Toxoplasmosis gondii: An Atypical Presentation of Optic Neuritis

Toxoplasmosis gondii is a parasite whose natural host is the cat. Ocular toxoplasmosis can be categorized into two forms of infections: congenital, where an infant is infected in utero; and acquired, where an individual is typically infected by ingesting food contaminated with T. Gondii oocytes. Although acquired infections are rare in the United States, they can occur and toxoplasmosis should be in the differential diagnosis of an infectious optic neuritis. The typical manifestation of toxoplasmosis is a retinochoroiditis, with a “headlight in the fog” appearance, due to dense inflammation of the vitreous; consequently, the diagnosis is often made clinically. This case describes a healthy 36-year-old Hispanic male who had an atypical presentation, with minimal vitritis and papillomacular involvement; thus serology was necessary for a definitive diagnosis. Treatment led to a rapid improvement in vision and ultimately a good prognosis

Genome of the human hookworm Necator americanus

The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 1 19,151 1 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm’s invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases

Horner\u27s syndrome secondary to neuroblastoma

Horner’s syndrome is classically characterized by a triad of miosis, partial ptosis and anhidrosis. The etiology is due to an interruption in the sympathetic innervation to the eye. A prompt diagnosis is crucial, given that Horner’s syndrome could be a manifestation of a life-threatening condition. A thorough case history and clinical evaluation must be employed to arrive at the diagnosis. An important means for confirming Horner’s syndrome is pharmacological testing, which is also used to localize the level where the sympathetic chain is compromised. Following the diagnosis and localization of the lesion, an algorithm should be followed to determine the testing indicated, in order to ascertain the underlying cause of the condition. There is a known association between mediastinal neuroblastoma and preganglionic Horner’s syndrome. We present a case of a seven-year-old boy with a history of excision of a mediastinal neuroblastoma at age two, who soon after presented with signs and symptoms associated with a residual Horner’s syndrome

Time scale synchronization of chaotic oscillators

This paper presents the result of the investigation of chaotic oscillator synchronization. A new approach for detecting of synchronized behaviour of chaotic oscillators has been proposed. This approach is based on the analysis of different time scales in the time series generated by the coupled chaotic oscillators. This approach has been applied for the coupled Rossler and Lorenz systems.Comment: 19 pages, 12 figure

Genome of the human hookworm \u3ci\u3eNecator americanus\u3c/i\u3e

The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm\u27s invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases

Synchronization of chaotic oscillator time scales

This paper deals with the chaotic oscillator synchronization. A new approach to detect the synchronized behaviour of chaotic oscillators has been proposed. This approach is based on the analysis of different time scales in the time series generated by the coupled chaotic oscillators. It has been shown that complete synchronization, phase synchronization, lag synchronization and generalized synchronization are the particular cases of the synchronized behavior called as "time--scale synchronization". The quantitative measure of chaotic oscillator synchronous behavior has been proposed. This approach has been applied for the coupled Rossler systems.Comment: 29 pages, 11 figures, published in JETP. 100, 4 (2005) 784-79

Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.

The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage

Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes

We report on single-molecule nanopore sensing combined with position-encoded DNA molecular probes, with chemistry tuned to simultaneously identify various antigen proteins and multiple RNA gene fragments of SARS-CoV-2 with high sensitivity and selectivity. We show that this sensing strategy can directly detect spike (S) and nucleocapsid (N) proteins in unprocessed human saliva. Moreover, our approach enables the identification of RNA fragments from patient samples using nasal/throat swabs, enabling the identification of critical mutations such as D614G, G446S, or Y144del among viral variants. In particular, it can detect and discriminate between SARS-CoV-2 lineages of wild-type B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.539 (Omicron) within a single measurement without the need for nucleic acid sequencing. The sensing strategy of the molecular probes is easily adaptable to other viral targets and diseases and can be expanded depending on the application required

Numerical study of linear and circular model DNA chains confined in a slit: metric and topological properties

Advanced Monte Carlo simulations are used to study the effect of nano-slit confinement on metric and topological properties of model DNA chains. We consider both linear and circularised chains with contour lengths in the 1.2--4.8 $\mu$m range and slits widths spanning continuously the 50--1250nm range. The metric scaling predicted by de Gennes' blob model is shown to hold for both linear and circularised DNA up to the strongest levels of confinement. More notably, the topological properties of the circularised DNA molecules have two major differences compared to three-dimensional confinement. First, the overall knotting probability is non-monotonic for increasing confinement and can be largely enhanced or suppressed compared to the bulk case by simply varying the slit width. Secondly, the knot population consists of knots that are far simpler than for three-dimensional confinement. The results suggest that nano-slits could be used in nano-fluidic setups to produce DNA rings having simple topologies (including the unknot) or to separate heterogeneous ensembles of DNA rings by knot type.Comment: 12 pages, 10 figure

Teprotumumab for Thyroid-Associated Ophthalmopathy

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .)