Showcasing a General Surgery Residency Program During the COVID-19 Pandemic.

OBJECTIVE: The virtual interview season has challenged general surgery residency programs to recruit applicants through the loss of visiting clerkships, tours, and time with residents. Webinars, increased informal resident and faculty sessions, and live-narrated video tours are potential solutions. This study aimed to assess the effectiveness of these elements in virtually showcasing a residency program during the virtual interview season. DESIGN/SETTING: Prospective applicants to one general surgery residency program (Mayo Clinic in Rochester, Minnesota) were invited to attend six webinars: Program Overview, Simulation Education, Diversity, Resident Life, Mingle with Residents, and Last-Minute Q&A. An anonymous survey was sent to all registered participants of the webinars. Interviewees participated in a preinterview social hour with resident and faculty and a live-narrated video tour of our facilities during their interview. A second anonymous survey was sent to all interviewees. PARTICIPANTS: Webinars - 33% of 159 unique registrants surveyed participated. Interviews - 46% of 109 interviewees surveyed participated. RESULTS: Average satisfaction with the webinars was 9.4/10. Overall, 98% of attendees felt that the webinars gave them a "feel" for the program. Attendees found the Last-Minute Q&A webinar and Program Overview to be most useful. For resident-led webinars, 100% of attendees felt that themed break-out rooms were effective. Average satisfaction with the interviews was 4.4/5. Interviewees rated access to faculty and residents highly (4.4/5 and 4.5/5, respectively). 98% of interviewees found the live-narrated video tour helpful. CONCLUSIONS: A webinar curriculum can be effective in virtual residency recruitment, as prospective applicants developed a good understanding of the resident program after participating. Further, live-narrated video tours and purposefully incorporating several avenues for informal conversations with residents and faculty can successfully address applicant concerns about virtual interviews.

Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's disease and vascular cognitive impairment.

An intact blood-brain barrier (BBB) limits entry of proinflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer's disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive, and no interventions are available for treatment or prevention. We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD. To test whether mTOR inhibition protects the BBB in neurological diseases of aging, we treated hAPP(J20) mice modeling AD and low-density lipoprotein receptor-null (LDLR-/-) mice modeling vascular cognitive impairment with rapamycin. We found that inhibition of mTOR abrogates BBB breakdown in hAPP(J20) and LDLR-/- mice. Experiments using an in vitro BBB model indicated that mTOR attenuation preserves BBB integrity through upregulation of specific tight junction proteins and downregulation of matrix metalloproteinase-9 activity. Together, our data establish mTOR activity as a critical mediator of BBB breakdown in AD and, potentially, vascular cognitive impairment and suggest that rapamycin and/or rapalogs could be used for the restoration of BBB integrity. NEW & NOTEWORTHY This report establishes mammalian/mechanistic target of rapamycin as a critical mediator of blood-brain barrier breakdown in models of Alzheimer's disease and vascular cognitive impairment and suggests that drugs targeting the target of rapamycin pathway could be used for the restoration of blood-brain barrier integrity in disease states.

Evaluating the electronic structure of formal LnII ions in LnII(C5H4SiMe3)31- using XANES spectroscopy and DFT calculations.

The isolation of [K(2.2.2-cryptand)][Ln(C5H4SiMe3)3], formally containing LnII, for all lanthanides (excluding Pm) was surprising given that +2 oxidation states are typically regarded as inaccessible for most 4f-elements. Herein, X-ray absorption near-edge spectroscopy (XANES), ground-state density functional theory (DFT), and transition dipole moment calculations are used to investigate the possibility that Ln(C5H4SiMe3)31- (Ln = Pr, Nd, Sm, Gd, Tb, Dy, Y, Ho, Er, Tm, Yb and Lu) compounds represented molecular LnII complexes. Results from the ground-state DFT calculations were supported by additional calculations that utilized complete-active-space multi-configuration approach with second-order perturbation theoretical correction (CASPT2). Through comparisons with standards, Ln(C5H4SiMe3)31- (Ln = Sm, Tm, Yb, Lu, Y) are determined to contain 4f6 5d0 (SmII), 4f13 5d0 (TmII), 4f14 5d0 (YbII), 4f14 5d1 (LuII), and 4d1 (YII) electronic configurations. Additionally, our results suggest that Ln(C5H4SiMe3)31- (Ln = Pr, Nd, Gd, Tb, Dy, Ho, and Er) also contain LnII ions, but with 4f n 5d1 configurations (not 4f n+1 5d0). In these 4f n 5d1 complexes, the C3h-symmetric ligand environment provides a highly shielded 5d-orbital of a' symmetry that made the 4f n 5d1 electronic configurations lower in energy than the more typical 4f n+1 5d0 configuration.

A rare case of disseminated Sporothrix schenckii with bone marrow involvement in a patient with idiopathic CD4 lymphocytopenia.

Sporothrix schenckii is a pathogen with a predilection for dissemination in immunocompromised individuals, often with HIV. We report a case of disseminated sporotrichosis in an unfortunate 25 year old male (without HIV) who was originally treated for presumed pneumonia. The patient continued to worsen clinically and further work-up eventually revealed Sporothrix schenckii species with involvement of multiple organs including the skin, heart, lungs and bone marrow. Despite treatment with multiple antibacterials and antifungals, he ultimately passed away. This case illustrates the aggressive nature of this disease along with the importance of early/proper diagnosis and treatment.

Does Admission to the ICU Prevent African American Disparities in Withdrawal of Life-Sustaining Treatment?

OBJECTIVE: We sought to determine whether black patients admitted to an ICU were less likely than white patients to withdraw life-sustaining treatments. DESIGN: We performed a retrospective cohort study of hospital discharges from October 20, 2015, to October 19, 2016, for inpatients 18 years old or older and recorded those patients, along with their respective races, who had an "Adult Comfort Care" order set placed prior to discharge. A two-sample test for equality of two proportions with continuity correction was performed to compare the proportions between blacks and whites. SETTING: University of Florida Health. PATIENTS: The study cohort included 29,590 inpatient discharges, with 21,212 Caucasians (71.69%), 5,825 African Americans (19.69%), and 2,546 non-Caucasians/non-African Americans (8.62%). INTERVENTIONS: Withdrawal of life-sustaining treatments. MEASUREMENTS AND MAIN RESULTS: Of the total discharges (n = 29,590), 525 (1.77%) had the Adult Comfort Care order set placed. Seventy-eight of 5,825 African American patients (1.34%) had the Adult Comfort Care order set placed, whereas 413 of 21,212 Caucasian patients (1.95%) had this order set placed (p = 0.00251; 95% CI, 0.00248-0.00968). Of the 29,590 patients evaluated, 6,324 patients (21.37%) spent at least one night in an ICU. Of these 6,324 patients, 4,821 (76.24%) were white and 1,056 (16.70%) were black. Three hundred fifty of 6,324 (5.53%) were discharged with an Adult Comfort Care order set. Two hundred seventy-one White patients (5.62%) with one night in an ICU were discharged with an Adult Comfort Care order set, whereas 54 Black patients (5.11%) with one night in an ICU had the order set (p = 0.516). CONCLUSIONS: This study suggests that Black patients may be less likely to withdraw life-supportive measures than whites, but that this disparity may be absent in patients who spend time in the ICU during their hospitalization.

Coordination chemistry of 2,2'-biphenylenedithiophosphinate and diphenyldithiophosphinate with U, Np, and Pu.

New members of the dithiophosphinic acid family of potential actinide extractants were prepared: heterocyclic 2,2'-biphenylenedithiophosphinic acids of stoichiometry HS2P(R2C12H6) (R = H or (t)Bu). The time- and atom-efficient syntheses afforded multigram quantities of pure HS2P(R2C12H6) in reasonable yields (∼60%). These compounds differed from other diaryldithiophosphinic acid extractants in that the two aryl groups were connected to one another at the ortho positions to form a 5-membered dibenzophosphole ring. These 2,2'-biphenylenedithiophosphinic acids were readily deprotonated to form S2P(R2C12H6)(1-) anions, which were crystallized as salts with tetraphenylpnictonium cations (ZPh4(1+); Z = P or As). Coordination chemistry between [S2P((t)Bu2C12H6)](1-) and [S2P(C6H5)2](1-) with U, Np, and Pu was comparatively investigated. The results showed that dithiophosphinate complexes of U(IV) and Np(IV) were redox stable relative to those of U(III), whereas reactions involving Pu(IV) gave intractable material. For instance, reactions involving U(IV) and Np(IV) generated An[S2P((t)Bu2C12H6)]4 and An[S2P(C6H5)2]4 whereas reactions between Pu(IV) and [S2P(C6H5)2](1-) generated a mixture of products from which we postulated a transient Pu(III) species based on UV-Vis spectroscopy. However, the trivalent Pu[S2P(C6H5)2]3(NC5H5)2 compound is stable and could be isolated from reactions between [S2P(C6H5)2](1-) and the trivalent PuI3(NC5H5)4 starting material. Attempts to synthesize analogous trivalent compounds with U(III) provided the tetravalent U[S2P(C6H5)2]4 oxidation product.

Covalency in lanthanides. An X-ray absorption spectroscopy and density functional theory study of LnCl6(x-) (x = 3, 2).

Covalency in Ln-Cl bonds of Oh-LnCl6(x-) (x = 3 for Ln = Ce(III), Nd(III), Sm(III), Eu(III), Gd(III); x = 2 for Ln = Ce(IV)) anions has been investigated, primarily using Cl K-edge X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TDDFT); however, Ce L3,2-edge and M5,4-edge XAS were also used to characterize CeCl6(x-) (x = 2, 3). The M5,4-edge XAS spectra were modeled using configuration interaction calculations. The results were evaluated as a function of (1) the lanthanide (Ln) metal identity, which was varied across the series from Ce to Gd, and (2) the Ln oxidation state (when practical, i.e., formally Ce(III) and Ce(IV)). Pronounced mixing between the Cl 3p- and Ln 5d-orbitals (t2g* and eg*) was observed. Experimental results indicated that Ln 5d-orbital mixing decreased when moving across the lanthanide series. In contrast, oxidizing Ce(III) to Ce(IV) had little effect on Cl 3p and Ce 5d-orbital mixing. For LnCl6(3-) (formally Ln(III)), the 4f-orbitals participated only marginally in covalent bonding, which was consistent with historical descriptions. Surprisingly, there was a marked increase in Cl 3p- and Ce(IV) 4f-orbital mixing (t1u* + t2u*) in CeCl6(2-). This unexpected 4f- and 5d-orbital participation in covalent bonding is presented in the context of recent studies on both tetravalent transition metal and actinide hexahalides, MCl6(2-) (M = Ti, Zr, Hf, U).

Using solution- and solid-state S K-edge X-ray absorption spectroscopy with density functional theory to evaluate M-S bonding for MS4(2-) (M = Cr, Mo, W) dianions.

Herein, we have evaluated relative changes in M-S electronic structure and orbital mixing in Group 6 MS4(2-) dianions using solid- and solution-phase S K-edge X-ray absorption spectroscopy (XAS; M = Mo, W), as well as density functional theory (DFT; M = Cr, Mo, W) and time-dependent density functional theory (TDDFT) calculations. To facilitate comparison with solution measurements (conducted in acetonitrile), theoretical models included gas-phase calculations as well as those that incorporated an acetonitrile dielectric, the latter of which provided better agreement with experiment. Two pre-edge features arising from S 1s → e* and t electron excitations were observed in the S K-edge XAS spectra and were reasonably assigned as (1)A1 → (1)T2 transitions. For MoS4(2-), both solution-phase pre-edge peak intensities were consistent with results from the solid-state spectra. For WS4(2-), solution- and solid-state pre-edge peak intensities for transitions involving e* were equivalent, while transitions involving the t orbitals were less intense in solution. Experimental and computational results have been presented in comparison to recent analyses of MO4(2-) dianions, which allowed M-S and M-O orbital mixing to be evaluated as the principle quantum number (n) for the metal valence d orbitals increased (3d, 4d, 5d). Overall, the M-E (E = O, S) analyses revealed distinct trends in orbital mixing. For example, as the Group 6 triad was descended, e* (π*) orbital mixing remained constant in the M-S bonds, but increased appreciably for M-O interactions. For the t orbitals (σ* + π*), mixing decreased slightly for M-S bonding and increased only slightly for the M-O interactions. These results suggested that the metal and ligand valence orbital energies and radial extensions delicately influenced the orbital compositions for isoelectronic ME4(2-) (E = O, S) dianions.

Tetrahalide complexes of the [U(NR)2]2+ ion: synthesis, theory, and chlorine K-edge X-ray absorption spectroscopy.

Synthetic routes to salts containing uranium bis-imido tetrahalide anions [U(NR)(2)X(4)](2-) (X = Cl(-), Br(-)) and non-coordinating NEt(4)(+) and PPh(4)(+) countercations are reported. In general, these compounds can be prepared from U(NR)(2)I(2)(THF)(x) (x = 2 and R = (t)Bu, Ph; x = 3 and R = Me) upon addition of excess halide. In addition to providing stable coordination complexes with Cl(-), the [U(NMe)(2)](2+) cation also reacts with Br(-) to form stable [NEt(4)](2)[U(NMe)(2)Br(4)] complexes. These materials were used as a platform to compare electronic structure and bonding in [U(NR)(2)](2+) with [UO(2)](2+). Specifically, Cl K-edge X-ray absorption spectroscopy (XAS) and both ground-state and time-dependent hybrid density functional theory (DFT and TDDFT) were used to probe U-Cl bonding interactions in [PPh(4)](2)[U(N(t)Bu)(2)Cl(4)] and [PPh(4)](2)[UO(2)Cl(4)]. The DFT and XAS results show the total amount of Cl 3p character mixed with the U 5f orbitals was roughly 7-10% per U-Cl bond for both compounds, which shows that moving from oxo to imido has little effect on orbital mixing between the U 5f and equatorial Cl 3p orbitals. The results are presented in the context of recent Cl K-edge XAS and DFT studies on other hexavalent uranium chloride systems with fewer oxo or imido ligands.

Patients with nontuberculous mycobacteria: comparison of updated and previous diagnostic criteria for lung disease.

We classified patients with respiratory nontuberculous mycobacteria (NTM) isolates using updated (2007) and previous (1997) American Thoracic Society/Infectious Diseases Society of America criteria for NTM lung disease. We found that a greater proportion of such patients have disease using updated criteria due to improved sensitivity of the microbiologic component of the disease definition.

Palladium(II)-catalyzed enantioselective synthesis of 2-vinyl oxygen heterocycles.

2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H-1,4-benzoxazines (3) can be prepared in high yields (90-98%) and excellent enantiomeric purities (87-98% ee) by [COP-OAc](2)-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can also be prepared in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective S(N)2' substitution reactions.

Catalytic Asymmetric Synthesis of Branched Chiral Allylic Phenyl Ethers from (E)-Allylic Alcohols.

The first di-µ-amidate dipalladium complexes and a new di-µ-carboxylate dipalladium complex of the COP (cobalt oxazoline palladacycle) palladium(II) catalyst family are reported and characterized crystallographically. The di-µ-amidate complex 3 or its enantiomer (ent-3) are the first asymmetric catalysts that allow commercially available, or readily accessible, (E)-2-alkene-1-ols to be transformed to enantioenriched branched allylic aryl ethers upon reaction of their trichloroacetimidate derivatives with phenols. The 3-aryloxy-1-alkene products are formed in high enantiomeric purity (typically 90-98% ee) and useful yields (61-88%).