The angiotensin II receptors AT
R and AT
R serve as key components of the renin-angiotensin-aldosterone system. AT
R has a central role in the regulation of blood pressure, but the function of AT
R ...is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT
R bound to an AT
R-selective ligand and to an AT
R/AT
R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or β-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure-activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of new selective ligands.
Nitrous acid (HONO) is a reservoir of NO
and an emerging pollutant having direct impacts on air quality, both in- and outdoors, as well as on human health. In this work, the amine-functionalized ...metal-organic framework (MOF), UiO-66-NH
, was investigated due to its potential to selectively decontaminate nitrous acid at environmentally relevant concentrations. UiO-66-NH
proved to be effective in the removal of nitrous acid from a continuous gaseous stream. This is observed
the formation of an aryl diazonium salt that subsequently converts to a phenol with a concomitant release of nitrogen gas. This process is preceded
the formation of the nitrosonium cation (likely protonation from an acidic proton on the node). Thus, UiO-66-NH
is capable of selectively converting the pollutant nitrous acid to benign products.
This study demonstrates the synergies and limits of multiple measurement types for the detection of smectite chemistry and oxidation state on planetary surfaces to infer past geochemical conditions. ...Smectite clay minerals are common products of water-rock interactions throughout the solar system, and their detection and characterization provides important clues about geochemical conditions and past environments if sufficient information about their composition can be discerned. Here, we synthesize and report on the spectroscopic properties of a suite of smectite samples that span the intermediate compositional range between Fe(II), Fe(III), Mg, and Al end-member species using bulk chemical analyses, X-ray diffraction, Vis/IR reflectance spectroscopy, UV and green-laser Raman spectroscopy, and Mössbauer spectroscopy. Our data show that smectite composition and the oxidation state of octahedral Fe can be reliably identified in the near infrared on the basis of combination and fundamental metal-OH stretching modes between 2.1–2.9 μm, which vary systematically with chemistry. Smectites dominated by Mg or Fe(III) have spectrally distinct fundamental and combination stretches, whereas Al-rich and Fe(II)-rich smectites have similar fundamental minima near 2.76 μm, but have distinct combination M-OH features between 2.24 and 2.36 μm. We show that with expanded spectral libraries that include intermediate composition smectites and both Fe(III) and Fe(II) oxidation states, more refined characterization of smectites from MIR data is now possible, as the position of the 450 cm–1 absorption shifts systematically with octahedral Fe content, although detailed analysis is best accomplished in concert with other characterization methods. Our data also provide the first Raman spectral libraries of smectite clays as a function of chemistry, and we demonstrate that Raman spectroscopy at multiple excitation wavelengths can qualitatively distinguish smectite clays of different structures and can enhance interpretation by other types of analyses. Our sample set demonstrates how X-ray diffraction can distinguish between dioctahedral and trioctahedral smectites using either the (02,11) or (06,33) peaks, but auxiliary information about chemistry and oxidation state aids in specific identifications. Finally, the temperature-dependent isomer shift and quadrupole splitting in Mössbauer data are insensitive to changes in Fe content but reliability differentiates Fe within the smectite mineral structure.
End-to-end microvascular anastomoses sacrifice downstream inline perfusion of the recipient vessels. End-to-side anastomoses, in theory, maintain distal inline flow of the recipient vessel. The ...proposed benefit of the end-to-side technique depends on patency of the distal vessels and subsequent flow parameters, but maintenance of distal perfusion has not been conclusively demonstrated.
Fifteen patients who underwent a successful extremity free flap procedure via end-to-side anastomoses to a noncritical vessel between 2003 and 2017 were enrolled. Recipient artery patency distal to the anastomosis was assessed using pulse volume recordings and duplex ultrasound imaging. Resistance indices, flow velocities, vessel diameters, volumetric flow, and turbulent flow dimensionless number (Reynolds number) were measured. Comparisons were made to the ipsilateral collateral vessel as well as to the vessels on the nonoperative contralateral limb using paired t tests.
Downstream flow was identified in 14 of 15 patients (93 percent patency). There was no statistical difference in resistive indices comparing the anastomotic vessel (0.859 ± 0.300) and the collateral vessel (0.853 ± 0.179) of the ipsilateral extremity. Ultrasound flows were similar; the anastomotic vessel demonstrated downstream volumetric flows of 139 ± 92.0 cm3/min versus 137 ± 41.6 cm3/min within the same vessel of the nonoperative contralateral limb. The anastomotic vessel had Reynolds numbers well below the turbulent threshold (448 ± 202 and 493 ± 127 for the anastomotic and nonoperative contralateral limb, respectively).
End-to-side anastomosis to noncritical vessels resulted in a 93 percent long-term recipient vessel patency rate, with no statistically significant changes in volumetric flows, resistive indices, or fluid dynamics in the vessels that remained patent.
Several improvised dynamic external fixation devices are used for treating unstable dorsal proximal interphalangeal (PIP) joint fracture-dislocations. We compared the effectiveness of 3 constructs ...for simulated dorsal PIP joint fracture-dislocations in a cadaver model.
We tested 30 digits from 10 fresh-frozen, thawed cadaver hands. We aimed to remove the palmar 50% of the base of each digit’s middle phalanx (P2), simulating an unstable dorsal PIP joint fracture-dislocation. Each PIP joint was then stabilized via external fixation with either a pins–and–rubber-bands construct, pins-only construct, or tuberculin syringe-pins construct. We allocated 10 digits per fixation group. The finger tendons were secured to a computer-controlled stepper motor–driven linear actuator. Via this mechanism, all PIP joints were taken through 1,400 cycles of flexion-extension. With the PIP joint in neutral extension, we measured the P2 dorsal translation at baseline, after fixator stabilization, and after the motion protocol.
The actual mean P2 palmar defect created was 48% of the base. All PIP joints were unstable after creating the defect, with a mean initial P2 dorsal displacement of 3.7 mm. After application of the fixators, all PIP joint dislocations were reduced. The median residual P2 dorsal displacements were 0.0 mm for the pins–rubber bands group, 0.1 mm for the pins-only group, and 0.5 mm for the syringe-pins group. There were no cases of PIP joint redislocation after flexion-extension cycling, and the median dorsal P2 displacements were 0.0 mm for the pins–rubber bands group; 0.0 mm for the pins-only group; and 0.5 mm for the syringe-pins group.
All 3 external fixators restored PIP joint stability following simulated dorsal fracture-dislocation, with all reductions maintained after motion testing. The syringe-pins construct had significantly greater median residual P2 dorsal displacement after the initial reduction and motion testing, which is of unclear clinical importance.
This study informs surgeon decision-making when considering dynamic external fixator options for dorsal PIP joint fracture-dislocations.
The value of the human fingertip is incalculable. More than just aesthetic, the fingertip is an instrument through which we navigate our environment and acquire information. All too often, fingertip ...reconstruction is either not attempted or attempted without adhering to the fundamental principle of “replacing like with like.” Through detailed description and case examples, this article highlights the power and utility of the anterograde homodigital neurovascular island flap in fingertip reconstruction. This single-stage flap can reliably resurface large soft tissue defects with sensate glabrous skin.
The recently validated Pittsburgh Fatigability Scale (PFS) Mental subscale improves upon shortfalls in existing global fatigue measures by standardizing mental fatigue to intensity and duration ...across a range of activities/tasks, thus eliminating self-pacing.1 A next step is to describe the prevalence and severity of perceived mental fatigability by age and sex to foster comparisons across cohorts and health conditions. We hypothesized that prevalence of perceived mental fatigability would be greater with advancing age and PFS Mental scores would be higher for women than men.
Zone I Flexor Digitorum Profundus Repair: A Surgical Technique Polfer, Elizabeth M.; Sabino, Jennifer M.; Katz, Ryan D.
The Journal of hand surgery (American ed.),
February 2019, 2019-Feb, 2019-02-00, 20190201, Letnik:
44, Številka:
2
Journal Article
Recenzirano
We present an all-inside technique for zone I flexor tendon repair that combines suture anchor fixation with buried back-up fixation. The back-up fixation uses transosseous tunnels and a dorsal ...counterincision to allow a suture tied dorsal to the distal phalanx and buried. This technique is strong and permits early active range of motion. The dorsal tie-over does not require a suture button and, therefore, does not imperil the nail matrix. The surgical technique is herein described including the proposed anesthesia (wide awake), the incisions (midlateral), the exposures, and the repair itself.
Guideline-based mammography screening is essential to lowering breast cancer mortality, yet women residing in rural areas have lower rates of up to date (UTD) breast cancer screening compared to ...women in urban areas. We tested the comparative effectiveness of a tailored DVD, and the DVD plus patient navigation (PN) intervention vs. Usual Care (UC) for increasing the percentage of rural women (aged 50 to 74) UTD for breast cancer screening, as part of a larger study. Four hundred and two women who were not UTD for breast cancer screening, eligible, and between the ages of 50 to 74 were recruited from rural counties in Indiana and Ohio. Consented women were randomly assigned to one of three groups after baseline assessment of sociodemographic variables, health status, beliefs related to cancer screening tests, and history of receipt of guideline-based screening. The mean age of participants was 58.2 years with 97% reporting White race. After adjusting for covariates, 54% of women in the combined intervention (DVD + PN) had a mammogram within the 12-month window, over 5 times the rate of becoming UTD compared to UC (OR = 5.11; 95% CI = 2.57, 10.860; p < 0.001). Interactions of the intervention with other variables were not significant. Significant predictors of being UTD included: being in contemplation stage (intending to have a mammogram in the next 6 months), being UTD with other cancer screenings, having more disposable income and receiving a reminder for breast screening. Women who lived in areas with greater Area Deprivation Index scores (a measure of poverty) were less likely to become UTD with breast cancer screening. For rural women who were not UTD with mammography screening, the addition of PN to a tailored DVD significantly improved the uptake of mammography. Attention should be paid to certain groups of women most at risk for not receiving UTD breast screening to improve breast cancer outcomes in rural women.
Comminuted intra-articular fractures and fracture dislocations of the metacarpophalangeal (MCP) and interphalangeal joints are challenging. Dynamic external fixation, permitting early joint motion ...while still minimizing forces across the healing joint, can result in acceptable postoperative active range of motion (AROM). However, some fractures are not initially stable enough for early dynamic motion; further, many available dynamic external fixation systems are costly and cumbersome. We reviewed our experience using an external fixator made from a 1-mL syringe and K-wires and report outcomes using it as a static fixator, dynamic fixator, or configured as a static fixator and then converted to a dynamic fixator in the clinic.
Patients with intra-articular fractures and fracture dislocations of the MCP and proximal interphalangeal (PIP) joints treated between 2014 and 2020 using syringe external fixators were retrospectively reviewed. We reviewed demographics, mechanisms, treatment types and durations, and postoperative AROM, as well as complications including infection, pin loosening, nonunion, hardware failure, and need for further surgery. Patients were analyzed by the level of joint injury (MCP versus PIP) and by treatment pattern.
After excluding 23 patients with 25 joint injuries who were lost to follow-up or had inadequate outcome data, 27 patients with 29 joint injuries were reviewed. The average follow-up was 171 days after surgery. The postoperative AROM at the MCP level averaged 55° for static fixation and 30° for static-to-dynamic fixation. The postoperative AROM at the PIP level averaged 64° for static fixation, 66° for static-to-dynamic fixation, and 80° for dynamic fixation. Three pin site infections and 2 loose pins were reported.
The syringe external fixator is an inexpensive, effective, and customizable treatment for intra-articular MCP and interphalangeal fractures and fracture dislocations, and results in acceptable postoperative AROM outcomes and complication rates.
Therapeutic IV.
PDF
