incidence and factors influencing retinal displacement in eyes treated for rhegmatogenous retinal detachment with vitrectomy and gas or silicone oil

n/

Fluorescein angiography findings in eyes with lamellar macular hole and epiretinal membrane foveoschisis

PURPOSE. The purpose of this paper was to study fluorescein angiography (FA) findings in eyes with lamellar macular hole (LMH), and epiretinal membrane (ERM) foveoschisis. METHODS. In this prospective, observational case series, 46 eyes of patients affected by either LMH or ERM foveoschisis were examined using optical coherence tomography (OCT) and FA. All patients underwent a comprehensive ophthalmological examination and a general workup to exclude uveitis. Main outcome measures were: presence of FA abnormalities, measurements of the areas of vascular leakage, and intensity of pixels in the vitreous. RESULTS. Twenty-four (52.2%) eyes with LMH and 22 (47.8%) with ERM foveoschisis were studied. Overall, FA abnormalities were found in 20 (83.3%) eyes with LMH and 18 (81.8%) with ERM foveoschisis. The median areas of posterior pole and peripheral leakage were 7.52 vs. 1.07 mm2 (P = 0.03) and 21.8 vs. 3.74 mm2 (P = 0.02) in the LMH and ERM foveoschisis group, respectively. Disk hyperfluorescence was found in 8 and 4 eyes and perivascular leak in 10 and 4 eyes with LMH and ERM foveoschisis, respectively. OCT-derived measurements of vitreous intensity did not differ between the two groups, and the investigational workup for uveitis was negative in all patients. CONCLUSIONS. Discrete areas of central and peripheral leakage are commonly found in eyes with LMH and ERM foveoschisis, whereas perivascular leak and hyperfluorescence of the disc are less frequently observed. These findings suggest that breakdown of the retinal blood barrier, involving the posterior pole and the periphery, is frequently associated with these two vitreoretinal disorders

Primary vitrectomy for degenerative and tractional lamellar macular holes: A systematic review and meta-analysis

Purpose To assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies. Methods PubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome. Results Thirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12; p<0.001), with no difference in visual improvement between the degenerative LMH and LHEP group and the tractional LMH group. The sensitivity analysis excluding LHEP group confirmed no difference in visual change between the degenerative LMH group (pre-post MD = -0.18;95%CI = -0.24,-0.12;p<0.001) and the tractional LMH group (MD = -0.16;95%CI = -0.26,-0.07;p<0.001). The incidence rate of post-operative FTMH was higher in the degenerative LMH and LHEP group than in the tractional LMH group (p = 0.002). Conclusion Primary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype

TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance

Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere (ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5′ end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3′ end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging

Risk Factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

This article is available from: http://www.biomedcentral.com/1471-2458/9/34

Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant

<p>Abstract</p> <p>Background</p> <p>The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for <it>CYP1A1</it>, <it>EPHX </it>and <it>GSTM1 </it>genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose).</p> <p>Methods</p> <p>The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for <it>CYP1A1</it>, <it>EPHX</it> and <it>GSTM1</it> were determined by PCR or PCR/RFLP analysis.</p> <p>Results</p> <p>1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32–5.05) associated to exposure to PAH. Polymorphisms in <it>EPHX</it> exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (<it>CYP1A1</it>, <it>EPHX</it>, and <it>GSTM1</it>) had any significant influence on primary DNA damage as evaluated by the comet assay.</p> <p>Conclusion</p> <p>The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk.</p

Patterns of GPS Tracks Suggest Nocturnal Foraging by Incubating Peruvian Pelicans (Pelecanus thagus)

Most seabirds are diurnal foragers, but some species may also feed at night. In Peruvian pelicans (Pelecanus thagus), the evidence for nocturnal foraging is sparse and anecdotal. We used GPS-dataloggers on five incubating Peruvian pelicans from Isla Lobos de Tierra, Perú, to examine their nocturnality, foraging movements and activities patterns at sea. All instrumented pelicans undertook nocturnal trips during a 5–7 day tracking period. Eighty-seven percent of these trips (n = 13) were strictly nocturnal, whereas the remaining occurred during the day and night. Most birds departed from the island after sunset and returned a few hours after sunrise. Birds traveled south of the island for single-day trips at a maximum range of 82.8 km. Overall, 22% of the tracking period was spent at sea, whereas the remaining time was spent on the island. In the intermediate section of the trip (between inbound and outbound commutes), birds spent 77% of the trip time in floating bouts interspersed by short flying bouts, the former being on average three times longer than the latter. Taken together, the high sinuosity of the bird's tracks during floating bouts, the exclusively nocturnal trips of most individuals, and the fact that all birds returned to the island within a few hours after sunrise suggest that pelicans were actively feeding at night. The nocturnal foraging strategy of Peruvian pelicans may reduce food competition with the sympatric and strictly diurnal Guanay cormorants (Phalacrocorax bougainvillii), Peruvian boobies (Sula variegata) and Blue-footed boobies (S. nebouxii), which were present on the island in large numbers. Likewise, plankton bioluminescence might be used by pelicans as indirect cues to locate anchovies during their upward migration at night. The foraging success of pelicans at night may be enhanced by seizing prey close to the sea surface using a sit-and-wait strategy

Incidence rates of in-hospital carpal tunnel syndrome in the general population and possible associations with marital status

<p>Abstract</p> <p>Background</p> <p>Carpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status.</p> <p>Methods</p> <p>Seven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χ_scoretest) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women.</p> <p>Results</p> <p>Age-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts).</p> <p>Conclusion</p> <p>This large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.</p

Prion Protein Amino Acid Determinants of Differential Susceptibility and Molecular Feature of Prion Strains in Mice and Voles

The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. At first, we found a differential susceptibility of bank and field voles compared to C57Bl/6 and wood mice. Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features. Infection with mouse-adapted scrapie 139A was faster in voles than in C57Bl/6 and wood mice. Moreover, a glycoprofile change was observed in voles, which was reverted upon back passage to mice. All strains replicated much faster in voles than in mice after adapting to the new species. PrP sequence comparison indicated a correlation between the transmission patterns and amino acids at positions 154 and 169 (Y and S in mice, N and N in voles). This correlation was confirmed when inoculating three additional rodent species: gerbils, spiny mice and oldfield mice with sheep scrapie and 139A. These rodents were chosen because oldfield mice do have the 154N and 169N substitutions, whereas gerbil and spiny mice do not have them. Our results suggest that PrP residues 154 and 169 drive the susceptibility, molecular phenotype and replication rate of prion strains in rodents. This might have implications for the assessment of host range and molecular traceability of prion strains, as well as for the development of improved animal models for prion diseases

Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994

<p>Abstract</p> <p>Background</p> <p>Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria.</p> <p>Methods</p> <p>We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR), as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models.</p> <p>Results</p> <p>Variants in several genes were found to be marginally associated (uncorrected P value < 0.05) with log(ACR) in at least one race/ethnic group, but none remained significant in crude or fully-adjusted models when correcting for the false-discovery rate (FDR). In analyses of sex-specific albuminuria, <it>IL1B </it>(rs1143623) among Mexican Americans remained significantly associated with increased odds, while <it>IL1B </it>(rs1143623), <it>CRP </it>(rs1800947) and <it>NOS3 </it>(rs2070744) were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P < 0.05). In contrast, no variants were found to be associated with albuminuria among non-Hispanic blacks after adjustment for multiple testing. The only variant among non-Hispanic whites significantly associated with any outcome was <it>TNF </it>rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within <it>MBL2</it>, <it>CRP</it>, <it>ADRB2, IL4R</it>, <it>NOS3</it>, and <it>VDR </it>were significantly associated (FDR-P < 0.05) with log(ACR) or albuminuria in at least one race/ethnic group.</p> <p>Conclusions</p> <p>Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the susceptibility to kidney damage.</p