The effect of polymer length in liquid-liquid phase separation.

Understanding the thermodynamics that drive liquid-liquid phase separation (LLPS) is quite important given the number of diverse biomolecular systems undergoing this phenomenon. Many studies have focused on condensates of long polymers, but very few systems of short-polymer condensates have been observed and studied. Here, we study a short-polymer system of various lengths of poly-adenine RNA and peptides formed by the RGRGG sequence repeats to understand the underlying thermodynamics of LLPS. Using the recently developed COCOMO coarse-grained (CG) model, we predicted condensates for lengths as short as 5-10 residues, which was then confirmed by experiment, making this one of the smallest LLPS systems yet observed. A free-energy model reveals that the length dependence of condensation is driven primarily by entropy of confinement. The simplicity of this system will provide the basis for understanding more biologically realistic systems.

Spectral classification by generative adversarial linear discriminant analysis.

Generative adversarial linear discriminant analysis (GALDA) is formulated as a broadly applicable tool for increasing classification accuracy and reducing overfitting in spectrochemical analysis. Although inspired by the successes of generative adversarial neural networks (GANs) for minimizing overfitting artifacts in artificial neural networks, GALDA was built around an independent linear algebra framework distinct from those in GANs. In contrast to feature extraction and data reduction approaches for minimizing overfitting, GALDA performs data augmentation by identifying and adversarially excluding the regions in spectral space in which genuine data do not reside. Relative to non-adversarial analogs, loading plots for dimension reduction showed significant smoothing and more prominent features aligned with spectral peaks following generative adversarial optimization. Classification accuracy was evaluated for GALDA together with other commonly available supervised and unsupervised methods for dimension reduction in simulated spectra generated using an open-source Raman database (Romanian Database of Raman Spectroscopy, RDRS). Spectral analysis was then performed for microscopy measurements of microsphereroids of the blood thinner clopidogrel bisulfate and in THz Raman imaging of common constituents in aspirin tablets. From these collective results, the potential scope of use for GALDA is critically evaluated relative to alternative established spectral dimension reduction and classification methods.

Analgesia in Postoperative Adult Strabismus Patients.

This survey of pediatric ophthalmic surgeons on analgesia for postoperative adult strabismus patients indicates that 65% prescribed acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDs), and 12% to 16% prescribed opioids. Most surgeons reported reasonable control of pain regardless of analgesia. Acetaminophen and/or NSAIDs may adequately control pain, although certain circumstances may warrant opioid prescriptions. [J Pediatr Ophthalmol Strabismus. 2023;60(1):e5-e7.].

The modified Kocher criteria for septic hip: Does it apply to the knee?

Background: Pediatric septic arthritis is a surgical emergency and timely diagnosis prevents serious complications. To differentiate between septic hip and transient synovitis, the predictive value of four original Kocher criteria (fever, inability to bear weight, elevated serum white blood cell count, and elevated erythrocyte sedimentation rate) plus Caird's addition of elevated C-reactive protein have been studied, termed the modified Kocher criteria. These criteria have not been tested extensively on septic knee. This study tested the utility of the modified Kocher criteria in predicting septic knee while validating it for septic hip. Methods: A retrospective chart review was conducted of pediatric patients evaluated at a single institution for irritable hip or knee between 2009 and 2018. Patients who underwent arthrocentesis were included and the modified Kocher criteria were applied to all. Results: One hundred fifty-five patients (96 hips and 59 knees) were identified. One hundred four (67.1%) patients had septic arthritis with 44/59 (74.6%) of knees and 60/96 (62.5%) of hips. The strongest predictors for septic hip and knee were elevated C-reactive protein (odds ratio = 26.9, p < 0.0001) and refusal to bear weight (odds ratio = 14.5, p < 0.0001), respectively. For hips, 5/5 criteria produced a 100% positive predictive value for septic arthritis. For knees, the combination of inability to bear weight and elevated C-reactive protein had a positive predictive value of 89.7%. Conclusion: While all five of the modified Kocher criteria are not predictive of pediatric septic knee, the combination of two specific factors (inability to bear weight and elevated C-reactive protein) is strongly predictive. This study validates previous work that the modified Kocher criteria are predictive of septic hip. Level of evidence: level III.

Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

PURPOSE: To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years. METHODS: Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation. RESULTS: Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to meta-static disease, and one patient has planned follow-up. CONCLUSIONS: Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 2022;59(5):338-343.].

Biodegradation of Functionalized Nanocellulose.

Nanocellulose has attracted widespread interest for applications in materials science and biomedical engineering due to its natural abundance, desirable physicochemical properties, and high intrinsic mineralizability (i.e., complete biodegradability). A common strategy to increase dispersibility in polymer matrices is to modify the hydroxyl groups on nanocellulose through covalent functionalization, but such modification strategies may affect the desirable biodegradation properties exhibited by pristine nanocellulose. In this study, cellulose nanofibrils (CNFs) functionalized with a range of esters, carboxylic acids, or ethers exhibited decreased rates and extents of mineralization by anaerobic and aerobic microbial communities compared to unmodified CNFs, with etherified CNFs exhibiting the highest level of recalcitrance. The decreased biodegradability of functionalized CNFs depended primarily on the degree of substitution at the surface of the material rather than within the bulk. This dependence on surface chemistry was attributed not only to the large surface area-to-volume ratio of nanocellulose but also to the prerequisite surface interaction by microorganisms necessary to achieve biodegradation. Results from this study highlight the need to quantify the type and coverage of surface substituents in order to anticipate their effects on the environmental persistence of functionalized nanocellulose.

Patterns of enrollment in a New Orleans women's substance use rehabilitation center.

BACKGROUND: Research has told us little about the demographics of individuals entering substance use programs in New Orleans, Louisiana, especially women accessing treatment programs. Considering that New Orleans is a predominantly Black city and both substance use treatment and research have historically left out Black patients, this study evaluates the age, race, insurance status, education level, and substance of choice for patients entering Grace House Rehabilitation Center, an all women nonprofit substance use treatment program in New Orleans, Louisiana. METHODS: Since 2013, Tulane School of Medicine students have held weekly primary care clinics at Grace House. This study used the clinic's patients' handwritten intake forms to collect demographic variables between 2013 and 2019. The study then evaluated the data using descriptive statistical analysis. RESULTS: The study analyzed 743 patient charts. We found that 78.4% of women admitted to Grace House were white (n = 627), and 14.5% of women were Black (n = 1160). The study excluded all other racial and ethnic groups due to the groups' small sample size. The average age at admittance was 34.7 years for both white and Black women; however, the average age for Black women was 42 years old. The 743 women studied reported the use of 1123 unique substances. While more than half of both populations used only one type of substance, Black women more commonly used only one substance. CONCLUSION: New Orleans is a predominantly Black community, yet young Black women are largely missing from the patient population that we studied. While multiple reasons exist for the lack of Black women in this population, Black substance-using women are clearly left out of the life-saving treatment that they deserve. The medical community must investigate further to make genuine, impactful changes to how substance use treatment is accessed by all minority groups, but especially Black women.

Spinal subarachnoid diverticula in dogs: A review.

Spinal subarachnoid diverticula are fluid dilations of the subarachnoid space that can cause a compressive myelopathy in dogs. These diverticula are usually associated with high motion areas in the cervical and caudal thoracic spine. The definitive etiopathogenesis has not been determined but likely involves congenital or acquired causes. Pugs, French bulldogs, and Rottweilers are overrepresented breeds. Clinical signs typically include ataxia, paresis, and upper motor neuron urinary and/or fecal incontinence; pain is a less common feature. Diagnosis is based on advanced imaging, with magnetic resonance imaging now being favored given the additional detail of the spinal cord parenchyma that can be obtained. Outcomes are better with surgical intervention than with medical therapies, though there is a lack of long-term data. No superior surgical technique has been identified, and questions remain on the significance of addressing leptomeningeal adhesions at the time of surgery. Clinical signs can recur, though not always due to recurrence of diverticulum formation, and pugs may be less likely to have a successful long-term outcome.

Diverticule subarachnoïdien spinal chez des chiens : une revue. Les diverticules subarachnoïdiens spinaux sont des dilatations liquides de l'espace subarachnoïdien qui peuvent causer une myélopathie compressive chez les chiens. Ces diverticules sont généralement associés à des régions à motion élevée de la colonne vertébrale cervicale et caudale. L'étiopathogénie définitive n'a pas été déterminée mais implique fort probablement des causes congénitales ou acquises. Les carlins, bulldogs français et rottweiler sont des races sur-représentées. Les signes cliniques inclus typiquement de l'ataxie, de la parésie et un neurone moteur supérieur d'incontinence urinaire et/ou fécale; la douleur est une caractéristique moins fréquente. Le diagnostic est basé sur des analyses avancées d'imagerie, avec l'imagerie par résonnance magnétique maintenant favorisée étant donné les détails additionnels du parenchyme de la colonne vertébrale qui peuvent être obtenus. Les résultats sont meilleurs avec l'intervention chirurgicale qu'avec les thérapies médicales, bien qu'il y ait un manque de données à long terme. Aucune technique chirurgicale supérieure n'a été identifiée, et des questions persistent sur l'importance de s'attarder aux adhésions leptoméningées au moment de la chirurgie. Les signes cliniques peuvent réapparaitre, quoique pas toujours à cause de la récurrence de la formation des diverticules, et les carlins pourraient être moins enclin à avoir une issue favorable à long terme.(Traduit par Dr Serge Messier).

Influence of Oxygen-Containing Functional Groups on the Environmental Properties, Transformations, and Toxicity of Carbon Nanotubes.

Carbon nanotubes (CNTs) have unique physical and chemical properties that drive their use in a variety of commercial and industrial applications. CNTs are commonly oxidized prior to their use to enhance dispersion in polar solvents by deliberately grafting oxygen-containing functional groups onto CNT surfaces. In addition, CNT surface oxides can be unintentionally formed or modified after CNTs are released into the environment through exposure to reactive oxygen species and/or ultraviolet irradiation. Consequently, it is important to understand the impact of CNT surface oxidation on the environmental fate, transport, and toxicity of CNTs. In this review, we describe the specific role of oxygen-containing functional groups on the important environmental behaviors of CNTs in aqueous media (e.g., colloidal stability, adsorption, and photochemistry) as well as their biological impact. We place special emphasis on the value of systematically varying and quantifying surface oxides as a route to identifying quantitative structure-property relationships. The role of oxygen-containing functional groups in regulating the efficacy of CNT-enabled water treatment technologies and the influence of surface oxides on other carbon-based nanomaterials are also evaluated and discussed.

Anomalous Diffusion Characterization by Fourier Transform-FRAP with Patterned Illumination.

Fourier transform fluorescence recovery after photobleaching (FT-FRAP) with patterned illumination is theorized and demonstrated for quantitatively evaluating normal and anomalous diffusion. Diffusion characterization is routinely performed to assess mobility in cell biology, pharmacology, and food science. Conventional FRAP is noninvasive, has low sample volume requirements, and can rapidly measure diffusion over distances of a few micrometers. However, conventional point-bleach measurements are complicated by signal-to-noise limitations, the need for precise knowledge of the photobleach beam profile, potential for bias due to sample heterogeneity, and poor compatibility with multiphoton excitation because of local heating. In FT-FRAP with patterned illumination, the time-dependent fluorescence recovery signal is concentrated to puncta in the spatial Fourier domain, with substantial improvements in signal-to-noise, mathematical simplicity, representative sampling, and multiphoton compatibility. A custom nonlinear optical beam-scanning microscope enabled patterned illumination for photobleaching through two-photon excitation. Measurements in the spatial Fourier domain removed dependence on the photobleach profile, suppressing bias from imprecise knowledge of the point spread function. For normal diffusion, the fluorescence recovery produced a simple single-exponential decay in the spatial Fourier domain, in excellent agreement with theoretical predictions. Simultaneous measurement of diffusion at multiple length scales was enabled through analysis of multiple spatial harmonics of the photobleaching pattern. Anomalous diffusion was characterized by FT-FRAP through a nonlinear fit to multiple spatial harmonics of the fluorescence recovery. Constraining the fit to describe diffusion over multiple length scales resulted in higher confidence in the recovered fitting parameters. Additionally, phase analysis in FT-FRAP was shown to inform on flow/sample translation.

Combination of single-molecule magnet behaviour and luminescence properties in a new series of lanthanide complexes with tris(pyrazolyl)borate and oligo(ß-diketonate) ligands.

A series of tris(pyrazolyl)borate mono-, di- and trinuclear complexes, [Tp2Ln]nX (Ln = Eu, Tb, Gd, Dy, Xn- = various mono-, bis- and tris(ß-diketonates) has been prepared. The Tb3+ and Dy3+ complexes are luminescent single molecular magnets (SMM) and exhibit luminescence quantum efficiencies up to 73% for the Tb3+ and 4.4% for the Dy3+ compounds. Similar Eu3+ complexes display bright emission only at lower temperatures. The Dy3+ and Tb3+ complexes possess SMM behavior in a non-zero dc field at low temperatures, while the polynuclear Dy3+ complexes also show slow magnetic relaxation even in zero dc field up to 8 K. Ueff-values determined from dynamic magnetic measurements were up to 31 and 6 cm-1 for the Dy3+ and Tb3+ complexes, respectively. It was found that within a series of Dy3+ and Tb3+ compounds, Ueff and luminescence quantum yields decreased with increasing nuclearity of the compounds and a shortening of the intramolecular Ln-Ln distance. ΔOrbach-values estimated from low-temperature luminescence spectra were significantly higher than those obtained from ac magnetic data, which may be due to involvement of additional processes in the relaxation mechanism (quantum tunneling, Raman, direct) reducing the energy barrier. Some of the Tb3+-compounds also display metal-centred electroluminescence, giving them potential as emitting layers in LEDs.

Post-mortem computed tomography in sudden death by asthma.

Ground glass attenuation (GGA) of the lungs is a common finding of post-mortem computed tomography (PMCT) that is associated with pulmonary congestion and edema due to cardiac failure during the agonal period, or due to post-mortem hypostasis. However, hypo-attenuation of the lung is an atypical finding of PMCT, and is usually a consequence of hypovolemic states before death or postmortem body posture after death. Previous studies have shown a few differential diagnoses, such as hypothermia, massive hemorrhage, asphyxiation by hanging, and dehydration, for hypo-attenuation of the lung. This report presents the case of a woman who died suddenly because of an asthma attack. Our PMCT analysis demonstrated hypoattenuation of the lung in this case. We suggest fatal asthma as a differential diagnosis for the appearance of hypo-attenuation of lungs on PMCT.

Stochastic Differential Scanning Calorimetry by Nonlinear Optical Microscopy.

Stochastic phase transformations within individual crystalline particles were recorded by integration of second harmonic generation (SHG) imaging with differential scanning calorimetry (DSC). The SHG activity of a crystal is highly sensitive to the specific molecular packing arrangement within a noncentrosymmetric lattice, providing access to information otherwise unavailable by conventional imaging approaches. Consequently, lattice transformations associated with dehydration/desolvation events were readily observed by SHG imaging and directly correlated to the phase transformations detected by the DSC measurements. Following studies of a model system (urea), stochastic differential scanning calorimetry (SDSC) was performed on trehalose dihydrate, which has a more complex phase behavior. From these measurements, SDSC revealed a broad diversity of single-particle thermal trajectories and direct evidence of a "cold phase transformation" process not observable by the DSC measurements alone.

Iterative Non-Negative Matrix Factorization Filter for Blind Deconvolution in Photon/Ion Counting.

A digital filter based on non-negative matrix factorization (NMF) enables blind deconvolution of temporal information from large data sets, simultaneously recovering both photon arrival times and the instrument impulse response function (IRF). In general, the measured digital signals produced by modern analytical instrumentation are convolved by the corresponding IRFs, which can complicate quantitative analyses. Common examples include photon counting (PC), chromatography, super resolution imaging, fluorescence imaging, and mass spectrometry. Scintillation counting, in particular, provides a signal-to-noise advantage in measurements of low intensity signals, but has a limited dynamic range due to pulse overlap. This limitation can complicate the interpretation of data by masking temporal and amplitude information on the underlying detected signal. Typical methods for deconvolution of the photon events require advanced knowledge of the IRF, which is not generally trivial to obtain. In this work, a sliding window approach was developed to perform NMF one pixel at a time on short segments of large (e.g., 25 million point) data sets. Using random initial guesses for the IRF, the NMF filter simultaneously recovered both the deconvolved photon arrival times and the IRF. Applying the NMF filter to the analysis of triboluminescence (TL) data traces of active pharmaceutical ingredients enabled discrimination between different hypothesized physical origins of the signal.

Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats.

BACKGROUND: Repeated oral administration of antiepileptic drugs can be challenging for cat owners, resulting in reduced compliance, poor seizure control, and reduced quality of life for cats. Levetiracetam (LEV) has several properties that make it an appealing drug for transdermal application. OBJECTIVES: The aims were to (1) determine if transdermal LEV, in a lipophilic, liposomic cream vehicle, resulted in serum concentrations above 5 µg/mL; (2) identify clinical adverse effects; and (3) evaluate the concentration of LEV in a lipophilic liposomic cream at set intervals. ANIMALS: Six healthy, client-owned cats weighing ≤5 kg. METHODS: Prospective clinical trial. Transdermal LEV was applied to the inner pinna at a dosage of 60 mg/kg (400 mg/mL concentration) at home for 6 days. Day 7, cats were hospitalized for blood sample collection for LEV concentration at times 0 (before dose administration), 0.5, 1, 2, 3, and 4 hours after administration. RESULTS: Median (range) timed serum concentrations were 16.6 (8.6-39.6) µg/mL, 16.1 (6.8-34.4) µg/mL, 15.4 (10.1-36.7) µg/mL, 17.4 (9.2-32.7) µg/mL, 15.1 (8.3-25.9) µg/mL, and 14.8 (11.9-28.4) µg/mL, respectively. Adverse events were limited to sedation (1/6 cats) and pinna crusting (1/6 cats). The LEV, in the proposed vehicle, retained concentration above 95% at 400 mg/mL up to 5 weeks. CONCLUSIONS AND CLINICAL IMPORTANCE: Thrice daily transdermal LEV resulted in median serum concentrations ≥5 µg/mL throughout the sampling period and clinical adverse events were minimal. Transdermal LEV can provide an alternative for cats resistant to administration of other forms of anticonvulsant medication.