The immunology of fibrosis.

Fibrosis is the production of excessive amounts of connective tissue, i.e., scar formation, in the course of reactive and reparative processes. Fibrosis develops as a consequence of various underlying diseases and presents a major diagnostically and therapeutically unsolved problem. In this review, we postulate that fibrosis is always a sequela of inflammatory processes and that the many different causes of fibrosis all channel into the same final stereotypical pathways. During the inflammatory phase, both innate and adaptive immune mechanisms are operative. This concept is exemplified by fibrotic diseases that develop as a consequence of tissue damage, primary inflammatory diseases, fibrotic alterations induced by foreign body implants, "spontaneous" fibrosis, and tumor-associated fibrotic changes.

The Wavelength-Shifting Optical Module.

The Wavelength-shifting Optical Module (WOM) is a novel photosensor concept for the instrumentation of large detector volumes with single-photon sensitivity. The key objective is to improve the signal-to-noise ratio, which is achieved by decoupling the photosensitive area of a sensor from the cathode area of its photomultiplier tube (PMT). The WOM consists of a transparent tube with two PMTs attached to its ends. The tube is coated with wavelength-shifting paint that absorbs ultraviolet photons with nearly 100% efficiency. Depending on the environment, e.g., air (ice), up to 73% (41%) of the subsequently emitted optical photons can be captured by total internal reflection and propagate towards the PMTs, where they are recorded. The optical properties of the paint, the geometry of the tube, and the coupling of the tube to the PMTs have been optimized for maximal sensitivity based on theoretical derivations and experimental evaluations. Prototypes were built to demonstrate the technique and to develop a reproducible construction process. Important measurable characteristics of the WOM are the wavelength-dependent effective area, the transit time spread of detected photons, and the signal-to-noise ratio. The WOM outperforms bare PMTs, especially with respect to the low signal-to-noise ratio with an increase of a factor up to 8.9 in air (5.2 in ice). Since the gain in sensitivity is mostly in the UV regime, the WOM is an ideal sensor for Cherenkov and scintillation detectors.

Longitudinal 16-year study of dominant intermediate CMT type C neuropathy.

BACKGROUND: Dominant-intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) is associated with mutations in the YARS gene. The aim of this study is to investigate the long-term natural history of the disease. METHODS: In a 5-generation DI-CMTC family, we compared data from 2016 to that of 2000 in 13 of 21 original participants. RESULTS: Five women and 8 men were examined. While most symptoms and signs progressed, only gait progression was statistically significant (P = .016). The median CMT Neuropathy Score was 6.08 in 2000 and 11 in 2016 (P = .001). Quality of life (QOL) deteriorated in mobility (P = .008), pain/discomfort (P = .011), and anxiety/depression (P = .014). Median and ulnar compound muscle action potential amplitudes decreased from 9.35 ± 2.90 mV to 6.0 ± 2.9 mV (P = .002), and from 9.24 ± 2.10 mV to 6.06 ± 1.81 mV (P = .004), respectively, whereas motor nerve conduction velocities remained unchanged. CONCLUSIONS: DI-CMTC in this family is a slowly progressive disease with axonal degeneration, deteriorating mobility and QOL.

Microbiota Associated with Dromedary Camel Milk from Algerian Sahara.

Despite the fact that camel milk represents a valuable food source, the fungal diversity of raw camel milk has been poorly studied so far. Here, we investigated the fungal and bacterial communities found in dromedary camel milk from Ghardaia, a representative region of Algerian Sahara. The application of both culture-dependent and independent molecular techniques, based on dHPLC analysis and metabarcoding of ITS region, provided a complementary biodiversity assessment of camel milk fungi which was composed of 15 different taxa. Yeast species belonged to Filobasidium, Naganishia, Malassezia, Mrakia, Rhodotorula, and Yarrowia genera; and mold species belonged to Fusarium, Cladosporium, and Penicillium genera. All three techniques revealed that the fungal community was dominated by species belonging to the former genus Cryptococcus (Filobasidium and Naganishia) although none of them was able to encompass the entire fungal diversity alone. In addition, massive parallel 16S rRNA tag sequencing was applied to gain an insight into the diversity of bacterial communities which were dominated by Pseudomonas spp. Our results provide an initial insight about fungal and bacterial population found in dromedary camel milk from Algerian Sahara.

Medical and neuropsychiatric phenomena depicted in two Spanish medieval texts of Marian miracles.

In the history of Christianity, veneration of the Virgin Mary reached its greatest intensity in the XIII century. Her perceived impact on daily life was tremendous and not surprisingly this extended to the spheres of disease and healing. The purpose of this study is to compare the medical and neuropsychiatric findings in two XIII century Spanish texts of Marian miracles, both examples of the popular Catholicism (vs. official catholic doctrine). We analyzed the medical and neuropsychiatric events in the Cantigas de Santa Maria (Canticles of St. Mary, CSM), composed at the court of Alfonso X and the Milagros de Nuestra Señora (The Miracles of Our Lady, MNS), written by Gonzalo de Berceo. Among the 25 miracles reported in the MNS, medically relevant facts were addressed in 19 miracles with a total of 23 recorded events (including resurrection or escape from death in five) and demonic possession in three (one with witchcraft/deicide). The most common medical subjects were ergotism, obstetric-gynecological, sudden death, intellectual disability/illiteracy, encephalopathy/alcohol intoxication, suicide (with self-mutilation/castration), infanticide, infections, and absence of body decomposition after death. The 427 canticles in the CSM contain 270 medically relevant facts. Neuropsychiatric conditions were alluded to in 98 songs. Blindness and dystonia/weakness/deformities were the most common phenomena. Illuminations detailed many of the medical facts in the CSM, but not in the MNS. Medically relevant facts were described in both texts, but with more details in the CSM. Neurological conditions were more often described in the CSM, psychiatric conditions in the MNS.

Permanent Cerebellar Degeneration After Acute Hyperthermia with Non-toxic Lithium Levels: a Case Report and Review of Literature.

This was a study of a 33-year-old man with bipolar disorder treated with lithium who developed cerebellar atrophy after an event of extreme hyperthermia. Unlike previously reported cases of acute cerebellar atrophy after heat stroke, neuroleptic syndrome or lithium toxicity, this case was characterized by a chronic cerebellar atrophy that developed after sepsis-induced hyperthermia in the setting of non-toxic lithium levels. Unique to this case also was the early finding of cerebellar atrophy on MRI 2 weeks after the episode of hyperthermia, long-term neurotoxicity after the novo lithium therapy, and longest follow-up case of chronic cerebellar syndrome after hyperthermia with non-toxic lithium levels.

Chronic herpes simplex type-1 encephalitis with intractable epilepsy in an immunosuppressed patient.

BACKGROUND: Chronic herpes simplex virus type-1 encephalitis (HSE-1) is uncommon. Past reports focused on its association with prior documented acute infection. Here, we describe a patient with increasingly intractable epilepsy from chronic HSE-1 reactivation without history of acute central nervous system infection. CASE PRESENTATION: A 49-year-old liver transplant patient with 4-year history of epilepsy after initiation of cyclosporine developed increasingly frequent seizures over 3 months. Serial brain magnetic resonance imaging showed left temporoparietal cortical edema that gradually improved despite clinical decline. Herpes simplex virus type-1 (HSV-1) DNA was detected in cerebrospinal fluid by polymerase chain reaction. Cerebrospinal fluid HSV-1&2 IgM was negative. Seizures were controlled after acyclovir treatment, and the patient remained seizure free at 1-year follow-up. CONCLUSION: Chronic HSE is a cause of intractable epilepsy, can occur without a recognized preceding acute phase, and the clinical course of infection may not directly correlate with neuroimaging changes.

Pathological laughter and crying: A case series and proposal for a new classification.

BACKGROUND: Disorders of laughter and crying (DLC) are seen in several neuropsychiatric conditions. Their nomenclature remains under debate. METHODS: We present the clinical and imaging findings of 17 patients with DLC and introduce a new classification based on phenomenology and pathogenesis. According to intensity and frequency of laughter and crying (observed behavioral output), patients were divided into hypoactive or hyperactive DLC and subdivided into 5 subtypes: sensory (positive and negative), motor (positive and negative), and mixed. The sensory subtype is represented by disorders of "feeling processing," whereas the motor subtype is represented by disorders of "emotion processing." "Positive" and "negative" describe elicitation by irritative vs destructive lesions, respectively. RESULTS: Among the patients studied, DLC resulted from ischemic stroke (n = 12), intracerebral hemorrhage (n = 2), gunshot wound (n = 1), amyotrophic lateral sclerosis (n = 1), or vestibular migraine (n = 1). Ten patients had lesions in the brainstem, 4 in the cerebral hemispheres, and 2 in sub-cortical-diencephalic structures. Six patients had negative motor DLC, 5 had positive sensory DLC, 4 had negative sensory DLC, and 2 had positive motor DLC. Phenomenology changed or progressed to mixed DLC in 7 patients. CONCLUSIONS: This novel phenomenological and pathomechanistic nomenclature explains all subtypes of DLC in neurologic, medical, and psychiatric conditions. Future studies are needed to validate it prospectively.

Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.

Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral nervous system caused by demyelination or axonal degeneration, or a combination of both features. We previously assigned the locus for autosomal dominant intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC. Biochemical experiments and genetic complementation in yeast show partial loss of aminoacylation activity of the mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce yeast growth. YARS localizes to axonal termini in differentiating primary motor neuron and neuroblastoma cultures. This specific distribution is significantly reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration.

Relation of Demographics and Reported Symptoms and Medication Use in Persons with Multiple Sclerosis.

A study using a cross-sectional descriptive design examined symptoms, race, sex, and use of disease-modifying therapies (DMT) in persons with relapsing remitting multiple sclerosis. Significant differences in symptoms and DMT use were found among women, men, and African Americans.

Comparing multicomponent interventions to improve skin care behaviors and prevent recurrence in veterans hospitalized for severe pressure ulcers.

OBJECTIVE: To compare a multicomponent motivational interviewing (MI)/self-management (SM) intervention with a multicomponent education intervention to improve skin-protective behaviors and prevent skin worsening in veterans with spinal cord injury (SCI) hospitalized for severe pressure ulcers (PrUs). DESIGN: Single-blinded, prospective, randomized controlled trial. SETTING: Six Veterans Affairs SCI centers. PARTICIPANTS: Veterans admitted for a severe (stage III/IV) PrU were followed up to 6 months postdischarge. INTERVENTION: Telephone-based individual MI counseling plus SM skills group (SM+MI; n=71) versus an active control group of telephone-based individual educational counseling plus group education (n=72). MAIN OUTCOME MEASURES: Self-reported skin-protective behaviors, objective skin worsening. RESULTS: Intention-to-treat analyses found nonsignificant increases in skin behaviors in the SM+MI versus education control intervention arms at 3 and 6 months. The difference in behaviors used between SM+MI and education control intervention participants was 4.6% (95% confidence interval [CI], -11.3 to 2.7) (0-3mo) and 3.0% (95% CI, -8.7 to 3.9) (0-6mo). High rates of skin worsening were observed (n=74, 51.7%), usually within 3 months postdischarge and most frequently within the month postdischarge. Skin worsening, skin-related visits, and readmissions did not differ by study arm. Study limitations are presented. CONCLUSIONS: For persons with chronic SCI and severe PrUs, complicated by multiple comorbidities, a primary focus on improving patient behavior is likely insufficient to address the complex problem of PrUs in SCI. More health care systems-level changes such as collaborative care may be needed to reduce PrU recurrence, especially in this era in which many people are discharged from the hospital unhealed or with little sitting tolerance.

Personality dimensions, depression, and eating behavior in individuals seeking bariatric surgery: a cluster analysis.

Introduction: Psychiatric comorbidity is frequent in bariatric surgery candidates. This study aimed to classify bariatric surgery patients according to patterns of preoperative measures of the severity of the eating disorder (ED), depression, and personality traits. Methods: In the present cross-sectional study, 115 adult candidates for bariatric surgery (75 females, 65.22% of sample; mean age 37) were considered for analysis. Patients' sociodemographic and psychopathological variables were collected. K-Means clustering analysis was adopted to classify bariatric surgery candidates according to their preoperative Eating Disorder Inventory-2 (EDI-2) scores. In addition, we assessed depression and personality traits using the Beck Depression Inventory-2 (BDI-2) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: Cluster analysis based on EDI-2 revealed two preoperative patterns: higher severity (n = 39), and low severity (n = 76). The more severe EDI-2 group had higher scores on the BDI-2 and presented higher scores on several MMPI-2 dimensions, particularly those related to anxiety (Psychasthenia, Anxiety, Fears, Obsessiveness), depression (Depression, including both content and clinical MMPI-2 subscales), externalizing symptoms (Anger, Cynicism, Type A Behavior), and social functioning (Social Introversion, Family Problems, Work Interference). Discussion: Eating disorders symptoms in candidates for bariatric surgery are closely related to depression and different psychological conditions assessed with MMPI-2. These psychological variables should be evaluated preoperatively and targeted with more specific psychological interventions.

A web-based survey to map the electromyography practice in Brazil.

BACKGROUND: Detailed information about the electromyography practice in Brazil is largely unavailable. OBJECTIVE: To evaluate where and how electromyography is performed in Brazil, as well as regional disparities and the professional and academic credentials of electromyographers. METHODS: We conducted an internet-based survey of active Brazilian electromyographers. The websites of health insurance companies, professional academies, medical cooperatives, online search engines, and social networks in each Brazilian state were screened and we evaluated the credentials of each electromyographer listed in the Brazilian Federal Medical Board (BFMB) registration website and their online curricula vitae in the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, in Portuguese). We also evaluated the same parameters in a control group of non-electromyographer neurologists randomly matched by geographical distribution and gender. RESULTS: We found 469 electromyographers (384 neurologists and 85 non-neurologists), with a male predominance. In total, 81.9% were BFMB-certified neurologists, 49.9%, BFMB-certified clinical neurophysiologists, and 10.4%, BFMB-certified physiatrists. Among the non-neurologists, 48.2% were physiatrists. Most electromyographers practiced in states on the Southern and Southeastern regions of Brazil. When adjusted by population, the Federal District and the states of Mato Grosso do Sul and Goiás presented the highest of eletromyographers density. Electromyographers were not more likely to have current/past academic affiliations. CONCLUSION: In Brazil, electromyography is performed predominantly by neurologists, and half of them are BFMB-certified clinical neurophysiologists. The present study highlights regional disparities and may guide government-based initiatives, for instance, to improve the diagnosis of leprosy and the management of neuromuscular disorders within the Brazilian territory.

ANTECEDENTES: Informações detalhadas sobre a prática de eletromiografia no Brasil são em grande parte indisponíveis. OBJETIVO: Avaliar onde e como a eletromiografia é realizada no Brasil, as disparidades regionais, e as credenciais profissionais e acadêmicas dos eletromiografistas. MéTODOS: Realizamos uma enquete via internet de eletromiografistas brasileiros ativos. Foram rastreados sites de operadoras de planos de saúde, academias profissionais médicas, cooperativas médicas, ferramentas de busca online e redes sociais em cada estado brasileiro. Em seguida, avaliamos as credenciais de cada eletromiografista listado no site de registro do Conselho Federal de Medicina (CFM) e seus curricula vitae online no Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Também avaliamos os mesmos parâmetros em um grupo controle de neurologistas não eletromiografistas pareados aleatoriamente por distribuição geográfica e gênero. RESULTADOS: Encontramos 469 eletromiografistas (384 neurologistas e 85 não neurologistas), com predominância do sexo masculino. Ao todo, 81,9% eram neurologistas com certificação confirmada pelo site do CFM, 49,9%, neurofisiologistas clínicos com certificação confirmada pelo site do CFM, e 10,4%, fisiatras com certificação confirmada pelo mesmo site. Entre os não neurologistas, 48,2% eram fisiatras. A maioria dos eletromiografistas atuava nos estados do Sul e do Sudeste. Quando ajustados pela população, o Distrito Federal e os estados de Mato Grosso do Sul e Goiás apresentaram a maior densidade de eletromiografistas. Os eletromiografistas não eram mais propensos a ter vínculos acadêmicos atuais/passados. CONCLUSãO: No Brasil, a eletromiografia é realizada predominantemente por neurologistas, e metade deles são neurofisiologistas clínicos com certificação confirmada pelo site do CFM. Este estudo destacou as disparidades regionais, e pode orientar ações governamentais para, por exemplo, melhorar o diagnóstico da hanseníase e o manejo das doenças neuromusculares no território brasileiro.

Custom order entry for Parkinson's medications in the hospital improves timely administration: an analysis of over 31,000 medication doses.

Background: Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital. Material and methods: We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed. Results: 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p<.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p<0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time (p<0.001 for all comparisons). Conclusion: This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications.

Effectiveness of supported employment for veterans with spinal cord injuries: results from a randomized multisite study.

OBJECTIVE: To examine whether supported employment (SE) is more effective than treatment as usual (TAU) in returning veterans to competitive employment after spinal cord injury (SCI). DESIGN: Prospective, randomized, controlled, multisite trial of SE versus TAU for vocational issues with 12 months of follow-up data. SETTING: SCI centers in the Veterans Health Administration. PARTICIPANTS: Subjects (N=201) were enrolled and completed baseline interviews. In interventional sites, subjects were randomly assigned to the SE condition (n=81) or the TAU condition (treatment as usual-interventional site [TAU-IS], n=76). In observational sites where the SE program was not available, 44 subjects were enrolled in a nonrandomized TAU condition (treatment as usual-observational site [TAU-OS]). INTERVENTIONS: The intervention consisted of an SE vocational rehabilitation program called the Spinal Cord Injury Vocational Integration Program, which adhered as closely as possible to principles of SE as developed and described in the individual placement and support model of SE for persons with mental illness. MAIN OUTCOME MEASURES: The primary study outcome measurement was competitive employment in the community. RESULTS: Subjects in the SE group were 2.5 times more likely than the TAU-IS group and 11.4 times more likely than the TAU-OS group to obtain competitive employment. CONCLUSIONS: To the best of our knowledge, this is the first and only controlled study of a specific vocational rehabilitation program to report improved employment outcomes for persons with SCI. SE, a well-prescribed method of integrated vocational care, was superior to usual practices in improving employment outcomes for veterans with SCI.

Laser-Assisted Micro-Solder Bumping for Copper and Nickel-Gold Pad Finish.

Flip-chip bonding is a key packaging technology to achieve the smallest form factor possible. Using copper as a direct under-bump metal and performing bonding under little force and at a low temperature eliminates the processing step for the deposition of a suitable wetting metal and offers an economical solution for electronic chip packaging. In this paper, various samples with copper and nickel-gold surface finishes are used to apply an in-house solder bumping, flip-chip bonding and reflow process to exhibit the bump-bond feasibility. Native oxides are reduced using process gases, and copper surface protection and solder wetting are achieved using copper formate. Lead-free 40 µm solder balls were bumped on 80 µm copper pads and 120 µm copper pillars to demonstrate a full intermetallic Cu-Cu bond as a base study for stacking applications. Using a low-force bonding technique, various chips with different dimensions were bonded at 0.5-16 MPa, followed by a reflow step at a maximum temperature of 270 °C. Then, 30 µm solder balls are utilized to bump the samples with NiAu and Cu bond pads at 50 µm pitch. A mean shear strength of 44 MPa was obtained for the 30 µm Cu samples. To the best of our knowledge, 30 µm solder bumping directly on the copper pads by producing copper formate is a novel research contribution.

High-frequency rTMS modulates emotional behaviors and structural plasticity in layers II/III and V of the mPFC.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique, and it has been increasingly used as a nonpharmacological intervention for the treatment of various neurological and neuropsychiatric diseases, including depression. In humans, rTMS over the prefrontal cortex is used to induce modulation of the neural circuitry that regulates emotions, cognition, and depressive symptoms. However, the underlying mechanisms are still unknown. In this study, we investigated the effects of a short (5-day) treatment with high-frequency (HF) rTMS (15 Hz) on emotional behavior and prefrontal cortex morphological plasticity in mice. Mice that had undergone HF-rTMS showed an anti-depressant-like activity as evidenced by decreased immobility time in both the Tail Suspension Test and the Forced Swim Test along with increased spine density in both layer II/III and layer V apical and basal dendrites. Furthermore, dendritic complexity assessed by Sholl analysis revealed increased arborization in the apical portions of both layers, but no modifications in the basal dendrites branching. Overall, these results indicate that the antidepressant-like activity of HF-rTMS is paralleled by structural remodeling in the medial prefrontal cortex.

Position-dependent arm dyskinesia due to severe craniocervical malformation.

CONTEXT: Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and central nervous system involvement. In this case report, we describe a novel form of position-dependent dyskinesia due to severe craniocervical malformation. FINDINGS: An 83-year-old woman with basilar invagination at the C2 vertebra above the line of Chamberlain, occipitocervical lordosis, platybasia with a short clivus, ankylosis of the C1-C2 complex and fusion of the C1 arch developed an unusual pattern of position-dependent left arm dyskinesia triggered by bending her neck forward with simultaneous contact of the flexed elbow with a flat surface. Symptoms did not improve with anticonvulsants and she progressed and died suddenly. CONCLUSION/CLINICAL RELEVANCE: A newly described form of position-dependent arm dyskinesia can be associated with severe craniocervical malformation.

Motor Cortex Response to Pleasant Odor Perception and Imagery: The Differential Role of Personality Dimensions and Imagery Ability.

Background: Neuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil (BEO) is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor (BEO) on motor cortex using Transcranial magnetic stimulation (TMS). Materials and Methods: We examined the primary motor cortex (M1) excitability during perception of a pleasant odor (BEO) or perception of odorless saline (experiment 1). Furthermore, we tested the effect of olfactory imagery (OI) of BEO on corticospinal excitability (experiment 2). The increase in motor evoked potential (MEP) amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability. Results: The results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor (BEO). The correlation analysis shows an association with neuroticism personality trait (experiment 1) and with general olfactory imagery ability (experiment 2). Conclusion: Both perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems.

Patient-Reported Symptom Burden of Charcot-Marie-Tooth Disease Type 1A: Findings From an Observational Digital Lifestyle Study.

OBJECTIVES: This study aims to explore the impact of Charcot-Marie-Tooth disease type 1A (CMT1A) and its treatment on patients in European (France, Germany, Italy, Spain, and the United Kingdom) and US real-world practice. METHODS: Adults with CMT1A (n = 937) were recruited to an ongoing observational study exploring the impact of CMT. Data were collected via CMT&Me, an app through which participants completed patient-reported outcome measures. RESULTS: Symptoms ranked with highest importance were weakness in the extremities, difficulty in walking, and fatigue. Almost half of participants experienced a worsening of symptom severity since diagnosis. Anxiety and depression were each reported by over one-third of participants. Use of rehabilitative interventions, medications, and orthotics/walking aids was high. CONCLUSIONS: Patient-reported burden of CMT1A is high, influenced by difficulties in using limbs, fatigue, pain, and impaired quality of life. Burden severity appears to differ across the population, possibly driven by differences in rehabilitative and prescription-based interventions, and country-specific health care variability.