Withdrawal of Immunomodulators or TNF Antagonists in Patients With Inflammatory Bowel Diseases in Remission on Combination Therapy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy. METHODS: Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence. RESULTS: We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy. CONCLUSIONS: In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.

The role of chest X-rays when screening for latent tuberculosis infection in patients with inflammatory bowel disease before starting biologic treatment.

BACKGROUND: Guidelines generally recommend a combination of immunological assays and chest X-ray imaging (CXR) when screening for latent tuberculosis infection (LTBI) prior to biologic treatment in inflammatory bowel disease (IBD). OBJECTIVE: To investigate whether CXR identify patients with suspected LTBI/TB who were not identified with QuantiFERON tests (QFT) when screening for LTBI/TB before starting biologic treatment in IBD patients. METHODS: Single-center, retrospective cohort study of patients with inflammatory bowel disease who had a QFT and a CXR prior to initiation of biologic treatment in a 5-year period (October 1st, 2017 to September 30th, 2022). RESULTS: 520 patients (56% female, mean age 40.1 years) were included. The majority had none or few risk factors for TB (as reflected by the demographic characteristics) but some risk factors for having false negative QFT results (concurrent glucocorticoid treatment and inflammatory activity). QFT results were positive in 8 patients (1.5%), inconclusive in 18 (3.5%) and negative in 494 (95.0%). Only 1 patient (0.19%) had CXR findings suspicious of LTBI. This patient also had a positive QFT and was subsequently diagnosed with active TB. All patients with negative or inconclusive QFT had CXR without any findings suggesting LTBI/TB. One patient developed active TB after having initiated biologic treatment in spite of having negative QFT and a normal CXR at screening. CONCLUSION: In a population with low risk of TB, the benefits of supplementing the QFT with a CXR are limited and are unlikely to outweigh the cost in both patient test-burden, radioactive exposure, and economic resources.

Epidemiology of pediatric spinal trauma with neurological deficits in Catalonia: a 36-year experience.

PURPOSE: Existing literature on pediatric traumatic spinal cord injury (PTSCI) demonstrates large variations in characteristics, incidence, time-periods and etiology, worldwide. Epidemiological studies addressing injuries to the total spine, conducted in Southern European regions are remarkably scarce; therefore we aimed to investigate long-term trends analyzing etiology, fracture location and type, single or multiple fractures, associated lesions and neurological status in Catalonia, Spain. METHODS: We conducted a retrospective observational study. We analyzed post-acute patients after PTSCI, aged 0-17, admitted with neurological deficits between 1986 and 2022 to a specialized hospital in Catalonia. Neurological deficits were assessed using the American Spinal Injury Association Impairment Scale (AIS). RESULTS: Two hundred and forty nine children were included, 174 (69.9%) boys and 75 (30.1%) girls; mean age was 13.9 years (range, 2 months to 17 years). Two hundred and four children (82%) had ≥ 1 spinal fractures, 66 (26.5%) dislocations and 8 (3.2%) SCIWORA. Fractures were multilevel contiguous in 108 (43.4%) cases. Fracture types comprised 81 vertebral compactions (32.5%), 22 burst fractures (8.8%), 7 odontoid (2.8%) and 4 tear-drops (1.6%). There were ≥ 1 associated lesions in 112 cases (45%): in limbs in 23 cases (9.2%), thorax or abdomen in 59 (23.7%) and skull or face in 81 (32.5%). In 44 cases (39% of the 112) there were multiple lesions. Locations comprised cervical spine in 105 cases (42%), thoracic spine in 124 (49%), lumbar spine in 18 (7%), and sacrum in 2 (0.8%). Road traffic accidents (RTAs) were the main etiology (62.2%) over the whole period. However, from 2016 onwards, RTAs dropped below the rate of falls and sports injuries. The most common sites for injury in those aged 9 years or older were in the cervical (41.1%) and thoracic (50.7%) regions. Those aged 8 or under were far more likely to sustain a complete SCI (80.0%) or an accompanying traumatic brain injury (45.0%) likely due to higher numbers of pedestrian versus car RTAs. A significant peak in the occurrence of cases during 2006-2010 (20.1%) was identified with an absolute drop immediately after, during 2011-2015 (8.8%). A marked shift in trend is observed between 2016-2022 regarding age of injuries (an increase in 9 years or older), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical versus lumbar and thoracic injuries). CONCLUSIONS: A shift in trend is observed in the past 7 years regarding age of injuries (increase in those older than 9), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical). LEVEL OF EVIDENCE: IV.

Electron circular dichroism in hot electron emission from metallic nanohelix arrays.

We investigate the electron emission from 3D chiral silver alloy nanohelices initiated by femtosecond laser pulses with a central photon energy of hν = 1.65 eV, well below the work function of the material. We find hot but thermally distributed electron spectra and a strong anisotropy in the electron yield with left- and right-circularly polarized light excitations, which invert in sign between left- and right-handed helices. We analyze the kinetic energy distribution and discuss the role of effective temperatures. Measurements of the reflectance and simulations of the absorbance of the helices based on retarded field calculations are compared to the anisotropy in photoemission. We find a significant enhancement of the anisotropy in the electron emission in comparison to the optical absorption. Neither simple thermionic nor a multiphoton photoemission can explain the experimentally observed asymmetries. Single photon deep-UV photoemission from these helices together with a change of the work function suggests a contribution of the chirally induced spin selectivity effect to the observed asymmetries.

Falls During Inpatient Rehabilitation After Spinal Cord Injury: Characterization, Clock-Hour Visualization, and Time to Event Predictors.

OBJECTIVES: To (1) determine fall characteristics (eg, cause, location, witnesses) of inpatients with spinal cord injury (SCI) and whether they were different for ambulatory persons vs wheelchair users; (2) visualize the total number of daily falls per clock-hour for different inpatients' features (eg, cause of injury, age); (3) compare clinical and demographic characteristics of inpatients who experienced a first fall event vs inpatients who did not experience such event; and (4) identify first fall event predictors. DESIGN: Retrospective observational cohort study. SETTING: Institution for inpatient neurologic rehabilitation. PARTICIPANTS: Persons with SCI (N=1294) admitted to a rehabilitation facility between 2005 and 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional independence measure (FIM), Hospital Anxiety and Depression Scale (HADS), American Spinal Injury Association Impairment Scale (AIS), and Spinal Cord Independence Measure (SCIM) at admission. Kaplan-Meier survival curves and Cox proportional hazards models were used. RESULTS: A total of 502 fall events were experienced by 369 ambulatory inpatients (19.8%) and wheelchair users (80.2%) in 63.9% of cases being alone, with cause, situation, and location significantly different in both groups. Clock-hour visualizations revealed an absolute peak at 12 AM (complete or incomplete injuries, with paraplegia or tetraplegia) but a relative peak at 9 AM mainly including incomplete patients with paraplegia. Of the (n=1294) included patients, 16.8% experienced at least 1 fall. Fallen patients reported higher levels of HADS depression, lower total SCIM, and longer time since injury to admission, with no differences in age, sex, educational level, FIM (quasi-significant), and AIS grade. Multivariable Cox proportional hazards identified time since injury to admission and AIS grade D as significant predictors of first fall event. CONCLUSIONS: Falls identification, characterization, and clock-hour visualization can support decisions for mitigation strategies specifically addressed to inpatients with SCI. Fall predictors were identified as a first step for future research.

From harmful nutrients to ultra-processed foods: exploring shifts in 'foods to limit' terminology used in national food-based dietary guidelines.

OBJECTIVE: The choice of terms used to describe 'foods to limit' (FTL) in food-based dietary guidelines (FBDG) can impact public understanding, policy translation and research applicability. The choice of terms in FBDG has been influenced by available science, values, beliefs and historical events. This study aimed to analyse the terms used and definitions given to FTL in FBDG around the world, including changes over time and regional differences. DESIGN: A review of terms used to describe FTL and their definitions in all current and past FBDG for adults was conducted, using a search strategy informed by the FAO FBDG website. Data from 148 guidelines (96 countries) were extracted into a pre-defined table and terms were organised by the categories 'nutrient-based', 'food examples' or 'processing-related'. SETTING: National FBDG from all world regions. PARTICIPANTS: None. RESULTS: Nutrient-based terms (e.g. high-fat foods) were the most frequently used type of term in both current and past dietary guidelines (91 %, 85 %, respectively). However, food examples (e.g. cakes) and processing-related terms (e.g. ultra-processed foods) have increased in use over the past 20 years and are now often used in conjunction with nutrient-based terms. Regional differences were only observed for processing-related terms. CONCLUSION: Diverse, and often poorly defined, terms are used to describe FTL in FBDG. Policymakers should ensure that FTL terms have clear definitions and can be integrated with other disciplines and understood by consumers. This may facilitate the inclusion of the most contemporary and potentially impactful terminology in nutrition research and policies.

Multicentric investigation on the safety, feasibility and usability of the ABLE lower-limb robotic exoskeleton for individuals with spinal cord injury: a framework towards the standardisation of clinical evaluations.

BACKGROUND: Robotic lower-limb exoskeletons have the potential to provide additional clinical benefits for persons with spinal cord injury (SCI). However, high variability between protocols does not allow the comparison of study results on safety and feasibility between different exoskeletons. We therefore incorporated key aspects from previous studies into our study protocol and accordingly conducted a multicentre study investigating the safety, feasibility and usability of the ABLE Exoskeleton in clinical settings. METHODS: In this prospective pretest-posttest quasi-experimental study across two SCI centres in Germany and Spain, in- and outpatients with SCI were recruited into a 12-session training and assessment protocol, utilising the ABLE Exoskeleton. A follow-up visit after 4 weeks was included to assess after-training outcomes. Safety outcomes (device-related adverse events (AEs), number of drop-outs), feasibility and usability measures (level of assistance, donning/doffing-time) were recorded at every session together with changes in gait parameters and function. Patient-reported outcome measures including the rate of perceived exertion (RPE) and the psychosocial impact of the device were performed. Satisfaction with the device was evaluated in both participants and therapists. RESULTS: All 24 participants (45 ± 12 years), with mainly subacute SCI (< 1 year after injury) from C5 to L3, (ASIA Impairment Scale A to D) completed the follow-up. In 242 training sessions, 8 device-related AEs (pain and skin lesions) were reported. Total time for don and doff was 6:50 ± 2:50 min. Improvements in level of assistance and gait parameters (time, steps, distance and speed, p < 0.05) were observed in all participants. Walking function and RPE improved in participants able to complete walking tests with (n = 9) and without (n = 6) the device at study start (p < 0.05). A positive psychosocial impact of the exoskeleton was reported and the satisfaction with the device was good, with best ratings in safety (participants), weight (therapists), durability and dimensions (both). CONCLUSIONS: Our study results prove the feasibility of safe gait training with the ABLE Exoskeleton in hospital settings for persons with SCI, with improved clinical outcomes after training. Our study protocol allowed for consistent comparison of the results with other exoskeleton trials and can serve as a future framework towards the standardisation of early clinical evaluations. Trial Registration https://trialsearch.who.int/ , DRKS00023503, retrospectively registered on November 18, 2020.

Hip arthroscopy for femoroacetabular impingement is associated with significant improvement in early patient reported outcomes: analysis of 4963 cases from the UK non-arthroplasty registry (NAHR) dataset.

PURPOSE: Results from recent randomised controlled trials demonstrate the superiority of surgery over physiotherapy in patients with femoroacetabular impingement (FAI) of the hip in early follow-up. However, there is paucity of evidence regarding which factors influence outcomes of FAI surgery, particularly notable is the lack of information on the effect of impingement subtype (cam or pincer or mixed) on patient reported outcomes measures (PROMs). This study aims to evaluate the early outcomes of hip arthroscopy for FAI, and their determinants. METHODS: This is a retrospective analysis of prospectively collected data from the UK Non-Arthroplasty Hip Registry (NAHR) of patients undergoing arthroscopic intervention for FAI between 2012 and 2019. The null hypothesis was that there is no difference in PROMs, based on morphological subtype of FAI treated or patient characteristics, at each follow-up timepoint. The outcome measures used for the study were the iHOT-12 score and the EQ5D Index and VAS 6- and 12-month follow-up. RESULTS: A cohort of 4963 patients who underwent arthroscopic treatment of FAI were identified on the NAHR database. For all FAI pathology groups, there was significant improvement from pre-operative PROMs when compared to those at 6 and 12 months. Overall, two-thirds of patients achieved the minimum clinically important difference (MCID), and almost half achieved substantial clinical benefit (SCB) for iHOT-12 by 12 months. Pre-operatively, and at 12-month follow-up, iHOT-12 scores were significantly poorer in the pincer group compared to the cam and mixed pathology groups (p < 0.01). Multivariable analysis revealed PROMS improvement in the setting of a higher-grade cartilage lesion. CONCLUSION: This registry study demonstrates that hip arthroscopy is an effective surgical treatment for patients with symptomatic FAI and results in a statistically significant improvement in PROMs which are maintained through 12 months follow-up. LEVEL OF EVIDENCE: III.

Tele-rehabilitation on independence in activities of daily living after stroke: A Matched Case-Control Study.

OBJECTIVES: To compare independence in activities of daily living (ADLs) in post-acute patients with stroke following tele-rehabilitation and matched in-person controls. MATERIALS AND METHODS: Matched case-control study. A total of 35 consecutive patients with stroke who followed tele-rehabilitation were compared to 35 historical in-person patients (controls) matched for age, functional independence at admission and time since injury to rehabilitation admission (<60 days). The tele-rehabilitation group was also compared to the complete cohort of historical controls (n=990). Independence in ADLs was assessed using the Functional Independence Measure (FIM) and the Barthel Index (BI). We formally compared FIM and BI gains calculated as discharge score - admission scores, efficiency measured as gains / length of stay and effectiveness defined as (discharge score-admission score)/ (maximum score-admission score). We analyzed the minimal clinically important difference (MCID) for FIM and BI. RESULTS: The groups showed no significant differences in type of stroke (ischemic or hemorrhagic), location, severity, age at injury, length of stay, body mass index, diabetes, dyslipidemia, hypertension, aphasia, neglect, affected side of the body, dominance or educational level. The groups showed no significant differences in gains, efficiency nor effectiveness either using FIM or Barthel Index. We identified significant differences in two specific BI items (feeding and transfer) in favor of the in-person group. No differences were observed in the proportion of patients who achieved MCID. CONCLUSIONS: No significant differences were seen between total ADL scores for tele-rehabilitation and in-person rehabilitation. Future research studies should analyze a combined rehabilitation approach that utilizes both models.

Inpatient Rehabilitation Falls: Comparing Patients With Traumatic Brain Injury Versus Patients With Stroke.

BACKGROUND: Cognitively impaired neurological rehabilitation inpatients are at an increased risk for falls; yet, little is known regarding fall risk of different groups, such as stroke versus traumatic brain injury. OBJECTIVES: To determine if rehabilitation patients' fall characteristics differ for patients with stroke versus patients with traumatic brain injury. METHODS: This retrospective observational cohort study evaluates inpatients with stroke or traumatic brain injury admitted to a rehabilitation center in Barcelona, Spain, between 2005 and 2021. We assessed independence in daily activities with the Functional Independence Measure. We compared fallen versus nonfallen patients' features and examined the association between time to first fall and risk using Cox proportional hazards models. RESULTS: A total of 1,269 fall events were experienced by 898 different patients with traumatic brain injury ( n = 313; 34.9%) and stroke ( n = 585; 65.1%). A higher proportion of falls for patients with stroke occurred while performing rehabilitation activities (20.2%-9.8%), whereas falls were significantly higher for patients with traumatic brain injury during the night shift. Fall timing revealed completely different behaviors (stroke vs. traumatic brain injury), for example, an absolute peak at 6 a.m. due to young male traumatic patients. Nonfallen patients ( n = 1,363; 78.2%) were younger, with higher independence in daily activities scores, and having a larger time since injury to admission; all three were significant fall predictors. CONCLUSIONS: Patients with traumatic brain injury and stroke showed different fall behaviors. Knowledge of fall patterns and characteristics in the inpatient rehabilitation setting can help design management protocols to mitigate their risk.

HIV-1 bispecific antibody iMab-N6 exhibits enhanced breadth but not potency over its parental antibodies iMab and N6.

The recently published AMP trial (HVTN 703/HPTN 081 and HVTN704/HPTN 085) results have validated broad neutralising antibodies (bNAbs) as potential anti-HIV-1 agents. However, single bNAb preparations are unlikely to cope with the onslaught of existing and de novo resistance mutations, thus necessitating the use of bNAb combinations to achieve clinically relevant results. Specifically engineered antibodies incorporating two bNAbs into a single antibody structure have been developed. These bispecific antibodies (bibNAbs) retain the benefits of bNAb combinations, whilst several conformations exhibit improved neutralisation potency over the parental bNAbs. Here we report on the engineering of a bibNAb comprising of an HIV-1 spike targeting bNAb N6 and a host CD4 targeting antibody ibalizumab (iMab). Antibodies were expressed in HEK293T cells and purified by protein-A affinity chromatography followed by size exclusion chromatography to achieve homogenous, monomeric, bibNAb preparations. Antibody purity was confirmed by SDS-PAGE whilst epitope specificity and binding were confirmed by ELISA. Finally, antibody breadth and potency data were generated by HIV-1 neutralisation assay (n = 21, inclusive of the global panel). iMab-N6 exhibited better neutralisation breadth (100% coverage) in comparison to its parental bNAbs iMab (90%) and N6 (95%). This is encouraging as exceptional neutralisation breadth is necessary for HIV-1 treatment or prevention. Unfortunately, iMab-N6 did not exhibit any enhancement in potency over the most potent parental antibody, iMab (p = 0.1674, median IC50 of 0.0475 µg/ml, and 0.0665 µg/ml respectively) or the parental combination, iMab + N6 (p = 0.1964, median IC50: combination 0.0457 µg/ml). This result may point to a lack of dual engagement of the bibNAb Fab moieties necessary for potency enhancement. Against the previously reported bibNAbs; iMab-CAP256, 10E08-iMab, and PG9-iMab; iMab-N6 was the lowest performing bibNAb. The re-engineering of iMab-N6 to enhance its potency, while retaining breadth, is a worthwhile endeavour due to its clinical potential.

A systematic monitoring approach to biologic therapies in inflammatory bowel disease: patients' and physicians' preferences and adherence.

OBJECTIVES: Treatment of patients with inflammatory bowel disease (IBD) should aim at achieving mucosal healing. However, monitoring schedules to support this goal remain undefined. We aimed to identify patients' and physicians' preferences regarding monitoring strategy and investigated the feasibility of such a strategy. METHODS: Elements considered relevant for monitoring were identified in questionnaire surveys among 1) patients with IBD receiving biologic agents (n = 172) and 2) their physicians (n = 87). Adherence to a monitoring strategy incorporating these elements was investigated in a retrospective cohort of patients with IBD treated with biologic agents (n = 139). RESULTS: Patients considered blood and stool samples, endoscopies, and magnetic resonance imaging (MRI) to be relevant aspects of monitoring their disease. However, patients also considered stool samples and endoscopies unpleasant. Physicians considered blood samples (99%), medical consultations (99%), fecal calprotectin (85%), endoscopy (78%), and MRI (71%) to be important aspects of IBD monitoring but considered endoscopies and MRI relevant only at clinical signs of relapse. A review of the clinical use of monitoring strategies including the elements identified above revealed high adherence for blood samples and disease activity indices (92%), but low adherence for fecal calprotectin (38%), therapeutic drug monitoring (38%), and endoscopies (32%). CONCLUSION: Important tools for evaluating mucosal healing (e.g., endoscopy) were rated highly unpleasant by patients, and physicians found endoscopies/MRI relevant only in case of relapse. These findings were reflected by low rates of adherence to use of these monitoring tools. In defining monitoring schedules to help achieve treatment goals, these important barriers must be addressed.

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics.

BACKGROUND: Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy. METHODS: Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue. RESULTS: Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies. CONCLUSION: Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

Holograms for acoustics.

Holographic techniques are fundamental to applications such as volumetric displays, high-density data storage and optical tweezers that require spatial control of intricate optical or acoustic fields within a three-dimensional volume. The basis of holography is spatial storage of the phase and/or amplitude profile of the desired wavefront in a manner that allows that wavefront to be reconstructed by interference when the hologram is illuminated with a suitable coherent source. Modern computer-generated holography skips the process of recording a hologram from a physical scene, and instead calculates the required phase profile before rendering it for reconstruction. In ultrasound applications, the phase profile is typically generated by discrete and independently driven ultrasound sources; however, these can only be used in small numbers, which limits the complexity or degrees of freedom that can be attained in the wavefront. Here we introduce monolithic acoustic holograms, which can reconstruct diffraction-limited acoustic pressure fields and thus arbitrary ultrasound beams. We use rapid fabrication to craft the holograms and achieve reconstruction degrees of freedom two orders of magnitude higher than commercial phased array sources. The technique is inexpensive, appropriate for both transmission and reflection elements, and scales well to higher information content, larger aperture size and higher power. The complex three-dimensional pressure and phase distributions produced by these acoustic holograms allow us to demonstrate new approaches to controlled ultrasonic manipulation of solids in water, and of liquids and solids in air. We expect that acoustic holograms will enable new capabilities in beam-steering and the contactless transfer of power, improve medical imaging, and drive new applications of ultrasound.

What are the benefits and risks of nutrition policy actions to reduce added sugar consumption? An Australian case study.

OBJECTIVE: This study aimed to critically analyse Australia's current and proposed policy actions to reduce added sugar consumption. Over-consumption of added sugar is a significant public health nutrition issue. The competing interests, values and beliefs among stakeholders mean they have disparate views regarding which policy actions are preferable to reduce added sugar consumption. DESIGN: Semi-structured interviews using purposive, snowball sampling and policy mapping. Policy actions were classified by two frameworks: NOURISHING (e.g. behaviour change communication, food environment and food system) and the Orders of Change (e.g. first order: technical adjustments, second order: reforming the system, third order: transforming the system). SETTING: Australia. PARTICIPANTS: Twenty-two stakeholders from the food industry, food regulation, government, public health groups and academia. RESULTS: All proposed and existing policy actions targeted the food environment/behaviour change; most were assessed as first-order changes, and reductionist (nutrient specific) in nature. Influences on policy actions included industry power, stakeholder fragmentation, government ideology/political will and public pressure. Few stakeholders considered potential risks of policy actions, particularly of non-nutritive sweetener substitution or opportunity costs for other policies. CONCLUSIONS: Most of Australia's policy actions to reduce added sugar consumption are reductionist. Preferencing nutrient specific, first-order policy actions could reflect the influence of vested interests, a historically dominant reductionist orientation to nutrition science and policy, and the perceived difficulty of pursuing second- or third-order changes. Pursuing only first-order policy actions could lead to 'regrettable' substitutions and creates an opportunity cost for more comprehensive policy aimed at adjusting the broader food system.

Clinical Prediction Rule Validation for Ambulation Outcome After Traumatic Spinal Cord Injury in a Spanish Population.

BACKGROUND: Predicting the ability to walk after traumatic spinal cord injury is of utmost importance in the clinical setting. Nevertheless, only a small fraction of predictive models are evaluated on their performance by other authors using external data. The Dutch Clinical Prediction Rule for long-term walking ability was developed and validated using neurological assessments performed within 15 days postinjury. However, in reality, this assessment is most often performed between 11 and 55 days. When considering a longer time from injury to neurological assessments, the Dutch Clinical Prediction Rule has only been externally validated for patients after non-traumatic spinal cord injury. OBJECTIVE: We aimed to validate the Dutch Clinical Prediction Rule with neurological assessment performed within 3-90 days after traumatic spinal cord injury, using (a) the Dutch Clinical Prediction Rule logistic regression coefficients (Equation 1); (b) the Dutch Clinical Prediction Rule weighted coefficients (Equation 2); and (c) the reestimated (using a Spanish population) weighted coefficients (Equation 3). METHODS: We conducted a retrospective (STROBE-compliant) study involving 298 adults with traumatic spinal cord injury admitted to a hospital between 2010 and 2019 in Spain. The Spinal Cord Independence Measure item-12 was used for walking assessment. RESULTS: Using Equation 1, the model yielded 86.2% overall classification accuracy, 94.5% sensitivity, and 83.4% specificity (area under the curve [AUC] = 0.939, 95% confidence interval [CI]: 0.915-0.965; p < .001).Using Equation 2 yielded 86.2% overall classification accuracy, 93.2% sensitivity, and 83.9% specificity (AUC = 0.9392, 95% CI: 0.914-0.964; p < .001).Using Equation 3 yielded 86.9% overall classification accuracy, 68.9% sensitivity, and 92.8% specificity (AUC = 0.939, 95% CI: 0.914-0.964; p < .001). CONCLUSIONS: This study validates the Dutch Clinical Prediction Rule in a Spanish traumatic spinal cord injury population with assessments performed up to 90 days postinjury with similar performance, using the original coefficients and including a reestimation of the coefficients.

Mass Spectrometry Reveals New Insights into the Production of Superoxide Anions and 4-Hydroxynonenal Adducted Proteins in Human Sperm.

The free-radical theory of male infertility suggests that reactive oxygen species produced by the spermatozoa themselves are a leading cause of sperm dysfunction, including loss of sperm motility. However, the field is overshadowed on several fronts, primarily because: i) the probes used to measure reactive oxygen species (ROS) are imprecise; and ii) many reports suggesting that oxygen radicals are detrimental to sperm function add an exogenous source of ROS. Herein, a more reliable approach to measure superoxide anion production by human spermatozoa based on MS analysis is used. Furthermore, the formation of the lipid-peroxidation product 4-hydroxynonenal (4-HNE) during in vitro incubation using proteomics is also investigated. The data demonstrate that neither superoxide anion nor other free radicals that cause 4-HNE production are related to the loss of sperm motility during incubation. Interestingly, it appears that many of the 4-HNE adducted proteins, found within spermatozoa, originate from the prostate. A quantitative SWATH analysis demonstrate that these proteins transiently bind to sperm and are then shed during in vitro incubation. These proteomics-based findings propose a revised understanding of oxidative stress within the male reproductive tract.

Engineering and characterising a novel, highly potent bispecific antibody iMab-CAP256 that targets HIV-1.

The existing repertoire of HIV-1 patient derived broadly neutralising antibodies (bNAbs) that target the HIV-1 envelope glycoprotein (Env) present numerous and exciting opportunities for immune-based therapeutic and preventative strategies against HIV-1. Combination antibody therapy is required to ensure greater neutralization coverage and limit Env mediated escape mutations following treatment pressure. Engineered bispecific bNAbs (bibNAbs) assimilate the advantages of combination therapy into a single antibody molecule with several configurations reporting potency enhancement as a result of the increased avidity and simultaneous engagement of targeted epitopes. We report the engineering of a novel bibNAb (iMab-CAP256) comprising the highly potent, CAP256.VRC26.25 bNAb with anticipated extension in neutralization coverage through pairing with the host directed, anti-CD4 antibody, ibalizumab (iMab). Recombinant expression of parental monoclonal antibodies and the iMab-CAP256 bibNAb was performed in HEK293T (Human embryonic kidney 293 T antigen) cells, purified to homogeneity by Protein-A affinity chromatography followed by size exclusion chromatography. Antibody assembly and binding functionality of Fab moieties was confirmed by SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) and ELISA, respectively. Breadth and potency were evaluated against a geographical diverse HIV-1 pseudovirus panel (n = 20). Overall, iMab-CAP256 demonstrated an expanded neutralizing coverage, neutralizing single, parental antibody resistant pseudovirus strains and an enhanced neutralization potency against all dual sensitive strains (average fold increase over the more potent parental antibody of 11.4 (range 2 to 31.8). Potency enhancement was not observed for the parental antibody combination treatment (iMab + CAP256) suggesting the presence of a synergistic relationship between the CAP256 and iMab paratope combination in this bibNAb configuration. In addition, iMab-CAP256 bibNAbs exhibited comparable efficacy to other bibNAbs PG9-iMab and 10E08-iMab previously reported in the literature. The enhanced neutralization coverage and potency of iMAb-CAP256 over the parental bNAbs should facilitate superior clinical performance as a therapeutic or preventative strategy against HIV-1.

Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital Mycoplasma genitalium infection.

BACKGROUND: Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. OBJECTIVES: To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. METHODS: A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. RESULTS: M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. CONCLUSION: A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

Intermolecular Forces Model for Lipid Microbubble Shells.

Lipid-coated microbubbles are currently used clinically as ultrasound contrast agents for echocardiography and radiology and are being developed for many new diagnostic and therapeutic applications. Accordingly, there is a growing need to engineer specific formulations by employing rational design to guide lipid selection and processing. This approach requires a quantitative relationship between lipid chemistry and interfacial properties of the microbubble shell. Just such a model is proposed here on the basis of lateral Coulomb and van der Waals interactions between lipid head- and tailgroups, using previous coarse graining and force fields developed for molecular dynamics simulations. The model predicts with sufficient accuracy the monolayer permeability, the elasticity as a function of either lipid composition or temperature, and the equilibrium spreading surface tension of the lipid onto an air/water interface. In the future, the intermolecular forces model could be employed to elucidate more complex phenomena and to engineer novel microbubble formulations.