SARS-CoV-2 variant introduction following spring break travel and transmission mitigation strategies.

BACKGROUND: University spring break carries a two-pronged SARS-CoV-2 variant transmission risk. Circulating variants from universities can spread to spring break destinations, and variants from spring break destinations can spread to universities and surrounding communities. Therefore, it is critical to implement SARS-CoV-2 variant surveillance and testing strategies to limit community spread before and after spring break to mitigate virus transmission and facilitate universities safely returning to in-person teaching. METHODS: We examined the SARS-CoV-2 positivity rate and changes in variant lineages before and after the university spring break for two consecutive years. 155 samples were sequenced across four time periods: pre- and post-spring break 2021 and pre- and post-spring break 2022; following whole genome sequencing, samples were assigned clades. The clades were then paired with positivity and testing data from over 50,000 samples. RESULTS: In 2021, the number of variants in the observed population increased from four to nine over spring break, with variants of concern being responsible for most of the cases; Alpha percent composition increased from 22.2% to 56.4%. In 2022, the number of clades in the population increased only from two to three, all of which were Omicron or a sub-lineage of Omicron. However, phylogenetic analysis showed the emergence of distantly related sub-lineages. 2022 saw a greater increase in positivity than 2021, which coincided with a milder mitigation strategy. Analysis of social media data provided insight into student travel destinations and how those travel events may have impacted spread. CONCLUSIONS: We show the role that repetitive testing can play in transmission mitigation, reducing community spread, and maintaining in-person education. We identified that distantly related lineages were brought to the area after spring break travel regardless of the presence of a dominant variant of concern.

Occipital Nerve Stimulation: An Alternative Treatment of Chronic Migraine.

PURPOSE OF REVIEW: This paper will examine the efficacy and safety of occipital nerve stimulation as a non-pharmacological alternative treatment for migraine. RECENT FINDINGS: Migraine is characterized as a primary headache disorder with possible premonitory and aura phases, both of which vary greatly in symptomatology. The most common treatments for chronic migraine are pharmacological and are aimed at both acute relief (e.g., nonsteroidal anti-inflammatory drugs, triptans, and ergots) and prophylaxis (e.g., propranolol, valproic acid, and topiramate). For patients with medically refractory migraine, acute relief medication overuse can increase the risk of developing more severe and more frequent migraine attacks. Occipital nerve stimulation is a non-pharmacological alternative treatment for chronic migraine, which could eliminate the risk of adverse effects from acute relief medication overuse. Neurostimulation is thought to prevent pain by blocking signal transduction from small nociceptive fibers with non-painful signaling in larger adjacent fibers. Existing data from clinical trials support the overall safety and efficacy of occipital nerve stimulation for the treatment of chronic migraine. However, few large controlled, double-blinded studies have been conducted, due to both practical and ethical concerns. Currently, occipital nerve stimulation is available as an off-label use of neurostimulation for pain prevention but is not approved by the FDA specifically for the treatment of chronic migraine.

The Antisense Oligonucleotide Nusinersen for Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular degenerative disease characterized by loss of spinal cord motor neurons leading to progressive muscle wasting. The most common pathology results from a homozygous disruption in the survival motor neuron 1 (SMN1) gene on chromosome 5q13 via deletion, conversion, or mutation. SMN2 is a near duplicate of SMN1 that can produce full-length SMN mRNA transcripts, but its overall production capability of these mRNA transcripts is lower than that seen in SMN1. This leads to lower levels of functional SMN protein within motor neurons. The FDA approved nusinersen in December 2016 to treat SMA associated with SMN1 gene mutation. It is administered directly to the central nervous system by intrathecal injection. An antisense oligonucleotide (ASO) drug, nusinersen, provides an upcoming and promising treatment option for SMA and represents a novel pharmacological approach with a mechanism of action relevant for other neurodegenerative disorders. Nusinersen begins with four initial loading doses that are followed by three maintenance doses per year. Three major studies (CHERISH, ENDEAR, and NURTURE) have shown to improve motor function in early and late-onset individuals and reduce the chances of ventilator requirements in pre-symptomatic infants. Studies investigating the timing of drug delivery in mouse models of SMA report the best outcomes when drugs are delivered early before any significant motor function is lost. Nusinersen is a novel therapeutic approach with consistent results in all three studies and is proof of the novel concept for treating SMA and other neurodegenerative disorders in the future.

Surface characterization of a silicone hydrogel contact lens having bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer layer in hydrated state.

A silicone hydrogel contact lens material, with a unique chemical and physical structure has been designed for long-term ocular performance. Enhancement of this silicone hydrogel contact lens material was achieved through surface modification using a cross-linkable bioinspired 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which creates a soft surface gel layer on the silicone hydrogel base material. The surface properties of this MPC polymer-modified lens were characterized under hydrated condition revealing, inter alia, its unique polymer structure, excellent hydrophilicity, lubricity, and flexibility. Analysis of the MPC polymer layer in a hydrated state was performed using a combination of a high-resolution environmental scanning electron microscopy and atomic force microscopy. Compared to the silicone hydrogel base material, this surface had a higher captive bubble contact angle, which corresponds to higher hydrophilicity of the surface. In addition, the hydrated MPC polymer layer exhibited an extremely soft surface and reduced the coefficient of friction by more than 80 %. These characteristics were attributed to the hydration state of the MPC polymer layer on the surface of the silicone hydrogel base material. Also, interaction force of protein deposition was lowered on the surface. Such superior surface properties are anticipated to contribute to excellent ocular performance.

Extended elution of phospholipid from silicone hydrogel contact lenses.

Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of these lenses for phospholipid delivery to increase eye comfort to patients who prefer reusable wear lenses. Contact lenses were loaded with 200 µg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. To simulate 30 days of diurnal use with overnight cleaning, these lenses were eluted for 16 h at 35 °C into artificial tear fluid (ATF), and then eluted at room temperature (~22 °C) for 8 h in one of three commercial contact lens cleaning systems. This was repeated for 30 days. The elution of DMPC into ATF was greater on the first day, followed by a fairly constant amount of elution each day thereafter. The type of cleaning system had a statistically significant effect on the elution rate during daily exposure to ATF. The rate of elution into cleaning solutions did not show any enhanced elution on the first day; there was a fairly constant elution rate. Again, the type of cleaning system significantly influenced the elution rate into the nightly cleaner.

Transport of phospholipid in silicone hydrogel contact lenses.

Characterization of the transport and release of phospholipids from a silicone hydrogel contact lens is required to assess the possible use of these lenses for phospholipid delivery to increase patient comfort. Contact lenses of silicone hydrogel composition were loaded with varying amounts of radiolabeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. These lenses were eluted at 35°C into artificial tear fluid (ATF) or ATF containing varying amounts of DMPC. The amount of DMPC loaded into a lens is a linear function of the time of exposure to the DMPC/propanol solution. The initial rate of elution into ATF appears to be diffusion controlled for at least 10 h and is proportional to the amount of DMPC loaded. The elution rate decreases as the DMPC concentration in the ATF increases. The ease of loading and the controllable release of DMPC from silicone hydrogels presents the possibility of using such lenses to counter eye discomfort caused by inherently low levels of phospholipid in tears.

Loading and release of a phospholipid from contact lenses.

PURPOSE: Dry eye syndrome has been associated with the lack of phospholipids in the tear film, leading to disruption of the tear film and subsequent irritation. This study explores the feasibility of loading a phospholipid into contact lenses for controlled release to the eye. METHODS: Silicone hydrogel contact lenses were loaded with 33 µg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. The loaded lenses were soaked at 35°C in either water or artificial tear solution (ATF), and the elution of DMPC was quantified by scintillation counting. RESULTS: About 33 µg of DMPC was loaded into the lenses. An average of nearly 1 µg of DMPC was eluted into ATF within the first 10 h. Elution was about five times faster in ATF than in water. The elution appears to be controlled by the diffusivity of DMPC in the contact lens and the properties of the elution solution. CONCLUSIONS: This type of lens technology may have the potential to deliver phospholipids to help address contact lens-related dryness through lipid layer stabilization.

Tear oxygen under hydrogel and silicone hydrogel contact lenses in humans.

PURPOSE: To determine the tear oxygen tension under a variety of conventional and silicone hydrogel contact lenses in human subjects. METHODS: Three hydrogel and five silicone hydrogel lenses (Dk/t = 17 to 329) were coated on the back surface with an oxygen sensitive, bovine serum albumin-Pd meso-tetra (4-carboxyphenyl) porphine complex (BSA-porphine). Each lens type was placed on the right eye of 15 non-contact lens wearers to obtain a steady-state open eye tear oxygen tension using oxygen sensitive phosphorescence decay of BSA-porphine. A closed-eye oxygen tension estimate was obtained by measuring the change in tear oxygen tension after 5 min of eye closure. In separate experiments, a goggle was placed over the lens wearing eye and a gas mixture (PO2 = 51 torr) flowed over the lens to simulate anterior lens oxygen tension during eye closure. RESULTS: Mean open eye oxygen tension ranged from 58 to 133 torr. Closed eye estimates ranged from 11 to 42 torr. Oxygen tension under the goggle ranged from 8 to 48 torr and was higher than the closed eye estimate for six out of the eight lenses, suggesting that the average closed eye anterior lens surface oxygen tension is <51 torr. For Dk/t >30, the measured tear oxygen tension is significantly lower than that predicted from previous studies. CONCLUSIONS: The phosphorescence decay methodology is capable of directly measuring the in vivo post lens PO2 of high Dk/t lenses without disturbing the contact lens or cornea. Our data indicate that increasing Dk/t up to and beyond 140 continues to yield increased flux into the central cornea.

Neural signatures of phonetic learning in adulthood: a magnetoencephalography study.

The present study used magnetoencephalography (MEG) to examine perceptual learning of American English /r/ and /l/ categories by Japanese adults who had limited English exposure. A training software program was developed based on the principles of infant phonetic learning, featuring systematic acoustic exaggeration, multi-talker variability, visible articulation, and adaptive listening. The program was designed to help Japanese listeners utilize an acoustic dimension relevant for phonemic categorization of /r-l/ in English. Although training did not produce native-like phonetic boundary along the /r-l/ synthetic continuum in the second language learners, success was seen in highly significant identification improvement over twelve training sessions and transfer of learning to novel stimuli. Consistent with behavioral results, pre-post MEG measures showed not only enhanced neural sensitivity to the /r-l/ distinction in the left-hemisphere mismatch field (MMF) response but also bilateral decreases in equivalent current dipole (ECD) cluster and duration measures for stimulus coding in the inferior parietal region. The learning-induced increases in neural sensitivity and efficiency were also found in distributed source analysis using Minimum Current Estimates (MCE). Furthermore, the pre-post changes exhibited significant brain-behavior correlations between speech discrimination scores and MMF amplitudes as well as between the behavioral scores and ECD measures of neural efficiency. Together, the data provide corroborating evidence that substantial neural plasticity for second-language learning in adulthood can be induced with adaptive and enriched linguistic exposure. Like the MMF, the ECD cluster and duration measures are sensitive neural markers of phonetic learning.

Training the perception of Hindi dental and retroflex stops by native speakers of American English and Japanese.

Perception of second language speech sounds is influenced by one's first language. For example, speakers of American English have difficulty perceiving dental versus retroflex stop consonants in Hindi although English has both dental and retroflex allophones of alveolar stops. Japanese, unlike English, has a contrast similar to Hindi, specifically, the Japanese /d/ versus the flapped /r/ which is sometimes produced as a retroflex. This study compared American and Japanese speakers' identification of the Hindi contrast in CV syllable contexts where C varied in voicing and aspiration. The study then evaluated the participants' increase in identifying the distinction after training with a computer-interactive program. Training sessions progressively increased in difficulty by decreasing the extent of vowel truncation in stimuli and by adding new speakers. Although all participants improved significantly, Japanese participants were more accurate than Americans in distinguishing the contrast on pretest, during training, and on posttest. Transfer was observed to three new consonantal contexts, a new vowel context, and a new speaker's productions. Some abstract aspect of the contrast was apparently learned during training. It is suggested that allophonic experience with dental and retroflex stops may be detrimental to perception of the new contrast.

Treatment of painful temporomandibular joint dysfunction with the sagittal split ramus osteotomy.

PURPOSE: We describe a new indication for the sagittal split ramus osteotomy with rigid fixation to treat patients with painful dysfunction of the temporomandibular joint. PATIENTS AND METHODS: Ten patients for whom nonsurgical management failed were found to have a mandibular condyle positioned postero-superior within the glenoid fossa with reduced joint space on corrected-axis tomograms. The sagittal split ramus osteotomy was used to reposition the proximal segment and to increase joint space. Preoperative and long-term postoperative (average, 44.7 months) symptoms and tomographic findings were retrospectively compared. RESULTS: Significant pain relief occurred postoperatively in all patients. One patient had a relapse after initial improvement. No patient developed a malocclusion. The long-term radiographic condyle-fossa relationship tended to return to its preoperative position with no relapse of clinical symptoms, except in the 1 patient. CONCLUSION: The sagittal split ramus osteotomy with rigid fixation is another procedure that can be used to treat painful temporomandibular joint dysfunction by changing the position of the mandibular condyle in the glenoid fossa.

Sequestration and ultrasound-induced release of doxorubicin from stabilized Pluronic P105 micelles.

Controlled drug delivery from micelles requires that the micelles remain stable when diluted below their critical micelle concentration, such as upon injection into blood. A cross-linked, interpenetrating network of N,N-diethylacrylamide (NNDEA) was polymerized in the core of Pluronic P105 micelles to stabilize temporarily the micelles at concentrations below the critical micellar concentration of free P105. The stabilized Pluronic micelles (called Plurogels) were able to sequester the drug doxorubicin (Dox) and protect HL-60 cells from the drug at concentrations where non-stabilized Pluronic provided no protection. The protection lasted approximately 12 hr, which is similar to the half-life of the particles. Application of low-frequency ultrasound resulted in a synergistic killing effect with Dox and low concentrations of either Pluronic P105 or stabilized Plurogels, most probably due to release of Dox and permeabilization of the cell membrane.

The Graphite Calorimeter as a Standard of Absorbed Dose for Cobalt-60 Gamma Radiation.

Absorbed dose to water in a cobalt-60 gamma-ray beam has been determined using a thick-walled graphite ionization chamber. The chamber was calibrated in a graphite phantom against a graphite calorimeter, and the graphite calibration factor was converted to a water calibration factor using published energy absorption coefficient ratios and a measured replacement factor. Comparisons between the graphite and water measurements were made at pairs of points that were scaled in position according to the ratio of electron densities, so that the photon spectra were the same for the two points in a given pair. Measurements performed in graphite over a wide range of phantom depths, field sizes, and source distances, showed that the calibration factor varies slowly with the phantom depth and field size, and probably has a negligible dependence on source distance. By comparison with the thick-walled chamber in a cobalt-60 gamma-ray beam, a secondary ionization chamber can be calibrated in terms of absorbed dose to water with an estimated uncertainty of about ± 1 percent.