules with locomotion capabilities and on-board sampling mechanism have great potential for non-invasive diagnostic and interventional use in the gastrointestinal tract. Real-time tracking of capsule location and operational state is necessary for clinical application, yet remains a significant challenge. To this end, we propose an approach that can simultaneously determine the mechanism state and in-plane 2D pose of millimeter capsule robots in an anatomically representative environment using ultrasound imaging. Our work proposes an attention-based hierarchical deep learning approach and adapts the success of transfer learning towards solving the multi-task tracking problem with limited dataset. To train the neural networks, we generate a representative dataset of a robotic capsule within ex-vivo porcine stomachs. Experimental results show that the accuracy of capsule state classification is 97%, and the mean estimation errors for orientation and centroid position are 2.0 degrees and 0.24 mm (1.7% of the capsule's body length) on the hold-out test set. Accurate detection of the capsule while manipulated by an external magnet in a porcine stomach and colon is also demonstrated. The results suggest our proposed method has the potential for advancing the wireless capsule-based technologies by providing accurate detection of capsule robots in clinical scenarios.

Treatment of acquired perforant dermatoses with allopurinol / Tratamento de dermatose perfurante adquirida com alopurinol

Perforating dermatoses are papulonodular cutaneous pathologies characterized by transepithelial extrusion of components of the extracellular matrix of the dermis, by inflammation or degeneration. When secondary, the systemic diseases are called Acquired Perforating Diseases. Our letter aims to report a case of acquired perforating dermatoses secondary to chronic renal dialysis. The treatment with Allopurinol proved to be effective in this case. Allopurinol would act as an antioxidant, reducing the inflammatory reaction in tissues and consequent damage to the collagen fibers (AU)

Dermatoses perfurantes são patologias cutâneas papulonodulares que se caracterizam pela extrusão transepitelial de componentes da matriz extracelular da derme, por inflamação ou degeneração. Quando são secundárias as doenças sistêmicas são chamadas Doenças Perfurantes Adquiridas. Nossa carta tem como objetivo relatar caso de dermatose perfurante adquirida secundária a insuficiência renal crônica dialítica. O tratamento com Alopurinol se mostrou eficaz neste caso. O Alopurinol atuaria como antioxidante, reduzindo a reação inflamatória nos tecidos e consequentes danos nas fibras colágenas (AU)

Fabrication of Customizable Intraplaque Hemorrhage Phantoms for Magnetic Resonance Imaging.

PURPOSE: Magnetic resonance (MR) imaging detection of methemoglobin, a molecular marker of intraplaque hemorrhage (IPH), in atherosclerotic plaque is a promising method of assessing stroke risk. However, the multicenter imaging studies required to further validate this technique necessitate the development of IPH phantoms to standardize images acquired across different scanners. This study developed a set of phantoms that modeled methemoglobin-laden IPH for use in MR image standardization. PROCEDURES: A time-stable material mimicking the MR properties of methemoglobin in IPH was created by doping agarose hydrogel with gadolinium and sodium alginate. This material was used to create a phantom that consisted of 9 cylindrical IPH sites (with sizes from 1 to 8 mm). Anatomical replicas of IPH-positive atherosclerosis were also created using 3D printed molds. These plaque replicas also modeled other common plaque components including a lipid core and atheroma cap. T1 mapping and a magnetization-prepared rapid acquisition gradient echo (MPRAGE) carotid imaging protocol were used to assess phantom realism and long-term stability. RESULTS: Cylindrical phantom IPH sites possessed a T1 time of 335 ± 51 ms and exhibited little change in size or MPRAGE signal intensity over 31 days; the mean (SD) magnitude of changes in size and signal were 6.4 % (2.7 %) and 7.3 % (6.7 %), respectively. IPH sites incorporated into complex anatomical plaque phantoms exhibited contrast comparable to clinical images. CONCLUSIONS: The cylindrical IPH phantom accurately modeled the short T1 time characteristic of methemoglobin-laden IPH, with the IPH sites exhibiting little variation in imaging properties over 31 days. Furthermore, MPRAGE images of the anatomical atherosclerosis replicas closely matched those of clinical plaques. In combination, these phantoms will allow for IPH imaging protocol standardization and thus facilitate future multicenter IPH imaging.

The influence of intelligence and cognitive abilities on the reading ability of Japanese students with developmental disorders.

OBJECTIVE: We examined the differences in reading skills between Japanese students with developmental dyslexia (DD) having developmental disorders who had borderline IQ (BIQ) and those who had normal IQ (NIQ), and the influence of cognitive factors through subscale scores of the Wechsler Intelligence Scale for Children - Fourth Edition on the reading skills of all students with DD having developmental disorders. METHODS: One-way analysis of variance revealed differences in reading scores among the four groups (DD with NIQ, DD with BIQ, as well as non-DD with NIQ and non-DD with BIQ as control groups). To examine the influence of cognitive factors, we used multiple regression analysis for all participants, and then for participants with DD. RESULTS: Regarding hiragana nonword fluency reading, no difference was observed between the two DD groups, and cognitive factors did not affect the performance of all participants with DD. Concerning hiragana word fluency reading, DD with NIQ group performed better than DD group with BIQ, and working memory index affected reading skills of participants with DD. Regarding kanji accuracy reading, DD with NIQ group performed better than DD with BIQ group, and processing speed index affected performance of participants with DD. CONCLUSIONS: The results of hiragana reading suggest that the two DD groups shared similar weak sub-lexical route processing, while the acquisition of lexical route processing was hindered by lower IQ and weak phonological working memory in transparent phonographic hiragana reading. For kanji reading, lower IQ and weak visuomotor processing ability hampered the learning of visually complex logographic kanji characters.

Evaluation of hemodynamic changes using near-infrared spectroscopy in patients with tic-related obsessive-compulsive disorder.

AIM: A tic-related specifier is included in the DSM-5 diagnostic criteria to identify a clinically specific obsessive-compulsive disorder (OCD) subtype. The current study sought to evaluate hemodynamic changes during executive function tasks among OCD patients with and without a lifetime history of tic disorder (TD) and healthy controls, and to investigate the relation between brain activation and clinical variables in each group using structured equation modeling. METHODS: Twenty-nine OCD patients diagnosed according to the DSM-IV-TR and 15 healthy controls were recruited. Patients were divided into two groups according to the presence or absence of a lifetime history of TD (TD+, n = 11; TD-, n = 18). Prefrontal hemodynamic changes were measured using multi-channel near-infrared spectroscopy during the Verbal Fluency Task, Trail-Making Task, and Tower of London (ToL) Task. RESULTS: There were significant brain activation differences in the frontopolar cortex between OCD patients with and without TD during Verbal Fluency Task and ToL performance. Brain activation in the dorsolateral prefrontal cortex (DLPFC) during the ToL Task in OCD patients with TD exerted a direct causal effect on the severity of compulsions. In addition, we detected a direct causal effect of the severity of obsessions in OCD patients without TD on brain activation in the DLPFC during the ToL Task. CONCLUSION: Brain activation in the frontopolar cortex exhibits different hemodynamics depending on the task, and DLPFC function may play a different role in the neural basis of developing OCD symptoms between OCD patients with and without TD.

Tunable rainbow light trapping in ultrathin resonator arrays.

Rainbow light trapping in plasmonic devices allows for field enhancement of multiple wavelengths within a single device. However, many of these devices lack precise control over spatial and spectral enhancement profiles and cannot provide extremely high localised field strengths. Here we present a versatile, analytical design paradigm for rainbow trapping in nanogroove arrays by utilising both the groove-width and groove-length as tuning parameters. We couple this design technique with fabrication through multilayer thin-film deposition and focused ion beam milling, which enables the realisation of unprecedented feature sizes down to 5 nm and corresponding extreme normalised local field enhancements up to 103. We demonstrate rainbow trapping within the devices through hyperspectral microscopy and show agreement between the experimental results and simulation. The combination of expeditious design and precise fabrication underpins the implementation of these nanogroove arrays for manifold applications in sensing and nanoscale optics.

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing.

Nanoscale perfluorocarbon (PFC) droplets have enormous potential as clinical theranostic agents. They are biocompatible and are currently used in vivo as contrast agents for a variety of medical imaging modalities, including ultrasound, computed tomography, photoacoustic and 19F-magnetic resonance imaging. PFC nanodroplets can also carry molecular and nanoparticulate drugs and be activated in situ by ultrasound or light for targeted therapy. Recently, there has been renewed interest in using PFC nanodroplets for hypoxic tumor reoxygenation towards radiosensitization based on the high oxygen solubility of PFCs. Previous studies showed that tumor oxygenation using PFC agents only occurs in combination with enhanced oxygen breathing. However, recent studies suggest that PFC agents that accumulate in solid tumors can contribute to radiosensitization, presumably due to tumor reoxygenation without enhanced oxygen breathing. In this study, we quantify the impact of oxygenation due to PFC nanodroplet accumulation in tumors alone in comparison with other reoxygenation methodologies, in particular, carbogen breathing. Methods: Lipid-stabilized, PFC (i.e., perfluorooctyl bromide, CF3(CF2)7Br, PFOB) nanoscale droplets were synthesized and evaluated in xenograft prostate (DU145) tumors in male mice. Biodistribution assessment of the nanodroplets was achieved using a fluorescent lipophilic indocarbocyanine dye label (i.e., DiI dye) on the lipid shell in combination with fluorescence imaging in mice (n≥3 per group). Hypoxia reduction in tumors was measured using PET imaging and a known hypoxia radiotracer, [18F]FAZA (n≥ 3 per group). Results: Lipid-stabilized nanoscale PFOB emulsions (mean diameter of ~250 nm), accumulated in the xenograft prostate tumors in mice 24 hours post-injection. In vivo PET imaging with [18F]FAZA showed that the accumulation of the PFOB nanodroplets in the tumor tissues alone significantly reduced tumor hypoxia, without enhanced oxygen (i.e., carbogen) breathing. This reoxygenation effect was found to be comparable with carbogen breathing alone. Conclusion: Accumulation of nanoscale PFOB agents in solid tumors alone successfully reoxygenated hypoxic tumors to levels comparable with carbogen breathing alone, an established tumor oxygenation method. This study confirms that PFC agents can be used to reoxygenate hypoxic tumors in addition to their current applications as multifunctional theranostic agents.

Polyelectrolyte Coatings Can Control Charged Fluorocarbon Nanodroplet Stability and Their Interaction with Macrophage Cells.

Fluorocarbon nanodroplets, ∼100 to ∼400 nm in diameter, are of immense interest in a variety of medical applications including the imaging and therapy of cancer and inflammatory diseases. However, fluorocarbon molecules are both hydrophobic and lipophobic; therefore, it is challenging to synthesize fluorocarbon nanodroplets with the optimal stability and surface properties without the use of highly specialized surfactants. Here, we hypothesize that we can decouple the control of fluorocarbon nanodroplet size and stability from its surface properties. We use a simple, two-step procedure where standard, easily available anionic fluorosurfactants are used to first stabilize the fluorocarbon nanodroplets, followed by electrostatically attaching functionalized polyelectrolytes to the nanodroplet surfaces to independently control their surface properties. Herein, we demonstrate that PEGylated polyelectrolyte coatings can effectively alter the fluorocarbon nanodroplet surface properties to reduce coalescence and its uptake into phagocytic cells in comparison with non-PEGylated polyelectrolyte coatings and uncoated nanodroplets, as measured by flow cytometry and fluorescence microscopy. In this study, perfluorooctyl bromide (PFOB) was used as a representative fluorocarbon material, and PEGylated PFOB nanodroplets with diameters between 250 and 290 nm, depending on the poly(ethylene glycol) block length, were prepared. The PEGylated PFOB nanodroplets had superior size stability in comparison with uncoated and non-PEGylated polyelectrolyte nanodroplets in saline and within macrophage cells. Of significance, non-PEGylated nanodroplets were rapidly internalized by macrophage cells, whereas PEGylated nanodroplets were predominantly colocalized on the cell membrane. This suggests that the PEGylated-polyelectrolyte coating on the charged PFOB nanodroplets may afford adjustable shielding from cells of the reticuloendothelial system. This report shows that using the same fluorosurfactant as a base layer, modularly assembled PFOB nanodroplets tailored for a variety of end applications can be created by selecting different polyelectrolyte coatings depending on their unique requirements for stability and interaction with phagocytic cells.

Ten-year follow-up study of Japanese patients with obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is a well-known chronic illness. This study retrospectively investigated 10-year outcomes and associated clinical factors in Japanese OCD patients. We focused on the impact of several sociocultural factors, including medical expenses and insurance systems specific to each country, on the differences or biases in follow-up procedures of OCD. METHODS: Seventy-nine patients diagnosed with OCD who received a standardized combination of treatments for 10 continuous years were divided into three groups according to their improvement rates on the Yale-Brown Obsessive-Compulsive Scale after 10 years of treatment. RESULTS: A survival analysis revealed that the rate of patients achieving full remission increased every year. Following 10 years of treatment, 56% of OCD patients experienced 'full remission' for at least 1 year. Consequently, 48% exhibited full remission, and 37% exhibited partial remission at the end-point of this study. We identified several factors that were predictive of poorer outcomes, including lower Global Assessment of Functioning Scale scores and the presence of hoarding symptoms or involvement behaviors. In addition, improvement rates after 1 year significantly predicted better 10-year outcomes. CONCLUSION: Our findings highlight the transcultural nature of long-term outcomes of OCD treatment, which appear to be independent of sociocultural differences.

Impaired Visuospatial Short-Term Memory in Children with ADHD.

Previous studies provide clear evidence that visuospatial memory performance in children with attention-deficit/hyperactivity disorder (ADHD) is significantly lower than in typically developing children. In the present study, we investigated a major cause of their low performance using a spatial span test. Possibly, inattention resulting from lack of motivation or interest causes their low performance so that they do not correctly encode targets to be remembered. On the other hand, a deficit in temporary maintenance per se may cause their low performance; that is, their inefficient use of rehearsal during a retention interval may lead to memory traces' fast decay. Results in this study indicated that children with ADHD could sustain attention during the encoding phase. Furthermore, their performance at delayed recall was significantly lower than immediate recall, but delayed recall did not affect typically developing children's performance. These results provide evidence for the likelihood that a factor causing children with ADHD difficulty in temporarily maintaining visuospatial information is fast decay of memory traces as a result of inefficient use of rehearsal, not inattention in the encoding phase.

18F-Labeled perfluorocarbon droplets for positron emission tomography imaging.

INTRODUCTION: Nanoscale perfluorocarbon (PFC) droplets have been used to create imaging agents and drug delivery vehicles. However, development and characterization of new formulations of PFC droplets are hindered because of the lack of simple methods for quantitative and sensitive assessment of whole body tissue distribution and pharmacokinetics of the droplets. To address this issue, a general-purpose method for radiolabeling the inner core of nanoscale perfluorocarbon droplets with a hydrophobic and lipophobic fluorine-18 compound was developed, so that positron emission tomography (PET) and quantitative biodistribution studies can be employed to evaluate PFC nanodroplets in vivo. METHODS: A robust method to produce [18F]CF3(CF2)7(CH2)3F from a tosylate precursor using [18F]F- was developed. The product's effectiveness as a general label for different PFCs and its ability to distinguish the in vivo behavior of different PFC droplet formulations was evaluated using two types of PFC nanodroplets: fluorosurfactant-stabilized perfluorohexane (PFH) nanodroplets and lipid-stabilized perfluorooctylbromide (PFOB) nanodroplets. In vivo assessment of the 18F-labeled PFH and PFOB nanodroplets were conducted in normal mice following intravenous injection using small animal PET imaging and gamma counting of tissues and fluids. RESULTS: [18F]CF3(CF2)7(CH2)3F was produced in modest yield and was stable with respect to loss of fluoride in vitro. The labeled fluorocarbon was successfully integrated into PFH nanodroplets (~175 nm) and PFOB nanodroplets (~260 nm) without altering their mean sizes, size distributions, or surface charges compared to their non-radioactive analogues. No leakage of the radiolabel from the nanodroplets was detected after droplet formation in vitro. PET imaging and biodistribution data for the two droplet types tested showed significantly different tissue uptake and clearance patterns. CONCLUSION: A convenient method for producing 18F-labeled PFC droplets was developed. The results highlight the potential utility of the strategy for pre-clinical evaluation of different PFC droplet formulations through direct PFC core labeling using a fluorinated radiolabel.

Methods of Generating Submicrometer Phase-Shift Perfluorocarbon Droplets for Applications in Medical Ultrasonography.

Continued advances in the field of ultrasound and ultrasound contrast agents have created new approaches to imaging and medical intervention. Phase-shift perfluorocarbon droplets, which can be vaporized by ultrasound energy to transition from the liquid to the vapor state, are one of the most highly researched alternatives to clinical ultrasound contrast agents (i.e., microbubbles). In this paper, part of a special issue on methods in biomedical ultrasonics, we survey current techniques to prepare ultrasound-activated nanoscale phase-shift perfluorocarbon droplets, including sonication, extrusion, homogenization, microfluidics, and microbubble condensation. We provide example protocols and discuss advantages and limitations of each approach. Finally, we discuss best practice in characterization of this class of contrast agents with respect to size distribution and ultrasound activation.

Altered frontal pole development affects self-generated spatial working memory in ADHD.

BACKGROUND: Spatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. METHOD: Using near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5 ± 1.6 years-old) and 35 TD children (9.0 ± 1.6 years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. RESULTS: Both groups showed a negative correlation with age and number of errors [ADHD: r(28)=-0.37, p=0.040; TD: r(33)=-0.59, p<0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p=0.013; 11ch; r(33)=0.44, p=0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p=0.049; 13ch; r(33)=0.54, p=0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p=0.021; 11ch: t(61)=2.05, p=0.044]. CONCLUSION: Children with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.

Size reduction of cosolvent-infused microbubbles to form acoustically responsive monodisperse perfluorocarbon nanodroplets.

Perfluorocarbon (PFC) nanodroplet agents are exciting new biomaterials that can be remotely vapourized by ultrasound or light to change into micron-scale gas bubbles in situ. After PFC nanodroplet vapourization, the micron-scale gas bubble can interact strongly with ultrasound radiation, such that the bubbles can be used for cancer imaging and therapy. For these phase-change agents to be useful, however, PFC nanodroplets must be produced in the range of 100 to 400 nm in diameter with high size control and monodispersity, restrictions that remain a challenge. Here, we address this challenge by taking advantage of the size control offered by microfluidics, in combination with the size reduction provided by cosolvent-infused PFC bubbles through both condensation and cosolvent dissolution. In this approach, PFC bubbles with a high percentage of cosolvent (in this study, diethyl ether, DEE) are produced using microfluidics at a temperature above the boiling point. After synthesis, these bubbles become much smaller through both condensation of the gas into liquid droplets and from dissolution of the DEE into the continuous phase. This approach demonstrates that monodisperse, cosolvent-incorporated PFC bubbles can directly form monodisperse PFC nanodroplets a factor of 24 times smaller than the precursor bubbles. We also demonstrate that these nanoscale droplets can be converted to echogenic microbubbles after exposure to ultrasound, showing that these PFC nanodroplets are viable for the in situ production of ultrasound contrast agents. We show that this system can overcome the minimum droplet size limit of standard microfluidics, and is a powerful new tool for generating monodisperse, PFC phase-change ultrasound contrast agents for treating and imaging cancer.

Clinically related or predictive factors and impacts on long-term treatment outcomes of involvement behaviors in patients with obsessive-compulsive disorder.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) frequently exhibit involvement behaviors (IBs) in which they accommodate their caregivers to their OCD symptoms by 1) asking them for reassurance, 2) forcing them to participate in their rituals, or 3) forcing them to assist in avoidance according to the patients' rules or demands. Such behaviors correspond to those of their caregivers, and are referred to as family accommodation (FA). METHODS: We performed multifactorial comparisons between 256 OCD patients with and without IBs in order to examine the clinical characteristics and long-term treatment outcomes of OCD patients with IBs. A multiple logistic regression analysis was also performed to identify the related and predictive factors of IBs. RESULTS: A total of 108 out of the 256 OCD patients examined (42%) were determined to exhibit IBs. OCD patients with IBs were differentially characterized by demographic and phenomenological characteristics (e.g. female predominance and poorer insight), more severe psychopathological features (e.g. lower GAFS, higher anxiety, or a depressive status), and poorer treatment outcomes. Furthermore, the predictive factors of IBs such as being female, having a higher compulsive score, and lower GAFS were identified by logistic analyses and structural equation modeling. CONCLUSION: The presence of IBs correlated with the severe clinical features, treatment refractoriness, and poorer long-term outcome of OCD. The severity of compulsions, being female, and lower GAFS were identified as predictive factors for the presence of IBs. Similar to FA, these findings appear to support the effectiveness of early identification and family-focused intervention in the treatment of OCD patients with IBs.