Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis.

Three new Au(I) complexes of the formula [Au(NHC)(NTf2)] (NHC = N-heterocyclic carbene) bearing bulky and flexible ligands have been synthesised. The ligands studied are IPent, IHept and INon which belong to the 'ITent' ('Tent' for 'tentacular') family of NHC derivatives. The effect of these ligands in gold-promoted transformations has been investigated.

Coil migration through two flow-diverting stents.

We report a case of a patient who initially presented with a subarachnoid haemorrhage secondary to a ruptured supraclinoid internal carotid artery (ICA) blister aneurysm. The patient was treated successfully with a flow diverter stent (FD) and coiling; however, a large aneurysm recurrence via a feeding posterior communicating artery (PCOM) was noted on the 1-year follow-up angiogram. During the retreatment, a second FD in the ICA resulted in insufficient aneurysm stasis. Therefore, the decision was made to coil sacrifice the PCOM via posterior circulation access. During the first coil deployment, the distal coil end migrated through the mesh of two overlapping FD into the middle cerebral artery. This complication was a previously unrecognised possibility given the composition of the FD. This case report aims to discuss this process as a potential complication during neurointerventional procedures using these devices.

Adverse outcomes in SARS-CoV-2 infected pregnant mice are gestational age-dependent and resolve with antiviral treatment.

SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at embryonic day (E) 6, E10, or E16 with a mouse adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age-dependent, with greater morbidity, reduced anti-viral immunity, greater viral titers, and more adverse fetal outcomes occurring with infection at E16 (3rd trimester-equivalent) than with infection at either E6 (1st trimester-equivalent) or E10 (2nd trimester-equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir (recommended for pregnant individuals with COVID-19), we treated E16-infected dams with mouse equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented adverse offspring outcomes. Our results highlight that severe COVID-19 during pregnancy and adverse fetal outcomes are associated with heightened virus replication in maternal lungs. Ritonavir-boosted nirmatrelvir mitigated adverse maternal and fetal outcomes of SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections.

The role of silver additives in gold-mediated C-H functionalisation.

The role of silver additives is examined in the context of gold-mediated functionalisation of aromatic C-H bonds. Doubt is cast on the commonly cited route of halide abstraction from gold and evidence of substrate activation is given.

Development and Implementation of an HPV Vaccination Survey for American Indians in Cherokee Nation.

Improving human papillomavirus (HPV) vaccination rates is a public health priority and a crucial cancer prevention goal. We designed a survey to estimate HPV vaccination coverage and understand factors associated with HPV vaccination among American Indian adolescents aged 9 to 17 years in Cherokee Nation, United States. The final survey contains 37 questions across 10 content areas, including HPV vaccination awareness, initiation, reasons, recommendations, and beliefs. This process paper provides an overview of the survey development. We focus on the collaborative process of a tribal-academic partnership and discuss methodological decisions regarding survey sampling, measures, testing, and administration.

Bioprinting of Cartilage and Skin Tissue Analogs Utilizing a Novel Passive Mixing Unit Technique for Bioink Precellularization.

Bioprinting is a powerful technique for the rapid and reproducible fabrication of constructs for tissue engineering applications. In this study, both cartilage and skin analogs were fabricated after bioink pre-cellularization utilizing a novel passive mixing unit technique. This technique was developed with the aim to simplify the steps involved in the mixing of a cell suspension into a highly viscous bioink. The resolution of filaments deposited through bioprinting necessitates the assurance of uniformity in cell distribution prior to printing to avoid the deposition of regions without cells or retention of large cell clumps that can clog the needle. We demonstrate the ability to rapidly blend a cell suspension with a bioink prior to bioprinting of both cartilage and skin analogs. Both tissue analogs could be cultured for up to 4 weeks. Histological analysis demonstrated both cell viability and deposition of tissue specific extracellular matrix (ECM) markers such as glycosaminoglycans (GAGs) and collagen I respectively.

A new specimen of Palvennia hoybergeti: implications for cranial and pectoral girdle anatomy in ophthalmosaurid ichthyosaurs.

The Late Jurassic Slottsmøya Member Lagerstätte on Spitsbergen preserves a diverse array of marine reptiles, including four named taxa of ophthalmosaurid ichthyosaurs. One of these, Palvennia hoybergeti, is based on the single holotype specimen (SVB 1451) with an incomplete skull. A newly discovered specimen (PMO 222.669) with a disarticulated but largely complete skull and anterior postcranium is described, which considerably expands our knowledge of this taxon. Two additional new ophthalmosaurid specimens with pectoral girdles from the same member are described. The taxonomic utility of the ophthalmosaurid pectoral girdle is contentious, and an assessment of seven pectoral girdles from the Slottsmøya Member provides a basis for addressing this question via a 2D landmark principal component analysis of baracromian coracoids. The analysis reveals a taxonomic signal in the coracoids but also highlights the degree of individual variation. Commonly used phylogenetic characters do not fully encapsulate the degree of variation seen in coracoids and in some cases combine analogous features.

K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China.

PURPOSE: The genetic alterations in biliary tract cancer and clinicopathological associations have not been studied in large population-based studies. EXPERIMENTAL DESIGN: We evaluated genetic alterations such as K-ras mutation, p53 overexpression, microsatellite instability (MSI), and alterations of the polyadenine tract present in the transforming growth factor beta receptor type II (TGFbetaRII) gene in 126 biliary tract cancers: 75 gallbladder cancers, 33 bile duct cancers, and 18 ampullary cancers. These genetic alterations were compared with patient demographics and clinicopathological characteristics of the tumors. RESULTS: Mutation of the K-ras gene was present in 18 of 126 (14.3%) biliary tract cancers. K-ras mutation was present in 11 of 18 (61.1%) ampullary cancers, 5 of 33 (15.2%) bile duct cancers, and 2 of 75 (2.7%) gallbladder cancers (P = 0.000001). The mean survival of patients who had bile duct carcinomas with K-ras mutation was 3.0 +/- 2.2 months compared with 15.5 +/- 12.5 months for those without mutation (P = 0.03) but was not different for other tumor sites. p53 overexpression was present in 34 of 123 (27.6%) cancers. MSI-high (allelic shifts in 40% or more loci or alteration of the TGFbetaRII gene) was present in 4 of 126 (3.2%) biliary tract cancers without hereditary nonpolyposis colorectal cancer. MSI-high was more common in mucinous adenocarcinomas (P = 0.006) and in patients with early age of onset of cancer (P = 0.04). CONCLUSIONS: The genetic alterations in biliary tract cancers are dependent on the tumor subsite, histology, and age of onset and are associated with prognosis.

Hydrofluorination of Alkynes Catalysed by Gold Bifluorides.

We report the synthesis of nine new N-heterocyclic carbene gold bifluoride complexes starting from the corresponding N-heterocyclic carbene gold hydroxides. A new methodology to access N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) fluoride starting from N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold(I) hydroxide and readily available potassium bifluoride is also reported. These gold bifluorides were shown to be efficient catalysts in the hydrofluorination of symmetrical and unsymmetrical alkynes, thus affording fluorinated stilbene analogues and fluorovinyl thioethers in good to excellent yields with high stereo- and regioselectivity. The method is exploited further to access a fluorinated combretastatin analogue selectively in two steps starting from commercially available reagents.

A new upper jurassic ophthalmosaurid ichthyosaur from the Slottsmøya Member, Agardhfjellet formation of central Spitsbergen.

Abundant new ichthyosaur material has recently been documented in the Slottsmøya Member of the Agardhfjellet Formation from the Svalbard archipelago of Norway. Here we describe a partial skeleton of a new taxon, Janusaurus lundi, that includes much of the skull and representative portions of the postcranium. The new taxon is diagnosed by a suite of cranial character states including a very gracile stapedial shaft, the presence of a dorsal process on the prearticular and autapomorphic postcranial features such as the presence of an interclavicular trough and a conspicuous anterodorsal process of the ilium. The peculiar morphology of the ilia indicates a previously unrecognized degree of morphological variation in the pelvic girdle of ophthalmosaurids. We also present a large species level phylogenetic analysis of ophthalmosaurids including new and undescribed ichthyosaur material from the Upper Jurassic of Svalbard. Our results recover all Svalbard taxa in a single unresolved polytomy nested within Ophthalmosaurinae, which considerably increases the taxonomic composition of this clade. The paleobiogeographical implications of this result suggest the presence of a single clade of Boreal ophthalmosaurid ichthyosaurs that existed during the latest Jurassic, a pattern also reflected in the high degree of endemicity among some Boreal invertebrates, particularly ammonoids. Recent and ongoing descriptions of marine reptiles from the Slottsmøya Member Lagerstätte provide important new data to test hypotheses of marine amniote faunal turnover at the Jurassic-Cretaceous boundary.

Personality clusters and family relationships in women with disordered eating symptoms.

Personality clusters in women with eating disorders predict important clinical variables (e.g., social functioning) better than eating disorder diagnoses. However, it is unknown whether these findings generalize to samples with subclinical pathology. Further, little is known about associations between personality clusters and family relationships. This study sought to address these limitations by replicating personality clusters in a college sample of women with disordered eating symptoms Based on reported symptoms, women were divided into a restricting, binging and purging, or control (i.e., symptom free) group. Participants completed measures of personality, social functioning, and family relationships. Cluster analyses suggested three personality groups (i.e., Adaptive, Rigid, Dysregulated) which corresponded to those identified previously in clinical samples. Personality clusters, and not disordered eating groups, significantly predicted social functioning, and these clusters were differentially associated with family conflict type. Meaningful personality clusters are present in subclinical populations and have clinical utility in predicting social functioning and family relationships.

Improving wait times and patient satisfaction in primary care.

A strong and inverse relationship between patient satisfaction and wait times in ambulatory care settings has been demonstrated. Despite its relevance to key medical practice outcomes, timeliness of care in primary care settings has not been widely studied. The goal of the quality improvement project described here was to increase patient satisfaction by minimizing wait times using the Dartmouth Microsystem Improvement Curriculum (DMIC) framework and the Plan-Do-Study-Act (PDSA) improvement process. Following completion of an initial PDSA cycle, significant reductions in mean waiting room and exam room wait times (p = .001 and p = .047, respectively) were observed along with a significant increase in patient satisfaction with waiting room wait time (p = .029). The results support the hypothesis that the DMIC framework and the PDSA method can be applied to improve wait times and patient satisfaction among primary care patients. Furthermore, the pretest-posttest preexperimental study design employed provides a model for sequential repetitive tests of change that can lead to meaningful improvements in the delivery of care and practice performance in a variety of ambulatory care settings over time.

Segmental spinal muscular atrophy localised to the lower limbs - first case from Oman

Spinal muscular atrophy [SMA] is a genetic lower motor neuron disease. It usually involves all of the skeletal muscles innervated by the anterior horn cells of the spinal cord. In rare cases, there is also localized involvement of the spinal cord. We report a 10-year-old boy who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2015 with muscle weakness restricted to the lower limbs. The presence of a homozygous deletion within the survival of motor neuron 1 gene confirmed the diagnosis of SMA. To the best of the authors' knowledge, this is the first report of an Omani patient with segmental SMA involving only the lower limbs. Treatment for this rare and relatively benign form of SMA is symptomatic and includes physiotherapy