PurposeTo assess the preoperative features of patients with idiopathic macular hole (IMH) and vitreomacular adhesion (VMA) treated with ocriplasmin (OCP) that can predict successful ...closure.MethodData were prospectively collected on all patients with IMH treated with OCP in three British ophthalmic centres. Several preoperative variables were recorded including the IMH base diameter (BD), minimum linear diameter (MLD), and VMA width measured on spectral domain optical coherence tomography. Several other IMH indices were derived including a 'width factor', defined as the BD minus the MLD in μm. The occurrence of VMA release and hole closure were used as the main outcome measures.ResultsThirty-three patients in total with IMH were treated with OCP. Two patients developed rhegmatogenous retinal detachment and were excluded. The mean age of the remaining 31 patients was 71 years, and 71% were female. VMA release occurred in 19 of the 31 (61%) patients and macular hole closure in 11 (35%). Width factor was the most predictive feature for closure on multivariate analysis. The deviance R(2) was 67% (P<0.001). An IMH with a width factor of <60 μm had a 95% certainty of closure, whereas if >290 μm then there was less than a 5% chance of closure. Neither VMA width nor MLD alone was associated with VMA release or closure.ConclusionsPatients with macular holes where the BD was close in size to the MLD had an improved probability of closure than holes with wider base configurations.
Canine T‐zone lymphoma (TZL) is a subtype of T‐cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical ...behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.
The aim of this study was to measure the heritability estimates for metabolic traits and the features of the insulin resistance syndrome in families with an increased genetic susceptibility to Type 2 ...diabetes.
A total of 811 non-diabetic relatives from 278 pedigrees of northern European extraction in which there was a sib-pair with Type 2 diabetes were recruited and studied at the six Diabetes UK Warren Type 2 diabetes centres. Heritability estimates were calculated, allowing for key covariates (age, sex, BMI and recruitment centre). Values greater than 0.10 were considered statistically significant in comparison to zero.
Fasting glucose concentration and homeostasis model assessment of pancreatic beta cell function (HOMA %B) had the highest heritability estimates of 0.72 and 0.78 respectively. Heritability estimates for the features of the insulin resistance syndrome (BMI, WHR, systolic and diastolic blood pressure, serum lipids and homeostasis model assessment of insulin sensitivity HOMA %S) were also high. The heritability estimate for fasting glucose was markedly higher in the present study (0.77 vs 0.21 adjusted for age and sex; p<0.001) than in a comparable study of families from the same background population but with no increased susceptibility to diabetes. However, the estimates for the features of the insulin resistance syndrome were similar in the two studies.
In families with a high risk of Type 2 diabetes, the heritability estimates for fasting glucose, pancreatic beta cell function and the features of the insulin resistance syndrome were all high. The higher heritability estimate for pancreatic beta cell function suggests that this resource may be most effective when investigating genetic susceptibility to beta cell dysfunction.
Mercury is a global contaminant that bioaccumulates in a tissue-specific manner in long-lived predators such as Steller sea lions (SSL). Bone is a well-preserved material amenable for studying ...millennial scale trends; however, little is known about the distribution and variability of total mercury concentrations (THg) within individual bones and among bone elements in SSL. We assessed SSL bone THg variability with respect to physiologic age, bone type, longitudinally within a bone, and among bone elements. Pup bones (mean ± SD; 31.4 ± 13.58 ppb) had greater THg than adults (7.9 ± 1.91 ppb). There were greater and more variable THg within individual long bones near epiphyses compared to mid-diaphysis. Pup spongy bone in ribs (62.7 ± 44.79 ppb) had greater THg than long bones (23.5 ± 8.83 ppb) and phalanges (19.6 ± 10.78 ppb). These differences are likely due to variability in bone composition, growth, and turnover rate. This study informs standardized sampling procedures for THg in bone to improve interpretations of mercury variability over time and space.
•Steller sea lion bone has low total mercury concentrations and high variability.•Steller sea lion total mercury concentrations vary within an individual long bone.•Steller sea lion total mercury concentrations differ among skeletal elements.
Summary
The relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary ...vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients’ genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 μg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0·2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter‐patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.
Diffuse large B‐cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be ...prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow‐up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.
Using 20.7 pb(-1) of e(+)e(-) annihilation data taken at sq.rt(r) = 3.671 GeV with the CLEO-c detector, precision measurements of the electromagnetic form factors of the charged pion, charged kaon, ...and proton have been made for timelike momentum transfer of |Q(2)| = 13.48 GeV(2) by the reaction e(+)e(-) --> h(+)h(-). The measurements are the first ever with identified pions and kaons of |Q(2)| > 4 GeV(2), with the results F(13.48 GeV(2)) = 0.075 +/- 0.008(stat) +/- 0.005(syst) and F(K)(13.48 GeV(2)) = 0.063 +/- 0.004(stat) +/- 0.001(syst). The result for the proton, assuming G(p)(E) = G(p)(M), is G(p)(M)(13.48 GeV(2)) = 0.014 +/- 0.002(stat) +/- 0.001(syst), which is in agreement with earlier results.
Mercury (Hg) can be neurotoxic to mammals and impact reproduction, whereas selenium (Se) is an important antioxidant known to ameliorate some adverse effects of Hg. Total Hg concentrations (THg) were ...measured in lanugo (pelage grown in utero) of 812 Steller sea lion (Eumetopias jubatus) pups across Alaska and Russia to assess fetal exposure during late gestation. The molar ratio of total Se to THg (TSe:THg) was determined in whole blood collected from 291 pups. Stable isotope ratios of carbon and nitrogen were measured in sections of vibrissae (whiskers, n = 498) and in lanugo (n = 480) of pups grown during late gestation to track diet variations among adult females that can drive Hg and Se exposure during this critical fetal development period.
Lanugo THg ranged from 1.4 to 73.7 μg/g dry weight with the lowest median THg in Southeast Alaska. Pups from the Western Aleutian Islands had higher median lanugo THg than pups from other metapopulations in Alaska. Over 25% of pups in the Western Aleutian Islands had THg above published risk thresholds (20 μg/g) for other mammals. Whole blood molar TSe:THg was significantly lower in the Western Aleutian Islands and in some parts of the Central Aleutian Islands with higher molar ratios found in the Eastern Aleutian Islands and Central Gulf of Alaska. This suggests a limitation on potential protective functions of Se in the western regions with the highest relative THg. The Central Aleutian Island pups with THg over 20 μg/g had higher δ15N ratios than pups with lower THg suggesting dams consuming higher trophic level prey is a key driver for Hg exposure. However, regional differences likely reflect variability in diet of the dam during gestation and in Hg food web dynamics between oceanic regimes east and west of key passes in the Aleutian Islands.
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•Steller sea lions were studied from Alaska across the Aleutian Islands to Russia.•δ15N and δ13C were used to understand feeding ecology drivers of Hg and Se concentrations.•>25% of Western Aleutian Island pups had THg above adverse risk thresholds.•Pups with highest THg showed increased risk of Hg-dependent Se deficiency.•Pregnant dam diet and food web dynamics are regionally dependent.
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