Lateral Extra-Articular Tenodesis Combined With Anterior Cruciate Ligament Reconstruction Is Effective in Knees With Additional Features of Lateral, Hyperextension, or Increased Rotational Laxity: A Matched Cohort Study.

PURPOSE: To investigate the patient-reported outcome measures (PROMs) and graft survival of combined anterior cruciate ligament reconstruction (ACLR) and lateral extra-articular tenodesis (ACLR-LET) compared with a matched cohort having ACLR alone. METHODS: Patients were retrospectively recruited from a consecutive series of primary ACLR-LET, between 1996 and 2015, with a minimum postsurgical time of 4 years. ACLR-LET were matched with isolated ACLR for age, gender, and operation year. The indications for adding lateral extra-articular tenodesis were lateral laxity of grade 1 or 2, hyperextension laxity, and/or increased rotational laxity of 5° to 10°. The technique used involved detaching a strip of iliotibial band proximally, before being passed deep to the lateral collateral ligament, looped through Kaplan's fibers, and sutured back onto itself at physiological tension. The PROMs used were the Lysholm Knee Scoring Scale, Tegner Activity Scale, Oxford Knee Score, and International Knee Documentation Committee subjective knee form. Failure was defined as graft rupture. Student's t-test was used to compare the matched groups and Kaplan-Meier analysis for survivorship. RESULTS: Eighty-three patients had ACLR-LET between 1996 and 2015. Nine revision cases and 2 with less than 4 years follow-up were excluded. The remaining 72 ACLR-LET patients were matched and included in the survival analysis. Seventy percent of patients completed the PROMs. In both groups, 76% were males, and the mean age was 25 years (standard deviation ± 8.5). The median follow-up was 10 years (interquartile range, 6.7 years). There was no significant change of PROMs (Lysholm Knee Scoring Scale: P = .82, 95% confidence interval (CI) -13 to 11; International Knee Documentation Committee: P = .07, CI -1 to 24; Oxford Knee Score: P = .5, CI -8 to 4; Tegner Activity Scale: P = .5, CI -1 to 3) between the groups. The pre- to postoperative PROMs, except the Tegner Activity Scale, improved significantly, clinically and statistically. There was no statistically significant difference in graft failure between the ACLR-LET group (n = 4, 5%) and the ACLR group (n = 9, 11%) (log-rank P = .099). CONCLUSION: ACLR-LET shows good graft survival and PROMs in a high-risk population. This suggests that lateral extra-articular tenodesis is an effective technique to restore joint stability to a knee with additional features of laxity. LEVEL OF EVIDENCE: III, matched cohort study.

Homozygous GRN mutations: new phenotypes and new insights into pathological and molecular mechanisms.

Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders, usually beginning between 13 and 25 years of age. This is a rare condition, previously reported in only four families. In contrast, heterozygous GRN mutations are a major cause of frontotemporal dementia associated with neuronal cytoplasmic TDP-43 inclusions. We identified homozygous GRN mutations in six new patients. The phenotypic spectrum is much broader than previously reported, with two remarkably distinct presentations, depending on the age of onset. A childhood/juvenile form is characterized by classical CLN11 symptoms at an early age at onset. Unexpectedly, other homozygous patients presented a distinct delayed phenotype of frontotemporal dementia and parkinsonism after 50 years; none had epilepsy or cerebellar ataxia. Another major finding of this study is that all GRN mutations may not have the same impact on progranulin protein synthesis. A hypomorphic effect of some mutations is supported by the presence of residual levels of plasma progranulin and low levels of normal transcript detected in one case with a homozygous splice-site mutation and late onset frontotemporal dementia. This is a new critical finding that must be considered in therapeutic trials based on replacement strategies. The first neuropathological study in a homozygous carrier provides new insights into the pathological mechanisms of the disease. Hallmarks of neuronal ceroid lipofuscinosis were present. The absence of TDP-43 cytoplasmic inclusions markedly differs from observations of heterozygous mutations, suggesting a pathological shift between lysosomal and TDP-43 pathologies depending on the mono or bi-allelic status. An intriguing observation was the loss of normal TDP-43 staining in the nucleus of some neurons, which could be the first stage of the TDP-43 pathological process preceding the formation of typical cytoplasmic inclusions. Finally, this study has important implications for genetic counselling and molecular diagnosis. Semi-dominant inheritance of GRN mutations implies that specific genetic counselling should be delivered to children and parents of CLN11 patients, as they are heterozygous carriers with a high risk of developing dementia. More broadly, this study illustrates the fact that genetic variants can lead to different phenotypes according to their mono- or bi-allelic state, which is a challenge for genetic diagnosis.

Changes in Parkinsonian gait kinematics with self-generated and externally-generated cues: a comparison of responders and non-responders.

Purpose: Rhythmic auditory stimulation such as listening to music can alleviate gait bradykinesia in people with Parkinson disease (PD) by increasing spatiotemporal gait features. However, evidence about what specific kinematic alterations lead to these improvements is limited, and differences in responsiveness to cueing likely affect individual motor strategies. Self-generated cueing techniques, such as singing or mental singing, provide similar benefits but no evidence exists about how these techniques affect lower limb joint movement. In this study, we assessed immediate effects of external and self-generated cueing on lower limb movement trajectories during gait.Methods: Using 3D motion capture, we assessed sagittal plane joint angles at the hip, knee, and ankle across 35 participants with PD, divided into responders (n = 23) and non-responders (n = 12) based on a clinically meaningful change in gait speed. Joint motion was assessed as overall range of motion as well as at two key time points during the gait cycle: initial contact and toe-off.Results: Responders used both cue types to increase gait speed and induce increases in overall joint ROM at the hip while only self-generated cues also increased ROM at the ankle. Increased joint excursions for responders were also evident at initial contact and toe-off.Conclusions: Our results indicate that self-generated rhythmic cues can induce similar increases in joint excursions as externally-generated cues and that some people may respond more positively than others. These results provide important insight into how self-generated cueing techniques may be tailored to meet the varied individual needs of people with PD.

Editorial Commentary: Meniscus Message-What Is Possible or What Is Advisable?

Distal femoral varus osteotomy combined with meniscal allograft transplantation is a major surgical undertaking, not without risk and not to be taken on lightly by either the surgeon or the patient. It really is a salvage operation for a knee that is deteriorating and heading for arthroplasty at some future point. It is not an operation that should be offered to patients to allow them to return to sport. The fact that some patients do return to sport is good and is a credit to the operation and the patient's tenacity with rehabilitation, but we must question the rationale of such activity, which will most likely hasten the demise of the joint.

Cross-Sectional Analysis of Backward, Forward, and Dual Task Gait Kinematics in People With Parkinson Disease With and Without Freezing of Gait.

People with Parkinson disease demonstrate increased gait variability, but the primary variability sources are poorly understood. People with Parkinson disease and freezing of gait (freezers) have greater gait impairments than people with Parkinson disease without freezing of gait (nonfreezers), which may relate to cerebellar dysfunction. Thirteen freezers and 31 nonfreezers completed backward, forward, and forward with dual task gait trials. Sagittal joint angle waveforms were extracted for the hip, knee, and ankle using 3D motion capture. Decomposition indices were calculated for the 3 joint combinations. Principal component analysis extracted variance sources from the joint waveforms. Freezers had significantly greater decomposition between hip-ankle (F1,42 = 5.1, P = .03) and hip-knee (F1,42 = 5.3, P = .03) movements. The principal component analysis did not differentiate freezers and nonfreezers; however, primary variance sources differed between conditions. Primary variance during forward and forward with dual task gait came from joint angle magnitude and peak angle timing. Backward gait showed primary variance from joint angle magnitude and range of motion. The results show that freezers decompose movement more than nonfreezers, implicating cerebellar involvement in freezing of gait. Primary variance differs between gait conditions, and tailoring gait interventions to address variability sources may improve intervention efficacy.

What Is the Risk of Repeat Revision When Patellofemoral Replacement Is Revised to TKA? An Analysis of 482 Cases From a Large National Arthroplasty Registry.

BACKGROUND: Patellofemoral replacements (PFRs) have a higher rate of revision than unicompartmental knee arthroplasty or TKA. However, there is little information regarding why PFRs are revised, the components used for these revisions, or the outcome of the revision procedure. Some contend that PFR is a bridging procedure that can easily be revised to a TKA with similar results as a primary TKA; however, others dispute this suggestion. QUESTIONS/PURPOSES: (1) In the setting of a large national registry, what were the reasons for revision of PFR to TKA and was the level of TKA constraint used in the revision associated with a subsequent risk of rerevision? (2) Is the risk of revision of the TKA used to revise a PFR greater than the risk of revision after a primary TKA and greater than the risk of rerevision after revision TKA? METHODS: Data were obtained from the Australian Orthopaedic Association Joint Replacement Registry through December 31, 2016, for TKA revision procedures after PFR. Because revisions for infection may be staged procedures resulting in further planned operations, for the revision analyses, these were excluded. There were 3251 PFRs, 482 of which were revised to TKA during the 17-year study period. The risk of second revision was calculated using Kaplan-Meier estimates of survivorship for PFRs revised to TKAs, and that risk was compared with the risk of first revision after TKA and also with the risk of a second revision after revision TKA. Hazard ratios (HRs) from Cox proportional hazards models were used to compare second revision rates among the different levels of prosthesis constraint used in the index revision after PFR (specifically, cruciate-retaining versus cruciate-substituting). RESULTS: The main reasons for revising a PFR to TKA were progression of disease (56%), loosening (17%), and pain (12%). With the numbers available for analysis, there was no difference in the risk of a second revision when a PFR was revised to a cruciate-retaining TKA than when it was revised to a cruciate-substituting TKA (HR, 1.24 [0.65-2.36]; p = 0.512). A total of 204 (42%) of the PFR revisions had the patella component revised when the PFR was converted to a TKA. There difference in rates of second revision when the patella component was revised or not revised (HR, 1.01 [0.55-1.85]; p = 0.964). When we eliminated the devices that ceased to be used before 2005 (older devices), we found no change in the overall risk of repeat revision. The risk of a PFR that was revised to a TKA undergoing a second revision was greater than the risk of TKA undergoing a first revision (HR, 2.39 [1.77-3.24]; p < 0.001), but it was less than the risk of a revision TKA undergoing a second revision (HR, 0.60 [0.43-0.81]; p = 0.001). CONCLUSIONS: The risk of second revision when a PFR is revised is not altered if cruciate-retaining or posterior-stabilized TKA is used for the revision nor if the patella component is revised or not revised. The risk of repeat revision after revision of a PFR to a TKA was much higher than the risk of revision after a primary TKA, and these findings did not change when we analyzed only devices in use since 2005. When PFR is used for the management of isolated patellofemoral osteoarthritis, patients should be counselled not only about the high revision rate of the primary procedure, but also the revision rate after TKA. Further studies regarding the functional outcomes of these procedures may help clarify the value of PFRs and subsequent revisions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Meniscal allograft transplantation: undersizing grafts can lead to increased rates of clinical and mechanical failure.

PURPOSE: To assess mid-term survivorship of meniscal allograft transplantation (MAT) and determine the effect that pre-operative meniscal sizing has upon functional outcome and mechanical survivorship. METHODS: A prospectively collected database of patients receiving MAT from 2001 to 2017 was analysed. Data include demographics; sizing measurements, complications, further surgery, and patient-reported outcome measures (PROMs). Allografts were fresh frozen, non-irradiated, and sized using the Pollard technique. RESULTS: Seventy-three MATs were performed in 67 patients; mean age at MAT was 34 years (range 14-52 years). 56% were male and 62% were medial. The mean follow-up was 75 months (6.25 years). Mechanical survival at 5 and 10 years was 96% and 89.4%, respectively. There were statistically significant improvements in all PROMs; mean Lysholm score improved by 17.5 points [95% confidence interval (CI) 22.2-12.9, p < 0.001]; mean IKDC score improved significantly by 13.3 points (CI 19.3-7.4, p < 0.001); mean OKS improved by 5.6 points (CI 9.2-2.2, p < 0.002); and the median Tegner improved by 1 point. Forty-one MATs (56%) were undersized for width (range 1-11 mm). Seven MATs (10%) were undersized for length (range 1-4 mm). There was no statistically significant difference in mechanical survivorship or clinical outcomes between undersized, matched, or oversized grafts overall; however, sub-group analysis demonstrated increased failure when allografts were undersized by more than 5 mm in width. CONCLUSIONS: MAT is an effective treatment to improve function and alleviate pain with excellent survivorship in this series. Accepting an allograft that is more than 5 mm smaller in width than pre-operative templating increases the likelihood of clinical and mechanical failure. We, therefore, urge surgeons to be familiar with the measuring process used by their individual tissue bank provider to avoid graft-host mismatch that could affect outcome.

Meniscal Allograft Transplantation: The Effect of Cartilage Status on Survivorship and Clinical Outcome.

PURPOSE: To evaluate the survivorship of meniscal allograft transplantations (MATs), their clinical outcomes, and to compare the effect of perioperative cartilage status on survivorship. METHOD: A consecutive series of MATs with a minimum postsurgical time of 4 years were included from a prospectively collected database from 2001 to 2015. Mechanical failure was defined as transplant removal or knee arthroplasty. The effect of peri-operative cartilage status on survivorship was analyzed using a Kaplan-Meier analysis. Also, pre- and postoperative outcome scores were evaluated. The clinical outcome tools used were the Lysholm Knee Scoring Scale, Tegner Activity Level Scale, Oxford Knee Score (OKS) and International Knee Documentation Committee (IKDC) subjective knee form. RESULTS: The mean (±SD) postsurgical follow-up (n = 45 MATs, 43 knees) was 8.6 ± 3.4 years. Among the 45 MATs, 31 had an Outerbridge Cartilage Score (OCS) of 3 to 4. Eight transplants (17.7%) failed at an average of 6.1 ± 4.4 years postoperatively, and all occurred in patients with an OCS of 3 to 4. Functional outcomes showed significant improvement in the Lysholm by 17.7 points (95% confidence interval [CI], 8.5-26.9, P < .001), OKS by 8 (CI, 0.81-15.11, P = .031), and IKDC scores by 15.6 (CI, 6-25.2, P = .001). However, the Tegner score improvement by 0.6 was not statistically significant (CI, 0.3545-1.6212, P = .2). In a subanalysis, the OCS 3-4 group had a significant improvement in all the clinical outcomes except the Tegner score. In the OCS 0-2 group, the Lysholm and Tegner significantly improved, whereas the improvement in the OKS and IKDC was not significant. CONCLUSIONS: MAT is a viable and effective surgical option for the painful meniscus-deficient knee, with good survivorship and functional outcomes in the medium to long term. Mechanical failure is associated with advanced OCS. Patients with minimal cartilage damage have improved MAT survivorship but both groups benefit clinically. LEVEL OF EVIDENCE: Level IV, case series.

Humanizing folk devils using ethnography.

The sociological concepts of the "moral panic" and the deviant "folk devil" apply to the drug panics in the United States over methamphetamine, heroin, and crack cocaine. Mothers or pregnant women who smoke crack cocaine, and their babies, are assigned exaggerated "demonic" attributes that result in stigma and societal rejection. Otherwise, ethnographic studies of drug users demonstrate realities that are other than what might be considered were one to merely look at their use and the consequences. These considerations are examined with respect to the image of folk devils, methadone program attendees, smokers of "blunts," opium den habitués, and others grouped together as negative influences as a result of their drug habits.

Meniscal allograft transplantation: how should we be doing it? A systematic review.

PURPOSE: We undertook a systematic review to assess a number of the technical aspects of meniscal allograft transplantation (MAT) that have not been covered in other reviews. Specific variables studied included the indications for MAT, graft fixation method, rehabilitation protocols, outcome scores, and definition of failure. METHODS: We performed a systematic literature review of the PubMed, EMBASE, and Cochrane databases to determine the outcomes of meniscal transplantation at greater than 2 years postoperatively. PRISMA (Preferred Reporting for Systematic Reviews and Meta-Analyses) guidelines were followed with a PRISMA checklist. The search was completed on January 5, 2014. RESULTS: These queries returned 629 results from which 41 articles were identified as meeting the inclusion criteria. No studies in this review were randomized or controlled. CONCLUSIONS: MAT is a worthwhile procedure, with evidence that it provides pain relief and improved function, and good results reported in mid- to long-term studies. The procedure should be considered only in a patient with localized pain and a stable (or stabilized) and well-aligned (or realigned) knee. The controversial areas studied in this review include the following: there is no evidence to support fixation with either bone plugs or soft tissue; there is no standardized rehabilitation program, but it appears that full weight bearing by 6 weeks is not detrimental; and a clear and uniform definition of failure and use of consistent outcome scores would aid future reporting and analysis of the results of meniscal transplantation. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

Synthesis of nanospheres-on-microsphere silica with tunable shell morphology and mesoporosity for improved HPLC.

Core-shell particles have a wide range of applications. Most of the core-shell particles are prepared in two or multiple steps. Core-shell silica microspheres, with solid core and porous shell, have been used as novel packing materials in recent years for highly efficient liquid chromatography separation with relatively low back-pressure. These core-shell silica microspheres are usually prepared by the time-consuming layer-by-layer technique. Built on our previous report of one-pot synthesis of core-shell nanospheres-on-microspheres (termed as SOS particles for "spheres-on-spheres"), we describe here a two-stage synthesis for the introduction of shell mesoporosity into SOS particles with tunable shell morphology by co-condensation of tetraethyl orthosilicate (TEOS) with 3-mercaptopropyltrimethoxysilane (MPTMS) in the presence of surfactant in the second stage. With MPTMS as the primary precursor at the first stage, some other silica precursors (apart from TEOS) are also employed at the second stage. Expansion of the surfactant-templated mesopores with swelling agents during the reaction and by hydrothermal postsynthesis treatment is then performed to allow the pore sizes (> 6 nm) suitable for separation of small molecules in liquid chromatography. Compared to the standard SOS silica (both the nanospheres and microspheres contain nearly no mesopores), the introduction of mesoporosity into the nanosphere shell increases the separation efficiency of small molecule mixtures by 4 times as judged by the height equivalent plate number, while the separation of protein mixtures is not negatively affected.

Monodisperse sphere-on-sphere silica particles for fast HPLC separation of peptides and proteins.

Monodisperse sphere-on-sphere (SOS) silica particles are produced in a one-pot reaction, removing the need for time-consuming preparation and classification steps. Analysis of peptides and proteins using HPLC displays faster separation at lower operating pressure than commercially available fused core materials.

Replication and reliability of Parkinson's disease clinical subtypes.

BACKGROUND: We recently identified three distinct Parkinson's disease subtypes: "motor only" (predominant motor deficits with intact cognition and psychiatric function); "psychiatric & motor" (prominent psychiatric symptoms and moderate motor deficits); "cognitive & motor" (cognitive and motor deficits). OBJECTIVE: We used an independent cohort to replicate and assess reliability of these Parkinson's disease subtypes. METHODS: We tested our original subtype classification with an independent cohort (N = 100) of Parkinson's disease participants without dementia and the same comprehensive evaluations assessing motor, cognitive, and psychiatric function. Next, we combined the original (N = 162) and replication (N = 100) datasets to test the classification model with the full combined dataset (N = 262). We also generated 10 random split-half samples of the combined dataset to establish the reliability of the subtype classifications. Latent class analyses were applied to the replication, combined, and split-half samples to determine subtype classification. RESULTS: First, LCA supported the three-class solution - Motor Only, Psychiatric & Motor, and Cognitive & Motor- in the replication sample. Next, using the larger, combined sample, LCA again supported the three subtype groups, with the emergence of a potential fourth group defined by more severe motor deficits. Finally, split-half analyses showed that the three-class model also had the best fit in 13/20 (65%) split-half samples; two-class and four-class solutions provided the best model fit in five (25%) and two (10%) split-half replications, respectively. CONCLUSIONS: These results support the reproducibility and reliability of the Parkinson's disease behavioral subtypes of motor only, psychiatric & motor, and cognitive & motor groups.

Long-term results of per-operative knee arthroscopy in confirming suitability for unicompartmental arthroplasty.

BACKGROUND: Patient selection is key to the success of medial unicondylar knee arthroplasty (UKA). Progression of arthritis is the most common indication for revision surgery. Per-operative arthroscopy is a means of directly assessing the integrity of the lateral compartment. The aim of the study is to assess the long-term survivorship of UKA performed when per-operative arthroscopy is used as a final means of deciding whether to proceed with UKA. METHODS: We used per-operative arthroscopy as a means to confirm suitability for UKA in a consecutive series of 279 Oxford medial UKA. Our series of UKA with per-operative arthroscopy (Group 1) was compared to all Oxford UKA (Group 2) and all UKA in the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) (Group 3). RESULTS: The 14-year cumulative percentage revision (CPR) was 18.5% (95% CI 12.7, 26.4) for group 1, 19.7% (95% CI 18.8, 20.6) for group 2, and 19.2% (95% CI 18.5, 19.8) for group 3. There was no statistically significant difference in the (CPR) for the entire period when group 1 was compared to groups 2 or 3. Progression of arthritis was least in Group 1 compared to groups 2 and 3; 3.6 versus 4.4 and 4.1% respectively. Following per-operative arthroscopy 21.6% (77/356) of knees underwent a change of surgical plan from UKA to TKA. CONCLUSION: In our practice, which includes per-operative arthroscopy, we have identified a reduced risk of revision due to progression of arthritis but no difference in overall long-term implant survivorship.

Attaching protein-adsorbing silica particles to the surface of cotton substrates for bioaerosol capture including SARS-CoV-2.

The novel coronavirus pandemic (COVID-19) has necessitated a global increase in the use of face masks to limit the airborne spread of the virus. The global demand for personal protective equipment has at times led to shortages of face masks for the public, therefore makeshift masks have become commonplace. The severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) has a spherical particle size of ~97 nm. However, the airborne transmission of this virus requires the expulsion of droplets, typically ~0.6-500 µm in diameter (by coughing, sneezing, breathing, and talking). In this paper, we propose a face covering that has been designed to effectively capture SARS-CoV-2 whilst providing uncompromised comfort and breathability for the wearer. Herein, we describe a material approach that uses amorphous silica microspheres attached to cotton fibres to capture bioaerosols, including SARS CoV-2. This has been demonstrated for the capture of aerosolised proteins (cytochrome c, myoglobin, ubiquitin, bovine serum albumin) and aerosolised inactivated SARS CoV-2, showing average filtration efficiencies of ~93% with minimal impact on breathability.

Prevalence and Burden of Migraine in Switzerland: Cross-Sectional Study in ten Specialised Headache Centres from the BECOME Study.

INTRODUCTION: There is limited real-world evidence on the burden of migraine among patients with prior preventive treatment failure (PPTF). In the BECOME Swiss subanalysis, we aimed to assess current prevalence of PPTF in patients with migraine seen at specialised headache centres in Switzerland and burden of migraine in these patients. Furthermore, we assessed this burden in subgroups stratified by monthly migraine days (MMDs) and number of PPTFs. METHODS: BECOME was a prospective, multicentre, non-interventional two-part study conducted in 17 countries across Europe and Israel. This subanalysis includes patients visiting ten headache specialist centres in Switzerland. In part 1, patients visiting the centres over 3 months were screened by physicians for frequency of PPTF, MMD and other migraine characteristics. Patients with ≥ 1 PPTF and ≥ 4 MMDs were invited to take part in part 2. The primary endpoint was the proportion of patients with ≥ 1 PPTF (part 1). Other endpoints included proportion of patients specified by number of PPTF and MMD (part 1, part 2), and impact of migraine on patient-reported outcomes (PROs; part 2). RESULTS: Patients (1677) from ten Swiss centres were included in part 1, of which 855 (51.0%) reported ≥ 1 PPTF. One hundred fifty-five patients were included in part 2: 6.5% reported ≥ 4 PPTFs and 43.2% reported ≥ 15 MMDs. Mean EuroQoL 5 and EuroQoL visual analogue scale (EQ-VAS) were 0.8 ± 0.2 and 69.6 ± 20.2, respectively, suggesting a mild level of impairment in the daily functioning and self-reported health of the patients. Mean six-item Headache Impact Test (HIT-6) and modified Migraine Disability Assessment (mMIDAS) scores were 63.3 ± 6.5 and 22.7 ± 21.8, respectively, corresponding to severe migraine burden. Patients also reported impairment in work-related productivity and general activities (48.6 ± 22.8) but no associations of anxiety (7.2 ± 4.4) or depression (6.0 ± 4.4) with migraine were noted. Burden of migraine increased with increasing frequency of PPTF and MMD. CONCLUSIONS: Migraine-related quality of life, as well as work productivity are significantly affected in Swiss patients with migraine. Increasing migraine burden is associated with increasing migraine frequency and prior treatment failures.

Proteinopathy and Longitudinal Cognitive Decline in Parkinson Disease.

BACKGROUND AND OBJECTIVES: People with Parkinson disease (PD) commonly experience cognitive decline, which may relate to increased α-synuclein, tau, and ß-amyloid accumulation. This study examines whether the different proteins predict longitudinal cognitive decline in PD. METHODS: All participants (PD n = 152, controls n = 52) were part of a longitudinal study and completed a lumbar puncture for CSF protein analysis (α-synuclein, total tau [tau], and ß-amyloid42 [ß-amyloid]), a ß-amyloid PET scan, and/or provided a blood sample for APOE genotype (ε4+, ε4-), which is a risk factor for ß-amyloid accumulation. Participants also had comprehensive, longitudinal clinical assessments of overall cognitive function and dementia status, as well as cognitive testing of attention, language, memory, and visuospatial and executive function. We used hierarchical linear growth models to examine whether the different protein metrics predict cognitive change and multivariate Cox proportional hazard models to predict time to dementia conversion. Akaike information criterion was used to compare models for best fit. RESULTS: Baseline measures of CSF ß-amyloid predicted decline for memory (p = 0.04) and overall cognitive function (p = 0.01). APOE genotypes showed a significant group (ε4+, ε4-) effect such that ε4+ individuals declined faster than ε4- individuals in visuospatial function (p = 0.03). Baseline ß-amyloid PET significantly predicted decline in all cognitive measures (all p ≤ 0.004). Neither baseline CSF α-synuclein nor tau predicted cognitive decline. All 3 ß-amyloid--related metrics (CSF, PET, APOE) also predicted time to dementia. Models with ß-amyloid PET as a predictor fit the data the best. DISCUSSION: Presence or risk of ß-amyloid accumulation consistently predicted cognitive decline and time to dementia in PD. This suggests that ß-amyloid has high potential as a prognostic indicator and biomarker for cognitive changes in PD.

Silica Microspheres-in-Pores Composite Monoliths with Fluorescence and Potential for Water Remediation.

Water pollution is a severe worldwide issue. Constructing advanced porous composite materials has been an efficient route to water remediation via adsorption. In this study, a unique microspheres-in-pores monolithic structure was fabricated. An emulsion-templated polymer monolith was first prepared and silica microspheres were subsequently formed in the porous polymer. A silica precursor was modified with a fluorescent dye and co-condensed with other precursors to fabricate porous composites with fluorescent properties, which were enhanced by the presence of Ag nanoparticles in the polymer matrix. This unique material showed good promise in water remediation by removing organic dyes and heavy metal ions from wastewater via a flowing filter or monolithic column separation.

Resting-state functional connectivity associated with gait characteristics in people with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a movement disorder caused by dysfunction in the basal ganglia (BG). Clinically relevant gait deficits, such as decreased velocity and increased variability, may be caused by underlying neural dysfunction. Reductions in resting-state functional connectivity (rs-FC) between networks have been identified in PD compared to controls; however, the association between gait characteristics and rs-FC of brain networks in people with PD has not yet been explored. The present study aimed to investigate these associations. METHODS: Gait characteristics and rs-FC MRI data were collected for participants with PD (N = 50). Brain networks were identified from a set of seeds representing cortical, subcortical, and cerebellar regions. Gait outcomes were correlated with the strength of rs-FC within and between networks of interest. A stepwise regression analysis was also conducted to determine whether the rs-FC strength of brain networks, along with clinical motor scores, were predictive of gait characteristics. RESULTS: Gait velocity was associated with rs-FC within the visual network and between motor and cognitive networks, most notably BG-thalamus internetwork rs-FC. The stepwise regression analysis showed strength of BG-thalamus internetwork rs-FC and clinical motor scores were predictive of gait velocity. CONCLUSION: The results of the present study demonstrate gait characteristics are associated with functional organization of the brain at the network level, providing insight into the neural mechanisms of clinically relevant gait characteristics. This knowledge could be used to optimize the design of gait rehabilitation interventions for people with neurological conditions.

Distinct progression patterns across Parkinson disease clinical subtypes.

OBJECTIVE: To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes. METHODS: We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, "Motor Only," "Psychiatric & Motor," and "Cognitive & Motor," which differed in dementia and mortality rates. Parkinson disease participants ("Motor Only": n = 61, "Psychiatric & Motor": n = 17, "Cognitive & Motor": n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow-up = 4.6 years). Hierarchical linear modeling examined group differences in symptom progression. A three-way interaction among time, group, and symptom duration (or baseline age, separately) was incorporated to examine disease stages. RESULTS: All three subtypes increased in motor dysfunction compared to controls. The "Motor Only" subtype did not show significant cognitive or psychiatric changes compared to the other two subtypes. The "Cognitive & Motor" subtype's cognitive dysfunction at baseline further declined compared to the other two subtypes, while also increasing in psychiatric symptoms. The "Psychiatric & Motor" subtype's elevated psychiatric symptoms at baseline remained steady or improved over time, with mild, steady decline in cognition. The pattern of behavioral changes and analyses for disease staging yielded no evidence for sequential disease stages. INTERPRETATION: Parkinson disease clinical subtypes progress in clear, temporally distinct patterns from one another, particularly in cognitive and psychiatric features. This highlights the importance of comprehensive clinical examinations as the order of symptom presentation impacts clinical prognosis.