Retrolental cohesive ophthalmic viscoelastic injection in severely subluxated cataracts: The "Viscolift technique".

INTRODUCTION: To describe a novel surgical approach in the management of subluxated cataracts. METHODS: A 70-year-old Caucasian male with a subluxated cataract in the left eye was referred to our clinic at the Azienda Ospedaliero-Universitaria di Bologna- Ophthalmology Unit. The ophthalmic examination revealed a best-corrected visual acuity (BCVA) of 20/200 in the left eye with monocular diplopia and a severely subluxated NO6/NC6 cataract and the fundus examination did not reveal any vitreoretinal abnormalities. The right eye had 20/20 BCVA and was pseudophakic. After a 300° conjunctival peritomy, a single 25-gauge valved trocar 4 mm was inserted from the limbus in the inferotemporal quadrant, where the cataract was mainly dislocated and a corneal paracentesis to reduce the anterior chamber intraocular pressure was performed. Subsequently cohesive viscoelastic was progressively injected in the retrolental space through the trocar, to recenter and elevate the subluxated cataract. Thereafter, a complete centered capsulorhexis was performed, four capsular hooks were inserted to stabilize the bag, and complete phacoemulsification was performed with intact posterior capsular support. In the end, given the lack of capsular support elements such as the Cionni ring or Ahmed segment, a sutureless scleral fixated intraocular lens was implanted. RESULTS: One week after surgery, the BCVA was 20/25, and the final BCVA at 6 months was 20/20, without any complications. CONCLUSIONS: Retrolental cohesive ophthalmic viscoelastic injection could represent a novel effective surgical approach in recentering and elevating subluxated cataracts, facilitating the capsulorhexis, and reducing the risk of a pars plana approach.

Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer.

Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu4N[Fe(CO)3NO]-catalyzed carbene transfer of α-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy-N-acetylcylindrocarine.

Antarctic permafrost degassing in Taylor Valley by extensive soil gas investigation.

Ongoing studies conducted in northern polar regions reveal that permafrost stability plays a key role in the modern carbon cycle as it potentially stores considerable quantities of greenhouse gases. Rapid and recent warming of the Arctic permafrost is resulting in significant greenhouse gas emissions, both from physical and microbial processes. The potential impact of greenhouse gas release from the Antarctic region has not, to date, been investigated. In Antarctica, the McMurdo Dry Valleys comprise 10 % of the ice-free soil surface areas in Antarctica and like the northern polar regions are also warming albeit at a slower rate. The work presented herein examines a comprehensive sample suite of soil gas (e.g., CO2, CH4 and He) concentrations and CO2 flux measurements conducted in Taylor Valley during austral summer 2019/2020. Analytical results reveal the presence of significant concentrations of CO2, CH4 and He (up to 3.44 vol%, 18,447 ppmv and 6.49 ppmv, respectively) at the base of the active layer. When compared with the few previously obtained measurements, we observe increased CO2 flux rates (estimated CO2 emissions in the study area of 21.6 km2 ≈ 15 tons day-1). We suggest that the gas source is connected with the deep brines migrating from inland (potentially from beneath the Antarctic Ice Sheet) towards the coast beneath the permafrost layer. These data provide a baseline for future investigations aimed at monitoring the changing rate of greenhouse gas emissions from Antarctic permafrost, and the potential origin of gases, as the southern polar region warms.

Iron-Catalysed Carbene Transfer to Isocyanides as a Platform for Heterocycle Synthesis.

An iron-catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H-tetrazoles) in a one-pot process. The electron-rich Hieber anion ([Fe(CO)3 NO]- ) facilitates efficient catalytic carbene transfer from acceptor-type α-diazo carbonyl compounds to isocyanides, providing a cost-efficient and benign alternative to similar noble metal-catalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α-diazo carbonyl carbene precursor and ketenimine formation is provided.

Synthesis of Densely Functionalized Pyrimidouracils by Nickel(II)-Catalyzed Isocyanide Insertion.

A robust nickel-catalyzed oxidative isocyanide insertion/C-H amination by reaction of readily available N-uracil-amidines with isocyanides affording polysubstituted pyrimidouracils has been reported. The reaction proceeds in moderate to quantitative yield, under mild conditions (i.e., green solvent, air atmosphere, moderate temperature). The broad range of structurally diverse isocyanides and N-uracil-amidines that are tolerated make this method an interesting alternative to the currently available procedures toward pyrimidouracils.

Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.

Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9). The results showed a significant reduction of SOD3, phospho-Akt and Akt protein levels in AsAA tissues from patients with BAV, compared to controls, whereas the differences observed between controls and patients with TAV  were not significant. The decreased levels of SOD3 and Akt in BAV aortic tissues are associated with decreased Erk1/Erk2 phosphorylation and MMP-9 levels increase. The authors suggest a role of decreased SOD3 protein levels in the progression of AsAA with BAV and a link between ECM modifications of aortic media layer and impaired Erk1/Erk2 and Akt signaling in the late stages of the aortopathy associated with BAV.

A universal procedure for the [¹8F]trifluoromethylation of aryl iodides and aryl boronic acids with highly improved specific activity.

Herein, we describe a valuable method for the introduction of the [(18)F]CF3 group into arenes with highly improved specific activity by the reaction of [(18)F]trifluoromethane with aryl iodides or aryl boronic acids. This [(18)F]trifluoromethylation reaction is the first to be described in which the [(18)F]CF3 products are generated in actual trace amounts and can therefore effectively be used as PET tracers. The method shows broad scope with respect to possible aryl iodide and aryl boronic acid substrates, as well as good to excellent conversion. In particular, the [(18)F]trifluoromethylation of boronic acids was found to outperform [(18)F]trifluoromethylation reactions of halogenated aryl precursors with regard to conversion, reaction conditions, and kinetics.

TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy.

We assess the level of tumour necrosis factor alpha (TNF-alpha) in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls) and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR) and 16 with nonproliferative retinopathy (NDPR, background/preproliferative). Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (P < 0.05). Glycemia in NPDR: 6.6 mmol/L (range: 5.8-6.3); in PDR: 6.7 mmol/L (range: 6.1-7.2); in control: 5.7 mmol/L (range: 4.9-6.1); microalbuminurea in NPDR: 10.6 mg/L (range: 5.6-20); in PDR: 25.2 mg/L (range: 17-40); in control: 5.3 mg/L (range: 2.6-10); Body mass index in NPDR: 26 Kg/m(2) (range: 20.3-40); in PDR: 28 Kg/m(2) (range 20.3-52); in control: 21 Kg/m(2) (range 19-26). The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

Multiplex ligation-dependent probe amplification detection of an unknown large deletion of the CREB-binding protein gene in a patient with Rubinstein-Taybi syndrome.

Rubinstein-Taybi syndrome is a rare autosomal dominant congenital disorder characterized by postnatal growth retardation, psychomotor developmental delay, skeletal anomalies, peculiar facial morphology, and tumorigenesis. Mutations in the gene encoding the cAMP response element-binding protein (CREB, also known as CREBBP or CBP) on chromosome 16p13.3 have been identified. In addition, some patients with low intelligence quotients and autistic features bear large deletions. Based on these observations, we used multiplex ligation-dependent probe amplification to search for large deletions affecting the CREBBP gene in a Rubinstein-Taybi syndrome patient. We identified a novel heterozygote deletion removing five exons (exons 17-21), encoding the histone acetyltransferase domain. We propose the use of multiplex ligation-dependent probe amplification as a fast, accurate and cheap test for detecting large deletions in the CREBBP gene in the sub-group of Rubinstein-Taybi syndrome patients with low intelligence quotients and autistic features.

A microwave-assisted diastereoselective multicomponent reaction to access dibenzo[c,e]azepinones: synthesis and biological evaluation.

An unprecedented microwave-assisted multicomponent strategy has been elaborated for the fast, efficient, and diastereoselective generation of the dibenzo[c,e]azepinone scaffold. The generated compounds were evaluated for their bioactivity.

YidC is involved in the biogenesis of the secreted autotransporter hemoglobin protease.

Autotransporters (ATs) constitute an important family of virulence factors secreted by Gram-negative bacteria. Following their translocation across the inner membrane (IM), ATs temporarily reside in the periplasmic space after which they are secreted into the extracellular environment. Previous studies have shown that the AT hemoglobin protease (Hbp) of Escherichia coli requires a functional signal recognition particle pathway and Sec translocon for optimal targeting to and translocation across the IM. Here, we analyzed the mode of IM translocation of Hbp in more detail. Using site-directed photocross-linking, we found that the Hbp signal peptide is adjacent to YidC early during biogenesis. Notably, YidC is in part associated with the Sec translocon but has until now primarily been implicated in the biogenesis of IM proteins. In vivo, YidC appeared critical for the biogenesis of the ATs Hbp and EspC. For Hbp, depletion of YidC resulted in the formation of secretion-incompetent intermediates that were sensitive to degradation by the periplasmic protease DegP, indicating that YidC activity affects Hbp biogenesis at a late stage, after translocation across the IM. This is the first demonstration of a role for YidC in the biogenesis of an extracellular protein. We propose that YidC is required for maintenance of the translocation-competent state of certain ATs in the periplasm. The large periplasmic domain of YidC is not critical for this novel functionality as it can be deleted without affecting Hbp biogenesis.

Computer-aided pulmonary nodule detection - performance of two CAD systems at different CT dose levels.

PURPOSE: To evaluate the impact of dose reduction on the performance of computer-aided lung nodule detection systems (CAD) of two manufacturers by comparing respective CAD results on ultra-low-dose computed tomography (ULD-CT) and standard dose CT (SD-CT). MATERIALS AND METHODS: Multi-slice computed tomography (MSCT) data sets of 26 patients (13 male and 13 female, patients 31 - 74 years old) were retrospectively selected for CAD analysis. Indication for CT examination was staging of a known primary malignancy or suspected pulmonary malignancy. CT images were consecutively acquired at 5 mAs (ULD-CT) and 75 mAs (SD-CT) with 120 kV tube voltage (1 mm slice thickness). The standard of reference was determined by three experienced readers in consensus. CAD reading algorithms (pre-commercial CAD system, Philips, Netherlands: CAD-1; LungCARE, Siemens, Germany: CAD-2) were applied to the CT data sets. RESULTS: Consensus reading identified 253 nodules on SD-CT and ULD-CT. Nodules ranged in diameter between 2 and 41 mm (mean diameter 4.8 mm). Detection rates were recorded with 72 % and 62 % (CAD-1 vs. CAD-2) for SD-CT and with 73 % and 56 % for ULD-CT. Median false positive rates per patient were calculated with 6 and 5 (CAD-1 vs. CAD-2) for SD-CT and with 8 and 3 for ULD-CT. After separate statistical analysis of nodules with diameters of 5 mm and greater, the detection rates increased to 83 % and 61 % for SD-CT and to 89 % and 67 % for ULD-CT (CAD-1 vs. CAD-2). For both CAD systems there were no significant differences between the detection rates for standard and ultra-low-dose data sets (p > 0.05). CONCLUSION: Dose reduction of the underlying CT scan did not significantly influence nodule detection performance of the tested CAD systems.

Synthesis of conformationally constrained peptidomimetics using multicomponent reactions.

A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV beta-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure.

Linear and volume measurements of pulmonary nodules at different CT dose levels - intrascan and interscan analysis.

PURPOSE: To compare the interobserver variability of the unidimensional diameter and volume measurements of pulmonary nodules in an intrascan and interscan analysis using semi-automated segmentation software on ultra-low-dose computed tomography (ULD-CT) and standard dose CT (SD-CT) data. MATERIALS AND METHODS: In 33 patients with pulmonary nodules, two chest multi-slice CT (MSCT) datasets (1 mm slice thickness; 20 % reconstruction overlap) had been consecutively acquired with an ultra-low dose (120 kV, 5 mAs) and standard dose technique (120 kV, 75 mAs). MSCT data was retrospectively analyzed using the segmentation software OncoTREAT (MeVis, Bremen, Germany, version 1.3). The volume of 229 solid pulmonary nodules included in the analysis as well as the largest diameter according to RECIST (Response Evaluation Criteria for Solid Tumors) were measured by two radiologists. Interobserver variability was calculated and SD-CT and ULD-CT data compared in an intrascan and interscan analysis. RESULTS: The median nodule diameter (n = 229 nodules) was registered with 8.2 mm (range: 2.8 to 43.6 mm, mean: 10.8 mm). The nodule volume ranged between 0.01 and 49.1 ml (median 0.1 ml, mean 1.5 ml). With respect to interobserver variability, the intrascan analysis did not reveal statistically significant differences (p > 0.05) between ULD-CT and SD-CT with broader limits of agreement for relative differences of RECIST measurements (-31.0 % + 27.0 % mean -2.0 % for SD-CT; -27.0 % + 38.6 %, mean 5.8 % for ULD-CT) than for volume measurements (-9.4 %, 8.0 %, mean 0.7 % for SD-CT; -13 %, 13 %, mean 0.0 % for ULD-CT). The interscan analysis showed broadened 95 % confidence intervals for volume measurements (-26.5 % 29.1 % mean 1.3 %, and -25.2 %, 29.6 %, mean 2.2 %) but yielded comparable limits of agreement for RECIST measurements. CONCLUSION: The variability of nodule volumetry assessed by semi-automated segmentation software as well as nodule size determination by RECIST appears to be independent of the acquisition dose in the CT source dataset. This is particularly important regarding size determination of pulmonary nodules in screening trials using low-dose CT data for follow-up imaging.

Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders.

The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush et al. (1997): Hum Mol Genet 6: 1241-1250]. Since this original observation, only one association study [Marui et al. (2004): Brain Dev 26: 5-7] has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intron/exon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that is, C6S and L181F, involve amino acid changes identified in two patients with ASD and Rett syndrome, respectively. Both the leucine at position 181 and the cysteine at position 6 are strongly conserved in vertebrates. C6S and L181F mutant proteins were expressed in COS-7 and BALB/3T3 cells, but they did not affect either GRP's binding affinity or its potency for stimulating phospholipase C-mediated production of inositol 1,4,5-trisphosphate. In summary, our results do not provide support for a major role of the GRPR gene in ASD in the population of patients we have studied. However, there is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders in the two patients.

[Oral administration of intravenous contrast media: a tasty alternative to conventional oral contrast media in computed tomography]. / Intravenöse Kontrastmittel oral appliziert: Eine wohlschmeckende Alternative zum herkömmlichen oralen Kontrastmittel in der Computertomografie.

PURPOSE: Many patients dislike oral contrast media due to their bad taste. The aim of the present study was to identify a solution that tastes better while providing the same opacification in order to offer oncological patients an alternative to the routinely used bad tasting oral contrast media. MATERIALS AND METHODS: In a single blinded, prospective clinical study, the orally administered intravenous contrast media iohexol (Omnipaque), iopromide (Ultravist), and iotrolan (Isovist) as well as the oral contrast media sodium amidotrizoate (Gastrografin) and ioxithalamate (Telebrix) were each compared to the oral contrast medium lysine amidotrizoate as the reference standard at a constant dilution. The density values of all contrast media with the same dilutions were first measured in a phantom study. The patient study included 160 patients who had undergone a prior abdominal CT scan with lysine amidotrizoate within 6 months. The patients rated their subjective taste impression on a scale of 0 (very bad) to 10 (excellent). In addition, adverse events and opacification were recorded and prices were compared. RESULTS: The phantom study revealed identical density values. Patients assigned much higher taste impression scores of 8 and 7 to iohexol and iotrolan, respectively, as compared to a score of 3 for the conventional lysine amidotrizoate (p< 0.05). Iopromide and sodium amidotrizoate did not differ significantly from lysine amidotrizoate. The opacification of all contrast media and experienced adverse events did not differ significantly. Iotrolan (ca. 120 euro/100 ml), Iohexol and Iopromide (ca. 70 euro/100 ml) are more expensive than the conventional oral contrast media (ca. 10 - 20 euro/100 ml). CONCLUSION: Orally administered solutions of non-ionic contrast media improve patient comfort due to the better taste and provide the same opacification in comparison to conventional oral contrast media. At present, their use should be limited to individual cases due to the higher costs.

Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.

OBJECTIVE: To analyse the SLC22A12 (URAT1) gene in primary gout patients, first-grade relatives and healthy controls and the possible association of them with demographic and clinical data. SUBJECTS AND METHODS: We included 69 consecutive patients with diagnosis of primary gout, as well as 29 first-grade relatives and 120 healthy volunteers. Demographic and clinical data were obtained from the patients and relatives. DNA was purified from peripheral blood and all 10 exons of the SLC22A12 (URAT1) gene were sequenced. RESULTS: We found six different mutations in the SLC22A12 gene in 16 out of 69 (23%) patients with primary gout. Five mutations were in exon 5 and one in exon 4; five out of six mutations were heterozygous (one compound heterozygous) and one homozygous. The C850G mutation (exon 5) was found in 11 gout patients, these patients have lower levels of triglycerides than the rest of the group: 160 +/- 56 vs 292 +/- 203 mg/dl (P = 0.038). In one family, we found SLC22A12 mutations in three relatives within exon 5. We did not find mutations in the other exons studied (1-3 and 6-10), nor in any of the 10 exons of the 120 healthy volunteers. CONCLUSIONS: We found several mutations in SLC22A12 gene associated with primary gout, the definite role of these mutations in URAT1 activity needs to be further studied.