Optimal Immobilization After Fixation of Bennett's Fracture: A Cadaveric Study.

OBJECTIVE: Treating high-level athletes involves a balance between early and safe return to play. Various types of protective immobilization have been recommended after operatively treated Bennett's fracture. The purpose of this study was to investigate if hand-based immobilization offers protection equivalent to forearm-based immobilization. MATERIALS AND METHODS: A cadaveric model of Bennett's fracture was created in 8 fresh-frozen, cadaveric forearms. Osteosynthesis was performed using a single headless compression screw. Three matched pairs were casted in either hand-based or forearm length, thumb spica casts, while 2 specimens remained un-casted as controls. Specimens were mounted on a custom testing apparatus. Weights were added in 6.8-kg increments until fixation failed and the fracture displaced. Fluoroscopy was performed after each trial. We used the Kruskal-Wallis non-parametric test to compare the groups. We considered P<.05 statistically significant. RESULTS: Failure of fixation occurred at 6.8 kg in the control specimens. Fixation failed in hand-based and forearm length casts at a mean of 18.1±5.1 kg. We did not find a statistically significant difference between median values of load at failure in kilograms across control specimens and 2 immobilization categories (P=.114). All specimens in the hand-based group sustained additional wrist injuries, while no additional injuries were noted in the forearm length group. CONCLUSION: Our study results showed that hand-based immobilization provides equivalent protection against fixation failure for operatively treated Bennett's fractures but may predispose athletes to increased risk of wrist injury compared with traditional, forearm-based casting. [Orthopedics. 2024;47(3):157-160.].

Articular Surface Involvement With Retrograde Headless Screw Fixation of the Proximal Phalanx.

PURPOSE: Intramedullary (IM) screw fixation of proximal phalanx (P1) fractures is a treatment option increasing in popularity. This study aimed to quantify the articular surface loss after retrograde screw insertion and to determine the range of motion (ROM) of the proximal interphalangeal (PIP) joint while the defect in the P1 head is engaged with the base of the middle phalanx (P2). METHODS: Twelve fresh frozen cadaver hand specimens were analyzed for prefixation ROM of the PIP joint. A retrograde screw was placed using a percutaneous technique under fluoroscopic guidance. Following screw insertion, specimens were dissected to determine size of the extensor mechanism defect, evaluate the lateral bands with passive ROM of the PIP joint, and determine the angle at which the dorsal aspect of P2 ceases to engage with the defect and the amount of articular surface loss. The percentage of articular surface loss was calculated using a digital image software program. RESULTS: The angle at which P2 ceased to engage with the articular surface defect was an average of 36.8° of PIP joint flexion. In full PIP joint flexion, the average extensor mechanism defect was 8.8%. The average total articular surface loss was 4.4% across all digits. CONCLUSION: Percutaneous retrograde P1 intramedullary screw fixation results in minimal damage to the extensor mechanism and articular surface. The arc during which the defect in the head of P1 engages the base of the P2 is almost entirely outside the functional ROM of the PIP joint. CLINICAL RELEVANCE: Quantifying the amount of articular surface loss through the P1 head and extensor apparatus damage in IM screw fixation can inform surgeons of the consequences of this technique. This study supports the use of a retrograde intramedullary screw as a safe option for fixation of P1 fractures.

Operation Blood Rain Phase 2: Evaluating the Effect of Airdrop on Fresh and Stored Whole Blood.

BACKGROUND: Transfusion of whole blood (WB) is a lifesaving treatment that prolongs life until definitive surgical intervention can be performed; however, collecting WB is a time-consuming and resource-intensive process. Furthermore, it may be difficult to collect sufficient WB at the point of injury to treat critically wounded patients or multiple hemorrhaging casualties. This study is a follow-up to the proof-of-concept study on the effect of airdrop on WB. In addition, this study confirms the statistical significance for the plausibility of using airdrop to deliver WB to combat medics treating casualties in the pre-hospital setting when Food and Drug Administration (FDA)-approved cold-stored blood products are not available. METHODS: Forty-eight units of WB were collected and loaded into a blood cooler that was dropped from a fixed-wing aircraft under a Standard Airdrop Training Bundle (SATB) parachute or 68-in pilot chute. Twenty-four of these units were dropped from a C-145 aircraft, and 24 were dropped from a C-130 aircraft. A control group of 15 units of WB was storedin a blood cooler that was not dropped. Baseline and post-intervention laboratory tests were measured in both airdroppedand control units, including complete blood count; prothrombin time/partial thromboplastin time (PT/PTT); pH, lactate,potassium, bilirubin, glucose, fibrinogen, and lactate dehydrogenase (LDH) levels; and peripheral blood smears. RESULTS: The blood cooler, cooling packs, and all 48 WB units did notsustain any major damage from the airdrop. There was noevidence of hemolysis. Except for the one slightly damagedbag that was not sampled, all airdropped blood met parameters for transfusion per the Joint Trauma System Whole BloodTransfusion Clinical Practice Guideline and the Associationfor the Advancement of Blood and Biotherapies (AABB) Circular of Information for the Use of Human Blood and BloodComponents. CONCLUSIONS: Airdrop of fresh or stored WB in ablood cooler with a chute is a viable way of delivering bloodproducts to combat medics treating hemorrhaging patientsin the pre-hospital setting. This study also demonstrated theportability of this technique for multiple aircraft. The techniques evaluated in this study have the potential for utilizationin other austere settings such as wilderness medicine or humanitarian disasters where an acute need for WB delivery by airdrop is the only option.

Sustained reduction in numbers of Australian fur seal pups: Implications for future population monitoring.

Fur seal populations in the Southern Hemisphere were plundered in the late 1700s and early 1800s to provide fur for a clothing industry. Millions of seals were killed resulting in potentially major ecosystem changes across the Southern Hemisphere, the consequences of which are unknown today. Following more than a century of population suppression, partly through on-going harvesting, many of the fur seal populations started to recover in the late 1900s. Australian fur seals (Arctocephalus pusillus doriferus), one of the most geographically constrained fur seal species, followed this trend. From the 1940s to 1986, pup production remained at approximately 10,000 per year, then significant growth commenced. By 2007, live pup abundance had recovered to approximately 21,400 per year and recovery was expected to continue However, a species-wide survey in 2013 recorded a 20% decline, to approximately 16,500 live pups. It was not known if this decline was due to 2013 being a poor breeding year or a true population reduction. Here we report the results of a population-wide survey conducted in 2017 and annual monitoring at the most productive colony, Seal Rocks, Victoria that recorded a large decline in live pup abundance (-28%). Sustained lower pup numbers at Seal Rocks from annual counts between 2012-2017 (mean = 2908 ± 372 SD), as well as the population-wide estimate of 16,903 live pups in 2017, suggest that the pup numbers for the total population have remained at the lower level observed in 2013 and that the 5-yearly census results are not anomalies or representative of poor breeding seasons. Potential reasons for the decline, which did not occur range-wide but predominantly in the most populated and long-standing breeding sites, are discussed. To enhance adaptive management of this species, methods for future monitoring of the population are also presented. Australian fur seals occupy several distinct regions influenced by different currents and upwellings: range-wide pup abundance monitoring enables comparisons of ecosystem status across these regions. Forces driving change in Australian fur seal pup numbers are likely to play across other marine ecosystems, particularly in the Southern Hemisphere where most fur seals live.

Variation of stress levels, burnout, and resilience throughout the academic year in first-year medical students.

Medical student wellness is of great concern in the health care field. A growing number of studies point to increases in suicide, depression, anxiety, mood disorders, and burnout related to physician lifestyles. Mental health issues commencing in medical school have been suggested to have a significant impact on future physician lifestyle and burnout. Tracking the mental health of medical students at the University of Toledo College of Medicine and Life Sciences (UTCOMLS) with standardized indices will help elucidate triggers of poor mental health. Anonymous surveys were developed and distributed to preclinical medical students at five strategic time points throughout the 2018 2019 academic year. Surveys collected basic demographic information as well as inventories measuring perceived stress, burnout, resilience, and mindfulness. 172 M1s (83 males and 89 females) were included in the study and average response rate for the first 4 (out of 5) surveys averaged 74.8%. M1 males and females had on average increased personal burnout over time with females consistently scoring higher. Both males and females had an increase in stress from August to each subsequent month (p<0.05). Females reported a higher level of perceived stress than males in the beginning and middle of the academic year (p<0.05). Both males and females report a gradual decrease in resiliency throughout the academic year. These surveys demonstrated over half of males and females in medical school reported higher perceived stress scores than their gender-matched peers in the general United States population. Our study strengthens documented trends in resiliency, perceived stress, and burnout amongst medical students. More study in designing targeted approaches to ameliorate these findings in the medical student population is warranted.

Understanding meta-population trends of the Australian fur seal, with insights for adaptive monitoring.

Effective ecosystem-based management requires estimates of abundance and population trends of species of interest. Trend analyses are often limited due to sparse or short-term abundance estimates for populations that can be logistically difficult to monitor over time. Therefore it is critical to assess regularly the quality of the metrics in long-term monitoring programs. For a monitoring program to provide meaningful data and remain relevant, it needs to incorporate technological improvements and the changing requirements of stakeholders, while maintaining the integrity of the data. In this paper we critically examine the monitoring program for the Australian fur seal (AFS) Arctocephalus pusillus doriferus as an example of an ad-hoc monitoring program that was co-ordinated across multiple stakeholders as a range-wide census of live pups in the Austral summers of 2002, 2007 and 2013. This 5-yearly census, combined with historic counts at individual sites, successfully tracked increasing population trends as signs of population recovery up to 2007. The 2013 census identified the first reduction in AFS pup numbers (14,248 live pups, -4.2% change per annum since 2007), however we have limited information to understand this change. We analyse the trends at breeding colonies and perform a power analysis to critically examine the reliability of those trends. We then assess the gaps in the monitoring program and discuss how we may transition this surveillance style program to an adaptive monitoring program than can evolve over time and achieve its goals. The census results are used for ecosystem-based modelling for fisheries management and emergency response planning. The ultimate goal for this program is to obtain the data we need with minimal cost, effort and impact on the fur seals. In conclusion we identify the importance of power analyses for interpreting trends, the value of regularly assessing long-term monitoring programs and proper design so that adaptive monitoring principles can be applied.

Glutathionylation of Yersinia pestis LcrV and Its Effects on Plague Pathogenesis.

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that Yersinia pestis LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys273 and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates Y. pestis type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys273Ala in lcrV Moreover, the lcrVC273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala substitution. Furthermore, macrophages infected by the lcrVC273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of gshB, which encodes glutathione synthetase of Y. pestis, resulted in undetectable levels of intracellular glutathione, and we used a Y. pestis ΔgshB mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.IMPORTANCEYersinia pestis, the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of Y. pestis in mouse and rat models for bubonic plague. These data suggest that Y. pestis exploits glutathione in host tissues to activate a virulence strategy, thereby accelerating plague pathogenesis.

Clinical, microbiological and pathological findings of Mycobacterium ulcerans infection in three Australian Possum species.

BACKGROUND: Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans, with endemicity predominantly in sub-Saharan Africa and south-eastern Australia. The mode of transmission and the environmental reservoir(s) of the bacterium and remain elusive. Real-time PCR investigations have detected M. ulcerans DNA in a variety of Australian environmental samples, including the faeces of native possums with and without clinical evidence of infection. This report seeks to expand on previously published findings by the authors' investigative group with regards to clinical and subclinical disease in selected wild possum species in BU-endemic areas of Victoria, Australia. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-seven clinical cases of M. ulcerans infection in free-ranging possums from southeastern Australia were identified retrospectively and prospectively between 1998-2011. Common ringtail possums (Pseudocheirus peregrinus), a common brushtail possum (Trichosurus vulpecula) and a mountain brushtail possum (Trichosurus cunninghami) were included in the clinically affected cohort. Most clinically apparent cases were adults with solitary or multiple ulcerative cutaneous lesions, generally confined to the face, limbs and/or tail. The disease was minor and self-limiting in the case of both Trichosurus spp. possums. In contrast, many of the common ringtail possums had cutaneous disease involving disparate anatomical sites, and in four cases there was evidence of systemic disease at post mortem examination. Where tested using real-time PCR targeted at IS2404, animals typically had significant levels of M. ulcerans DNA throughout the gut and/or faeces. A further 12 possums without cutaneous lesions were found to have PCR-positive gut contents and/or faeces (subclinical cases), and in one of these the organism was cultured from liver tissue. Comparisons were made between clinically and subclinically affected possums, and 61 PCR-negative, non-affected individuals, with regards to disease category and the categorical variables of species (common ringtail possums v others) and sex. Animals with clinical lesions were significantly more likely to be male common ringtail possums. CONCLUSIONS/SIGNIFICANCE: There is significant disease burden in common ringtail possums (especially males) in some areas of Victoria endemic for M. ulcerans disease. The natural history of the disease generally remains unknown, however it appears that some mildly affected common brushtail and mountain brushtail possums can spontaneously overcome the infection, whereas some severely affected animals, especially common ringtail possums, may become systemically, and potentially fatally affected. Subclinical gut carriage of M. ulcerans DNA in possums is quite common and in some common brushtail and mountain brushtail possums this is transient. Further work is required to determine whether M. ulcerans infection poses a potential threat to possum populations, and whether these animals are acting as environmental reservoirs in certain geographical areas.

YfbA, a Yersinia pestis regulator required for colonization and biofilm formation in the gut of cat fleas.

For transmission to new hosts, Yersinia pestis, the causative agent of plague, replicates as biofilm in the foregut of fleas that feed on plague-infected animals or humans. Y. pestis biofilm formation has been studied in the rat flea; however, little is known about the cat flea, a species that may bridge zoonotic and anthroponotic plague cycles. Here, we show that Y. pestis infects and replicates as a biofilm in the foregut of cat fleas in a manner requiring hmsFR, two determinants for extracellular biofilm matrix. Examining a library of transposon insertion mutants, we identified the LysR-type transcriptional regulator YfbA, which is essential for Y. pestis colonization and biofilm formation in cat fleas.

LcrV mutants that abolish Yersinia type III injectisome function.

LcrV, the type III needle cap protein of pathogenic Yersinia, has been proposed to function as a tether between YscF, the needle protein, and YopB-YopD to constitute the injectisome, a conduit for the translocation of effector proteins into host cells. Further, insertion of LcrV-capped needles from a calcium-rich environment into host cells may trigger the low-calcium signal for effector translocation. Here, we used a genetic approach to test the hypothesis that the needle cap responds to the low-calcium signal by promoting injectisome assembly. Growth restriction of Yersinia pestis in the absence of calcium (low-calcium response [LCR(+)] phenotype) was exploited to isolate dominant negative lcrV alleles with missense mutations in its amber stop codon (lcrV(*327)). The addition of at least four amino acids or the eight-residue Strep tag to the C terminus was sufficient to generate an LCR(-) phenotype, with variant LcrV capping type III needles that cannot assemble the YopD injectisome component. The C-terminal Strep tag appears buried within the cap structure, blocking effector transport even in Y. pestis yscF variants that are otherwise calcium blind, a constitutive type III secretion phenotype. Thus, LcrV(*327) mutants arrest the needle cap in a state in which it cannot respond to the low-calcium signal with either injectisome assembly or the activation of type III secretion. Insertion of the Strep tag at other positions of LcrV produced variants with wild-type LCR(+), LCR(-), or dominant negative LCR(-) phenotypes, thereby allowing us to identify discrete sites within LcrV as essential for its attributes as a secretion substrate, needle cap, and injectisome assembly factor.

Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis*.

OBJECTIVE: To evaluate the effects of single-dose etomidate on the adrenal axis and mortality in patients with severe sepsis and septic shock. DESIGN: A systematic review of randomized controlled trials and observational studies with meta-analysis. SETTING: Literature search of EMBASE, Medline, Cochrane Database, and Evidence-Based Medical Reviews. SUBJECTS: Sepsis patients who received etomidate for rapid sequence intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a systematic review of randomized controlled trials and observational studies with meta-analysis assessing the effects of etomidate on adrenal insufficiency and all-cause mortality published between January 1950 and February 2012. We only examined studies including septic patients. All-cause mortality served as our primary end point, whereas the prevalence of adrenal insufficiency was our secondary end point. Adrenal insufficiency was determined using a cosyntropin stimulation test in all studies. We used a random effects model for analysis; heterogeneity was assessed with the I statistic. Publication bias was evaluated with Begg's test. Five studies were identified that assessed mortality in those who received etomidate. A total of 865 subjects were included. Subjects who received etomidate were more likely to die (pooled relative risk 1.20; 95% confidence interval 1.02-1.42; Q statistic, 4.20; I2 statistic, 4.9%). Seven studies addressed the development of adrenal suppression associated with the administration of etomidate; 1,303 subjects were included. Etomidate administration increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% confidence interval 1.22-1.46; Q statistic, 10.7; I2 statistic, 43.9%). CONCLUSIONS: Administration of etomidate for rapid sequence intubation is associated with higher rates of adrenal insufficiency and mortality in patients with sepsis.

Hereditary hemochromatosis restores the virulence of plague vaccine strains.

Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.

Novel tools for visualizing and exploring intermolecular interactions in molecular crystals.

A new way of exploring packing modes and intermolecular interactions in molecular crystals is described, using Hirshfeld surfaces to partition crystal space. These molecular Hirshfeld surfaces, so named because they derive from Hirshfeld's stockholder partitioning, divide the crystal into regions where the electron distribution of a sum of spherical atoms for the molecule (the promolecule) dominates the corresponding sum over the crystal (the procrystal). These surfaces reflect intermolecular interactions in a novel visual manner, offering a previously unseen picture of molecular shape in a crystalline environment. Surface features characteristic of different types of intermolecular interactions can be identified, and such features can be revealed by colour coding distances from the surface to the nearest atom exterior or interior to the surface, or by functions of the principal surface curvatures. These simple devices provide a striking and immediate picture of the types of interactions present, and even reflect their relative strengths from molecule to molecule. A complementary two-dimensional mapping is also presented, which summarizes quantitatively the types of intermolecular contacts experienced by molecules in the bulk and presents this information in a convenient colour plot. This paper describes the use of these tools in the compilation of a pictorial glossary of intermolecular interactions, using identifiable patterns of interaction between small molecules to rationalize the often complex mix of interactions displayed by large molecules.

XSophe-Sophe-XeprView. A computer simulation software suite (v. 1.1.3) for the analysis of continuous wave EPR spectra.

The XSophe-Sophe-XeprView computer simulation software suite enables scientists to easily determine spin Hamiltonian parameters from isotropic, randomly oriented and single crystal continuous wave electron paramagnetic resonance (CW EPR) spectra from radicals and isolated paramagnetic metal ion centers or clusters found in metalloproteins, chemical systems and materials science. XSophe provides an X-windows graphical user interface to the Sophe programme and allows: creation of multiple input files, local and remote execution of Sophe, the display of sophelog (output from Sophe) and input parameters/files. Sophe is a sophisticated computer simulation software programme employing a number of innovative technologies including; the Sydney OPera HousE (SOPHE) partition and interpolation schemes, a field segmentation algorithm, the mosaic misorientation linewidth model, parallelization and spectral optimisation. In conjunction with the SOPHE partition scheme and the field segmentation algorithm, the SOPHE interpolation scheme and the mosaic misorientation linewidth model greatly increase the speed of simulations for most spin systems. Employing brute force matrix diagonalization in the simulation of an EPR spectrum from a high spin Cr(III) complex with the spin Hamiltonian parameters g(e) = 2.00, D=0.10 cm(-1), E/D = 0.25, A(x) = 120.0, A(y) = 120.0, A(z) = 240.0 x 10 (-4) cm(-1) requires a SOPHE grid size of N = 400 (to produce a good signal to noise ratio) and takes 229.47 s. In contrast the use of either the SOPHE interpolation scheme or the mosaic misorientation linewidth model requires a SOPHE grid size of only N = 18 and takes 44.08 and 0.79 s, respectively. Results from Sophe are transferred via the Common Object Request Broker Architecture (CORBA) to XSophe and subsequently to XeprView where the simulated CW EPR spectra (1D and 2D) can be compared to the experimental spectra. Energy level diagrams, transition roadmaps and transition surfaces aid the interpretation of complicated randomly oriented CW EPR spectra and can be viewed with a web browser and an OpenInventor scene graph viewer.

An AM1 semiempirical study of host-guest complexation in hemicarcerand complexes.

Semiempirical AM1 calculations have been carried out on host-guest complexes of model hemicarcerands 1a and 2a. The justification for the choice of the AM1 Hamiltonian was based on a comparison between reported X-ray data for the smaller tetrabromocavitand 4a and computational results obtained using several different Hamiltonians. The complexation behavior of hemicarcerands 1a and 2a have been compared with experimental results reported by Cram et al. for the related hemicarcerands 1b and 2b. Based on this comparison, a criterion for predicting guest encapsulation was developed, E(complexation), which relies on the calculation of AM1 heats of formation for host, guest, and hemicarceplex. If E(complexation) is lower than 10 kcal/mol, then a guest will be encapsulated, while if it is greater than 30 kcal/mol, a guest will not be encapsulated. The use of constrained-path AM1 optimizations to determine the energy barriers to guest entry and exit from the host was found to be a useful tool for examining suitable host-guest combinations when the E(complexation) criteria does not hold. We have computed the barriers to exit of N, N-dimethylformamide (dmf) and furan from the hemicarcerand 1a, the former has been compared with the experiment and shows excellent agreement. Based on the success of the above computational methods in predicting which host-guest combinations will form stable hemicarceplexes we have synthesized a new target hemicarceplex 1b.furan.

The design and synthesis of selective prostaglandin analogs as bone anabolic agents for the potential treatment of osteoporosis.

A series of prostaglandins selective for the human FP receptor have been synthesized and evaluated as potential therapeutics for the treatment of osteoporosis. The compounds proved to be potent (nanomolar binding affinity) and selective (> 100x) ligands for the human FP receptor in vitro, and increased bone volume in the ovariectomized rat in vivo.