Are Kinematics an Indicator of Outcome After Total Knee Arthroplasty?

BACKGROUND: A proportion of total knee arthroplasty (TKA) patients are dissatisfied postoperatively, particularly with their ability to perform higher-demand activities including deep-kneeling and step-up where kinematic parameters are more demanding. The purpose of this study was to examine the relationship between knee kinematics of step-up and deep-kneeling and patient-reported outcome measures following TKA. METHODS: Sixty-four patients were included at minimum 1-year follow-up. Participants performed a step-up and deep-kneeling task which was imaged via single-plane fluoroscopy. 3-dimensional prosthesis computer-aided design models were registered to the fluoroscopy, yielding in-vivo kinematic data. Associations between kinematics and patient-reported outcome measures, including Oxford Knee Score, American Knee Society Score, surgical satisfaction, and pain were assessed using log-transformed step-wise linear regressions. RESULTS: A higher total Oxford Knee Score was associated with more external rotation and more adduction at maximal flexion during kneeling and more external rotation and minimum flexion during step-up. Improved American Knee Society Score was associated with increased internal-external rotation during step-up. Improved surgical satisfaction was associated with greater maximum flexion and more external rotation at maximal flexion during deep-kneeling and more femoral internal rotation at terminal extension during step-up. An improved pain score was associated with greater maximum flexion and more femoral external rotation during deep-kneeling, as well as greater internal femoral rotation during step-up. CONCLUSION: The ability to move through full flexion/extension range and end-of-range rotation is important kinematic parameters that influence patient-reported outcome measures. Implant designs and postoperative rehabilitation should continue to focus on achieving these kinematic targets for enhanced outcomes after TKA.

A higher plant FAD synthetase is fused to an inactivated FAD pyrophosphatase.

The riboflavin derivatives FMN and flavin adenine dinucleotide (FAD) are critical cofactors for wide-ranging biological processes across all kingdoms of life. Although it is well established that these flavins can be readily interconverted, in plants, the responsible catalysts and regulatory mechanisms remain poorly understood. Here, we report the cloning and biochemical characterization of an FAD synthetase encoded by the gene At5g03430, which we have designated AtFADS1 (A. thaliana FADS1). The catalytic properties of the FAD synthetase activity are similar to those reported for other FAD synthetases, except that we observed maximum activity with Zn2+ as the associated divalent metal cation. Like human FAD synthetase, AtFADS1 exists as an apparent fusion with an ancestral FAD pyrophosphatase, a feature that is conserved across plants. However, we detected no pyrophosphatase activity with AtFADS1, consistent with an observed loss of a key catalytic residue in higher plant evolutionary history. In contrast, we determined that algal FADS1 retains both FAD synthetase and pyrophosphatase activity. We discuss the implications, including the potential for yet-unstudied biologically relevant noncatalytic functions, and possible evolutionary pressures that have led to the loss of FAD pyrophosphatase activity, yet universal retention of an apparently nonfunctional domain in FADS of land plants.

Streptococcus pneumoniae serotyping and antimicrobial susceptibility: assessment for vaccine efficacy in Canada after the introduction of PCV13.

BACKGROUND: Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries. OBJECTIVES: To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines. METHODS: SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation. RESULTS: The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020). CONCLUSIONS: The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Shape modelling of the oropharynx distinguishes associations with body morphology but not whiplash-associated disorder.

Characterization of the oropharynx, a subdivision of the pharynx between the soft palate and the epiglottis, is limited to simple measurements. Structural changes in the oropharynx in whiplash-associated disorder (WAD) cohorts have been quantified using two-dimensional (2D) and three-dimensional (3D) measures but the results are inconsistent. Statistical shape modelling (SSM) may be a more useful tool for systematically comparing morphometric features between cohorts. This technique has been used to quantify the variability in boney and soft tissue structures, but has not been used to examine a hollow cavity such as the oropharynx. The primary aim of this project was to examine the utility of SSM for comparing the oropharynx between WAD cohorts and control; and WAD severity cohorts. The secondary aim was to determine whether shape is associated with sex, height, weight and neck length. Magnetic resonance (MR) T1-weighted images were obtained from healthy control (n = 20), acute WAD (n = 14) and chronic WAD (n = 14) participants aged 18-39 years. Demographic, WAD severity (neck disability index) and body morphometry data were collected from each participant. Manual segmentation of the oropharynx was undertaken by blinded researchers between the top of the soft palate and tip of the epiglottis. Digital 3D oropharynx models were constructed from the segmented images and principal component (PC) analysis was performed with the PC weights normalized to z-scores for consistency. Statistical analyses were undertaken using multivariate linear models. In the first statistical model the independent variable was group (acute WAD, chronic WAD, control); and in the second model the independent variable was WAD severity (recovered/mild, moderate/severe). The covariates for both models included height, weight, average neck length and sex. Shape models were constructed to visualize the effect of perturbing these covariates for each relevant mode. The shape model revealed five modes which explained 90% of the variance: mode 1 explained 59% of the variance and primarily described differences in isometric size of the oropharynx, including elongation; mode 2 (13%) primarily described lateral (width) and AP (depth) dimensions; mode 3 (8%) described retroglossal AP dimension; mode 4 (6%) described lateral dimensions at the retropalatal-retroglossal junction and mode 5 (4%) described the lateral dimension at the inferior retroglossal region. There was no difference in shape (mode 1 p = 0.52; mode 2 p = 0.96; mode 3 p = 0.07; mode 4 p = 0.54; mode 5 p = 0.74) between control, acute WAD and chronic WAD groups. There were no statistical differences for any mode (mode 1 p = 0.12; mode 2 p = 0.29; mode 3 p = 0.56; mode 4 p = 0.99; mode 5 p = 0.96) between recovered/mild and moderate/severe WAD. Sex was not significant in any of the models but for mode 1 there was a significant association with height (p = 0.007), mode 2 neck length (p = 0.044) and in mode 3 weight (p = 0.027). Although SSM did not detect differences between WAD cohorts, it did detect associations with body morphology indicating that it may be a useful tool for examining differences in the oropharynx.

Adaptive mechanisms of plant specialized metabolism connecting chemistry to function.

As sessile organisms, plants evolved elaborate metabolic systems that produce a plethora of specialized metabolites as a means to survive challenging terrestrial environments. Decades of research have revealed the genetic and biochemical basis for a multitude of plant specialized metabolic pathways. Nevertheless, knowledge is still limited concerning the selective advantages provided by individual and collective specialized metabolites to the reproductive success of diverse host plants. Here we review the biological functions conferred by various classes of plant specialized metabolites in the context of the interaction of plants with their surrounding environment. To achieve optimal multifunctionality of diverse specialized metabolic processes, plants use various adaptive mechanisms at subcellular, cellular, tissue, organ and interspecies levels. Understanding these mechanisms and the evolutionary trajectories underlying their occurrence in nature will ultimately enable efficient bioengineering of desirable metabolic traits in chassis organisms.

Cuticle thickness affects dynamics of volatile emission from petunia flowers.

The plant cuticle is the final barrier for volatile organic compounds (VOCs) to cross for release to the atmosphere, yet its role in the emission process is poorly understood. Here, using a combination of reverse-genetic and chemical approaches, we demonstrate that the cuticle imposes substantial resistance to VOC mass transfer, acting as a sink/concentrator for VOCs and hence protecting cells from the potentially toxic internal accumulation of these hydrophobic compounds. Reduction in cuticle thickness has differential effects on individual VOCs depending on their volatility, and leads to their internal cellular redistribution, a shift in mass transfer resistance sources and altered VOC synthesis. These results reveal that the cuticle is not simply a passive diffusion barrier for VOCs to cross, but plays the aforementioned complex roles in the emission process as an integral member of the overall VOC network.

Statistical shape modelling reveals differences in hamstring morphology between professional rugby players and sprinters.

Hamstring morphology may play an important role in understanding the aetiology of hamstring injury. Currently, the methods available to capture detailed morphological data such as muscle shape have not been utilized for the hamstring muscles. The aim of this study was to examine the utility of statistical shape modelling (SSM) for describing and comparing hamstring muscle shape in rugby and sprinting athletes. Magnetic resonance images of both thighs of nine elite male rugby players and nine track and field sprinters were analysed. Images were converted to three-dimensional models enabling generation of four statistical shape models. Principal components describing the shape variation in the cohort were derived and evaluated. Six principal components were sufficient to discriminate differences in the shape of the hamstring muscles of rugby and sprinting athletes with 89% classification accuracy. Distinct shape features distinguishing rugby players from sprinters included size, curvature and axial torsion. These data demonstrate that SSM is useful for understanding hamstring muscle shape and that meaningful variation can be identified within a small sample. This method can be used in future research to enhance the anatomical specificity of musculoskeletal modelling and to understand the relationship between hamstring shape and injury.

Overexpression of arogenate dehydratase reveals an upstream point of metabolic control in phenylalanine biosynthesis.

Out of the three aromatic amino acids, the highest flux in plants is directed towards phenylalanine, which is utilized to synthesize proteins and thousands of phenolic metabolites contributing to plant fitness. Phenylalanine is produced predominantly in plastids via the shikimate pathway and subsequent arogenate pathway, both of which are subject to complex transcriptional and post-transcriptional regulation. Previously, it was shown that allosteric feedback inhibition of arogenate dehydratase (ADT), which catalyzes the final step of the arogenate pathway, restricts flux through phenylalanine biosynthesis. Here, we show that in petunia (Petunia hybrida) flowers, which typically produce high phenylalanine levels, ADT regulation is relaxed, but not eliminated. Moderate expression of a feedback-insensitive ADT increased flux towards phenylalanine, while high overexpression paradoxically reduced phenylalanine formation. This reduction could be partially, but not fully, recovered by bypassing other known metabolic flux control points in the aromatic amino acid network. Using comparative transcriptomics, reverse genetics, and metabolic flux analysis, we discovered that transcriptional regulation of the d-ribulose-5-phosphate 3-epimerase gene in the pentose phosphate pathway controls flux into the shikimate pathway. Taken together, our findings reveal that regulation within and upstream of the shikimate pathway shares control over phenylalanine biosynthesis in the plant cell.

The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.

Modulation of auxin formation by the cytosolic phenylalanine biosynthetic pathway.

In plants, phenylalanine biosynthesis occurs via two compartmentally separated pathways. Overexpression of petunia chorismate mutase 2 (PhCM2), which catalyzes the committed step of the cytosolic pathway, increased flux in cytosolic phenylalanine biosynthesis, but paradoxically decreased the overall levels of phenylalanine and phenylalanine-derived volatiles. Concomitantly, the levels of auxins, including indole-3-acetic acid and its precursor indole-3-pyruvic acid, were elevated. Biochemical and genetic analyses revealed the existence of metabolic crosstalk between the cytosolic phenylalanine biosynthesis and tryptophan-dependent auxin biosynthesis mediated by an aminotransferase that uses a cytosolic phenylalanine biosynthetic pathway intermediate, phenylpyruvate, as an amino acceptor for auxin formation.

Pseudomonas aeruginosa Pneumonia: Evolution of Antimicrobial Resistance and Implications for Therapy.

Pseudomonas aeruginosa (PA), a non-lactose-fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of urinary tract, intra-abdominal, wounds, skin/soft tissue, and bloodstream. PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (e.g., urinary or intravascular catheters, foreign bodies). Treatment of pseudomonal infections is difficult, as PA is intrinsically resistant to multiple antimicrobials, and may acquire new resistance determinants even while on antimicrobial therapy. Mortality associated with pseudomonal VAP or bacteremias is high (> 35%) and optimal therapy is controversial. Over the past three decades, antimicrobial resistance (AMR) among PA has escalated globally, via dissemination of several international multidrug resistant "epidemic" clones. We discuss the importance of PA as a cause of pneumonia including health care-associated pneumonia, hospital-acquired pneumonia, VAP, the emergence of AMR to this pathogen, and approaches to therapy (both empirical and definitive).

Infections Due to Acinetobacter baumannii-calcoaceticus Complex: Escalation of Antimicrobial Resistance and Evolving Treatment Options.

Bacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that most often cause infections in nosocomial settings. Community-acquired infections are rare, but may occur in patients with comorbidities, advanced age, diabetes mellitus, chronic lung or renal disease, malignancy, or impaired immunity. Most common sites of infections include blood stream, skin/soft-tissue/surgical wounds, ventilator-associated pneumonia, orthopaedic or neurosurgical procedures, and urinary tract. Acinetobacter species are intrinsically resistant to multiple antimicrobials, and have a remarkable ability to acquire new resistance determinants via plasmids, transposons, integrons, and resistance islands. Since the 1990s, antimicrobial resistance (AMR) has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-ABC strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive antibiotic use amplifies this spread. Many isolates are resistant to all antimicrobials except colistimethate sodium and tetracyclines (minocycline or tigecycline); some infections are untreatable with existing antimicrobial agents. AMR poses a serious threat to effectively treat or prevent ABC infections. Strategies to curtail environmental colonization with MDR-ABC require aggressive infection-control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy with existing antibiotics as well as development of novel antibiotic classes.

Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review.

Importance: Sarcoidosis is an inflammatory granulomatous disease of unknown cause that affects an estimated 2 to 160 people per 100 000 worldwide and can involve virtually any organ. Approximately 10% to 30% of patients with sarcoidosis develop progressive pulmonary disease. Observation: Among patients with pulmonary sarcoidosis, the rate of spontaneous remission without serious sequelae ranges from 10% to 82%. However, lung disease progression occurs in more than 10% of patients and can result in fibrocystic architectural distortion of the lung, which is associated with a mortality rate of 12% to 18% within 5 years. Overall, the mortality rate for sarcoidosis is approximately 7% within a 5-year follow-up period. Worldwide, more than 60% of deaths from sarcoidosis are due to pulmonary involvement; however, more than 70% of deaths from sarcoidosis are due to cardiac involvement in Japan. Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40%. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues. Although optimal doses of oral glucocorticoids for pulmonary sarcoidosis are unknown, oral prednisone typically starting at a dose of 20 mg/d to 40 mg/d for 2 to 6 weeks is recommended for patients who are symptomatic (cough, dyspnea, and chest pain) and have parenchymal infiltrates and abnormal pulmonary function test results. Oral glucocorticoids can be tapered over 6 to 18 months if symptoms, pulmonary function test results, and radiographs improve. Prolonged use of oral glucocorticoids may be required to control symptoms and stabilize disease. Patients without adequate improvement while receiving a dose of prednisone of 10 mg/d or greater or those with adverse effects due to glucocorticoids may be prescribed immunosuppressive agents, such as methotrexate, azathioprine, or an anti-tumor necrosis factor medication, either alone or with glucocorticoids combined with appropriate microbial prophylaxis for Pneumocystis jiroveci and herpes zoster. Effective treatments are not available for advanced fibrocystic pulmonary disease. Conclusions and Relevance: Sarcoidosis has a mortality rate of approximately 7% within a 5-year follow-up period. More than 10% of patients with pulmonary sarcoidosis develop progressive disease and more than 60% of deaths are due to advanced pulmonary sarcoidosis. Oral glucocorticoids with or without another immunosuppressive agent are the first-line therapy for symptomatic patients with abnormal pulmonary function test results and lung infiltrates. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues.

A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.

Glycine receptors (GlyRs) are the major mediators of fast synaptic inhibition in the adult human spinal cord and brainstem. Hereditary mutations to GlyRs can lead to the rare, but potentially fatal, neuromotor disorder hyperekplexia. Most mutations located in the large intracellular domain (TM3-4 loop) of the GlyRα1 impair surface expression levels of the receptors. The novel GLRA1 mutation P366L, located in the TM3-4 loop, showed normal surface expression but reduced chloride currents, and accelerated whole-cell desensitization observed in whole-cell recordings. At the single-channel level, we observed reduced unitary conductance accompanied by spontaneous opening events in the absence of extracellular glycine. Using peptide microarrays and tandem MS-based analysis methods, we show that the proline-rich stretch surrounding P366 mediates binding to syndapin I, an F-BAR domain protein involved in membrane remodeling. The disruption of the noncanonical Src homology 3 recognition motif by P366L reduces syndapin I binding. These data suggest that the GlyRα1 subunit interacts with intracellular binding partners and may therefore play a role in receptor trafficking or synaptic anchoring, a function thus far only ascribed to the GlyRß subunit. Hence, the P366L GlyRα1 variant exhibits a unique set of properties that cumulatively affect GlyR functionality and thus might explain the neuropathological mechanism underlying hyperekplexia in the mutant carriers. P366L is the first dominant GLRA1 mutation identified within the GlyRα1 TM3-4 loop that affects GlyR physiology without altering protein expression at the whole-cell and surface levels.SIGNIFICANCE STATEMENT We show that the intracellular domain of the inhibitory glycine receptor α1 subunit contributes to trafficking and synaptic anchoring. A proline-rich stretch in this receptor domain forms a noncanonical recognition motif important for the interaction with syndapin I (PACSIN1). The disruption of this motif, as present in a human patient with hyperekplexia led to impaired syndapin I binding. Functional analysis revealed that the altered proline-rich stretch determines several functional physiological parameters of the ion channel (e.g., faster whole-cell desensitization) reduced unitary conductance and spontaneous opening events. Thus, the proline-rich stretch from the glycine receptor α1 subunit represents a multifunctional intracellular protein motif.

GluClR-mediated inhibitory postsynaptic currents reveal targets for ivermectin and potential mechanisms of ivermectin resistance.

Glutamate-gated chloride channel receptors (GluClRs) mediate inhibitory neurotransmission at invertebrate synapses and are primary targets of parasites that impact drastically on agriculture and human health. Ivermectin (IVM) is a broad-spectrum pesticide that binds and potentiates GluClR activity. Resistance to IVM is a major economic and health concern, but the molecular and synaptic mechanisms of resistance are ill-defined. Here we focus on GluClRs of the agricultural endoparasite, Haemonchus contortus. We demonstrate that IVM potentiates inhibitory input by inducing a tonic current that plateaus over 15 minutes and by enhancing post-synaptic current peak amplitude and decay times. We further demonstrate that IVM greatly enhances the active durations of single receptors. These effects are greatly attenuated when endogenous IVM-insensitive subunits are incorporated into GluClRs, suggesting a mechanism of IVM resistance that does not affect glutamate sensitivity. We discovered functional groups of IVM that contribute to tuning its potency at different isoforms and show that the dominant mode of access of IVM is via the cell membrane to the receptor.

Natural fumigation as a mechanism for volatile transport between flower organs.

Plants synthesize volatile organic compounds (VOCs) to attract pollinators and beneficial microorganisms, to defend themselves against herbivores and pathogens, and for plant-plant communication. In general, VOCs accumulate in and are emitted from the tissue of their biosynthesis. However, using biochemical and reverse genetic approaches, we demonstrate a new physiological phenomenon: inter-organ aerial transport of VOCs via natural fumigation. Before petunia flowers open, a tube-specific terpene synthase produces sesquiterpenes, which are released inside the buds and then accumulate in the stigma, potentially defending the developing stigma from pathogens. These VOCs also affect reproductive organ development and seed yield, which are previously unknown functions of terpenoid compounds.

A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.

Phospholipids are key components of cellular membranes and are emerging as important functional regulators of different membrane proteins, including pentameric ligand-gated ion channels (pLGICs). Here, we take advantage of the prokaryote channel ELIC (Erwinia ligand-gated ion channel) as a model to understand the determinants of phospholipid interactions in this family of receptors. A high-resolution structure of ELIC in a lipid-bound state reveals a phospholipid site at the lower half of pore-forming transmembrane helices M1 and M4 and at a nearby site for neurosteroids, cholesterol or general anesthetics. This site is shaped by an M4-helix kink and a Trp-Arg-Pro triad that is highly conserved in eukaryote GABAA/C and glycine receptors. A combined approach reveals that M4 is intrinsically flexible and that M4 deletions or disruptions of the lipid-binding site accelerate desensitization in ELIC, suggesting that lipid interactions shape the agonist response. Our data offer a structural context for understanding lipid modulation in pLGICs.

Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment.

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.

Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies.

The primary factor that limits long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD continues to evolve. Consensus definitions of CLAD and the major CLAD phenotypes were recently updated and clarified, but it remains to be seen whether the current definitions will lead to advances in management or impact care. Understanding the potential differences in pathogenesis for each CLAD phenotype may lead to novel therapeutic strategies, including precision medicine. Recognition of CLAD risk factors may lead to earlier interventions to mitigate risk, or to avoid risk factors all together, to prevent the development of CLAD. Unfortunately, currently available therapies for CLAD are usually not effective. However, novel therapeutics aimed at both prevention and treatment are currently under investigation. We provide an overview of the updates to CLAD-related terminology, clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential strategies to treat and prevent CLAD.

Influence of component design on in vivo tibiofemoral contact patterns during kneeling after total knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Modern TKR prostheses are designed to restore healthy kinematics including high flexion. Kneeling is a demanding high-flexion activity. There have been many studies of kneeling kinematics using a plethora of implant designs but no comprehensive comparisons. Visualisation of contact patterns allows for quantification and comparison of knee kinematics. The aim of this systematic review was to determine whether there are any differences in the kinematics of kneeling as a function of TKR design. METHODS: A search of the published literature identified 26 articles which were assessed for methodologic quality using the MINORS instrument. Contact patterns for different implant designs were compared at 90° and maximal flexion using quality-effects meta-analysis models. RESULTS: Twenty-five different implants using six designs were reported. Most of the included studies had small-sample sizes, were non-consecutive, and did not have a direct comparison group. Only posterior-stabilised fixed-bearing and cruciate-retaining fixed-bearing designs had data for more than 200 participants. Meta-analyses revealed that bicruciate-stabilised fixed-bearing designs appeared to achieve more flexion and the cruciate-retaining rotating-platform design achieved the least, but both included single studies only. All designs demonstrated posterior-femoral translation and external rotation in kneeling, but posterior-stabilised designs were more posterior at maximal flexion when compared to cruciate retaining. However, the heterogeneity of the mean estimates was substantial, and therefore, firm conclusions about relative behaviour cannot be drawn. CONCLUSION: The high heterogeneity may be due to a combination of variability in the kneeling activity and variations in implant geometry within each design category. There remains a need for a high-quality prospective comparative studies to directly compare designs using a common method. LEVEL OF EVIDENCE: Systematic review and meta-analysis Level IV.