Marine Proteobacteria metabolize glycolate via the ß-hydroxyaspartate cycle.

One of the most abundant sources of organic carbon in the ocean is glycolate, the secretion of which by marine phytoplankton results in an estimated annual flux of one petagram of glycolate in marine environments1. Although it is generally accepted that glycolate is oxidized to glyoxylate by marine bacteria2-4, the further fate of this C2 metabolite is not well understood. Here we show that ubiquitous marine Proteobacteria are able to assimilate glyoxylate via the ß-hydroxyaspartate cycle (BHAC) that was originally proposed 56 years ago5. We elucidate the biochemistry of the BHAC and describe the structure of its key enzymes, including a previously unknown primary imine reductase. Overall, the BHAC enables the direct production of oxaloacetate from glyoxylate through only four enzymatic steps, representing-to our knowledge-the most efficient glyoxylate assimilation route described to date. Analysis of marine metagenomes shows that the BHAC is globally distributed and on average 20-fold more abundant than the glycerate pathway, the only other known pathway for net glyoxylate assimilation. In a field study of a phytoplankton bloom, we show that glycolate is present in high nanomolar concentrations and taken up by prokaryotes at rates that allow a full turnover of the glycolate pool within one week. During the bloom, genes that encode BHAC key enzymes are present in up to 1.5% of the bacterial community and actively transcribed, supporting the role of the BHAC in glycolate assimilation and suggesting a previously undescribed trophic interaction between autotrophic phytoplankton and heterotrophic bacterioplankton.

The Effect of Knee Height Asymmetry on Gait Biomechanics.

BACKGROUND: Though the primary goal for limb length discrepancy (LLD) management is to equalize the leg lengths, symmetry between corresponding long bones is usually not achieved, leading to knee height asymmetry (KHA). To date, there is minimal information on what effect KHA has on gait biomechanics and joint loading. Thus, the purpose of this study is to determine the impact of KHA on gait biomechanics. METHODS: Seventeen subjects with KHA after limb equalizing surgery and 10 healthy controls were enrolled. Subjects participated in 3D gait analysis collected using self-selected speed. Lower extremity kinematics, kinetics, work generated/absorbed, and total work were calculated. Standing lower limb x-rays and scanograms were used to measure LLD and calculate the tibia-to-femur (TF) ratio for each limb. Two sample t tests were used to compare differences in standing LLD, TF ratio, and work between groups. Bivariate correlation using Pearson correlation coefficients was conducted between TF ratio and total mechanical work, as well as between knee height asymmetry indices and total work asymmetry (α=0.05). RESULTS: Among participants, there were no differences between LLD; however, there were differences between TF ratio and knee height asymmetry. We found a nonsignificant relationship between TF ratio and total mechanical work for individual lower extremities. Therefore, the length of individual bones (TF ratio) relative to each other within the individual lower extremity was not associated with the amount of work produced. However, when a difference exists between sides (asymmetry, ie, TF ratio asymmetry), there were associated differences in work (work asymmetry) produced between sides (r=0.54, P=0.003). In other words, greater knee height asymmetry between limbs resulted in more asymmetrical mechanical work during walking. CONCLUSIONS: These findings may have implications for the management of LLD. Asymmetrical total mechanical work could lead to atypical joint loading during gait. Surgeons may want to consider prioritizing achieving knee height symmetry as a postoperative goal when correcting limb length discrepancy. LEVEL OF EVIDENCE: Level III, Case Control Study.

[Chronic cough in adult patients-evidence-based approach]. / Chronischer Husten bei erwachsenen Patienten ­ evidenzbasiertes Vorgehen.

Approximately 10% of the population suffer from a cough lasting longer than 8 weeks. Compared to acute cough, which usually occurs in the context of banal respiratory tract infections, the differential diagnoses of chronic cough require an increased use of diagnostic tests and thus a structured, evidence-based approach according to current international guidelines. A targeted history (smoking status, medication, previous diseases) and ENT status are always followed by chest x­ray and pulmonary function tests before extended diagnostics. In the case of angiotensin-converting enzyme (ACE) inhibitor use and unremarkable physical examination, a drug discontinuation test can be carried out first. In case of inconspicuous findings, a disease entity that can be treated empirically such as upper airway cough syndrome is most likely. If the cough remains unexplained, cough suppression techniques, physiotherapy or speech therapy should be sought before off-label-use of medication.

A multicenter study to evaluate pain characteristics in osteogenesis imperfecta.

The objective was to describe pain characteristics and treatments used in individuals with varying severity of osteogenesis imperfecta (OI) and investigate pain-associated variables. This work was derived from a multicenter, longitudinal, observational, natural history study of OI conducted at 12 clinical sites of the NIH Rare Diseases Clinical Research Network's Brittle Bone Disorders Consortium. Children and adults with a clinical, biochemical, or molecular diagnosis of OI were enrolled in the study. We did a cross-sectional analysis of chronic pain prevalence, characteristics, and treatments used for pain relief and longitudinal analysis to find the predictors of chronic pain. We included 861 individuals with OI, in 41.8% chronic pain was present, with similar frequency across OI types. Back pain was the most frequent location. Nonsteroidal anti-inflammatory drugs followed by bisphosphonates were the most common treatment used. Participants with chronic pain missed more days from school or work/year and performed worse in all mobility metrics than participants without chronic pain. The variables more significantly associated with chronic pain were age, sex, positive history of rodding surgery, scoliosis, other medical problems, assistive devices, lower standardized height, and higher body mass index. The predictors of chronic pain for all OI types were age, use of a wheelchair, and the number of fractures/year. Chronic pain is prevalent in OI across all OI types, affects mobility, and interferes with participation. Multiple covariates were associated with chronic pain.

Do Bisphosphonates Alleviate Pain in Children? A Systematic Review.

PURPOSE OF REVIEW: The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement. RECENT FINDINGS: We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension. Only 38% of studies used validated tools; visual analogue scale was the most frequently employed. BPs were used to alleviate bone pain in a wide variety of pediatrics conditions such as osteogenesis imperfecta, secondary osteoporosis, osteonecrosis related to chemotherapy, chronic non-bacterial osteitis, idiopathic juvenile osteoporosis, unresectable benign bone tumor, and cancer-related pain. Twenty of the 24 studies reported a positive effect of BPs for alleviating pain in different pathologies, but 58% of the studies were categorized as having high risk of bias. Intravenous BPs are helpful in alleviating bone pain in children and adolescents. It is advised that our results be interpreted with caution due to the heterogeneity of the doses used, duration of treatments, and types of pathologies included. In addition, this review shows the paucity of high-quality evidence in the available literature and further research is needed. TRIAL REGISTRATION: Before the completion of this review, the protocol was registered to PROSPERO (International prospective register of systematic reviews), PROSPERO 2020 ID # CRD42020158316. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158316.

Mobility in osteogenesis imperfecta: a multicenter North American study.

PURPOSE: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder that causes bone fragility. Phenotypic severity influences ability to walk, however, little is known about ambulatory characteristics of individuals with OI, especially in more severe forms. The purpose of this work was to characterize mobility in OI using standard clinical assessment tools and determine if patient characteristics could be used to predict mobility outcomes. METHODS: We collected mobility data at five clinical sites to analyze the largest cohort of individuals with OI (n = 491) to date. Linear mixed models were developed to explore relationships among subject demographics and mobility metrics. RESULTS: Results showed minor limitations in the mild group while the more severe types showed more significant limitations in all mobility metrics analyzed. Height and weight were shown to be the most significant predictors of mobility. Relationships with mobility and bisphosphonates varied with OI type and type used (oral/IV). CONCLUSION: These results are significant to understanding mobility limitations of specific types of OI and beneficial when developing rehabilitation protocols for this population. It is important for physicians, patients, and caregivers to gain insight into severity and classification of the disease and the influence of disease-related characteristics on prognosis for mobility.

Polysaccharide utilisation loci of Bacteroidetes from two contrasting open ocean sites in the North Atlantic.

Marine Bacteroidetes have pronounced capabilities of degrading high molecular weight organic matter such as proteins and polysaccharides. Previously we reported on 76 Bacteroidetes-affiliated fosmids from the North Atlantic Ocean's boreal polar and oligotrophic subtropical provinces. Here, we report on the analysis of further 174 fosmids from the same libraries. The combined, re-assembled dataset (226 contigs; 8.8 Mbp) suggests that planktonic Bacteroidetes at the oligotrophic southern station use more peptides and bacterial and animal polysaccharides, whereas Bacteroidetes at the polar station (East-Greenland Current) use more algal and plant polysaccharides. The latter agrees with higher abundances of algae and terrigenous organic matter, including plant material, at the polar station. Results were corroborated by in-depth bioinformatic analysis of 14 polysaccharide utilisation loci from both stations, suggesting laminarin-specificity for four and specificity for sulfated xylans for two loci. In addition, one locus from the polar station supported use of non-sulfated xylans and mannans, possibly of plant origin. While peptides likely represent a prime source of carbon for Bacteroidetes in open oceans, our data suggest that as yet unstudied clades of these Bacteroidetes have a surprisingly broad capacity for polysaccharide degradation. In particular, laminarin-specific PULs seem widespread and thus must be regarded as globally important.

THA Retrievals: The Need to Mark the Anatomic Orientation of the Femoral Head.

The hypothesis of this study was that the rotational orientation of femoral head damage would greatly affect the volumetric wear rate of the opposing polyethylene (PE) liner. Damage on twenty retrieved cobalt-chromium femoral heads was simulated in a validated damage-feature-based finite element model. For each individual retrieval, the anatomic orientation of the femoral head about the femoral neck axis was systematically varied, in 30° increments. The PE wear rate differential between the maximum- versus minimum-wear orientations was often sizable, as high as 7-fold. Knowing the correct femoral head anatomic orientation is therefore important when analyzing the effects of femoral head damage on PE liner wear. Surgeons retrieving modular femoral heads should routinely mark the anatomic orientation of those components.

Modeling polyethylene wear acceleration due to femoral head dislocation damage.

Scratching, scraping, and metal transfer to femoral heads commonly accompany acetabular shell contact during dislocation and closed reduction maneuvers. While head damage conceptually leads to accelerated wear, reports on this subject are mainly anecdotal, and differ widely on the potency of such effect. Towards better understanding this relationship, a physically validated finite element (FE) model was used to compute polyethylene wear acceleration propensity of specific head damage patterns on thirteen retrievals. These FE models estimated wear increases averaging half an order of magnitude when compared to simulations for undamaged heads. There was no correlation between the number of dislocations sustained and wear acceleration. These results underscore the importance of implant-gentle closed reduction, and heightened wear monitoring of successfully reduced dislocation patients.

Recommendation of minimal distal tibial length for long axis coordinate system definitions.

Accurate anatomical coordinate systems for the foot and ankle are critical for interpreting their complex biomechanics. The tibial superior-inferior axis is crucial for analyzing joint kinematics, influencing bone motion analysis during gait using CT imaging and biplane fluoroscopy. However, the lack of consensus on how to define the tibial axis has led to variability in research, hindering generalizability. Even as advanced imaging techniques evolve, including biplane fluoroscopy and weightbearing CT, there exist limitations to imaging the entire foot together with the full length of the tibia. These limitations highlight the need to refine axis definitions. This study investigated various superior-inferior axes using multiple distal tibia lengths to determine the minimal field of view for representing the full tibia long-axis. Twenty human cadaver tibias were imaged and segmented to generate 3D bone models. Axes were calculated based on coordinate definitions that required user manual input, and a gold standard mean superior-inferior axis was calculated based on the population's principal component analysis axis. Four manually calculated superior-inferior tibial axes groups were established based on landmarks and geometric fittings. Statistical analysis revealed that geometrically fitting a cylinder 1.5 times the mediolateral tibial width, starting 5 cm above the tibial plafond, yielded the smallest angular deviation from the gold standard. From these findings, we recommend a minimum field of view that includes 1.5 times the mediolateral tibial width, starting 5 cm above the tibial plafond for tibial long-axis definitions. Implementing these findings will help improve foot and ankle research generalizability and impact clinical decisions.

Creating an autoencoder single summary metric to assess gait quality to compare surgical outcomes in children with cerebral palsy: The Shriners Gait Index (SGI).

Gait for individuals with movement disorders varies widely and the variability makes it difficult to assess outcomes of surgical and therapeutic interventions. Although specific joints can be assessed by fewer individual measures, gait depends on multiple parameters making an overall assessment metric difficult to determine. A holistic, summary measure can permit a standard comparison of progress throughout treatments and interventions, and permit more straightforward comparison across varied subjects. We propose a single summary metric (the Shriners Gait Index (SGI)) to represent the quality of gait using a deep learning autoencoder model, which helps to capture the nonlinear statistical relationships among a number of disparate gait metrics. We utilized gait data of 412 individuals under the age of 18 collected from the Motion Analysis Center (MAC) at the Shriners Children's - Chicago. The gait data includes a total of 114 features: temporo-spatial parameters (7), lower extremity kinematics (64), and lower extremity kinetics (43) which were min-max normalized. The developed SGI score captured more than 89% variance of all 144 features using subject-wise cross-validation. Such summary metrics holistically quantify an individual's gait which can then be used to assess the impact of therapeutic interventions. The machine learning approach utilized can be leveraged to create such metrics in a variety of contexts depending on the data available. We also utilized the SGI to compare overall changes to gait after surgery with the goal of improving mobility for individuals with gait disabilities such as Cerebral Palsy.

Enhancing damage visibility on metallic bearing surfaces: a simple technique for photography and viewing.

Damage to metallic bearing surfaces typically involves scratches, scrapes, metal transfer, and organic deposits. This damage can cause accelerated wear of the opposing surface and subsequent implant failure. Photography and viewing of metallic bearing surfaces, for documenting this damage, are hindered by optical reflectivity. This note demonstrates a simple, practical technique for metallic bearing surface photography and viewing that minimizes this reflectivity problem, that does not involve any modification of the bearing surface, and that allows for improved observation and documentation of overall damage. When the metallic bearing surface is placed within a tube of translucent material, the appearance of damage on that bearing surface is dramatically enhanced, showing up against a smooth, even background with excellent contrast and with fine detail achievable.

Biomechanical Implications of Congenital Conditions of the Foot/Ankle.

Segmental foot and ankle models are often used as part of instrumented gait analysis when planning interventions for complex congenital foot conditions. More than 40 models have been used for clinical analysis, and it is important to understand the technical differences among models. These models have been used to improve clinical planning of pediatric foot conditions including clubfoot, planovalgus, and equinovarus. They have also been used to identify clinically relevant subgroups among pediatric populations, quantify postoperative outcomes, and explain variability in healthy populations.

Comparing genomes recovered from time-series metagenomes using long- and short-read sequencing technologies.

BACKGROUND: Over the past years, sequencing technologies have expanded our ability to examine novel microbial metabolisms and diversity previously obscured by isolation approaches. Long-read sequencing promises to revolutionize the metagenomic field and recover less fragmented genomes from environmental samples. Nonetheless, how to best benefit from long-read sequencing and whether long-read sequencing can provide recovered genomes of similar characteristics as short-read approaches remains unclear. RESULTS: We recovered metagenome-assembled genomes (MAGs) from the free-living fraction at four-time points during a spring bloom in the North Sea. The taxonomic composition of all MAGs recovered was comparable between technologies. However, differences consisted of higher sequencing depth for contigs and higher genome population diversity in short-read compared to long-read metagenomes. When pairing population genomes recovered from both sequencing approaches that shared ≥ 99% average nucleotide identity, long-read MAGs were composed of fewer contigs, a higher N50, and a higher number of predicted genes when compared to short-read MAGs. Moreover, 88% of the total long-read MAGs carried a 16S rRNA gene compared to only 23% of MAGs recovered from short-read metagenomes. Relative abundances for population genomes recovered using both technologies were similar, although disagreements were observed for high and low GC content MAGs. CONCLUSIONS: Our results highlight that short-read technologies recovered more MAGs and a higher number of species than long-read due to an overall higher sequencing depth. Long-read samples produced higher quality MAGs and similar species composition compared to short-read sequencing. Differences in the GC content recovered by each sequencing technology resulted in divergences in the diversity recovered and relative abundance of MAGs within the GC content boundaries.

Automatic anatomical foot and ankle coordinate toolbox.

Accurate analysis of bone position and orientation in foot and ankle studies relies on anatomical coordinate systems (ACS). Reliable ACSs are necessary for many biomechanical and clinical studies, especially those including weightbearing computed tomography and biplane fluoroscopy. Existing ACS approaches suffer from limitations such as manual input, oversimplifications, or non-physiological methods. To address these shortcomings, we introduce the Automatic Anatomical Foot and Ankle Coordinate Toolbox (AAFACT), a MATLAB-based toolbox that automates the calculation of ACSs for the major fourteen foot and ankle bones. In this manuscript, we present the development and evaluation of AAFACT, aiming to provide a standardized coordinate system toolbox for foot and ankle studies. The AAFACT was evaluated using a dataset of fifty-six models from seven pathological groups: asymptomatic, osteoarthritis, pilon fracture, progressive collapsing foot deformity, clubfoot, Charcot Marie Tooth, and cavovarus. Three analyses were conducted to assess the reliability of AAFACT. Firstly, ACSs were compared between automatically and manually segmented bone models to assess consistency. Secondly, ACSs were compared between individual bones and group mean bones to assess within-population precision. Lastly, ACSs were compared between the overall mean bone and group mean bones to assess the overall accuracy of anatomical representation. Statistical analyses, including statistical shape modeling, were performed to evaluate the reliability, accuracy, and precision of AAFACT. The comparison between automatically and manually segmented bone models showed consistency between the calculated ACSs. Additionally, the comparison between individual bones and group mean bones, as well as the comparison between the overall mean bone and group mean bones, revealed accurate and precise ACSs calculations. The AAFACT offers a practical and reliable solution for foot and ankle studies in clinical and engineering settings. It accommodates various foot and ankle pathologies while accounting for bone morphology and orientation. The automated calculation of ACSs eliminates the limitations associated with manual input and non-physiological methods. The evaluation results demonstrate the robustness and consistency of AAFACT, making it a valuable tool for researchers and clinicians. The standardized coordinate system provided by AAFACT enhances comparability between studies and facilitates advancements in foot and ankle research.

[Sore Throat - Guideline-based Diagnostics and Therapy]. / Halsschmerzen ­ leitlinienbasierte Diagnostik und Therapie.

Background: Sore throat is a common reason for consultation of family physicians. Acute sore throat (< 14 days) is usually triggered by infections of the pharynx. Less than 35 % of cases are caused by bacterial infections; nevertheless, antibiotics are prescribed far more often. Evidence-based guideline recommendations are available to reduce non-indicated administration of antibiotics in the treatment of sore throat. Search Methods: Update of the clinical guideline "sore throat" of the German College of General Practitioners and Family Physicians (DEGAM) by means of a systematic search of the literature for international guidelines and systematic reviews. Main Messages: After excluding red flags such as immunosuppression and severe systemic infections, acute sore throat is usually self-limiting with a mean duration of 7 days. Patients should be encouraged in self-management; ibuprofen and naproxen are recommended for symptomatic treatment. If antibiotics are considered, clinical scores (Centor, McIsaac, FeverPAIN) should be used to assess the risk of bacterial pharyngitis. At low risk (< 3 points), antibiotics are not indicated; if at least moderate (3 points), delayed prescription is an option; if high (> 3 points), antibiotics can be taken immediately. Even if scores suggestive a bacterial cause, the evidence suggests that antibiotic treatment only shortens the duration of symptoms modestly. Penicillin is the first choice (clarithromycin as an alternative). The antibiotic should be taken for 5-7 days. Conclusions: In the absence of red flags, a regular use of symptomatic treatment will help to control discomfort. If administration of antibiotics is still considered a risk-adapted approach, using clinical scores is recommended.

[Acute and chronic cough - differential diagnosis and treatment]. / Akuter und chronischer Husten ­ Differenzialdiagnose und Behandlung.

Cough is a frequent reason for consultation in the general practitioner's office. Most of the time, the symptom is harmless and self-limiting, as in the case of a banal cold cough, for example - however, serious diseases such as malignancies can also be the cause. Evaluation is therefore not always easy. This article presents a targeted and appropriate approach and discusses which treatments are recommended and effective.Acute and chronic cough are differentiated according to the duration of symptoms (up to 8 weeks/longer than 8 weeks). The most common cause of acute cough is a self-limiting viral infection of the upper respiratory tract; the most important differential diagnosis is community-acquired pneumonia. If there are no defined warning signs (red flags), the history and clinical examination are sufficient to establish the diagnosis in the case of an acute cough; medication is not necessary. In the case of a chronic cough, a chest X-ray is usually ordered and then further investigations are carried out in accordance with the most probable suspected diagnosis; probationary therapies are an important part of the workup. Coughs that are refractory to treatment or unexplained require individualised treatment (pharmacological, including off-label, non-pharmacological) and regular re-evaluation.

[Acute Cough in Adult Patients]. / Akuter Husten bei erwachsenen Patient*innen.

Background: Acute cough (< 8 weeks) is a frequent complaint in family practice consultations. The most common cause are respiratory infections. The Guideline "Acute and chronic cough" of the German College of General Practitioners and Family Physicians (DEGAM) was updated in 2021 and contains recommendations for an evidence-based approach for the management of acute cough in primary care. Methods: The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed by an interdisciplinary guideline committee and agreed by formal consensus. Results: History-taking, exclusion of red flags and a physical examination are the basis of diagnostic evaluation. If an acute, uncomplicated bronchitis is likely, no laboratory tests, sputum diagnostics, or chest x-rays should be performed, and antibiotics should not be administered. Evidence based strategies to avoid antibiotic therapy (delayed prescribing, shared decision making, point-of-care-tests) can be used. There is inadequate evidence for the efficacy of antitussive or expectorant drugs against acute cough. The state of the evidence for phytotherapeutic agents is heterogeneous; clinical importance is minimal. COVID-19 should currently be considered in cases of acute respiratory symptoms. If specific symptoms or red flags occur, further diagnoses in the context of acute cough such as community-acquired pneumonia, influenza disease and exacerbations of chronic respiratory diseases (bronchial asthma, COPD) should be taken into consideration. Conclusions: These evidence-based recommendations are intended to reduce the use of antibiotics to treat colds and acute bronchitis, for which they are not indicated. Further clinical trials of symptomatic treatments for cough should be performed in order to extend the evidence base.

What are the long-term outcomes of lateral column lengthening for pes planovalgus in cerebral palsy?

BACKGROUND: Lateral column lengthening (LCL) is commonly performed on children and adolescents with cerebral palsy (CP) for correction of pes planovalgus (PPV). There are limited reports of the long-term outcomes of this procedure. The purpose of this study was to examine the long-term results of LCL for correction of PPV in individuals with CP by evaluating subjects when they had transitioned to adulthood and were entering the workforce. METHODS: Clinical assessments, quantitative gait analysis including the Milwaukee Foot Model (MFM) for segmental foot kinematics, and patient reported outcomes were collected from 13 participants with CP treated with LCL for PPV in childhood (average age 24.4 ± 5.7 years, average 15.3 ± 8.5 years since LCL). Additionally, 27 healthy adults average age 24.5 ± 3.6 years functioned as controls. RESULTS: Strength and joint range of motion were reduced in the PPV group (p < 0.05). Sixty nine percent showed operative correction of PPV based on radiologic criteria. Gait analysis showed reduced walking speed and stride length, as well as midfoot break and residual forefoot abduction. Patient reported outcomes indicated that foot pain was not the only factor that caused limited activity and participation. LCL surgery for PPV in childhood resulted in long-term operative correction. Decreased ankle passive range of motion and strength, subtalar joint arthritic changes, inefficient and less stable ambulation, and problems with participation (difficulties in physical function, education, and employment) were observed in the long-term. CONCLUSION: This study identified postoperative impairments and limitations to guide future clinical decision-making. These results provide clinicians and researchers the common residual and recurrent issues for these individuals as they age. The inclusion of contextual factors that influence the disease and impairments can equip these individuals with enhanced skills they need as they transition into adulthood.