Video Versus Nonvideo in a Rabbit Training Model for Establishing an Emergency Front of Neck Airway in Children: A Prospective Trial.

OBJECTIVES: Simulating a realistic "cannot intubate, cannot oxygenate" (CICO) situation to train an "emergency front of neck airway" is difficult. It further remains unclear if provision of regular technical refreshers improves performance in the setting of a real CICO situation. The purpose of this prospective study on an established surgical rabbit cadaver tracheostomy model was to evaluate the benefit of viewing training material shortly before performing "emergency front of neck airway." METHODS: Previously trained participants were randomized into 2 groups. The control group (video) was allowed to watch an instructional video before performing a tracheotomy on the training model, while the study group (nonvideo) was not. Queried outcomes included success rate, performance time, and severe secondary airway injuries between the 2 groups. RESULTS: In 29 tracheotomies performed by 29 participants, the overall success rate was 86% (92% video; 81% nonvideo, P = 0.4). Performance time was not different between the 2 groups (video: 80 s [IQR25-75: 53-86], nonvideo 64 s [IQR25-75: 47-102]; P = 0.93). Only in the nonvideo group, the performance time and the time between the workshops correlated positively (P = 0.048). Severe secondary injuries were noted in 4 of 29 rabbit cadavers, 2 in each group. Watching a refresher video before performing an emergency surgical tracheostomy in an infant training model did not influence the success rate and the performance time in previously trained anesthetists. CONCLUSIONS: These results highlight the ease of learning, memorization, and recall of this emergency surgical tracheostomy technique and may demonstrate its applicability in a real infant CICO situation.

Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

OPHTHALMOLOGIC INVOLVEMENT IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: The aim of this study was to determine the ophthalmologic involvement in patients with hereditary transthyretin amyloidosis and its correlation with the mutations described in the literature. METHODS: Cross-sectional, noninterventional study. Fifty-two eyes of 26 consecutive patients diagnosed with hereditary transthyretin amyloidosis who visited the Puerta de Hierro-Majadahonda University Hospital from September 2019 to March 2022. All patients underwent complete ophthalmologic examination and multimodal imaging. Cardiologic, neurologic, digestive, and renal examinations were also recorded. RESULTS: Eighteen eyes of the total (34.61%) showed amyloid-related ocular involvement, vitreous amyloid deposits being the most common ocular manifestation (18/52). Statistically significant differences were found for the presence of vitreous amyloid deposits ( P < 0.01), crystalline amyloid deposits ( P < 0.05), parenchymal amyloid deposits ( P < 0.01), and vascular alterations ( P < 0.01) when comparing affected and unaffected eyes. Moreover, affected eyes showed worse best-corrected visual acuity ( P < 0.01). CONCLUSION: Ocular manifestations are present in a substantial number of patients with ATTR that could potentially lead to devastating consequences to patients' best-corrected visual acuity and quality of life. Therefore, it is important to emphasize the importance of multidisciplinary management and ophthalmologic assessment, follow-up and surgical treatment when necessary. To the best of our knowledge, this represents the largest series in Spain of amyloidosis' ophthalmologic involvement.

ASSESSMENT AND ROLE OF ARTERY-VEIN COMPLEX IN MYOPIC CHOROIDAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze the presence of an artery-vein complex (AVC) underneath myopic choroidal neovascularization (mCNV) and to determine its relationship with neovascular activity. METHODS: Retrospective analysis of 681 eyes from 362 patients with high myopia defined by an axial length of >26 mm using optical coherence tomography (OCT) and OCT angiography imaging. Patients with clinical diagnosis of mCNV and good quality OCT angiography images were then selected. An AVC was defined by the identification of both perforating scleral vessels and dilated choroidal veins under or in contact with the mCNV in the same case. Swept source OCT (SS-OCT) and SS-OCT angiography images (TRITON; Topcon Corporation, Tokyo, Japan) were reviewed to detect AVC in the mCNV area. RESULTS: Fifty eyes of 49 highly myopic patients with mCNV were analyzed. Eyes with AVC were statistically older (69.95 ± 13.53 vs. 60.83 ± 10.47 years old; P < 0.01), needed less intravitreal injections/year along the follow-up period (0.80 ± 0.62 vs. 1.92 ± 0.17; P < 0.01), and showed less relapses/year (0.58 ± 0.75 vs. 0.46 ± 0.42; P < 0.05) when compared with eyes without AVC. Moreover, eyes with AVC were less likely to relapse during the first year from mCNV activation (n = 5/14 vs. n = 14/16; P < 0.01; P < 0.01). No significant differences were found regarding either axial length (30.55 ± 2.31 vs. 29.65 ± 2.24, P > 0.05) or best-corrected visual acuity (0.4 ± 0.5 vs. 0.4 ± 0.5 Logarithm of the Minimum Angle of Resolution (logMAR), P > 0.05) between groups. CONCLUSION: AVC complex has an influence over myopic choroidal neovascularization activity resulting in less aggressive neovascular lesions than those with perforating scleral vessels only.

Lower tear meniscus height measured by optical coherence tomography in children.

INTRODUCTION: While optical coherence tomography (OCT) measurements of the lower tear meniscus height (LTMH) have been reported in adults, here we obtained LTMH measurements through Fourier Domain OCT in healthy children and compared these with values obtained in healthy adults. METHODS: Participants were children 7-17 years of age and a control group of adults 20-40 years of age. Inclusion criteria were no abnormal eye conditions or the use of contact lenses. Candidates who fulfilled the TFOS DEWS II criteria for dry eye disease (DED) were excluded. All subjects underwent LTMH measurement (OCT Spectralis) and tests for non-invasive tear break-up time and ocular surface staining. Participants also completed the ocular surface disease index questionnaire. RESULTS: A total of 86 children and 27 adults were included. Mean LTMH values in the children and adult groups were 217.40 ± 71.40 µm and 225.0 ± 54.86 µm, respectively; p = 0.53. However, 59.3% of the children had an LTMH ≤210 µm suggestive of DED, compared with only 33.3% of adults (p = 0.02). For the children, no significant differences in LTMH were observed with sex or for those more or less than 12 years of age. CONCLUSIONS: Optical coherence tomography-derived LTMH measurements were obtained in healthy children. While values were similar in children and adults, a greater proportion of children had an LTMH compatible with a diagnosis of DED. More studies in different paediatric populations are required to establish a complete set of normative LTMH measurements.

Atrophic, Tractional, and Neovascular Grading System in a Dome-Shaped Macula and Ridge-Shaped Macula Highly Myopic Cohort.

INTRODUCTION: The aim of this study was to analyze the atrophic, tractional, and neovascular (ATN) components grading in highly myopic patients with dome-shaped macula (DSM) and ridge-shaped macula (RSM). METHODS: This was a cross-sectional, noninterventional study. 57 eyes of 38 different patients were included. They were classified as DSM or RSM based on the number of radial scans that showed an inward protrusion ≥50 µm in the swept-source optical coherence tomography (SS-OCT) (12 = DSM; <12 = RSM). All patients underwent a complete ophthalmological examination in addition to SS-OCT. They were graded using the ATN system for myopic maculopathy by 2 masked retina specialists that assessed the atrophic (A), tractional (T), and neovascular (N) components in order to analyze the differences between the groups. As complementary measurements, age, axial length, and best-corrected visual acuity were collected. Height and orientation of the macular bulge and the presence of Bruch's membrane defects, scleral perforating vessels, and staphyloma were recorded. RESULTS: Out of total 57 eyes, 13 eyes (22.8%) were classified as DSM. Regarding the atrophic component (A), there were statistically significant differences between groups, with DSM group showing a greater stage of atrophy (predominantly stage A3 in 69.2% of the sample) compared to the RSM group (predominantly stage A2 in 61.3% of the sample) (p < 0.05). For the T and N components, there were no significant differences between groups. The presence of Bruch's membrane defects was more frequently seen in DSM (p < 0.05). CONCLUSIONS: DSM group showed more Bruch's membrane defects and a greater stage of the atrophy component, based on the ATN grading system, compared with RSM group. As Bruch's membrane may have biomechanical properties in terms of strength, the defects found around the macula, added to the major atrophic component, may be a cause of a local relaxation that induce a central bulge forming the dome.

Predictive factors for anti-MDA5 antibody in patients with dermatomyositis: a retrospective multicenter study.

BACKGROUND AND OBJECTIVES: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5+ ). PATIENTS AND METHODS: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5+ . Demographic data, laboratory data, and clinical manifestations were collected. RESULTS: Anti-MDA5+ DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5+ patients (p <0.001), being a diagnostic marker of anti-MDA5+ (OR, 12.355; 95% CI 2.850-79.263; p  =  0.012 and OR, 7.447; 95% CI 2.103-46.718; p  =  0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5+ patients, because in our cohort, up to 97% of the anti-MDA5+ patients had ulcers. CONCLUSIONS: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor.

Unleashing the shape of L-DOPA at last.

Herein, we report the first rotational study of neutral L-DOPA, an extensively used supramolecular synthon and an amino acid precursor of the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) using broadband and narrowband Fourier transform microwave spectroscopies coupled with a laser ablation vaporization system. The spectroscopic parameters derived from the analysis of the rotational spectrum conclusively identify the existence of four distinct conformers of L-DOPA in the supersonic jet, further rejecting the previously reported catechol ring-induced conformational restriction. The analysis of the 14N nuclear quadrupole coupling hyperfine structure further revealed the orientation of the N-bearing functional group, proving the existence of stabilizing N-H⋯π interactions for the observed structures.

Cuffed versus uncuffed tracheal tubes in a rabbit training model for establishing an emergency front-of-neck airway in infants: a prospective trial.

BACKGROUND: There is a paucity of evidence regarding the optimal type of tracheal tube to be advanced over a Frova catheter when performing a 'bougie' emergency front-of-neck airway (eFONA) technique in infants during a 'cannot intubate, cannot oxygenate' situation. METHODS: A prospective non-inferiority trial in a rabbit cadaver surgical tracheotomy model to assess the performance of the eFONA technique with an uncuffed 3.5 mm ID tracheal tube vs a cuffed 3.0 mm ID tracheal tube. Queried outcomes include success rate, performance time, and severe secondary airway injuries among tracheal tube types. RESULTS: In 60 tracheostomies performed by 30 participants, the overall success rate was 98%. Performance time was independent from tracheal tube choice (uncuffed: 61 s [95% confidence interval (CI), 52-76], cuffed: 64 s [95% CI, 55-79]; P = 0.82). No tracheal tube type was preferred in terms of usability by participants. The cuffed tracheal tube required increased force to be advanced over the Frova catheter and was associated with a risk ratio of 2.5 (95% CI, 0.53-11.9; number needed to harm, 10) for severe secondary airway injuries when compared with the uncuffed tracheal tube. CONCLUSION: In performing eFONA in the rabbit cadaver model, an ID 3.5 uncuffed is non-inferior to an ID 3.0 cuffed tracheal tube regarding performance time and preference by the operator. Greater force application to advance the cuffed tube over the Frova catheter and more severe airway injuries may argue for the standardised performance of the eFONA technique with a uncuffed tracheal tube in infants.

Unbiased disentanglement of conformational baths with the help of microwave spectroscopy, quantum chemistry, and artificial intelligence: The puzzling case of homocysteine.

An integrated experimental-computational strategy for the accurate characterization of the conformational landscape of flexible biomolecule building blocks is proposed. This is based on the combination of rotational spectroscopy with quantum-chemical computations guided by artificial intelligence tools. The first step of the strategy is the conformer search and relative stability evaluation performed by means of an evolutionary algorithm. In this step, last generation semiempirical methods are exploited together with hybrid and double-hybrid density functionals. Next, the barriers ruling the interconversion between the low-lying conformers are evaluated in order to unravel the possible fast relaxation paths. The relative stabilities and spectroscopic parameters of the "surviving" conformers are then refined using state-of-the-art composite schemes. The reliability of the computational procedure is further improved by the inclusion of vibrational and thermal effects. The final step of the strategy is the comparison between experiment and theory without any ad hoc adjustment, which allows an unbiased assignment of the spectroscopic features in terms of different conformers and their spectroscopic parameters. The proposed approach has been tested and validated for homocysteine, a highly flexible non-proteinogenic α-amino acid. The synergism of the integrated strategy allowed for the characterization of five conformers stabilized by bifurcated N-H2⋯O=C hydrogen bonds, together with an additional conformer involving a more conventional HN⋯H-O hydrogen bond. The stability order estimated from the experimental intensities as well as the number and type of conformers observed in the gas phase are in full agreement with the theoretical predictions. Analogously, a good match has been found for the spectroscopic parameters.

Pathologic myopia and severe pathologic myopia: correlation with axial length.

PURPOSE: This study had three aims: (1) correlate axial length (AL), age and best-corrected visual acuity in high myopic patients scored on the ATN grading system; (2) determine AL cut-off values to distinguish between pathologic myopia (PM) and severe PM; and (3) identify clinical differences between PM and severe PM. METHODS: This is a cross-sectional, non-interventional study. All patients underwent complete ophthalmologic examination, ATN grading and multimodal imaging (colour fundus photography, swept-source OCT, fundus autofluorescence, OCT angiography and fluorescein angiography). RESULTS: Six hundred forty-four eyes from 345 high myopic patients were included. The eyes were graded on the ATN system and classified as PM (≥ A2) or severe PM (≥ A3, ≥ T3 and/or N2). Significant between-group (PM vs. severe PM) differences (p < 0.05) were observed on the individual ATN components (atrophic [A], tractional [T] and neovascular [N]), age, BCVA and AL. AL was also linearly correlated with the A, T and N components (r = 0.53, p < 0.01; r = 0.24, p < 0.01; r = 0.20, p < 0.01; respectively). ROC curve analysis showed the optimal AL cut-off value to distinguish between PM at 28 mm (AUC ROC curve: 0.813, specificity: 75%, sensitivity: 75%) and severe PM at 29.50 mm (AUC ROC curve: 0.760, specificity: 75%, sensitivity: 70%). CONCLUSION: AL is the main variable associated with myopic maculopathy. Due to the clinical differences found between PM and severe PM, there is need to create an objective cut-off point to distinguish these two different entities being the optimal cut-off points for AL 28 mm and 29.5 mm, respectively. These objective AL cut-off values should be taken into account for determining a correct follow-up, ophthalmic management and treatment.

RELATIONSHIP BETWEEN MYOPIC CHOROIDAL NEOVASCULARIZATION ACTIVITY AND PERFORATING SCLERAL VESSELS IN HIGH MYOPIA.

PURPOSE: To study perforating scleral vessels (PSVs) in patients with high myopia using swept-source optical coherence tomography and to determine their relationship with myopic choroidal neovascularization (mCNV) and its activity. METHODS: Retrospective analysis of patients with high myopia (≥-6 D or ≥26 mm of axial length) using multimodal imaging. The presence of PSVs and mCNV was assessed using swept-source optical coherence tomography images (TRITON; Topcon Corporation, Japan). RESULTS: Five hundred sixty-four eyes from 297 highly myopic patients were studied. One hundred fifty-five eyes (27.5%) showed signs of mCNV while PSVs were found in 500 eyes (88.6%). Perforating scleral vessels were found in 93.5% (145/155) of eyes with mCNV, and they were under or in contact with the mCNV in 80.6% (117/145). The mean number of intravitreal injections received by patients with mCNV was 4.06 ± 4.17 along 66.9 ± 4.1 months of follow-up. The number of injections per year was 1.32 ± 1.56, the mean number of relapses was 1.11 ± 1.83, and the mean number of relapses per year was 0.25 ± 0.41. CONCLUSION: Perforating scleral vessels are more common among highly myopic patients suffering from neovascular complications. Myopic CNV complexes that are coincident with PSVs on optical coherence tomography show higher rates of activity, needing more injections to control them and being more prone to relapses.

Minimal detectable change of the disc-fovea angle for ocular torsion assessment.

PURPOSE: The disc-fovea angle (DFA) is used as a relevant indicator of ocular torsion change in cyclovertical strabismus. However, interpretation of the variation in time must differentiate whether a real change has occurred or if the disparity is due to random measurement error. The aim of the study was to obtain the minimal detectable change (MDC) of the DFA. It represents the minimal variation between two measurements that may be considered a real ocular torsion change. METHODS: A prospective cross-sectional study was conducted in San Carlos Clinical Hospital of Madrid, Spain. Sixty healthy right eyes from 60 patients (31 men and 29 women) were recruited. Three digital fundus photographs were obtained, and between measurements, the patient moved their head away from the head support and then returned. Two observers quantified the DFA with software designed with MATLAB. Test-retest and interrater reliability were calculated. RESULTS: Mean participant age was 56.1 years (SD 16.6, range 25-85). Mean DFA was 8.1° (SD 3.5, range 1.3-18.5). Test-retest reliability for Observer 1 (Ob1), Observer 2 (Ob2) and interrater reliability were excellent (ICC 0.80, 0.83 and 0.95, respectively). Precision was 2.9° (Ob1) and 3.0° (Ob2), and the MDC95 was 4.1° (Ob1) and 4.2° (Ob2). Bland-Altman analysis revealed an absence of bias and a homoscedastic distribution of the differences. CONCLUSIONS: The MDC of the DFA in fundus photography was 4°, which represents the minimal change that may be considered a real change in ocular torsion. This result may improve the interpretation of ocular torsion changes in surgery and clinical scenarios.

Rotational Spectrum and Conformational Analysis of Perillartine: Insights into the Structure-Sweetness Relationship.

We used high-resolution rotational spectroscopy coupled to a laser ablation source to study the conformational panorama of perillartine, a solid synthetic sweetener. Four conformers were identified under the isolation conditions of the supersonic expansion, showing that all of them present an E configuration of the C=N group with respect to the double bond of the ring. The observed structures were verified against Shallenberger-Acree-Kier's sweetness theory to shed light on the structure-sweetness relationship for this particular oxime, highlighting a deluge of possibilities to bind the receptor.

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL.

In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Rabbit training model for establishing an emergency front of neck airway in children.

BACKGROUND: A 'cannot intubate, cannot oxygenate' (CICO) situation is rare in paediatric anaesthesia, but can always occur in children under certain emergency situations. There is a paucity of literature on specific procedures for securing an emergency invasive airway in children younger than 6 yr. A modified emergency front of neck access (eFONA) technique using a rabbit cadaver model was developed to teach invasive airway protection in a CICO situation in children. METHODS: After watching an instructional video of our eFONA technique (tracheotomy, intubation with Frova catheter over which a tracheal tube is inserted), 29 anaesthesiologists performed two separate attempts on rabbit cadavers. The primary outcome was the success rate and the performance time overall and in subgroups of trained and untrained participants. RESULTS: The overall success rate across 58 tracheotomies was 95% and the median performance time was 67 s (95% confidence interval [CI], 56-76). Performance time decreased from the first to the second attempt from 72 s (95% CI, 57-81) to 61 s (95% CI, 50-81). Performance time was 59 s (95% CI, 49-79) for untrained participants and 72 s (95% CI, 62-81) for trained participants. Clinical experience and age of the participants was not correlated with performance time, whereas the length of the tracheotomy incision showed a significant correlation (P=0.006). CONCLUSION: This eFONA training model for children facilitates rapid skill acquisition under realistic anatomical conditions to perform an emergency invasive airway in children younger than 2 yr.

Exploring the Maze of Cycloserine Conformers in the Gas Phase Guided by Microwave Spectroscopy and Quantum Chemistry.

Cycloserine has in common with isoxazolidines the saturated five-membered ring, which is an important scaffold for drug design, exhibiting diverse biological activities. The most remarkable feature of these compounds is the presence of the N-O bond framed in a cyclic moiety. The lack of an accurate characterization of this structural feature in an isolated system calls for a state-of-the-art theoretical-experimental study. A quantum-chemical investigation of cycloserine unveiled the presence of 11 local energy minima, with only two of them being separated by significant barriers. This picture has been experimentally confirmed: two species have been unequivocally detected in the gas phase by means of laser ablation microwave spectroscopy, also disentangling the complicated hyperfine structure originating from the presence of two nitrogen atoms. A thorough characterization of cycloserine and isoxazolidine, benchmarked by the semiexperimental investigation of hydroxylamine, provided the first accurate determination of their structures and pointed out that the rev-DSD-PBEP86 functional is competitive with respect to explicitly correlated coupled-cluster computations. This outcome paves the way toward accurate studies of large flexible molecules.

Evolution of Macular Bruch Membrane Defects of Patchy Chorioretinal Atrophy in Pathologic Myopia Based on a Recent Classification System.

PURPOSE: The purpose of this study was to analyze the progression of macular Bruch membrane defects (BMD) in highly myopic patients with patchy atrophy (PA); and study its correlation with the enlargement of PA and ATN grading. Setting/Venue: Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain. PATIENTS AND METHODS: This was a cross-sectional, noninterventional study. A series of 451 highly myopic eyes with spherical equivalent > -6.0 D and/or >26 mm of axial length (AL) were included. All patients underwent a complete ophthalmological examination and swept-source optical coherence tomography (SS-OCT), and were graded using the ATN system by 2 masked retina experts that assessed the atrophic (A), tractional (T), and neovascular (N) components. SS-OCT b-scans were employed to study PA and macular BMD at baseline and at a 1-year follow-up, in patients with good foveal fixation. RESULTS: Out of total 451 eyes, 126 eyes (27.9%) had PA (53 patients; 75.4% women). Mean T and N in eyes with PA were 1.1 ± 1.3 and 0.08 ± 0.2, respectively. Sixty-eight of them had >1-year follow-up with a good foveal fixation and enough image quality. From them, BMD were found in 44 eyes (64.7%) at baseline and increased to 59 eyes (86.7%) at a 1-year follow-up. The mean great linear dimension of PA and macular BMD increased with a median of 384.5 ± 462.5 µm (IR 68.0-660.2) and 265.6 ± 418.1 µm (IR 0-331.7), respectively. At 1-year, PA and BMD sizes increase, and were statistically significant (p < 0.001). There was a positive correlation between the growth of macular BMD and the growth of PA (r = 0.490, p < 0.00). T grading correlated significantly with PA growth (p < 0.05). CONCLUSIONS: Macular BMD increase its prevalence and its size over time in highly myopic patients with PA. There is a positive correlation between BMD and PA area growth. New studies with a larger sample size, longer follow-up, and AL elongation correlation are necessary to corroborate our findings.

Religiosity and Suicide: A Large-Scale International and Individual Analysis Considering the Effects of Different Religious Beliefs.

In a cohort of 82,898 participants from 60 countries, this study examined attitudes towards suicide among five religions (Buddhism, Christianity, Hinduism, Islam, and other non-specific religions), while simultaneously considering two different dimensions of religiosity: subjective religiosity and religious practices. At the national level, religiosity was an important negative predictor variable for suicide rates and an important positive predictor variable for negative attitudes towards suicide. At the individual level, however, attitudes towards suicide were found to vary significantly across the different religions. The findings emphasize the importance of considering religion perspectives and religiosity, along with its practices and subjective dimensions, in prevention and attention programmes to suicidal behaviour.