Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates.

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

Symptomatic Autonomic Dysfunction in Interstitial Cystitis/Bladder Pain Syndrome.

IMPORTANCE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a highly prevalent condition with incompletely understood pathophysiology, especially in relation to the systemic symptoms experienced. The role of autonomic nervous system dysfunction in IC/BPS remains poorly understood. OBJECTIVE: The purpose of this study was to assess the relationship between autonomic symptom severity and clinical characteristics of patients with IC/BPS. STUDY DESIGN: This is a retrospective cohort study of 122 IC/BPS patients who completed the Composite Autonomic Symptoms Score (COMPASS-31) questionnaire. Data were collected on anesthetic bladder capacity (BC), Hunner lesion (HL) status, results for validated IC/BPS symptom questionnaires (O'Leary Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index (ICSI/ICPI) and the Pelvic Pain and Urgency/Frequency (PUF) scale), and comorbid nonurologic associated syndromes. Using the first quartile of COMPASS-31 scores as the cutoff, we compared patients within the first quartile (low symptom load; n = 30), to the remainder of the patients (high symptom load; n = 92). RESULTS: Patients scoring ≥20.36 were significantly less likely to be HL positive (10.9% vs 26.7%; P = 0.043) and had a significantly higher BC (823.10 ± 396.07 vs 635.00 ± 335.06; P = 0.027), higher scores on the PUF questionnaire (23.80 ± 4.98 vs; 19.61 ± 5.22 P < 0.001), and a higher number of nonurologic associated syndromes (5.65 ± 2.90 vs 2.60 ± 1.89; P < 0.001). CONCLUSIONS: Patients with IC/BPS experience widespread symptoms associated with autonomic nervous system dysfunction. A higher symptom load strongly correlates with a nonbladder-centric phenotype. These findings provide further evidence that total body nervous system dysfunction is present in patients with nonbladder centric IC/BPS.

What is the best simulation approach for measuring local density fluctuations near solvo-/hydrophobes?

Measurements of local density fluctuations are crucial to characterizing the interfacial properties of equilibrium fluids. A specific case that has been well-explored involves the heightened compressibility of water near hydrophobic entities. Commonly, a spatial profile of local fluctuation strength is constructed from the measurements of the mean and variance of solvent particle number fluctuations in a set of contiguous subvolumes of the system adjacent to the solvo-/hydrophobe. An alternative measure proposed by Evans and Stewart [J. Phys.: Condens. Matter 27, 194111 (2015)] defines a local compressibility profile in terms of the chemical potential derivative of the spatial number density profile. Using Grand canonical Monte Carlo simulation, we compare and contrast the efficacy of these two approaches for a Lennard-Jones solvent at spherical and planar solvophobic interfaces and SPC/E water at a hydrophobic spherical solute. Our principal findings are as follows: (i) the local compressibility profile χ(r) of Evans and Stewart is considerably more sensitive to variations in the strength of local density fluctuations than the spatial fluctuation profile F(r) and can resolve much more detailed structure; and (ii) while the local compressibility profile is essentially independent of the choice of spatial discretization used to construct the profile, the spatial fluctuation profile exhibits a strong systematic dependence on the size of the subvolumes on which the profile is defined. We clarify the origin and nature of this finite-size effect.

The crystal structure of the human smacovirus 1 Rep domain.

Replication initiator proteins (Reps) from the HUH endonuclease family process specific single-stranded DNA sequences to initiate rolling-circle replication in viruses. Here, the first crystal structure of the apo state of a Rep domain from the smacovirus family is reported. The structure of the human smacovirus 1 Rep domain was obtained at 1.33 Šresolution and represents an expansion of the HUH endonuclease superfamily, allowing greater diversity in bioconjugation-tag applications.

Re: Pentosan polysulfate and a pigmentary maculopathy: causation versus correlation?

How should a conscientious physician advise patients with Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) when they want to know if taking Pentosan Polysulfate Sodium (PPS) will lead to loss of vision? Ever since the initial report from Pearce et al in 2018 suggesting that PPS usage can lead to the development of pigmented maculopathy (PM), my patients have been inundated with solicitations from attorneys looking to sign up clients for class action lawsuits.1 While there have been additional reports suggesting a relationship between PPS exposure and the development of PM, Ludwig et al found that there was no difference in the rate of macular disease between patients with documented IC/BPS who had taken PPS and those with IC/BPS with no history of PPS use.2 The large size of Ludwig's study certainly suggests that PPS may not cause PM to develop, and if the rate of PM in the IC population is higher than in controls, it may be due to the disease itself and not from the medication. In this manuscript, Proctor clearly describes the immune inflammatory response that is responsible for the development of the bladder damage seen with IC/BPS. Also, he describes how inflammatory mediators can enter the blood stream and might be a potential cause for the development of PM.3 This is a thought-provoking hypothesis that demands further evaluation. I have prescribed PPS since its approval and have many patients who feel it is an essential part of their IC treatment regimen. There is no other prescription medication that functions in the same fashion. I require them to follow the FDA recommendations for annual eye exams to look for PM development. I also advise patients that as they improve, we will discuss dose reduction and even discontinuation if their IC symptoms have abated. By following these suggestions, one should be able to continue to prescribe PPS for appropriate patients while carefully monitoring them for PM. I found this article extremely informative and will refer to it when counseling patients about IC/BPS and PPS.

Impact of Porous Silica Nanosphere Architectures on the Catalytic Performance of Supported Sulphonic Acid Sites for Fructose Dehydration to 5-Hydroxymethylfurfural.

5-hydroxymethylfurfural represents a key chemical in the drive towards a sustainable circular economy within the chemical industry. The final step in 5-hydroxymethylfurfural production is the acid catalysed dehydration of fructose, for which supported organoacids are excellent potential catalyst candidates. Here we report a range of solid acid catalysis based on sulphonic acid grafted onto different porous silica nanosphere architectures, as confirmed by TEM, N2 porosimetry, XPS and ATR-IR. All four catalysts display enhanced active site normalised activity and productivity, relative to alternative silica supported equivalent systems in the literature, with in-pore diffusion of both substrate and product key to both performance and humin formation pathway. An increase in-pore diffusion coefficient of 5-hydroxymethylfurfural within wormlike and stellate structures results in optimal productivity. In contrast, poor diffusion within a raspberry-like morphology decreases rates of 5-hydroxymethylfurfural production and increases its consumption within humin formation.

A qualitative study of the perceived benefits of participating in a spinal cord rehabilitation intervention in a low-middle income country.

PURPOSE: Improving quality of life (QoL) is a major goal of rehabilitation following spinal cord injury (SCI). However, people with disabilities in resource constrained contexts have limited access to rehabilitation and poorer health outcomes, including QoL. There is a paucity of qualitative research on the experiences of persons with SCI involved in rehabilitation programmes in low-middle income countries. This study aimed to assess participants' perceptions of the benefits of a 24-week SCI rehabilitation programme delivered as part of a pilot randomized controlled trial (RCT) in South Africa. MATERIALS AND METHODS: Sixteen participants, with chronic motor-incomplete tetraplegia, were enrolled in a two-arm pilot RCT involving robotic locomotor training, a novel technology, and standard activity-based training (Pan African Clinical Trial Registry (PACTR201608001647143)). Data were collected via in-depth interviews and analysed using thematic analysis. RESULTS: Participants described several improvements in QoL, including enhanced functional independence; reduced secondary complications; and improved psychosocial and emotional well-being. CONCLUSIONS: The holistic approach to rehabilitation calls for the involvement of individuals' views about what matters to them to inform clinical practice and to highlight the role that physical activity and the perceived successes play in shaping the lived experiences after SCI. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR201608001647143), registration date (21st May 2016), study start date (30th Nov 2016)https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1647.

Rehabilitation plays an integral role in prompting and integrating positive experiences and changes in QoL for people with spinal cord injury (SCI), especially in a resource constrained context where there is limited opportunity to participate in rehabilitation interventions.Locomotor training and activity-based training can enhance perceived functional independence and psychosocial well-being following SCI.Rather than focus on traditional physiological outcomes, rehabilitation interventions can address quality of life outcomes in order to improve well-being in a way that is meaningful to people with SCI.

Designing Efficient Enzymes: Eight Predicted Mutations Convert a Hydroxynitrile Lyase into an Efficient Esterase.

Hydroxynitrile lyase from rubber tree (HbHNL) shares 45% identical amino acid residues with the homologous esterase from tobacco, SABP2, but the two enzymes catalyze different reactions. The x-ray structures reveal a serine-histidine-aspartate catalytic triad in both enzymes along with several differing amino acid residues within the active site. Previous exchange of three amino acid residues in the active site of HbHNL with the corresponding amino acid residue in SABP2 (T11G-E79H-K236M) created variant HNL3, which showed low esterase activity toward p-nitrophenyl acetate. Further structure comparison reveals additional differences surrounding the active site. HbHNL contains an improperly positioned oxyanion hole residue and differing solvation of the catalytic aspartate. We hypothesized that correcting these structural differences would impart good esterase activity on the corresponding HbHNL variant. To predict the amino acid substitutions needed to correct the structure, we calculated shortest path maps for both HbHNL and SABP2, which reveal correlated movements of amino acids in the two enzymes. Replacing four amino acid residues (C81L-N104T-V106F-G176S) whose movements are connected to the movements of the catalytic residues yielded variant HNL7TV (stabilizing substitution H103V was also added), which showed an esterase catalytic efficiency comparable to that of SABP2. The x-ray structure of an intermediate variant, HNL6V, showed an altered solvation of the catalytic aspartate and a partially corrected oxyanion hole. This dramatic increase in catalytic efficiency demonstrates the ability of shortest path maps to predict which residues outside the active site contribute to catalytic activity.

Quantitative Low-Field 19 F Nuclear Magnetic Resonance Analysis of Carbonyl Groups in Pyrolysis Oils.

Invited for this month's cover is the collaboration between Dr Rob Evans at Aston University, Birmingham, UK and Prof. Art Ragauskas at University of Tennessee, Knoxville and Oak Ridge National Laboratory, Oak Ridge, USA. The image illustrates that low-field, or benchtop, NMR spectrometers can be as effective as their higher-field counterparts in the accurate, quantitative analysis of bio-oils. The Research Article itself is available at 10.1002/cssc.202300625.

Robotic locomotor training in a low-resource setting: a randomized pilot and feasibility trial.

PURPOSE: Activity-based Training (ABT) represents the current standard of neurological rehabilitation. Robotic Locomotor Training (RLT), an innovative technique, aims to enhance rehabilitation outcomes. This study aimed to conduct a randomized pilot and feasibility trial of a locomotor training program within South Africa. MATERIALS AND METHODS: Individuals with chronic traumatic motor incomplete tetraplegia (n = 16). Each intervention involved 60-minute sessions, 3x per week, for 24-weeks. Outcomes included feasibility measures and functional capacity. RESULTS: 17 out of 110 individuals initiated the program (recruitment rate = 15.4%) and 16 completed the program (drop-out rate = 5.8%) and attended sessions (attendance rate = 93.9%). Both groups showed a significant increase in upper extremity motor score (MS) and abdominal strength post intervention. Only the RLT group showed a significant change in lower extremity MS, with a mean increase of 3.00 [0.00; 16.5] points over time. Distance walked in the Functional Ambulatory Inventory (SCI-FAI) increased significantly (p = 0.02) over time only for the RLT group. CONCLUSIONS: Feasibility rates of the intervention and functional outcomes justify a subsequent powered RCT comparing RLT to ABT as an effective rehabilitation tool for potentially improving functional strength and walking capacity in people with incomplete SCI.

Spinal cord injury causes severe limitations to functional capacity, independence, and quality of life.Robotic Locomotor Training is growing rehabilitation modality for people with spinal cord injury, but currently its effects on functional capacity are limited.In a relatively small sample, this study shows that large, randomized control trials are feasible within a low-income setting.The preliminary findings of this study show that 12 weeks of locomotor training can improve ambulatory function and functional strength in individuals with spinal cord injury.

Postsurgery Opiate Use Is Significantly Lower in Patients With Interstitial Cystitis/Bladder Pain Syndrome Following Cystectomy With Urinary Diversion.

OBJECTIVE: To compare pre-and post-operative opiate use in a large cohort of interstitial cystitis/bladder pain syndrome (IC/BPS) patients who underwent cystectomy with urinary diversion (CWUD). METHODS: A retrospective analysis was completed using a database of IC/BPS patients who underwent CWUD at a single institution from 2014 to 2022. In addition to demographic information, bladder capacity and Hunner lesion status were documented for each patient. Opiate use (milligram morphine equivalents [MME]) was calculated for each patient and change in MME (ΔMME) was calculated by subtracting pre-CWUD MME from post-CWUD MME. Paired t test was used to compare ΔMME for all parameters except age, where a Pearson's correlation was used. RESULTS: The analysis included 82 patients (17 M; 65 F) that underwent CWUD as follows: 53 ileal conduit diversions, 11 neobladders, and 18 Indiana Pouches. Mean pre-CWUD MME use was 4509.57 and mean post-CWUD MME was 1788.48 with a ΔMME of - 2721.09 (P < .001). ΔMME was not significantly different based on gender (P = .597), bladder capacity (P = .754), age (P = .561), or Hunner lesion status (P = .085). CONCLUSION: IC/BPS patients using opiates primarily for relief of pain directly related to their condition show a significant decrease in opiate use following CWUD, which likely represents significant pain reduction and implicates the bladder as the primary source of that pain.

Quantitative Low-Field 19 F Nuclear Magnetic Resonance Analysis of Carbonyl Groups in Pyrolysis Oils.

Pyrolysis bio-oils, one of the products of lignocellulosic biomass pyrolysis, have the potential to be widely used as fuels. The chemical composition of bio-oils is very complicated as they contain hundreds, if not thousands, of different, mostly oxygen-containing, compounds with a wide distribution of physical properties, chemical structures, and concentrations. Detailed knowledge of bio-oil composition is crucial for optimizing both the pyrolysis processes and for any subsequent upgrading into a more viable fuel resource. Here we report the successful use of low-field, or benchtop, nuclear magnetic resonance (NMR) spectrometers in the analysis of pyrolysis oils. Pyrolysis oils from four different feedstocks were derivatized and analyzed using 19 F NMR techniques. The NMR results compare favorably with titrations for total carbonyl content. In addition, the benchtop NMR spectrometer proves able to reveal key spectral features, thus allowing the quantification of different carbonyl groups, such as aldehydes, ketones and quinones. Benchtop NMR spectrometers are typically compact, cheaper than their superconducting counterparts and do not require cryogens. Their use will make NMR analysis of pyrolysis oils easier and more accessible to a wide range of different potential users.

Robotic locomotor training for spasticity, pain, and quality of life in individuals with chronic SCI: A pilot randomized controlled trial.

Objective: The prevention and treatment of secondary complications is a key priority for people with spinal cord injury and a fundamental goal of rehabilitation. Activity-based Training (ABT) and Robotic Locomotor Training (RLT) demonstrate promising results for reducing secondary complications associated with SCI. However, there is a need for increased evidence through randomized controlled trials. Therefore, we aimed to investigate the effect of RLT and ABT interventions on pain, spasticity, and quality of life in individuals with spinal cord injuries. Methods: Participants with chronic motor incomplete tetraplegia (n = 16) were recruited. Each intervention involved 60-minute sessions, 3× per week, over 24-weeks. RLT involved walking in an Ekso GT exoskeleton. ABT involved a combination of resistance, cardiovascular and weight-bearing exercise. Outcomes of interest included the Modified Ashworth Scale, the International SCI Pain Basic Data Set Version 2, and the International SCI Quality of Life Basic Data Set. Results: Neither intervention altered symptoms of spasticity. Pain intensity increased from pre-post intervention for both groups, with a mean increase of 1.55 [-0.82, 3.92] (p = 0.03) and 1.56 [-0.43, 3.55] (p = 0.02) points for the RLT and ABT group, respectively. The ABT group had an increase in pain interference scores of 100%, 50%, and 109% for the daily activity, mood, and sleep domain, respectively. The RLT group had an increase in pain interference scores of 86% and 69% for the daily activity and mood domain respectively, but no change in the sleep domain. The RLT group had increased perceptions of quality of life with changes of 2.37 [0.32, 4.41], 2.00 [0.43, 3.56] and 0.25 [-1.63, 2.13] points, p = 0.03, for the general, physical, and psychological domains, respectively. The ABT group had increased perceptions of general, physical and psychological quality of life with changes of 0.75 [-1.38, 2.88], 0.62 [-1.83, 3.07] and 0.63 [-1.87, 3.13] points, respectively. Conclusions: Despite increased pain ratings and no change in symptoms of spasticity, there was an increase in perceived quality of life for both groups over 24-weeks. This dichotomy warrants additional investigation in future large-scale randomized controlled trials.

Understanding the physics of hydrophobic solvation.

Simulations of water near extended hydrophobic spherical solutes have revealed the presence of a region of depleted density and accompanying enhanced density fluctuations. The physical origin of both phenomena has remained somewhat obscure. We investigate these effects employing a mesoscopic binding potential analysis, classical density functional theory (DFT) calculations for a simple Lennard-Jones solvent, and Grand Canonical Monte Carlo (GCMC) simulations of a monatomic water (mw) model. We argue that the density depletion and enhanced fluctuations are near-critical phenomena. Specifically, we show that they can be viewed as remnants of the critical drying surface phase transition that occurs at bulk liquid-vapor coexistence in the macroscopic planar limit, i.e., as the solute radius Rs → ∞. Focusing on the radial density profile ρ(r) and a sensitive spatial measure of fluctuations, the local compressibility profile χ(r), our binding potential analysis provides explicit predictions for the manner in which the key features of ρ(r) and χ(r) scale with Rs, the strength of solute-water attraction ɛsf, and the deviation from liquid-vapor coexistence of the chemical potential, δµ. These scaling predictions are confirmed by our DFT calculations and GCMC simulations. As such, our theory provides a firm basis for understanding the physics of hydrophobic solvation.

Detection of Bacteria in Bladder Mucosa of Adult Females.

PURPOSE: Interstitial cystitis/bladder pain syndrome is a chronic urological condition diagnosed in nearly 8 million females in the United States. Whether urinary microbiota play an etiological role remains controversial. Most studies assessed the microbiota of interstitial cystitis/bladder pain syndrome patients with voided or catheterized urine as a proxy for bladder urothelium; however, urine may not be a true reflection of the bladder microbiota. Bladder biopsy tissue may provide a more accurate, and thus more clinically relevant, picture of bladder microbiota. MATERIALS AND METHODS: Bladder biopsy tissues were obtained from: (1) 30 females with interstitial cystitis/bladder pain syndrome (18-80 years old) via cystoscopically guided cold-cup biopsy following therapeutic bladder hydrodistention, and (2) 10 non-interstitial cystitis/bladder pain syndrome females undergoing pelvic organ prolapse repair. To detect bacteria, technical duplicates of each RNAlater-preserved biopsy were subjected to 16S rRNA gene sequencing. To visualize bacteria, paraformaldehyde-fixed, paraffin-embedded biopsies were subjected to a combined multiplexed fluorescence in situ hybridization and fluorescence immunohistochemistry assay and confocal microscopy. RESULTS: Bacteria were detected by 16S rRNA gene sequencing in at least 1 technical duplicate of most biopsies. The most abundant genus was Staphylococcus, followed by Lactobacillus; Escherichia was common but not abundant. There was no significant difference between interstitial cystitis/bladder pain syndrome patients and controls (P > .05). Combined fluorescence in situ hybridization and immunohistochemistry reproducibly detected 16S rRNA in epithelial cells and shed cells in the urothelium and lesioned areas and capillary walls in the lamina propria of human bladder biopsy tissue. CONCLUSIONS: We conclude that urothelial and urinary microbiota are similar but not identical in adult females.

Watson-Crick Base-Pairing Requirements for ssDNA Recognition and Processing in Replication-Initiating HUH Endonucleases.

Replication-initiating HUH endonucleases (Reps) are sequence-specific nucleases that cleave and rejoin single-stranded DNA (ssDNA) during rolling-circle replication. These functions are mediated by covalent linkage of the Rep to its substrate post cleavage. Here, we describe the structures of the endonuclease domain from the Muscovy duck circovirus Rep in complex with its cognate ssDNA 10-mer with and without manganese in the active site. Structural and functional analyses demonstrate that divalent cations play both catalytic and structural roles in Reps by polarizing and positioning their substrate. Further structural comparisons highlight the importance of an intramolecular substrate Watson-Crick (WC) base pairing between the -4 and +1 positions. Subsequent kinetic and functional analyses demonstrate a functional dependency on WC base pairing between these positions regardless of the pair's identity (i.e., A·T, T·A, G·C, or C·G), highlighting a structural specificity for substrate interaction. Finally, considering how well WC swaps were tolerated in vitro, we sought to determine to what extent the canonical -4T·+1A pairing is conserved in circular Rep-encoding single-stranded DNA viruses and found evidence of noncanonical pairings in a minority of these genomes. Altogether, our data suggest that substrate intramolecular WC base pairing is a universal requirement for separation and reunion of ssDNA in Reps. IMPORTANCE Circular Rep-encoding single-stranded DNA (CRESS-DNA) viruses are a ubiquitous group of viruses that infect organisms across all domains of life. These viruses negatively impact both agriculture and human health. All members of this viral family employ a multifunctional nuclease (Rep) to initiate replication. Reps are structurally similar throughout this family, making them targets of interest for viral inhibition strategies. Here, we investigate the functional dependencies of the Rep protein from Muscovy duck circovirus for ssDNA interaction. We demonstrate that this Rep requires an intramolecular Watson-Crick base pairing for origin of replication (Ori) recognition and interaction. We show that noncognate base pair swaps are well tolerated, highlighting a local structural specificity over sequence specificity. Bioinformatic analysis found that the vast majority of CRESS-DNA Oris form base pairs in conserved positions, suggesting this pairing is a universal requirement for replication initiation in the CRESS-DNA virus family.

Small-Fiber Polyneuropathy Is Prevalent in Patients With Interstitial Cystitis/Bladder Pain Syndrome.

IMPORTANCE: The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is imperfectly understood. Recent studies reported that small-fiber polyneuropathy (SFPN) is common in fibromyalgia, a condition commonly comorbid with IC/BPS. OBJECTIVE: The objective of this study was to determine the prevalence of SFPN in a large cohort of IC/BPS patients. METHODS: Adults diagnosed with IC/BPS scheduled to undergo either therapeutic hydrodistention (n = 97) or cystectomy with urinary diversion (n = 3) were prospectively recruited to this study. A skin biopsy obtained from the lower leg was used for intraepidermal nerve fiber density measurement. Small-fiber polyneuropathy (+/-) status was determined by comparing linear intraepidermal nerve fiber density (fibers/mm2) with normative reference values. Demographic information, medical history, and diagnoses for 14 conditions (both urologic and nonurologic) known to co-occur with IC/BPS were documented from self-report and electronic medical record. RESULTS: In this large cohort of patients with IC/BPS, 31% (31/100) were positive for SFPN. Intraepidermal nerve fiber density was below the median for age and sex in 81% (81/100) of patients. Approximately one-third (31%) of SFPN+ patients reported co-occurring chronic fatigue syndrome, compared with 10.6% of the SFPN- group (P = 0.034). Small-fiber polyneuropathy-positive patients reported significantly fewer allergies than SFPN- patients (37.9% vs 60.6%; P = 0.047). There were no significant differences in bladder capacity or Hunner lesion status between the SFPN+ and SFPN- subgroups. CONCLUSIONS: Small-fiber polyneuropathy is a common finding in patients with IC/BPS, and SFPN status is significantly correlated with co-occurring chronic fatigue syndrome and negatively correlated with the presence of allergies in this population.

Quantitative Interpretation of Protein Diffusion Coefficients in Mixed Protiated-Deuteriated Aqueous Solvents.

Diffusion-ordered nuclear magnetic resonance (NMR) spectroscopy is widely used for the analysis of mixtures, dispersing the signals of different species in a two-dimensional spectrum according to their diffusion coefficients. However, interpretation of these diffusion coefficients is typically purely qualitative, for example, to deduce which species are bigger or smaller. In studies of proteins in solution, important questions concern the molecular weight of the proteins, the presence or absence of aggregation, and the degree of folding. The Stokes-Einstein Gierer-Wirtz estimation (SEGWE) method has been previously developed to simplify the complex relationship between diffusion coefficient and molecular mass, allowing the prediction of a species' diffusion coefficient in a pure solvent based on its molecular weight. Here, we show that SEGWE can be extended to successfully predict both peptide and protein diffusion coefficients in mixed protiated-deuteriated water samples and, hence, distinguish effectively between globular and disordered proteins.

Pulsed Electromagnetic Field Therapy for Pain Management in Interstitial Cystitis/Bladder Pain Syndrome: A Proof-of-Concept Case Series.

OBJECTIVE: To evaluate the efficacy of pulsed electromagnetic field (PEMF) therapy for symptom and pain management in women with non-bladder centric interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Women with non-bladder centric IC/BPS and a numeric rating scale score for pelvic pain ≥6 underwent twice-daily 8-minute full body PEMF therapy sessions for 4 weeks. The primary outcome metric was a reduction in pelvic pain score ≥2 points. A 7-day voiding diary (collected at baseline and conclusion), 3 validated symptom scores, and the Short Form-36 Quality of Life questionnaire (completed at baseline, conclusion of treatment, and 8-week follow-up), were used to assess secondary outcomes. Treatment effects were analyzed via Wilcoxon-signed rank test; P < .05 was considered significant. RESULTS: The 4-week treatment protocol was completed by 8 of 10 enrolled patients, and 7:8 (87.5%) had a significant reduction in pelvic pain (-3.0 points, P = .011) after 4 weeks. There was also a significant decrease in scores on all validated IC/BPS questionnaires, daily number of voids, and nocturia symptom score (P < .05). Significant increases in several quality-of-life questionnaire sub-scores were also identified at 4 weeks (P < .05). At 8-week post-therapy, the positive effects were somewhat attenuated, yet 4:8 patients (50%) continued to have significant pain reduction (P = .047). No adverse events or side effects were reported. CONCLUSION: Whole body pulsed electromagnetic field therapy is an alternative treatment option for women with chronic bladder pain syndrome that warrants investigation through comparative trials.

Measures of fluctuations for a liquid near critical drying.

We investigate density fluctuations in a liquid close to a solvophobic substrate at which a surface critical drying transition occurs. Using classical density functional theory, we determine three measures of the spatial extent and strength of the fluctuations, i.e., the local compressibility χ_{µ}(z), the local thermal susceptibility χ_{T}(z), and the reduced density χ_{*}(z); z is the distance from the substrate. While the first measure is frequently used, the second and third were introduced very recently by Eckert et al., [T. Eckert et al., Phys. Rev. Lett. 125, 268004 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.268004]. For state points in the critical drying regime, all three measures, each scaled by its bulk value, exhibit very similar forms and the ratio of χ_{T}(z) to χ_{µ}(z), for fixed z in the vapor-liquid transition region, is constant. Using a scaling treatment of surface thermodynamics, we show that such behavior is to be expected on general grounds.