Thirty Years of Experience With Ocular Adnexal T-Cell Lymphoma.

PURPOSE: To evaluate the disease characteristics and survival of patients with ocular adnexal T-cell lymphoma. METHODS: A retrospective, observational study of patients with a histopathological diagnosis of T-cell lymphoma of the ocular adnexa seen between 1992 and 2022. Demographic data, clinical presentation, imaging, histology, immunohistochemistry, treatment, and outcomes were reviewed. RESULTS: Fifteen patients were included in the study with the mean age at diagnosis of 50 years old (range 7-85). The most common presenting symptoms were ulcerated eyelid skin lesions (40%) followed by eyelid swelling (13.3%), and lacrimal passageways obstruction (13.3%). The anaplastic large cell lymphoma (33%) and primary cutaneous T-cell lymphoma (33%) were the most diagnosed peripheral T-cell lymphoma subtypes, followed by the nasal type natural killer/T-cell lymphoma (27%) and peripheral T-cell lymphoma not otherwise specified (7%). The most prevalent stage of disease progression was stage I and stage IV (Ann Arbor classification) with seven (47%) patients each. Eight (53%) patients succumbed to the disease process of which three (37.5%) deceased in the first six months and six (75%) within the first year of diagnosis. We identified a strong statistical association between stage and disease-related death ( p = 0.003). CONCLUSIONS: Peripheral T-cell lymphoma occurring in the orbit and ocular adnexa is extremely rare. Advanced stage at diagnosis leads to almost certain death from the disease despite aggressive local and systemic treatment. Early diagnosis improves the chances of survival but can be hindered by this condition's ability to simulate benign inflammatory conditions both clinically and histologically.

Granulomatosis with polyangiitis-associated sclerokeratitis in a case of ocular adnexal B-cell lymphoma.

We describe the first reported case of granulomatosis polyangiitis (GPA)-associated sclerokeratitis in a patient with treated ocular adnexal lymphoma (OAL). The patient presented with pain and decreased vision in the left eye over several weeks. Past medical history was significant for recent bilateral relapsing OAL that was treated successfully with radiotherapy. Examination of the eyes revealed sectoral scleritis and peripheral ulcerative keratitis. Magnetic resonance imaging (MRI) of the orbits excluded recurrence of OAL and serum antineutrophil cytoplasmic autoantibody (ANCA) titres confirmed the diagnosis of GPA. Disease was poorly responsive to systemic steroids, azathioprine and rituximab. Ultimately, resolution was achieved with successive subconjunctival dexamethasone and subconjunctival triamcinolone injections. This case highlights the need to consider ocular inflammation in patients with a history of malignant hemopathies.

Long term follow-up of congenital infantile fibrosarcoma of the orbital region.

We present the long-term follow-up of a case of periorbital congenital infantile fibrosarcoma (CIFS) treated with chemotherapy and surgery. The tumor was detected on a routine prenatal ultrasound at 30 weeks of gestation and diagnosed via an orbital biopsy day 9 postnatal age. The patient underwent chemotherapy and surgical debulking within the first 3 months of life and has maintained complete tumor remission for 7 years. The case highlights that early recognition and prompt treatment of periorbital CIFS can lead to complete long-term remission of this uncommon malignancy.

Protection of forest ecosystems in the eastern United States from elevated atmospheric deposition of sulfur and nitrogen: A comparison of steady-state and dynamic model results.

Critical loads (CLs) and target loads (TLs) of atmospheric deposition of sulfur (S) and nitrogen (N) specify the thresholds of air pollution above which damage to ecosystems is expected to occur and are used to inform environmental regulation and natural resource management. Model estimates of CL and TL can vary for a given location, and these differences can be important for characterization of ecosystem effects from elevated S and N deposition. Moreover, TLs are used to evaluate associated timeframes of ecosystem recovery. We compared published CLs and TLs based on soil acidity criteria derived from steady-state versus dynamic models for terrestrial ecosystems. We examined the magnitude of differences in the CL/TL results from the two types of models for the same regions in the Eastern U.S. Results showed that CLs/TLs from dynamic models (or from steady state modeling using soil base cation weathering estimates from dynamic models) generally produce a broader range of values of acid-sensitivity, including lower CLs/TLs, as compared with a steady-state approach. Applications of dynamic biogeochemical models capable of developing CLs/TLs are relatively data intensive and typically limited to locations where measured soil and soil solution (or nearby stream water) chemistry are available for model parameterization, calibration, and testing. We recommend that CLs/TLs derived from dynamic models be used, where data permit, as they are likely more accurate and allow for evaluation of time-dependent phenomena and period needed for recovery. However, CLs derived from steady-state models remain a useful tool for understanding broad spatial patterns in soil acid-sensitivity throughout the U.S. Future work should focus on the development of more reliable model input parameters, particularly soil base cation weathering, and the extent to which CLs and TLs at a given location may vary and be altered with anticipated future climate change. In addition, dynamic models could be further developed to estimate CLs/TLs for nutrient N.

A rare case of epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland: case report and review of the literature.

A 92-year-old man presented with progressively worsening eye pain, diplopia on lateral gaze and blurred vision for the past 12 months. Radiological imaging confirmed a large left lacrimal gland lesion. The patient subsequently underwent a superio-lateral orbitotomy with left dacryoadenectomy and tumor removal, histopathology subsequently confirmed an epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland. Epithelial-myoepithelial carcinoma is a rare lacrimal gland tumour and the authors believe this case to be the first reported in the Australian population and associated with prolonged eye pain.

Low-coverage whole-genome sequencing reveals molecular markers for spawning season and sex identification in Gulf of Maine Atlantic cod (Gadus morhua, Linnaeus 1758).

Atlantic cod (Gadus morhua, Linnaeus 1758) in the western Gulf of Maine are managed as a single stock despite several lines of evidence supporting two spawning groups (spring and winter) that overlap spatially, while exhibiting seasonal spawning isolation. Low-coverage whole-genome sequencing was used to evaluate the genomic population structure of Atlantic cod spawning groups in the western Gulf of Maine and Georges Bank using 222 individuals collected over multiple years. Results indicated low total genomic differentiation, while also showing strong differentiation between spring and winter-spawning groups at specific regions of the genome. Guided regularized random forest and ranked F ST methods were used to select panels of single nucleotide polymorphisms (SNPs) that could reliably distinguish spring and winter-spawning Atlantic cod (88.5% assignment rate), as well as males and females (95.0% assignment rate) collected in the western Gulf of Maine. These SNP panels represent a valuable tool for fisheries research and management of Atlantic cod in the western Gulf of Maine that will aid investigations of stock production and support accuracy of future assessments.

Using web-based technologies to increase reach, inclusion, and generalizability in behavioral observation research.

Social scientists have long utilized observations of human behavior in research designs. For researchers studying couples, observation of romantic partners has led to important discoveries about how such behavior is associated with physical, mental, and family health. Historically, these methods have been used in in-person laboratory paradigms that place notable limitations on reach and inclusion. This has, in turn, restricted the generalizability of such research to couples who may not attend an in-person laboratory assessment. Transferring the observational laboratory into an online format has the potential to expand the capabilities of these methods to include more diverse couples. This article presents two empirical studies that used online methods to conduct observational behavioral research with sexual and gender minority couples, populations that could be difficult to reach using traditional methods in many places. We demonstrate that we were able to reach, recruit, and enroll diverse couples that more closely resemble the population of same-sex couples in the United States than likely would have been reached in-person. Further, we show that the quality of the observational data collected via the internet allowed for over 94% of collected data to be coded, with acceptable interrater reliabilities and convergent validity. These studies provide a proof-of-concept of online observational methods, accompanied by a tutorial for using such methods. We discuss possible extensions of these online methods, their limitations, and the potential to help further the field of close relationships by reaching more diverse relationships and increasing the generalizability of our research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Survival Strategies of Streptococcus pyogenes in Response to Phage Infection.

Bacteriophages exert strong evolutionary pressure on their microbial hosts. In their lytic lifecycle, complete bacterial subpopulations are utilized as hosts for bacteriophage replication. However, during their lysogenic lifecycle, bacteriophages can integrate into the host chromosome and alter the host's genomic make-up, possibly resulting in evolutionary important adjustments. Not surprisingly, bacteria have evolved sophisticated immune systems to protect against phage infection. Streptococcus pyogenes isolates are frequently lysogenic and their prophages have been shown to be major contributors to the virulence of this pathogen. Most S. pyogenes phage research has focused on genomic prophages in relation to virulence, but little is known about the defensive arsenal of S. pyogenes against lytic phage infection. Here, we characterized Phage A1, an S. pyogenes bacteriophage, and investigated several mechanisms that S. pyogenes utilizes to protect itself against phage predation. We show that Phage A1 belongs to the Siphoviridae family and contains a circular double-stranded DNA genome that follows a modular organization described for other streptococcal phages. After infection, the Phage A1 genome can be detected in isolated S. pyogenes survivor strains, which enables the survival of the bacterial host and Phage A1 resistance. Furthermore, we demonstrate that the type II-A CRISPR-Cas system of S. pyogenes acquires new spacers upon phage infection, which are increasingly detectable in the absence of a capsule. Lastly, we show that S. pyogenes produces membrane vesicles that bind to phages, thereby limiting the pool of phages available for infection. Altogether, this work provides novel insight into survival strategies employed by S. pyogenes to combat phage predation.

Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled "high titer." Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2. METHODS: Nine hundred eighty-one samples from 196 repeat CCP donors 0-119 days post-initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy. RESULTS: Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff. CONCLUSIONS: This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.

Orbital Schwannoma-Management and Clinical Outcomes.

PURPOSE: To evaluate the clinical features, management, and outcomes of orbital schwannomas. METHODS: Retrospective study analyzing 20 orbital schwannomas in 18 patients managed in an orbital service over 26 years. Clinical, radiological, histological, and surgical procedural data were analyzed. RESULTS: Mean age of the study population was 40.89 ± 20.84 years. The most common nerve of origin was frontal nerve (50%), and majority of patients (70%) had a superior and/or posteriorly located tumor. Five patients (27.8%) had optic neuropathy at presentation, and 3 of them showed improved vision after intervention. Surgical resection was performed for all except for 1 patient who underwent fractionated stereotactic radiotherapy. Six subjects had extension of tumor into the cavernous sinus, and 3 of them underwent combined neurosurgical intervention with stereotactic neuronavigation. Outcomes were largely favorable with majority achieving complete excision. Two out of 6 incomplete resections experienced regrowth requiring second surgical intervention. Surgical complications include decreased vision, diplopia, ptosis, and mydriasis. CONCLUSION: Orbital schwannomas are uncommon slow-growing tumors which can result in visual loss. Prognosis can be favorable even in presence of pre-operative optic neuropathy if there is early intervention. Schwannomas confined to the orbit can usually be completely excised with good outcomes. Schwannomas extending intra-cranially may undergo incomplete excision to preserve vital structures, leaving residual disease, but generally have satisfactory results. Stereotactic neuronavigation and frozen section are useful intra-operative tool to aid management and minimize complications. Fractionated radiotherapy can be considered as an alternative or adjunctive treatment for patients not amenable for surgical resections.

Bridge helix arginines play a critical role in Cas9 sensitivity to mismatches.

The RNA-programmable DNA-endonuclease Cas9 is widely used for genome engineering, where a high degree of specificity is required. To investigate which features of Cas9 determine the sensitivity to mismatches along the target DNA, we performed in vitro biochemical assays and bacterial survival assays in Escherichia coli. We demonstrate that arginines in the Cas9 bridge helix influence guide RNA, and target DNA binding and cleavage. They cluster in two groups that either increase or decrease the Cas9 sensitivity to mismatches. We show that the bridge helix is essential for R-loop formation and that R63 and R66 reduce Cas9 specificity by stabilizing the R-loop in the presence of mismatches. Additionally, we identify Q768 that reduces sensitivity of Cas9 to protospacer adjacent motif-distal mismatches. The Cas9_R63A/Q768A variant showed increased specificity in human cells. Our results provide a firm basis for function- and structure-guided mutagenesis to increase Cas9 specificity for genome engineering.

The response of stream ecosystems in the Adirondack region of New York to historical and future changes in atmospheric deposition of sulfur and nitrogen.

The present-day acid-base chemistry of surface waters can be directly linked to contemporary observations of acid deposition; however, pre-industrial conditions are key to predicting the potential future recovery of stream ecosystems under decreasing loads of atmospheric sulfur (S) and nitrogen (N) deposition. The integrated biogeochemical model PnET-BGC was applied to 25 forest watersheds that represent a range of acid sensitivity in the Adirondack region of New York, USA to simulate the response of streams to past and future changes in atmospheric S and N deposition, and calculate the target loads of acidity for protecting and restoring stream water quality and ecosystem health. Using measured data, the model was calibrated and applied to simulate soil and stream chemistry at all study sites. Model hindcasts indicate that historically stream water chemistry in the Adirondacks was variable, but inherently sensitive to acid deposition. The median model-simulated acid neutralizing capacity (ANC) of the streams was projected to be 55 µeq L-1 before the advent of anthropogenic acid deposition (~1850), decreasing to minimum values of 10 µeq L-1 around the year 2000. The median simulated ANC increased to 13 µeq L-1 by 2015 in response to decreases in acid deposition that have occurred over recent decades. Model projections suggest that simultaneous decreases in sulfate, nitrate and ammonium deposition are more effective in restoring stream ANC than individual decreases in sulfur or nitrogen deposition. However, the increases in stream ANC per unit equivalent decrease in S deposition is greater compared to decreases in N deposition. Using empirical algorithms, fish community density and biomass are projected to increase under several deposition-control scenarios that coincide with increases in stream ANC. Model projections suggest that even under the most aggressive deposition-reduction scenarios, stream chemistry and fisheries will not fully recover from historical acidification by 2200.

Primitive Myxoid Mesenchymal Tumor of Infancy in the Orbit: A New Location for a Rare Tumor.

Primitive myxoid mesenchymal tumor of infancy is a rare subtype of sarcoma. With the advent of relevant immunohistochemical and genetic analysis, it was defined by Alaggio et al. in a 2006 case series. Since then, 25 further cases are described in the literature-arising variably from the neck, chest, scalp, abdomen, back, or limbs. Here it is described for the first time arising in the orbit, confirmed by identification of BCOR immunopositivity with internal tandem duplication. All specialties involved in the management of orbital masses should be aware of the subtypes of sarcomas found in the orbit as approaches to their management may change depending on the diagnosis. As more cases are identified, a better understanding of this tumor's clinical behavior and appropriate management can be established.

Lack of sibling avoidance during mate selection in the butterfly Bicyclus anynana.

Species susceptible to inbreeding depression are hypothesized to combat this problem through a number of different mechanisms, including kin recognition. For species with kin recognition, it is unknown if filial recognition is innate or due to prior juvenile experience with siblings. Here, we first test for the presence of kin recognition, and then test these two hypotheses for the development of filial recognition, in the butterfly Bicyclus anynana, a species that suffers from inbreeding depression when forcibly inbred but recovers within a few generations when allowed to breed freely. We evaluate whether the rapid recovery from inbreeding depression is associated with either innate or learned filial recognition. First, we determined whether females innately prefer unrelated males over sibling males using females reared in isolation and then given a choice between an unrelated and a sibling male. Then, we determined if females raised with siblings learned to detect and avoid mating with siblings as adults when provided a choice between an unrelated male and a sibling male. Finally, we determined if females raised with siblings could learn to detect and avoid mating with familiar siblings when given a choice between familiar and unfamiliar siblings. We found that females mated randomly in all three choice combinations. Observed male behavior also did not influence female mating outcome. Our results suggest that adult females do not innately avoid or learn to avoid siblings during mate selection, and that filial detection may not be as critical to reproductive fitness in B. anynana as previously thought.

Bony orbital changes in allergic fungal sinusitis are reversible after treatment.

Allergic fungal sinusitis (AFS) arises from a host hypersensitivity reaction to fungi residing within the sino-nasal tract. Computed tomography imaging may show heterogenous sinus opacification with bony erosion and expansion into the orbits. With advanced orbital involvement there is a risk of optic neuropathy and irreversible vision loss. We present a patient with AFS who presented with bilateral proptosis and early optic neuropathy. Radiologically, there was evidence of bony erosion and orbital wall compression. Following oral corticosteroids and full-house endoscopic sinus surgery, these changes reversed considerably. This case shows that bony and anatomical orbital changes from AFS are reversible with adequate surgical treatment.

Orbital mycoses in an adult subtropical population.

BACKGROUND/OBJECTIVES: To report the spectrum of fungal infections involving the orbit encountered in an Australian subtropical population with respect to presentation, host risk factors, involved pathogens, treatment and outcomes. SUBJECTS/METHODS: A retrospective chart review was performed on all adult patients with orbital mycosis treated by the senior author (TJS) from 1986 to 2017 in a tertiary setting. RESULTS: Thirty cases of fungal infection involving the orbit were included in this case series. Of these, 26 patients had invasive disease and four patients had non-invasive disease. Causative organisms included mucormycosis (16), aspergillus (8) and other fungi (7). Common risk factors included haematological disorders or malignancy, neutropenia, corticosteroid use and diabetes mellitus. Mucormycosis in three immunocompetent patients was caused by Apophysomyces elegans. Orbital apex syndrome was observed in approximately one third of patients at initial ophthalmological assessment. Amphotericin B was used in most cases of mucormycosis, while there was a more varied spectrum of anti-fungal use in other fungal infections. Seven patients with mucormycosis proceeded to orbital exenteration with a survival rate of 43%. No patients with other orbital fungal infections were exenterated. CONCLUSIONS: Orbital mycoses are not only opportunistic but true pathogenic infections. While initial symptoms may be varied, the development of orbital apex syndrome should raise suspicion for this condition, regardless of patient immune status or age. Survival and visual outcomes are often poor with invasive disease. Multidisciplinary team management with early orbital specialist involvement is essential.

Three Years of Shared Service HIV Nucleic Acid Testing for Public Health Laboratories: Worthwhile for HIV-1 but Not for HIV-2.

BACKGROUND: In 2016, HIV-2 nucleic acid testing (NAT) was added to a shared service program that conducts HIV-1 NAT for public health laboratories performing the recommended algorithm for diagnosing HIV. Here, we evaluate the usefulness of HIV-2 NAT in this program as compared with HIV-1 NAT. METHODS: Specimens eligible for HIV-1 NAT were reactive on an HIV-1/2 antibody or antigen/antibody initial test and nonreactive or indeterminate on a supplemental antibody test or were reactive for HIV-1 antigen-only on an HIV-1/2 antigen/antibody initial test. Specimens eligible for HIV-2 NAT were reactive on an initial test, HIV-2 indeterminate or HIV indeterminate on a supplemental antibody test and had no detectable HIV-1 RNA or were reactive for HIV-2 antibody on an HIV-1/2 antigen/antibody test, and this reactivity was not confirmed with a supplemental antibody assay. All specimens were tested in a reference laboratory using APTIMA HIV-1 qualitative RNA and/or a validated qualitative HIV-2 RNA real-time PCR assay. RESULTS: During 2016 to 2019, HIV-1 RNA was detected in 234 (14%) of 1731 specimens tested. HIV-2 RNA was not detected in 52 specimens tested. Median time from specimen collection to reporting of HIV-1 and HIV-2 NAT results by year ranged from 9 to 10 days and from 22 to 27 days, respectively. Two specimens with HIV-2 indeterminate results on a supplemental antibody test had detectable HIV-1 RNA. CONCLUSIONS: A shared service model for HIV-1 NAT is both feasible and beneficial for public health laboratories. However, because no HIV-2 infections were detected, our data suggest that this program should reconsider the usefulness of HIV-2 NAT testing.

Rapid, CRISPR-Based, Field-Deployable Detection Of White Spot Syndrome Virus In Shrimp.

Rapid, sensitive, point-of-care diagnostics are critical for managing infectious diseases. Here we adapt the CRISPR-based SHERLOCK method to develop a rapid, accurate, single copy detection assay for White Spot Syndrome Virus, the most devastating virus impacting global shrimp aquaculture. Further, we combine paper matrix nucleic acid extraction and lateral flow colorimetric reporting to create a fully field-deployable, next-generation diagnostic with potential to transform veterinary pathology, disease ecology, and animal production.