Understanding Physician Preferences About Combined Thrombolysis and Thrombectomy in Patients with Large Vessel Occlusion: An International Cross-Sectional Survey.

BACKGROUND: A recently published individual participant-level meta-analysis found that EVT alone was not non-inferior to combined intravenous thrombolysis (IVT) and EVT. Our aim was to determine factors that influence physicians' treatment choice of IVT-alone versus EVT-alone versus a combined approach. METHODS: We performed an international, structured, invite-only survey among physicians treating patients presenting with AIS. Respondents were asked 16 multiple choice questions. Fourteen questions involved the respondent being provided with a clinical scenario. In each scenario, a patient was presenting with an AIS with LVO, varying a single clinical or imaging feature. RESULTS: A total of 282 stroke physicians (mean age 46 years, 75% males) participated in the survey. In LVO stroke, eligible for both IVT and EVT, without other qualifiers, 220 (85.9%) respondents chose to pursue a combined approach. For age over 80 years, 191 (74%) participants opted for combined approach, which decreased to 121 (48.2%) with dementia and 148 (57.4%) if the patient was on dual anti-platelet therapy (DAPT). Of respondents choosing combination therapy in a patient above the age of 80, only 105 (56.8%) would pursue the same in a patient with dementia. For imaging factors, 177 (72.8%) opted for a combined approach for intracranial carotid occlusion, which decreased to 160 (65.3%) in tandem occlusions. Overall, 88 (38%) respondents agreed to the statement "I am uncomfortable with uncertainty in patient care". CONCLUSIONS: In a typical patient with AIS due to LVO, most respondents still choose a combined revascularization approach but discrepancy in decision-making increases in complex scenarios.

On the theory of multi-target coded sources for high-energy, high-resolution, and high-brightness x-ray radiography.

X-ray radiography is a ubiquitous diagnostic technique in high energy density (HED) physics, with point projection backlighting commonly used for characterizing static and dynamic objects at high spatial and temporal resolutions. These are typically constrained in attainable resolution by their decrease in brightness, which is a limiting factor for high-Z HED experiments, such as double-shell implosions at the National Ignition Facility (NIF) requiring MeV-scale bremsstrahlung sources at high (<50µm) resolution. Coded source imaging is a technique using multiple point-projection sources to produce multiple overlapping radiographs, which are then decoded as a function of the source positions in a process akin to coded aperture imaging. Here, we discuss a new approach to coded source generation using multiple individual small-diameter wire targets within the footprint of a defocused large-scale a0 ≃ 1 laser to produce an MeV-scale high-resolution bright combined source for x-ray radiography. We outline optimal source designs with NIF-Advanced Radiography Capability as the case study, highlight the need for iterative reconstruction decoding, and discuss the research required to demonstrate a robust physical proof-of-concept.

High repetition-rate dual-channel X-ray spectrometer for high-intensity laser-plasma experiments.

We describe the development and demonstration of a high-repetition-rate-capable dual-channel (DC) x-ray spectrometer designed for high-intensity laser-plasma experiments (≥1×1021 W/cm2). The spectrometer, which operates at high repetition rates, is limited only by the refresh rate of targets and the camera's frame rate. It features two channels, each equipped with a flat highly oriented pyrolytic graphite (HOPG) crystal and a unique detector plane, allowing it to resolve two distinct x-ray bands: approximately 7-10 and 10-13 keV. Each detector plate carrier holds two slots for active (scintillators) or passive (imaging plates) x-ray detectors. We present the design and testing of the HR-DC-HOPG using both the COMET laser (10 J, 0.5 ps shot/4 min) at LLNL's Jupiter Laser Facility and the SCARLET laser (10 J, 30 fs shot/min) at Ohio State University. The results demonstrate the spectrometer's performance across various laser energies, target materials, pulse shapes, and detector types.

The development of international wound debridement best practice recommendations: Consensus between nurses specialized in Wound, Ostomy and Continence Canada and the society of tissue viability.

Debridement is an important component of wound management and can improve outcomes for patients. Debridement needs to be done by an appropriately trained health professional, but the scope of practice, credentials, training, competencies, and regulatory requirements regarding wound debridement can differ. Best Practice Recommendations were created to positively influence patient safety related to all methods of debridement, across the continuum of care, and to be implemented widely by nurses at all professional levels in Canada. AIM: To further develop the Best Practice Recommendations for wound debridement, with an international perspective, by creating a consensus document to support the global adoption of evidence-based debridement practice for health professionals. METHODS: A consensus meeting utilising Delphi methods was conducted between the authors to review the consensus statements. Once 80 % agreement was achieved, a wide range of wound care experts were identified by the authors and invited to participate in an external review of the statements. RESULTS: Fifteen consensus statements about wound debridement were agreed upon and are presented in this paper. CONCLUSIONS: These best practice recommendations have been reviewed by a wide range of practitioners from across the UK and Canada and aim to provide guidance on the standardisation of debridement practices for healthcare professionals.

The verification of the utility of a commercially available phantom combination for quality control in contrast-enhanced mammography.

Contrast-enhanced mammography is being increasingly implemented clinically, providing much improved contrast between tumour and background structures, particularly in dense breasts. Although CEM is similar to conventional mammography it differs via an additional exposure with high energy X-rays (≥ 40 kVp) and subsequent image subtraction. Because of its special operational aspects, the CEM aspect of a CEM unit needs to be uniquely characterised and evaluated. This study aims to verify the utility of a commercially available phantom set (BR3D model 020 and CESM model 022 phantoms (CIRS, Norfolk, Virginia, USA)) in performing key CEM performance tests (linearity of system response with iodine concentration and background subtraction) on two models of CEM units in a clinical setting. The tests were successfully performed, yielding results similar to previously published studies. Further, similarities and differences in the two systems from different vendors were highlighted, knowledge of which may potentially facilitate optimisation of the systems.

Systematic review: dorsal bridge plating in distal radius fractures.

PURPOSE: Distal radius fractures are the most common upper limb fractures in adults (up to 18% of all fractures in the Emergency Department). Conservative management is possible for the majority, the preferred surgical technique being volar plate fixation. Dorsal bridge plating (DBP) is an alternative method of treatment for complex fractures. DBP acts as an internal fixator and can be used in patients needing early rehabilitation. This systematic review assesses the demographics, functional and radiological outcomes and complications of using DBP in patients with distal radius fractures compared to volar plate fixation. METHODS: A literature search of PubMed, Cochrane, EMBASE and Google Scholar was performed according to PRISMA guidelines. Seven hundred and sixty-one articles were found; 11 articles met the inclusion criteria. Cadaveric studies and case studies of less than five patients were excluded. Primary outcome measures were functional and radiological outcomes. Complications were recorded as secondary outcomes. RESULTS: Three hundred and ninety-four patients were included in the study with an average age of 54.8 years (53.9% male and 46.1% female). Weighted mean follow-up was 55.2 weeks; the mean time to plate removal was 17.3 weeks with a mean DASH score of 25.7. The weighted range of movement was 46.9° flexion, 48.8° extension, 68.4° pronation and 67.5° supination. The radiological parameters show satisfactory outcomes with a mean radial height of 10mm, volar tilt of 3.1°, ulnar variance of 0.5mm and radial inclination of 18.8°. The complication rate was 11.4%. Digital stiffness was the most common complication but improved if tenolysis was performed at plate removal. CONCLUSIONS: DBP is a good alternative to volar plating for complex distal radius fractures. The functional outcomes showed a slight loss of range of movement, whereas the radiological outcomes were within recommended limits. A significant disadvantage of the plate is the need for further surgical removal.

The effect of age and sex on peak oxygen uptake during upper and lower body exercise: A systematic review.

BACKGROUND: Large scale population norms for peak oxygen uptake (VO2peak) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO2peak obtained during ACE and CE in the same participants. METHOD: The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken. RESULTS: The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO2peak with age during CE was consistent with previous studies. Decreases in VO2peak during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO2peak were considered below the age of 50 years little change was observed for absolute VO2peak during ACE and CE. In contrast, relative VO2peak demonstrated decreases in VO2peak for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO2peak demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO2peak between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age. CONCLUSIONS: These responses suggest that upper body VO2peak decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO2peak may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO2peak results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO2peak and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.

Author Correction: Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 127-136-DOI: 10.26355/eurrev_202312_34697 After publication and following some post-publication concerns, the authors have applied the following corrections to the galley proof. -       The conflict of interest section has been amended as follows: J. Kaftalli and G. Marceddu are employees at MAGI EUREGIO. K. Donato is employee at MAGI EUREGIO and MAGISNAT. M. Bertelli is president of MAGI EUREGIO, MAGISNAT, and MAGI's LAB. G. Bonetti, K. Dhuli, A. Macchia, and P.E. Maltese are employees at MAGI's LAB. M. Bertelli, P.E. Maltese, K. Louise Herbst, Sa. Michelini, Se. Michelini, and P. Chiurazzi are patent inventors (US20220362260A1). M. Bertelli, P.E. Maltese, G. Marceddu are patent inventors (US20230173003A1). M. Bertelli, K. Dhuli and P.E. Maltese are patent inventors (WO2022079498A1). M. Bertelli, P.E. Maltese, Sa. Michelini, Se. Michelini, P. Chiurazzi, K. Louise Herbst, J. Kaftalli, K. Donato, and A. Bernini are patent applicants (Application Number 18/516,241). M. Bertelli, K. Donato, P. Chiurazzi, G. Marceddu, K. Dhuli, G. Bonetti and J. Kaftalli are patent applicants (Application Number: 18/466.879). M. Bertelli, G. Bonetti, G. Marceddu, K. Donato, K. Dhuli, J. Kaftalli, Sa. Michelini, and K. Louise Herbst are patent applicants (Application Number 63/495,155). The remaining authors have no conflict of interest to disclose. -       Figure 5 has been modified as follows to better distinguish outliers: -       The legend of Figure 5 has to be modified as follows: Relative expression of AKR1C1 and AKR1C3 in different groups (CTR = non affected controls, L = lipedema patients without overexpression of AKR1C2, L-over = Lipedema patients with overexpression of AKR1C2), showing that lipedema patients expressed AKR1C1 and AKR1C3 levels similar to the control group. Outliers are reported as black triangles. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34697.

Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.

The influence of fear of falling on the control of upright stance across the lifespan.

BACKGROUND: Standing at height, and subsequent changes in emotional state (e.g., fear of falling), lead to robust alterations in balance in adults. However, little is known about how height-induced postural threat affects balance performance in children. Children may lack the cognitive capability necessary to inhibit the processing of threat and fear-related stimuli, and as a result, may show more marked (and perhaps detrimental) changes in postural control compared to adults. This work explored the emotional and balance responses to standing at height in children, and compared responses to young and older adults. METHODS: Children (age: 9.7 ± 0.8 years, n = 38), young adults (age: 21.8 ± 4.0 years, n = 45) and older adults (age: 73.3 ± 5.0 years, n = 15) stood in bipedal stance in two conditions: at ground level and 80 cm above ground. Centre of pressure (COP) amplitude (RMS), frequency (MPF) and complexity (sample entropy) were calculated to infer postural performance and strategy. Emotional responses were quantified by assessing balance confidence, fear of falling and perceived instability. RESULTS: Young and older adults demonstrated a postural adaptation characterised by increased frequency and decreased amplitude of the COP, in conjunction with increased COP complexity (sample entropy). In contrast, children demonstrated opposite patterns of changes: they exhibited an increase in COP amplitude and decrease in both frequency and complexity when standing at height. SIGNIFICANCE: Children and adults adopted different postural control strategies when standing at height. Whilst young and older adults exhibited a potentially protective "stiffening" response to a height-induced threat, children demonstrated a potentially maladaptive and ineffective postural adaptation strategy. These observations expand upon existing postural threat related research in adults, providing important new insight into understanding how children respond to standing in a hazardous situation.

Developing a Natural History Model for Duchenne Muscular Dystrophy.

BACKGROUND: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD. METHODS: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice. The primary source informing the NHM was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database. This was supplemented with expert input obtained via an elicitation exercise, and a systematic literature review and meta-analysis of mortality data. RESULTS: The NHM includes ambulatory, transfer and non-ambulatory phases, which capture loss of ambulation, ability to weight bear and upper body and respiratory function, respectively. The NHM estimates patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state and the remainder of their lives in non-ambulatory states. Median predicted survival is 34.8 years (95% CI 34.1-35.8). CONCLUSION: The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state. The NHM may be used to estimate the current trajectory of DMD in economic evaluations of new treatments, facilitating inclusion of a lifetime time horizon, and will help identify areas for further research.

Flexible tape-drive target system for secondary high-intensity laser-driven sources.

We present the development of a flexible tape-drive target system to generate and control secondary high-intensity laser-plasma sources. Its adjustable design permits the generation of relativistic MeV particles and x rays at high-intensity (i.e., ≥1 × 1018 W cm-2) laser facilities, at high repetition rates (>1 Hz). The compact and robust structure shows good mechanical stability and a high target placement accuracy (<4 µm RMS). Its compact and flexible design allows for mounting in both the horizontal and vertical planes, which makes it practical for use in cluttered laser-plasma experimental setups. The design permits ∼170° of access on the laser-driver side and 120° of diagnostic access at the rear. A range of adapted apertures have been designed and tested to be easily implemented to the targetry system. The design and performance testing of the tape-drive system in the context of two experiments performed at the COMET laser facility at the Lawrence Livermore National Laboratory and at the Advanced Lasers and Extreme Photonics (ALEPH) facility at Colorado State University are discussed. Experimental data showing that the designed prototype is also able to both generate and focus high-intensity laser-driven protons at high repetition rates are also presented.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 1 - Laparoscopic Greater Curvature Plication.

The long-term effects of bariatric surgery on postprandial profiles in patients with obesity and type 2 diabetes (T2D) have not yet been investigated. Therefore, this study examined postprandial profiles before laparoscopic greater curvature plication (LGCP), and then at 2 and 10 years after surgery.The studied cohort included 10 women (mean age= 54.4±5 years) with obesity (mean BMI= 42.5±7.8 kg/m?) and T2D who underwent LGCP. All subjects underwent a standardized liquid mixed-meal test. For statistical evaluation, ANOVA with Bonferroni multiple comparison was used. Mean postprandial levels were significantly decreased 2 years after surgery. Responses 10 years after the surgery also remained significantly lower than before surgery. Changes observed during the follow-up were significant: glucose: F=34.5, p<0.001; insulin: F=49.3, p<0.001; triglycerides F=9.2, p<0.001. The long-term favorable effects of bariatric surgery on cardiometabolic health may be partly mediated by reductions in postprandial glucose, insulin, and triglyceride levels.

The Endocannabinoid System and Its Relationship to Human Reproduction.

The endocannabinoid system is among the most important regulators of human reproduction. It already applies at the level of the sperm and the egg, plays an important role in the fertilization of the egg, its implantation, regulates the function of the placenta and participates in childbirth. The aim of this work is to summarize the knowledge accumulated so far and to show that the endocannabinoid system must be perfectly regulated in order to maintain a physiological pregnancy from implantation to delivery. Only an exceptional interplay of enzymes such as NAPE-PDL or FAAH, endogenous cannabinoids and cannabinoid receptors CB1 and CB2 can ensure the proper functioning of the reproductive organs and thus lead to delivery on time. Changes in the endocannabinoid system can lead to a number of pathological conditions, e.g., during blastocyst implantation, retardation of embryo development, impaired placental function or miscarriage. Soon, we can expect not only an understanding of all the regulatory events associated with the endocannabinoid system and other regulatory systems that participate in reproduction, but also several possibilities for pharmacotherapeutic interventions that can modify the formation, degradation and effect of endocannabinoids. It cannot be ruled out that some components of the endocannabinoid system could become a marker for monitoring pregnancy and childbirth.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

AKR1C1 and hormone metabolism in lipedema pathogenesis: a computational biology approach.

OBJECTIVE: Lipedema is an autosomal dominant genetic disease that mainly affects women. It is characterized by excess deposition of subcutaneous adipose tissue, pain, and anxiety. The genetic and environmental etiology of lipedema is still largely unknown. Although considered a rare disease, this pathology has been suggested to be underdiagnosed or misdiagnosed as obesity or lymphedema. Steroid hormones seem to be involved in the pathogenesis of lipedema. Indeed, aldo-keto reductase family 1 member C1 (AKR1C1), a gene coding for a protein involved in steroid hormones metabolism, was the first proposed to be correlated with lipedema. PATIENTS AND METHODS: In this study, we employed a molecular dynamics approach to assess the pathogenicity of AKR1C1 genetic variants found in patients with lipedema. Moreover, we combined information theory and structural bioinformatics to identify AKR1C1 polymorphisms from the gnomAD database that could predispose to the development of lipedema. RESULTS: Three genetic variants in AKR1C1 found in patients with lipedema were disruptive to the protein's function. Furthermore, eight AKR1C1  variants found in the general population could predispose to the development of lipedema. CONCLUSIONS: The results of this study provide evidence that AKR1C1 may be a key gene in lipedema pathogenesis, and that common polymorphisms could predispose to lipedema development.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors.

OBJECTIVE: Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. PATIENTS AND METHODS: Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature. RESULTS: Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role. CONCLUSIONS: This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.

Effects of free versus restricted arm movements on postural control in normal and modified sensory conditions in young and older adults.

The purpose of this study was to explore the effects of arm movements on postural control when standing under different sensory conditions in healthy young and older adults. Fifteen young (mean ± SD age; 21.3 ± 4.2 years) and 15 older (mean ± SD age; 73.3 ± 5.0 years) adults completed the modified Romberg test, which uses four task manipulations (i.e. eyes open and eyes closed on a firm and foam surface) to compromise the fidelity of sensory feedback mechanisms. Each participant completed the tasks under two arm movement conditions: restricted and free arm movements. Centre of pressure (COP) range and frequency were calculated to characterise postural performance and strategy, respectively. Older adults showed greater COP range with restricted compared to free arm movements during all modified sensory conditions, with these effects most prominent in the medio-lateral (ML) plane (all p < .05, Cohen's d = 0.69-1.61). Compared to the free arm movement condition, there was an increase in ML displacement and frequency when arm movements were restricted during only the most challenging (i.e. vestibular dominant) task in young adults (all p < .05, d = 0.645-0.83). Finally, main age effects for the arm restriction cost (p < .05) indicates a greater reliance on an upper body strategy in older compared to young adults, independent of sensory availability/accuracy. These findings indicate that older adults compensate for the loss of accuracy in sensory input by increasing reliance on upper body movement strategies.