Large retroperitoneal lymphangioma.

Abnormal cystic lymphangioma is a rare, benign tumour of lymphatic origin that often presents with subtle clinical symptoms. A man in his 20s sought medical attention for a progressively tender mass located in the right lower quadrant. Following ultrasound and CT imaging, surgical pathology confirmed the presence of abnormal cystic lymphangioma. This case is noteworthy because of the patient's young age and the retroperitoneal location. An exploratory laparotomy was performed, mitigating the risk of recurrence. In the future, if imaging identifies a cystic mass, consideration of abnormal cystic lymphangioma within the differential diagnosis is imperative. Despite its predominantly subtle symptoms and non-malignant nature, the mass effect by the abnormal cystic lymphangioma can compromise surrounding structures. Overall, clinicians confronted with a cystic mass should adopt a comprehensive diagnostic approach, encompassing abnormal cystic lymphangioma in the differential diagnosis due to its unknown and complex nature.

CRISPR screens and lectin microarrays identify novel high mannose N-glycan regulators.

Glycans play critical roles in cellular signaling and function. Unlike proteins, glycan structures are not templated from genes but the concerted activity of many genes, making them historically challenging to study. Here, we present a strategy that utilizes pooled CRISPR screens and lectin microarrays to uncover and characterize regulators of cell surface glycosylation. We applied this approach to study the regulation of high mannose glycans - the starting structure of all asparagine(N)-linked-glycans. We used CRISPR screens to uncover the expanded network of genes controlling high mannose surface levels, followed by lectin microarrays to fully measure the complex effect of select regulators on glycosylation globally. Through this, we elucidated how two novel high mannose regulators - TM9SF3 and the CCC complex - control complex N-glycosylation via regulating Golgi morphology and function. Notably, this method allowed us to interrogate Golgi function in-depth and reveal that similar disruption to Golgi morphology can lead to drastically different glycosylation outcomes. Collectively, this work demonstrates a generalizable approach for systematically dissecting the regulatory network underlying glycosylation.

Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

BACKGROUND: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. METHODS: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. RESULTS: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. CONCLUSIONS: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. We profiled 127 hospitalized patients with COVID-19 (n=79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. 48 species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID", suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with predicting whether stool was obtained from patients with severe vs. moderate COVID-19. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to validate these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Gender Differences in the Language of LORs Written for Anesthesiology Medical Student Applicants: Analysis of One Program's Recruitment Cycle.

BACKGROUND: Prior studies have demonstrated gender differences in language used in letters of recommendation (LOR) for residency applicants. No previous studies have investigated linguistic gender differences in LOR specifically in the field of anesthesiology. The objective of this study is to determine whether there are potential gender biases in the language of LOR written for anesthesiology residency applicants. METHODS: Letters sent through the Electronic Residency Application Service in application for a single training program in the Northeast in 2019-2020 were divided into self-identified male and female groups. The letters were deidentified, converted to machine-readable text, and input into software to analyze differences in language use. Differences in language use and word count between the 2 groups were compared. RESULTS: Included in this analysis were 316 applicants (113 female applicants and 203 male applicants) who submitted a total of 1132 letters, 409 of which were letters written for females and 723 were written for males. Analysis of 4 document characteristics and 19 psychological construct word categories showed that males had a higher frequency of tentative notations (P < .0110), while females had a higher frequency of ability notations (P < .0449). No other meaningful differences were found. CONCLUSIONS: While our results demonstrated 2 differences in language use between male and female anesthesiology residency applicants for LOR, it is reassuring that LOR are relatively free of linguistic bias. Future research should focus on identifying other areas of the specialty's recruitment process in order to recognize and mitigate gender differences in anesthesiology.

Catalytic asymmetric synthesis of a tertiary benzylic carbon center via phenol-directed alkene hydrogenation.

An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl(3)·2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.

Repeated attempts improve tracheal tube insertion time using the intubating laryngeal airway in a mannequin.

STUDY OBJECTIVE: To determine if repeated performance of endotracheal tube insertion via the intubating laryngeal airway (ILA) would shorten insertion time in mannequins. DESIGN: Prospective study. SETTING: Clinical Skills Laboratory, Department of Anesthesia, Toronto Western Hospital. PARTICIPANTS: 65 department anesthesiologists. MEASUREMENTS: After a video training session, anesthesiologists with no previous experience with the ILA performed 5 consecutive ILA-guided tracheal tube intubations on a mannequin. Each participant completed Task 1: insertion of an ILA; Task 2: blind insertion of a tracheal tube through the ILA, and Task 3: removal of the ILA. The time required for each task and the total intubation time for the three tasks over the 5 attempts were recorded. These times were compared using repeated-measures analysis of variance. The success rate among the 5 attempts was compared using Chi-Square analyses. MAIN RESULTS: A total of 65 anesthesiologists performed 5 ILA-guided tracheal intubations each. Total intubation time decreased from the first to the fifth attempt (92.6 ± 22.7 sec, 74.5 ± 19.2 sec, 66.5 ± 16.5 sec, 65.9 ± 19.9 sec, and 60.8 ± 16.3 sec; P < 0.001). Significant differences in intubation times were noted between the first and second, and the second and third attempts (P < 0.001 and P = 0.02, respectively). The success rate did not change over the 5 attempts (84.6%, 89.2%, 84.6%, 89.2%, and 90.8%; P = 0.737). CONCLUSIONS: Total intubation time decreased by 34% (92.6 to 60.8 sec) over the 5 attempts in mannequins. The success rate ranged from 84.6% to 90.8% and did not differ significantly over the 5 attempts.

Practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors: access to chiral beta-alkynyl acids.

The enantioselective conjugate addition of alkynyl nucleophiles has been a long-standing challenge in synthetic chemistry. This paper describes a highly practical asymmetric conjugate alkynylation of Meldrum's acid-derived acceptors using cinchonidine (<$100/kg) as the chiral mediator. The process provides practical access to chiral beta-alkynyl acids. Noteworthy attributes of the method are its broad scope, high functional-group compatibility, and ease of scalability.

Lighted stylet-guided intubation via the intubating laryngeal airway in a patient with Hallermann-Streiff syndrome.

PURPOSE: Hallermann-Streiff syndrome is a congenital syndrome associated with oculomandibulofacial abnormalities and potentially difficult airways. This case report describes the novel use of a lighted stylet-guided tracheal tube insertion through a new supraglottic airway, the intubating laryngeal airway (ILA), in a patient with Hallermann-Streiff syndrome who had anticipated difficult airway. CLINICAL FEATURES: A 26-year-old male with Hallermann-Streiff syndrome was scheduled for a vitrectomy. The patient had mandibulofacial dystocia with a bird-like appearance, a mouth opening of 4 cm, a receding chin, and a Mallampati class 3 examination. The surgeon requested muscle paralysis and no movement during surgery. After receiving midazolam, fentanyl and propofol, a size 3.5 ILA was inserted and lung ventilation was easy to perform. A 7.5-mm internal diameter tracheal tube was mounted on a lighted stylet with its inner rigid stylet removed. After succinylcholine administration, the lighted stylet-tracheal tube assembly was inserted via the ILA until the transillumination just vanished below the sternal notch. The lighted stylet was removed, the circuit was connected, and capnography confirmed tracheal placement of tube. The ILA was deflated and left in situ. Upon emergence from anesthesia, the tracheal tube, and subsequently the ILA, were removed without complications. CONCLUSIONS: This case presents a novel use of a lighted stylet-guided tracheal tube insertion through the ILA in a patient with Hallermann-Streiff syndrome. This intubation technique can be considered in patients with difficult airways as a primary route of intubation, or as a secondary rescue strategy.

Highly selective rhodium-catalyzed conjugate addition reactions of 4-oxobutenamides.

A variety of 4-oxobutenamides 1 were subjected to rhodium-catalyzed conjugate addition with arylboronic acids providing high regio- and enantioselectivity (97:3 to >99:1, >96% ee) and moderate to excellent yields (54-99%). The key to high selectivity is the use of sterically demanding P-chiral diphosphines, such as Tangphos or Duanphos. The product oxobutanamides 2 may be converted to alternate targets by selective derivatization of either the amide or ketone functional group. A stereochemical model predicting the absolute sense of induction was developed based on single-crystal X-ray structures of product and precatalyst.

A synthetic approach toward nitiol: construction of two 1,22-dihydroxynitianes.

Synthetic work toward the total synthesis of nitiol has culminated in the construction of two epimeric hydroxylated derivatives, the 1,22-dihydroxynitianes. Key stereodefining steps in the construction of the A-ring fragment (13) were the use of a siloxy-epoxide rearrangement reaction, a Pauson-Khand reaction, a Norrish 1 photochemical cleavage reaction, and a highly regio- and stereoselective hydrostannylation reaction of an ynoate. The stereochemistry of the synthetically challenging C-ring fragment (20) was established using an Ireland-Claisen reaction and a Grubbs ring-closing metathesis process as key steps. The 12-membered B-ring of the nitiane skeleton was constructed using a copper-promoted Stille cross-coupling and a Kishi-Hiyama-Nozaki carbonyl addition reaction. Unfortunately, the carbonyl addition reaction produced hydroxyl functionality that could not be selectively removed. Consequently, a synthesis of epimeric 1,22-dihydroxynitianes, which are compounds that are structural hybrids of two natural products, nitiol and variculanol, was completed.

A convenient method for the conversion of hindered carboxylic acids to N-methoxy-N-methyl (Weinreb) amides.

The conversion of sterically hindered carboxylic acids to N-methoxy-N-methyl amides can be efficiently carried out with 1.1 equiv of methanesulfonyl chloride, 3 equiv of triethylamine, and 1.1 equiv of N-methoxy-N-methylamine. Yields for this process range from 59% to 88%. The major byproduct in these reactions, N-methoxy-N-methylmethanesulfonamide, can be removed by placing the product mixture under vacuum for 14-24 h.

A general synthesis of substituted indoles from cyclic enol ethers and enol lactones.

[reaction: see text] X = CH2, C[double bond]O, R2 = H, alkyl. A general method was developed for the one-pot synthesis of highly functionalized indoles from simple, commercially available aryl hydrazines and cyclic enol ethers. Enol lactones were also used as substrates, affording substituted indole acetic acid or indole propionic acid derivatives. This procedure affords 2,3-disubstituted indoles as single regioisomers from the appropriately substituted enol ether or enol lactone. This method was highlighted in the efficient synthesis of the antimigraine drug sumitriptan and the antiinflammatory drug indomethacin.