Juvenile ocular myasthenia gravis: a report of two cases.

We report 2 cases of pediatric ocular myasthenia gravis. The first case was a 7-year-old girl who presented with bilateral ophthalmoplegia and ptosis that correlated with the onset of upper respiratory symptoms. Neuroimaging and acetylcholine receptor antibody testing were unremarkable. The ice pack test was positive. Symptoms greatly improved with pyridostigmine, with full resolution of ophthalmoplegia achieved by 8-month follow-up. The second case was a 4-year-old girl who presented emergently with ptosis and bilateral ophthalmoplegia. Acetylcholine receptor antibodies testing was positive. The patient was started on pyridostigmine and intravenous immunoglobulin and is scheduled to follow-up with pediatric ophthalmology in the outpatient setting.

Isolated primary sebaceous gland carcinoma of the bulbar conjunctiva.

Purpose: To report a rare case of primary sebaceous gland carcinoma of the bulbar conjunctiva without palpebral involvement. Observation: A 76-year-old male was referred to the cornea service for a suspicious lesion on the limbal conjunctiva and cornea of his left eye. On exam, there was a large fibrovascular growth with conjunctivalization of the cornea from 2:00 to 10:00 extending 6mm onto the cornea. Patient underwent treatment with 5-fluouracil, followed by excisional biopsy with cryotherapy. Histopathologic examination demonstrated poorly differentiated sebaceous gland carcinoma. Subsequent map biopsies of the palpebral and bulbar conjunctiva of the left eye were performed and ruled out pagetoid spread. Conclusions and Importance: Primary sebaceous gland carcinoma of the bulbar conjunctiva without eyelid involvement is a rare phenomenon. Our patient joins a few case reports in the literature. Of these cases, we are the second case to utilize 5-flurouracil preoperatively. We recommend clinicians consider sebaceous carcinoma on their differential when ocular surface neoplasms diagnosed as other conditions do not respond to conventional therapies.

Spontaneous orbital hemorrhage in a case of acute liver failure.

Purpose: To report an unusual case of spontaneous orbital hemorrhage in the setting of DIC and hepatic failure. Observations: A 33-year-old female presented to the Emergency Department (ED) with acute liver failure. During the first week of her hospital admission, she developed unilateral eyelid swelling and proptosis, prompting a consult to ophthalmology. Additional physical examination revealed significantly decreased visual acuity, extraocular muscle restriction, afferent pupillary defect, and increased intraocular pressure. Computed tomography (CT) and ultrasound confirmed the diagnosis of intraorbital hemorrhage. Aggressive management in the form of lateral canthotomy, cantholysis, and septolysis was unable to be performed due to the patient's multiple comorbidities outweighing the potential benefits. Conclusions and importance: This rare phenomenon is unique from previous existing literature in that the timing of the incident limited the therapeutic options for this patient, additional imaging in the form of ultrasound was utilized in the work-up, and to our knowledge this is the second case of spontaneous orbital hemorrhage as a complication of disseminated intravascular coagulation (DIC) caused by hepatic failure.

Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.

BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.

Age and insulin-like growth factor-1 impact PCNA monoubiquitination in UVB-irradiated human skin.

Nonmelanoma skin cancers occur primarily in individuals over the age of 60 and are characterized by an abundance of ultraviolet (UV) signature mutations in keratinocyte DNA. Though geriatric skin removes UV photoproducts from DNA less efficiently than young adult skin, it is not known whether the utilization of other prosurvival but potentially mutagenic DNA damage tolerance systems such as translesion synthesis (TLS) is altered in older individuals. Using monoubiquitination of the replicative DNA polymerase clamp protein PCNA (proliferating cell nuclear antigen) as a biochemical marker of TLS pathway activation, we find that UVB exposure of the skin of individuals over the age of 65 results in a higher level of PCNA monoubiquitination than in the skin of young adults. Furthermore, based on previous reports showing a role for deficient insulin-like growth factor-1 (IGF-1) signaling in altered UVB DNA damage responses in geriatric human skin, we find that both pharmacological inhibition of the IGF-1 receptor (IGF-1R) and deprivation of IGF-1 potentiate UVB-induced PCNA monoubiquitination in both human skin ex vivo and keratinocytes in vitro. Interestingly, though the TLS DNA polymerase Pol eta can accurately replicate the major photoproducts induced in DNA by UV radiation, we find that it fails to accumulate on chromatin in the absence of IGF-1R signaling and that this phenotype is correlated with increased mutagenesis in keratinocytes in vitro. Thus, altered IGF-1/IGF-1R signaling in geriatric skin may predispose epidermal keratinocytes to carry out a more mutagenic form of DNA synthesis following UVB exposure.

A Case of Orbital Granuloma Secondary to Dermal Filler Injection.

A foreign body granulomatous reaction is a rare complication of the subcutaneous injection of fillers. We describe a 57-year-old female that presented with a six-month history of a non-painful, right lower eyelid mass. She had a dermal filler in the zygomatic region several months before the onset of her symptoms. Anterior orbitotomy and pathology revealed multinuclear giant cells consistent with a hyaluronic acid-based filler. This case describes the clinical presentation, histopathologic features, and treatment of an orbital granuloma secondary to dermal filler injection. Our case was uncommon because the zygomatic filler migrated across the orbital septum. Additionally, transconjunctival orbitotomy was used instead of a hyaluronidase injection due to the inferior location of the granuloma.

Spironolactone and XPB: An Old Drug with a New Molecular Target.

Spironolactone (SP) is commonly used for the treatment of heart failure, hypertension, and complications of cirrhosis by antagonizing the mineralocorticoid receptor. However, SP also antagonizes the androgen receptor, and thus SP has also been shown to be effective in the treatment of acne, hair loss, and hirsutism in women. Interestingly, recent drug repurposing screens have identified new and diverse functions for SP as a simulator of tumor immunosurveillance and as an inhibitor of DNA repair and viral infection. These novel pharmacological effects of SP have all been linked to the ability of SP to induce the rapid proteolytic degradation of the xeroderma pigmentosum group B (XPB) protein. XPB is a critical enzymatic component of the multi-subunit complex known as transcription factor II-H (TFIIH), which plays essential roles in both DNA repair and the initiation of transcription. Given the critical functions for XPB and TFIIH in these processes, the loss of XPB by SP could lead to mutagenesis. However, the ability of SP to promote cancer stem cell death and facilitate immune recognition may counteract the negative consequences of SP to mitigate carcinogenic risk. Thus, SP appears to have new and interesting pharmacological effects that may extend its potential uses.

Utilizing functional near-infrared spectroscopy for prediction of cognitive workload in noisy work environments.

Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts' decision-making process. We investigated the effects of different noise stimuli on analysts' performance and workload in anomaly detection by simulating a noisy work environment. We utilized functional near-infrared spectroscopy (fNIRS) to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin concentration changes in the prefrontal cortex (PFC), as well as behavioral measures, which include eye tracking, reaction time, and accuracy rate. We hypothesized that noisy environments would have a negative effect on the participant in terms of anomaly detection performance due to the increase in workload, which would be reflected by an increase in PFC activity. We found that HbO for some of the channels analyzed were significantly different across noise types ([Formula: see text]). Our results also indicated that HbO activation for short-intermittent noise stimuli was greater in the PFC compared to long-intermittent noises. These approaches using fNIRS in conjunction with an understanding of the impact on human analysts in anomaly detection could potentially lead to better performance by optimizing work environments.