Smith-Lemli-Optiz syndrome: importance of ophthalmology referral and follow-up.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the 7-dehydrocholesterol reductase (DHCR7) gene, located on chromosomal region 11q13. This results in reduced cholesterol and increased 7-dehydrocholesterol (7DHC) levels. Accumulation of 7DHC in patients with SLOS can affect multiple organs and display a broad phenotypic expression. Ophthalmic abnormalities related to SLOS are variable but the most common is blepharoptosis. Over 50% of these patients present with self-injurious behavior, such as head banging, which can result in ocular complications and blindness. We report the first case of peripheral avascularity of the retina in a patient with SLOS. Physicians should be aware of the potential ocular complications associated with SLOS and confounding factors, such as prematurity, given that referral is usually delayed due to the lack of awareness of these potentially blinding associations. This case highlights the importance of early referral and continuous ophthalmologic follow-up in preventing further deterioration of visual development and complications that can lead to blindness.

Coats plus in prematurity.

BACKGROUND: Coats plus syndrome or cerebroretinal microangiopathy with calcifications and cysts (CMCC) is an exceedingly rare autosomal recessive disorder that predominantly affects the microvasculature in the retina, brain, bones, and gastrointestinal system. Unlike Coats disease, CMCC is bilateral and affects multiple organ systems. MATERIALS AND METHODS: Case report. RESULTS: We report the case of two brothers with Coats Plus syndrome who presented with variable phenotypic expression. One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients. Aggressive treatment with laser photocoagulation and intravitreal bevacizumab dramatically improved the retinal vascular and exudative changes. CONCLUSION: Coats Plus syndrome can have a variable phenotypic presentation, including retinal vascular findings. This rare genetic disease should be in the differential diagnosis in patients who present with atypical retinal pathology, including Retinopathy of Prematurity, Familial Exudative Vitreoretinopathy, or Coats disease associated with non-specific multiorgan abnormalities.

Red light delays programmed cell death in non-host interaction between Pseudomonas syringae pv tomato DC3000 and tobacco plants.

Light modulates almost every aspect of plant physiology, including plant-pathogen interactions. Among these, the hypersensitive response (HR) of plants to pathogens is characterized by a rapid and localized programmed cell death (PCD), which is critical to restrict the spread of pathogens from the infection site. The aim of this work was to study the role of light in the interaction between Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) and non-host tobacco plants. To this end, we examined the HR under different light treatments (white and red light) by using a range of well-established markers of PCD. The alterations found at the cellular level included: i) loss of membrane integrity and nuclei, ii) RuBisCo and DNA degradation, and iii) changes in nuclease profiles and accumulation of cysteine proteinases. Our results suggest that red light plays a role during the HR of tobacco plants to Pto DC3000 infection, delaying the PCD process.

Solitary Fibrous Tumor of the Orbit: A Case Series With Clinicopathologic Correlation and Evaluation of STAT6 as a Diagnostic Marker.

PURPOSE: To retrospectively describe the clinical characteristics, management, and outcomes of a series of patients with solitary fibrous tumor (SFT) of the orbit and to evaluate signal transducer and activator of transcription 6 (STAT6) as a diagnostic marker. METHODS: Review of a retrospective, noncomparative, consecutive series of patients treated at a single institution with a histopathologic diagnosis of SFT. Demographic, clinical, and imaging data were collected, and paraffin-embedded tissue sections were stained to evaluate for the presence of STAT6 and other pertinent markers. RESULTS: Twenty-one patients were identified. Most presented with painless progressive proptosis or eyelid swelling for less than 6 months. Imaging revealed well-circumscribed, firm, variably vascular contrast-enhancing lesions with low to medium reflectivity on ultrasound. Four tumors were histopathologically malignant. All tumors were primarily excised, and 1 patient required exenteration. Two patients were treated with adjuvant radiation therapy. Six patients had recurrent disease of which 3 underwent repeat excision, and 2 were observed. No metastatic disease or attributable deaths were observed. All lesions with available tissue stained positively for both CD34 and STAT6. CONCLUSION: This is the largest single institution case series of orbital SFT with clinicopathologic correlation and the largest series to confirm the presence of STAT6 in orbital lesions. The management of SFT remains challenging due to unpredictable tumor behavior, and complete excision is the generally recommended treatment. It remains unclear whether a subset of asymptomatic patients with histopathologically benign disease can be durably observed without negative sequelae.

First Locally Acquired Congenital Zika Syndrome Case in the United States: Neonatal Clinical Manifestations.

In the spring of 2017, a full-term infant with microcephaly was delivered in South Florida. During first trimester, the mother presented with fever, nausea, and vomiting. She reported no foreign travel for herself or her partner. The infant's neurologic, ophthalmologic, neuroradiologic, and audiologic findings were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM antibodies and plaque reduction neutralization test. New observations, including peripheral temporal retinal avascularity and peripapillary retinal nerve fiber layer thinning, are presented from this first known case of non-travel-associated CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93-e98.].

Frankia canadensis sp. nov., isolated from root nodules of Alnus incana subspecies rugosa.

Strain ARgP5T, an actinobacterium isolated from a root nodule present on an Alnus incana subspecies rugosa shrub growing in Quebec City, Canada, was the subject of polyphasic taxonomic studies to clarify its status within the genus Frankia. 16S rRNA gene sequence similarities and ANI values between ARgP5T and type strains of species of the genus Frankiawith validly published names were 98.8 and 82 % or less, respectively. The in silico DNA G+C content was 72.4 mol%. ARgP5T is characterised by the presence of meso-A2pm, galactose, glucose, mannose, rhamnose (trace), ribose and xylose as whole-organism hydrolysates; MK-9(H8) as predominant menaquinone; diphosphatidylglycerol, phosphatidylinositol and phosphatidylglycerol as polar lipids and iso-C16 : 0 and C17 : 1ω8c as major fatty acids. The proteomic results confirmed the distinct position of ARgP5T from its closest neighbours in Frankiacluster 1. ARgP5T was found to be infective on two alder (Alnus glutinosa and Alnusalnobetula subsp. crispa) and on one bayberry (Morella pensylvanica) species and to fix nitrogen in symbiosis and in pure culture. On the basis of phylogenetic (16S rRNA gene sequence), genomic, proteomic and phenotypic results, strain ARgP5T (=DSM 45898=CECT 9033) is considered to represent a novel species within the genus Frankia for which the name Frankia canadensis sp. nov., is proposed.

Blue Nevi of the Ocular Surface: Clinical Characteristics, Pathologic Features, and Clinical Course.

PURPOSE: Blue nevus is a melanocytic tumor that is commonly found in the skin. Extracutaneous presentations, including the ocular surface, are rare. As such, the purpose of this study was to characterize the clinical features and clinical course of congenital melanocytic tumor (blue nevus) of the conjunctiva. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-one patients with 23 blue nevi of the ocular surface that were excised surgically between 2000 and 2016. METHODS: Chart review of patients identified from a database search of the Florida Lions Ocular Pathology Laboratory records. Pathologic diagnoses were confirmed by 2 pathologists (S.R.D. and G.E.). All specimens were bleached and, tissue permitting, stained using SOX10 (MilliporeSigma, Darmstadt, Germany) and CD68 (Leica Biosystems, Nussloch, Germany). MAIN OUTCOME MEASURES: Clinical characteristics, pathologic features, and clinical course. RESULTS: Mean age of the population was 55±15 years; 71.4% (n = 15) were white and 57.1% (n = 12) were men. One patient had 3 lesions, for a total of 23 lesions examined. Clinically, 13 lesions were on the bulbar conjunctiva, 3 were on the tarsal conjunctiva, 3 were in the fornix, 2 were caruncular, 1 was episcleral, and 1 was at the limbus. Before excision, 8 patients were thought to have primary acquired melanosis, 4 with concern for primary conjunctival melanoma, and 1 thought to have metastatic disease from a plantar melanoma. Five lesions were thought to be benign, and in 8 patients, the lesions were identified incidentally after other ocular surgeries, with no diagnosis of the lesions before excision. Pathologic features were consistent with simple blue nevi in 21 lesions and cellular blue nevus in 2 lesions. No malignant transformations were noted in any patient over the mean 20.2-month follow-up period (range, 2 weeks-103 months). CONCLUSIONS: Blue nevus is a rare deeply pigmented congenital melanocytic lesion with a benign clinical course that can appear clinically similar to primary acquired melanosis or melanoma.

Expression of hypothalamic neurohormones and their receptors in the human eye.

Extrapituitary roles for hypothalamic neurohormones have recently become apparent and clinically relevant, based on the use of synthetic peptide analogs for the treatment of multiple conditions including cancers, pulmonary edema and myocardial infarction. In the eye, it has been suggested that some of these hormones and their receptors may be present in the ciliary body, iris, trabecular meshwork and retina, but their physiological role has yet to be elucidated. Our study intends to comprehensively demonstrate the expression of some hypothalamic neuroendocrine hormones and their receptors within different retinal and extraretinal structures of the human eye. Immunofluorescence, Western blot analysis, and RT-PCR were used to evaluate the qualitative and quantitative expression of Luteinizing Hormone Releasing Hormone (LHRH), Growth Hormone Releasing Hormone (GHRH), Thyrotropin Releasing Hormone (TRH), Gastrin Releasing Peptide (GRP) and Somatostatin as well as their respective receptors (LHRH-R, GHRH-R, TRH-R, GRP-R, SST-R1) in cadaveric human eye tissue and in paraffinized human eye tissue sections. The hypothalamic hormones LHRH, GHRH, TRH, GRP and Somatostatin and their respective receptors (LHRH-R, GHRH-R, TRH-R, GRPR/BB2 and SST-R1), were expressed in the conjunctiva, cornea, trabecular meshwork, ciliary body, lens, retina, and optic nerve.

Fluorescein angiography findings in diffuse retinoblastoma: two case reports with clinicopathologic correlation.

Whereas most retinoblastomas are seen as intraocular tumors, the diffuse infiltrating type is distinguished by a horizontal growth along the retina with minimal vertical growth. These findings can resemble other entities and present as a diagnostic challenge. Fluorescein angiography (FA) features of retinoblastoma have been described in the literature; however, to our knowledge, little information is available on the diffuse type. We present FA findings and the clinicopathlogic correlation of 2 patients with diffuse retinoblastoma. Changes observed on FA correlate with the vascular changes observed on histopathology and can therefore be helpful in the diagnosis of atypical retinoblastomas when the clinical presentation is equivocal.

Histopathologic Characterization of the Expression of Vascular Endothelial Growth Factor in a Case of Retinopathy of Prematurity Treated With Ranibizumab.

PURPOSE: To characterize the expression of vascular endothelial growth factor (VEGF) in a patient with retinopathy of prematurity (ROP) treated with ranibizumab (Case 1) and compare it with a case of ROP without treatment (Case 2), a case of a premature baby without ROP (Case 3), and a case of a baby without history of ROP or prematurity (Case 4). DESIGN: Observational case series. METHODS: The eyes of the deceased babies were removed postmortem and were sent to the Florida Lions Ocular Pathology Laboratory, where they were processed. The specimens were immunostained using an antibody against VEGF. RESULTS: All eyes except for the eyes in Case 4 disclosed positive VEGF staining. Positive staining was present within the nerve fiber layer, inner plexiform layer, and inner and outer nuclear layers and within the spindle-shaped cell population in the vanguard in Case 1. In the posterior pole, positive staining was only observed at the level of the nerve fiber layer. This case also demonstrated less positive staining when compared with Case 2, where positive staining was found within all layers of the retina. CONCLUSION: Less VEGF staining was observed within the retina of the eyes treated with ranibizumab when compared with the VEGF staining in Case 2. This supports the idea that anti-VEGF agents are effective in reducing the amount of VEGF present in the retina. Furthermore, the fact that some expression of VEGF remains in the immature retina after injection supports the idea that anti-VEGF agents can suppress uncontrolled neovascularization without completely blocking the vascular drive for the vascularization of the immature retina.

Oculographic, Clinical Test of Sensory Integration and Balance and Computerized Dynamic Posturography Findings in Patients With Psoriatic Arthritis.

OBJECTIVE: To assess the frequency and characteristics of the oculographic findings and the usefulness of the clinical test of sensory integration and balance (CTSIB) for the evaluation of balance in patients with psoriatic arthritis (PsA) by comparing this test with the computerized dynamic posturography (CDP). STUDY DESIGN: A series of consecutive patients that fulfilled the Moll and Wright criteria for PsA and matched controls were studied. SETTING: The study was performed at the Otolaryngology Division of a tertiary reference center. INTERVENTION: Vestibular evaluation including CTSIB followed by CDP was performed to all patients and age, sex, and ethnically frequency-matched controls. MAIN OUTCOME MEASURE: Patterns of CTSIB and CDP (gold standard) were assessed and compared. PATIENTS: Sixty PsA patients (63.3% women) and 60 matched controls. RESULTS: PsA patients had higher frequency of abnormal oculocephalic response (13.3%) and abnormal caloric test (26.7%) than controls (0% in both cases) (p = 0.006 and p < 0.001, respectively). Benign paroxysmal positional vertigo (BPPV) was diagnosed in two (3.4%) patients and none of the controls (p = 1). Significantly increased frequency of abnormal CTSIB test with vestibular loss pattern (33.3%) in patients compared with controls (6%) was observed (p = 0.002). Significantly increased frequency of abnormal CDP was also observed in PsA patients (14 [23.3%] versus 0 [0%] of controls) (p < 0.001). CTSIB yielded 100% sensitivity, 73% specificity, 48% positive predictive value, and 100% negative predictive value. CONCLUSIONS: This study indicates that oculographic findings are common in PsA. CTSIB is useful for assessing balance disorder screening in the routine clinical practice in these patients.

Investigations into audiovestibular manifestations in patients with psoriatic arthritis.

OBJECTIVE: Although psoriatic arthritis (PsA) is a common chronic inflammatory rheumatic disease, little is known about audiovestibular impairment in this condition. We aimed to establish whether audiovestibular manifestations were present in patients with PsA. METHODS: A set of 60 consecutive patients who fulfilled the Moll and Wright criteria for PsA and 60 matched controls were studied. During the period of recruitment, individuals were excluded who had a history of cardiovascular disease, cerebrovascular complications, peripheral artery disease, renal insufficiency, syphilis, Meniere disease and other vestibular syndromes, infections involving the inner ear, barotrauma, or were in treatment with ototoxic drugs. RESULTS: Most patients with PsA were men (63%). The mean age at the time of our study was 52.9 years and the mean age at the onset of symptoms was 33 years. Thirty-six (60%) of the 60 patients showed abnormal hearing loss in the audiogram compared to only 5 (8.3%) of the 60 controls (p < 0.001). Values of audiometric tests (pure-tone average and speech reception threshold) yielded significant differences between patients and controls (p < 0.001). The audiogram disclosed a bilateral and symmetrical sensorineural hearing loss (SNHL) in PsA with predominant pattern of high frequency SNHL in patients with PsA (46.7%) compared to controls (8.3%, p < 0.001). Patients with PsA exhibited abnormal vestibular tests more commonly than controls. A significantly increased frequency of abnormal computerized dynamic posturography with a predominant vestibular loss pattern was also observed in patients (23.3%) compared to controls (0%, p < 0.001). CONCLUSION: Our current study demonstrates strong evidence for inner ear damage in patients with PsA.

Evaluation of periimplant bone neoformation using different scanning electron microscope methods for measuring BIC. A dog study.

OBJECTIVES: [corrected] The aim of this study was to determine which of three methods for measuring BIC (bone-to-implant contact), using vestibular and lingual scanning electron microscopy (SEM) for different implant systems at 15, 30 and 90 days post-surgery was the most precise. An elemental analysis with SEM was used to evaluate neoformed bone composition for three implant systems at the same study times. MATERIAL AND METHODS: 36 implants were placed in eighteen Beagle dogs mandible about one year old and weighing approximately 12-13 kg in order to evaluate bone apposition to three different implant surfaces. It was used the third and fourth premolar and first molar distal sockets in both quadrants of the mandible (3P3, 4P4 and 1M1). Teeth were hemi-sected and the distal roots were removed. The specimens were prepared for histological examination and each section surface was stained using Masson's trichrome and hematoxylin and eosin stains. BIC evaluations were performed by the three methods, BIC I (the quantity of mineralized bone in direct contact with the implant's titanium surface across the entire threaded area); BIC II (along a line that passes from apex to apex of the implant threads); BIC III (both in areas around and above the threads and in between threads). RESULTS: Both BIC and bone content were analyzed for all implants placed in P3, P4 y M1 alveoli on both, the buccal and palatine sides (elemental analysis quantified Ca, P, O and C). It was seen it was only at the ninety-day mark that high percentages of calcium were present. CONCLUSIONS: This study suggest that BIC III evaluation is the most certain method for establishing the quantity of bone formed as the BIC area. Key words:Bone-to-impant contact, dogs, extraction socket, implants.

Effect of chronic ethanol feeding on 24-hour rhythms of mitogenic responses and lymphocyte subset populations in thymus and spleen of peripubertal male rats.

This work analyzes the effect of chronic ethanol feeding on the 24-hour variation of mitogenic responses and lymphocyte subset populations in thymus and spleen. Animals were maintained under a 12:12-hour light/dark photoperiod and they received a liquid diet for 4 weeks, starting on day 35 of life. The ethanol-fed group received a similar diet to controls except that maltose was isocalorically replaced by ethanol. Ethanol replacement provided 36% of the total caloric content of the diet. Rats were killed at 6 time intervals around the clock, beginning at Zeitgeber time (ZT) 1 (ZT 0 = lights on). Under ethanol intake the splenic and thymic weight decreased. In addition, mean values of the thymic, but not of the splenic T cell number decreased, and mean values of the thymic and splenic CD8+ and CD4+CD8+ number increased. Consequently, the thymic T/B ratio and the thymic and splenic CD4+/CD8+ ratio decreased in ethanol-fed rats. At the same time there was a significant increase in the response of the thymic cells to LPS. The ethanol diet modified the 24-hour rhythmicity of thymic and splenic T, B and CD4+CD8+ cells, thymic CD4+ and splenic CD8+ cells, thymic and splenic T/B and CD4+/CD8+ ratios, as well as of mitogenic responses in both tissues. Chronic ethanol administration presumably affects the endogenous clock that modulates the circadian variation of immune responsiveness in growing rats.

Ceruloplasmina y su actividad oxidásica en recién nacidos / Ceruloplasmin and its oxidase activity in newborn infants

En 45 recién nacidos a término se encontraron niveles medios de ceruloplasmina, actividad oxidásica y actividad oxidásica específica (actividad por gramo de ceruloplasmina) significativamente menores que en un grupo de 30 adultos (p < 0,001). Se obtuvo una correlación significativa de la ceruloplasmina con la actividad oxidásica tanto en el grupo de adultos (r = 0,934, p < 0,001) como en el de recién nacidos (r = 0,834, p < 0,001). En estos últimos se encontró una correlación significativa de la actividad oxidásica específica con la actividad oxidásica (r = 0,646, p < 0,001). Estos resultados plantean cuestiones de interés sobre la naturaleza de la actividad oxidásica de la ceruloplasmina y el mecanismo de la reacción de oxidación. En los recién nacidos se encontró una correlación negativa de la alfa-fetoproteína con la ceruloplasmina (r = 0,659, p < 0,001) y la actividad oxidásica (r = -0,455, p < 0,005). Se sugiere que en los neonatos la hipoceruloplasminemia sería el resultado de una inmadurez hepática