Surprising Chemistry of 6-Azidotetrazolo[5,1-a]phthalazine: What a Purported Natural Product Reveals about the Polymorphism of Explosives.

6-Azidotetrazolo[5,1-a]phthalazine (ATPH) is a nitrogen-rich compound of surprisingly broad interest. It is purported to be a natural product, yet it is closely related to substances developed as explosives and is highly polymorphic despite having a nearly planar structure with little flexibility. Seven solid forms of ATPH have been characterized by single-crystal X-ray diffraction. The structures show diverse patterns of molecular organization, including both stacked sheets and herringbone packing. In all cases, N···N and C-H···N interactions play key roles in ensuring molecular cohesion. The high polymorphism of ATPH appears to arise in part from the ability of virtually every atom of nitrogen and hydrogen in the molecule to take part in close N···N and C-H···N contacts. As a result, adjacent molecules can adopt many different relative orientations that are energetically similar, thereby generating a polymorphic landscape with an unusually high density of potential structures. This landscape has been explored in detail by the computational prediction of crystal structures. Studying ATPH has provided insights into the field of energetic materials, where access to multiple polymorphs can be used to improve performance and clarify how it depends on molecular packing. In addition, our work with ATPH shows how valuable insights into molecular crystallization, often gleaned from statistical analyses of structural databases, can also come from in-depth empirical and theoretical studies of single compounds that show distinctive behavior.

Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). METHODS: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. RESULTS: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. CONCLUSIONS: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. LAY SUMMARY: Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

Open Surgical Access for Transfemoral TAVR Should Not Be a Contraindication for Conscious Sedation.

OBJECTIVES: The use of monitored anesthesia care (MAC) for transcatheter aortic valve replacement (TAVR) is gaining favor in the United States, although general anesthesia (GA) continues to be common for these procedures. Open surgical cutdown for transfemoral TAVR has been a relative contraindication for TAVR with MAC at most centers. The objective of this study was to review the authors' results of transfemoral TAVR performed in patients with open surgical cutdown with the use of MAC. DESIGN: Retrospective study design from a prospectively recorded database. SETTING: Tertiary academic (teaching) hospital. PARTICIPANTS: Two hundred eighty-two patients undergoing transfemoral TAVR with open surgical cutdown under MAC from 2015 to 2017. INTERVENTIONS: Transfemoral TAVR under MAC with surgical cutdown for femoral vascular access. MEASUREMENTS AND MAIN RESULTS: The study cohort consisted of 282 patients with severe aortic stenosis (mean area 0.65 [± 0.16] cm2, mean gradient of 48.9 [±13.3] mmHg, and mean age of 82.7 [± 7.31] years). Eleven (3.9%) patients required conversion to GA. First postoperative pain score (0-10) was 2.9 and highest postoperative pain score was 4.6. Major and minor vascular complications occurred in 2 (0.7%) and 6 (2.1%) patients, respectively. Twenty-nine (10.3%) patients were readmitted within 30 days, and 6 (2.1%) patients had in-hospital mortality. CONCLUSIONS: Open surgical cutdown for transfemoral TAVR can be performed safely using MAC and ilioinguinal block with low rates of conversion to general anesthesia and acceptable postoperative outcomes and pain scores.

The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.

The seventh blind test of crystal structure prediction: structure ranking methods.

A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol-1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases.

Visual recovery after immediate sequential bilateral cataract surgery at a veterans' hospital.

PURPOSE: To answer patient questions about the expected timeline for recovery, the objective postoperative visual acuities were reviewed for patients undergoing immediate sequential bilateral cataract surgery (ISBCS). SETTING: Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri. DESIGN: Retrospective chart review. METHODS: All patients who underwent ISBCS in 2019 were evaluated. A total of 116 patients (232 eyes) were studied. Uncorrected distance visual acuity (UDVA) for postoperative day 0 or 1 (POD0/1), postoperative week 1 (POW1), and postoperative month 1 (POM1) were required for study inclusion. Patients with ocular comorbidities were not excluded, although all patients passed an initial screening to qualify for ISBCS. The outcome measures included POD0/1, POW1, and POM1 UDVA. RESULTS: Postoperative UDVA was stable or improved compared with preoperative corrected distance visual acuity (CDVA) for 48% (66/138) of eyes on POD0, 79% (74/94) of eyes on POD1, and 90% (209/232) of eyes on POW1. 83% of patients at POD1 and 90% of patients at POW1 had stable or improved visual acuity in at least 1 eye. 92% (214/232) of eyes had a POW1 UDVA of 20/40 or better. Of the 18 eyes with a postoperative POW1 UDVA of 20/50 or worse, 5 (28%) were known preoperatively to have limited visual potential. 99% (115/116) of patients had at least 1 eye 20/40 or better. CONCLUSIONS: Most of the patients who underwent ISBCS demonstrated meaningful improvement in UDVA compared with preoperative CDVA as early as POD1. These results serve to guide discussion of postoperative expectations with patients interested in ISBCS.

An Experimental Swallow Evoked Potential Protocol to Investigate the Neural Substrates of Swallowing.

Advancement in dysphagia intervention is hindered by our lack of understanding of the neural mechanisms of swallowing in health and disease. Evoking and understanding neural activity in response to normal and disordered swallowing is essential to bridge this knowledge gap. Building on sensory evoked potential methodology, we developed a minimally invasive approach to generate swallow evoked potentials (SwEPs) in response to repetitive swallowing induced by citric acid stimulation of the oropharynx in lightly anesthetized healthy adult rats. The SwEP waveform consisted of 8 replicable peaks within 10 milliseconds immediately preceding the onset of electromyographic swallowing activity. Methodology refinement is underway with healthy rats to establish normative SwEP waveform morphology before proceeding to models of advanced aging and age-related neurodegenerative diseases. Ultimately, we envision that this experimental protocol may unmask the pathologic neural substrates contributing to dysphagia to accelerate the discovery of targeted therapeutics.

Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSAS) is a potentially serious disorder attacking millions of people around the world. Many of these individuals are undiagnosed, and even though diagnosed often exhibit a poor compliance with the use of continuous positive airway pressure at nights, a very effective nonsurgical treatment. A variety of surgical procedures have been proposed to manage and treat OSA. This article throws insights into assessing the sites of obstruction and a number of surgical procedures designed to address OSA. The scope of this article is to provide information to dentists which enables them to identify the patients who have OSAS and to guide these patients in making informed decisions regarding treatment options.

Osteomielitis Crónica en Rodilla por Actinomicosis / Chronic Osteomyelitis Knee for Actinomycosis

Actinomicosis, causada por Actinomyces spp bacilo gram positivo, inmóvil, sin cápsula, anaerobio o anaerobio facultativo, forma parte de la flora nativa de la boca, ubicado en amígdalas, encías o boca de casi todas las personas. Generalmente se manifiesta después de un traumatismo, cirugía dental o proceso infeccioso. Las formas clínicas más frecuentemente observadas son: cérvico-facial, torácica y abdominal y rara vez en otras regiones. En el presente caso, se reporta a un paciente con cuadro clínico de aproximadamente un año de evolución, presentando dolor, inflamación y secreción amarillenta a nivel de rodilla izquierda. Al realizarse los estudios pertinentes, se identificó la presencia de infección por Actinomyces, ante la gravedad del caso el tratamiento se realizó con abordaje quirúrgico y antibióticoterapia prolongada (beta-lactámicos).

Actinomicosis caused by Actinomyces spp Bacillus gram positive, immobile, without capsule, anaerobic or anaerobic physician, part of the native flora of the mouth, located in tonsils, gums or mouth of almost all the persons. Generally it shows after a traumatism, dental surgery or infectious process. The clinical forms more frequently observed are: cérvico-facial, thoracic and abdominal and rarely in other regions. In the present case, it's reported a patient with approximately a year of evolution, with pain, inflammation and yellowish secretion of left knee. On the medical studies, the presence of infection by Actinomyces was identified, because of bad evolution the treatment was: surgical boarding and antibiotic terapy (Beta - lactamics).