Small magnetic nanoparticles that have surfaces decorated with stimuli-responsive polymers can be reversibly aggregated via a stimulus, such as temperature, to enable efficient and rapid biomarker separation. To fully realize the potential of these particles, the synthesis needs to be highly reproducible and scalable to large quantity. We have developed a new synthesis for temperature-responsive magnetic nanoparticles via an in situ co-precipitation process of Fe/Fe salts at room temperature with poly(acrylic acid)- block-poly( N-isopropylacrylamide) diblock co-polymer template, synthesized via the reversible addition-fragmentation chain-transfer polymerization method. These particles were 56% polymer by weight with a 6.5:1 Fe/COOH ratio and demonstrated remarkable stability over a 2 month period. The hydrodynamic diameter remained constant at ∼28 nm with a consistent transition temperature of 34 °C, and the magnetic particle separation efficiency at 40 °C was ≥95% over the 2 month span. These properties were maintained for all large-scale synthesis batches. To demonstrate the practical utility of the stimuli-responsive magnetic nanoparticles, the particles were incorporated into a temperature-responsive binary reagent system and efficiently separated a model protein biomarker (mouse IgG) as well as purified extracellular vesicles derived from a human biofluid, seminal plasma. The ease of using these particles will prove beneficial for various biomedical applications.

BACKGROUND. Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the Tyrosinase gene.METHODS. In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals.RESULTS. The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 ± 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient ≥ 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1], P = 0.04) and left eye (OS, 5 [1.0, 9.1], P = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41], P = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2}, P = 0.01]) and biochemically.CONCLUSION. Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials.TRIAL REGISTRATION. ClinicalTrials.gov NCT01838655.FUNDING. Intramural program of the National Eye Institute.

Although it is recognized that an enlarged thyroid may occasionally cause tracheal compression, the incidence in euthyroid goiter is unknown. Twenty patients with nontoxic goiter were investigated for upper airway obstruction. Although none of them had dyspnea as a chief complaint, on direct questioning 9/20 had a history of shortness of breath on exertion and choking sensation. Upper airway obstruction was detected in 7/20 (35%) by roentgenography, 12/20 (60%) by flow volume loop (FVL), and in 16/20 (80%) by combined roentgenography and FVL. After therapy for goiter, there was a reduction in the size of the goiter and an improvement in FVL in the whole group. The statistically significant change occurred in peak expiratory flow (P less than .01) and peak inspiratory flow (P less than .05). These findings and the change in configuration of the curve suggested less upper airway compression. We conclude that goiter often causes unsuspected upper airway obstruction, usually slow in onset and not noticed by the patient.

Introduction It is important to understand albinism, since it is a disorder associated with visual impairment, predisposition to malignant melanomas, and social stigma. The main objective of this article is to review the genetics and biologic mechanisms of the non-syndromic albinism subtypes and to describe associated clinical manifestations. We also discuss research on its treatments. Methods A review of the published literature on albinism subtypes was performed, spanning basic laboratory research, published case reports, and experiences of people with albinism. Results Clear progress has been made in comprehending the causes of albinism; research has shed light on the complexity of the disorder and has led to the molecular classification of subtypes. Discussion Despite the increase in knowledge with regards to albinism, gaps still exist. It is important to continue the pursuit of unraveling the mechanism of the disorder and to monitor the frequency of the subtypes worldwide in order to aid in the development of treatments. Furthermore, disseminating knowledge of albinism is crucial for future progress. Implications for practitioners Albinism is a disorder characterized by hypopigmentation of the hair, skin, and eyes, with accompanying ocular abnormalities that remain relatively stable throughout life. The disorder is defined by a spectrum of pigmentation where albinism is more evident among individuals of dark complexion than their lighter-pigmented peers. Patients with albinism require protection against sun exposure and special resources to address visual impairments. When albinism patients are diagnosed and properly accommodated, they generally report a positive quality of life.