Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

INTRODUCTION: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. METHODS: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. RESULTS: Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. CONCLUSION: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old). Comprehensive analysis of reproductive outcomes was conducted in our population. Various mitochondrial-related parameters were analyzed across distinct subsets. Specifically, mitochondrial membrane potential (∆Ψm) and mitochondrial mass were examined in 53 samples, mtDNA content in 25 samples, protein levels in 23 samples, bioenergetic profiles using an XF24 Extracellular Flux Analyzer in 6 samples, and levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in 39 and 43 samples, respectively. In our study, the reproductive potential of AMA women sharply decreased, as expected. Additionally, an impairment in the mitochondrial function of hCCs in older women was observed; however, no differences were found in terms of mitochondrial content. Regarding oxidative phosphorylation, metabolic profiling of hCCs from AMA women indicated a decrease in respiratory capacity, which was correlated with an age-dependent decrease in the ATP synthase (ATP5A1) protein level. However, intracellular ROS and ATP levels did not differ between groups. In conclusion, our study indicates that age-related dysfunction in hCCs is associated with impaired mitochondrial function, and, although further studies are required, ATP synthase could be relevant in this impairment.

Optimization of Platelet-Rich Plasma Preparation for Regenerative Medicine: Comparison of Different Anticoagulants and Resuspension Media.

Platelet-rich plasma (PRP) has emerged as a promising therapy in regenerative medicine. However, the lack of standardization in PRP preparation protocols presents a challenge in achieving reproducible and accurate results. This study aimed to optimize the PRP preparation protocol by investigating the impact of two different anticoagulants, sodium citrate (SC) and ethylenediaminetetraacetic acid (EDTA), and resuspension media, plasma versus sodium chloride (NaCl). Platelet recovery rates were calculated and compared between groups, in addition to platelet activity and vascular endothelial growth factor (VEGF) released into plasma after PRP activation. The platelet recovery rate was higher with EDTA in comparison to SC (51.04% vs. 29.85%, p = 0.005). Platelet activity was also higher, with a higher expression of two platelet antibodies, platelet surface P-Selectin (CD62p) and PAC-1, in the EDTA group. The concentration of VEGF was higher with SC in comparison to EDTA (628.73 vs. 265.44 pg/mL, p = 0.013). Platelet recovery rates and VEGF levels were higher in PRP resuspended in plasma when compared to NaCl (61.60% vs. 48.61%, p = 0.011 and 363.32 vs. 159.83 pg/mL, p = 0.005, respectively). Our study reinforces the superiority of EDTA (as anticoagulant) and plasma (for resuspension) in obtaining a higher platelet recovery and preserving platelet functionality during PRP preparation.

Treatment strategies and treatment-related adverse events in MG according to the age of onset.

Introduction: Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset. Methods: This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records. Results: In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0-64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%). Conclusion: Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.

Anti-titin antibodies in a cohort of myasthenia gravis patients.

Background: Anti-titin antibodies have been previously associated with thymoma-associated myasthenia gravis (MG) and a more clinically severe form of MG. While currently only serving as a disease biomarker, its possible utility as an indicator of underlying thymus malignancy may be of value in clinical practice. Methods: Data was retrospectively collected and analyzed from 2013 to 2022 using an institutional record of MG patients. Anti-titin antibodies were assessed using Line Blot immunoassay. Results: From 130 MG cases, 32 (24.6%) were anti-titin positive. Anti-titin positive cases were associated with older age of disease onset [median (IQR): 63.0 (44.3-70.8) vs. 35.5 (24.8-60.8) years] (P<0.01). Thymectomy was performed in 46 (35.4%) MG patients, 12 of which anti-titin positive (26.1%). Thymectomy samples from anti-titin positive patients comprised 10 (83.3%) cases of thymoma and 2 (16.7%) cases of thymus hyperplasia. There was a tendency towards anti-titin positive patients having more thymoma while anti-titin negative displayed more hyperplasia (P<0.01). Anti-titin positivity correlated with thymoma in patients with age of onset bellow 50 years (P=0.028). Anti-titin positivity was significantly associated with generalized MG in the late-onset group (P=0.005). Conclusions: The presence of anti-titin antibodies appears to correlate with underlying thymoma in early-onset MG cases and with generalized MG in late-onset cases. Prospective studies are needed to further study this association.

Towards standardized human platelet lysate production in Europe: An initiative of the European Blood Alliance.

Human platelet lysate (hPL) is a supplement for cell culture media that can be derived from platelet concentrates. As not-for-profit blood establishments, we endorse the evolution of maximally exploiting the potential of donated blood and its derived components, including platelets. The decision to use platelet concentrates to supply hPL as a cell culture supplement should align with the principles and values that blood establishments hold towards the use of donated blood components in transfusion. As a consequence, questions on ethics, practical standardization of hPL production and logistics as well as on assuring hPL quality and safety need careful consideration. We therefore propose an opinion on some of these matters based on available literature and on discussions within the proceedings of the Working Group on Innovation and New Products of the European Blood Alliance. In addition, we propose collaboration among European blood establishments to streamline efforts of hPL supply to maximize the potential of hPL and its application in the wider field of medicine.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

New Insights on Sperm Function in Male Infertility of Unknown Origin: A Multimodal Approach.

The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universitário de Coimbra (CHUC), from July 2018-July 2022. Based on the couples' clinical data, seminal/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.

Do the instruments used to assess fibromyalgia symptoms according to American College of Rheumatology criteria generate similar scores in other chronic musculoskeletal pain?

BACKGROUND: As with fibromyalgia, several musculoskeletal disorders are characterized by chronic pain, raising a clinical question - do the instruments used to assess fibromyalgia symptoms according to ACR criteria (ACR criteria) generate similar scores in other chronic musculoskeletal pain? OBJECTIVE: To compare the symptoms among fibromyalgia and other chronic musculoskeletal pain. Additionally, we also compared the most researched outcomes in fibromyalgia (i.e., present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptom). METHODS: A cross-sectional study. Participants over 18 years old were included if they presented report of chronic musculoskeletal pain (≥ 3 months) and after that, they were divided into two groups (fibromyalgia and chronic pain). They answered the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), Brief Pain Inventory (BPI), Numerical Pain Rating Scale (NPRS) for pain and fatigue, WPI, and SSS. RESULTS: A total of 166 participants were included in this study into two independent groups (chronic pain, n = 83; fibromyalgia, n = 83). We observed significant differences (p < 0.05) and large effect sizes (Cohen's d, ≥ 0.7) in clinical outcomes comparisons between groups (i.e., widespread pain; symptom severity; present pain at rest and after movement; fatigue; pain severity and impact; function, global impact, and fibromyalgia symptoms). CONCLUSION: Fibromyalgia patients (2016 ACR criteria) compared to other chronic musculoskeletal pain patients have higher levels of pain (at rest or after movement) and fatigue, greater impairment in both functionality and global impact, and worse symptoms. Therefore, the WPI and SSS instruments should be used exclusively to assess fibromyalgia symptoms.

Low responders may benefit from undergoing ovarian stimulation with a long GnRH agonist protocol with corifollitropin alfa followed by hMG.

OBJECTIVE: To evaluate the outcomes of a long GnRH agonist protocol with corifollitropin alfa followed by hMG in low responders. METHODS: Retrospective cohort study. Patients with a suboptimal previous ovarian response (<9 oocytes) and a normal ovarian reserve (Poseidon groups 1 and 2) were classified in 1) Group 1 (n=88), submitted to a second cycle with a GnRH antagonist protocol using rFSH/hMG; 2) Group 2 (n=66), submitted to a long GnRH agonist protocol with corifollitropin alfa followed by hMG (named as simplified long protocol). Clinical outcomes were compared between groups and between the first/second cycle of each group. RESULTS: Clinical outcomes were similar between groups. There were no differences in the number of oocytes [7(5-11.75) versus 7(5-10), p=0.802], clinical pregnancy (19.3% versus 18.2%, p=0.858) and live birth rates (18.2% versus 15.2%, p=0.619). However, baseline characteristics were different, decoding a poor prognosis among women in group 2. Both groups (1 and 2) had significantly higher number of oocytes, pregnancy, and live birth rates in the second cycle. In group 2, there was a higher rate of embryo transfer (56.1% versus 27.3%, p<0.001). In group 1, despite the similar rate of embryo transfer, there was a higher positive hCG (23.9% versus 8.0%, p=0.004). CONCLUSIONS: Both simplified long protocol and GnRH antagonist protocol are suitable for low responders. The best second cycle clinical outcomes experienced in a population with worse prognosis (group 2) suggests that the simplified long protocol may be a better option, although prospective well-conducted studies must explore this hypothesis.

Aging and oocyte competence: A molecular cell perspective.

Follicular microenvironment is paramount in the acquisition of oocyte competence, which is dependent on two interconnected and interdependent processes: nuclear and cytoplasmic maturation. Extensive research conducted in human and model systems has provided evidence that those processes are disturbed with female aging. In fact, advanced maternal age (AMA) is associated with a lower chance of pregnancy and live birth, explained by the age-related decline in oocyte quality/competence. This decline has largely been attributed to mitochondria, essential for oocyte maturation, fertilization, and embryo development; with mitochondrial dysfunction leading to oxidative stress, responsible for nuclear and mitochondrial damage, suboptimal intracellular energy levels, calcium disturbance, and meiotic spindle alterations, that may result in oocyte aneuploidy. Nuclear-related mechanisms that justify increased oocyte aneuploidy include deoxyribonucleic acid (DNA) damage, loss of chromosomal cohesion, spindle assembly checkpoint dysfunction, meiotic recombination errors, and telomere attrition. On the other hand, age-dependent cytoplasmic maturation failure is related to mitochondrial dysfunction, altered mitochondrial biogenesis, altered mitochondrial morphology, distribution, activity, and dynamics, dysmorphic smooth endoplasmic reticulum and calcium disturbance, and alterations in the cytoskeleton. Furthermore, reproductive somatic cells also experience the effects of aging, including mitochondrial dysfunction and DNA damage, compromising the crosstalk between granulosa/cumulus cells and oocytes, also affected by a loss of gap junctions. Old oocytes seem therefore to mature in an altered microenvironment, with changes in metabolites, ribonucleic acid (RNA), proteins, and lipids. Overall, understanding the mechanisms implicated in the loss of oocyte quality will allow the establishment of emerging biomarkers and potential therapeutic anti-aging strategies. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology.

Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor 1 (ESR1), have been studied in different populations with contradictory results. AIMS: To evaluate the influence of FSHR rs6166 (c.2039A>G) and of ESR1 rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS). MATERIALS AND METHODS: Genotyping of the FSHR rs6166 and the ESR1 rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups. RESULTS: We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of FSHR rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the ESR1 rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the FSHR polymorphism (9.2 vs 6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with FSHR or ESR1 genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the FSHR rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs 1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). CONCLUSION: Our data suggest that in the population, FSHR rs6166and ESR1 rs2234693 polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the FSHR rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.

Pain neuroscience education improves quality of life when added to aquatic exercise therapy for women with fibromyalgia: randomized controlled clinical trial.

PURPOSE: The aim of the present study was to investigate the effects of adding Pain Neuroscience Education (PNE) to an aquatic therapy protocol on pain, fibromyalgia (FMS) impact, quality of life and sleep. MATERIALS AND METHODS: Seventy-five women were randomly allocated into two groups: aquatic exercises (AEG, n = 36) and aquatic exercises + PNE (PNG, n = 39). The primary outcome was pain, and the secondary outcomes were FMS impact, quality of life, sleep and pain sensitivity (pressure pain thresholds - PPTs). Participants performed 45-min sessions of aquatic exercises, twice a week, for 12 weeks. PNG also received 4 PNE sessions during this period. Participants were assessed four times: initial (before treatment), after 6 weeks (intermediate) and 12 weeks (final) of treatment and after 12 weeks after the end of treatment (follow-up). RESULTS: Both groups improved pain after treatment, with no difference between them (p > 0.05, partial ƞ2 0.10). FMS impact and PPTs improved after treatment with no difference between groups, and sleep did not change. Quality of life improved several domains for both groups, with slightly better results for the PNG, with low effect sizes between groups. CONCLUSIONS: The present results show that the addition of PNE to an aquatic exercise intervention did not provide larger effects than aquatic exercises alone for people with FMS concerning pain intensity, but provided benefit for health-related quality of life for this population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03073642, version 2, April 1st, 2019). PERSPECTIVE: The addition of 4 Pain Neuroscience Education sessions to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome on pain, fibromyalgia impact, and sleep, but improved quality of life and pain sensitivity.IMPLICATIONS FOR REHABILITATIONAquatic exercises are commonly prescribed, but patient education is crucial for the treatment.The addition of Pain Neuroscience Education to an aquatic exercises protocol did not add benefits for women with fibromyalgia syndrome.The positive changes on quality of life and pain sensitivity that this combination led to had small effect sizes and did not achieve minimal important clinical difference.

Isolation of Extracellular Vesicles from Human Follicular Fluid: Size-Exclusion Chromatography versus Ultracentrifugation.

Follicular fluid (FF) is the microenvironment where a growing oocyte develops. Intrafollicular communication ensures oocyte competence and is carried out through paracrine signaling, the exchange of molecules via gap junctions, and the trafficking of extracellular vesicles (EVs). The study of FF-derived EVs is important for both translational and fundamental research in the female reproductive field. This study aimed to compare the efficacy and purity of two EV isolation methods: size-exclusion chromatography (SEC) and ultracentrifugation (UC). EVs isolated using SEC and UC were compared regarding their size and concentration using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA); protein contamination was assessed with microBCA; specific EV markers were detected with Western blot, and EV morphology was studied with transmission electron microscopy (TEM). Our results show that although both techniques isolated small EVs, a significantly increased yield in particle number was clear with UC compared with SEC. On the other hand, SEC generated purer EVs with fewer protein contaminants and aggregates. In conclusion, the selection of the most suited approach to isolate EVs must be conducted considering the degree of recovery, purity, and downstream application of the isolated EVs.

Characterization of a late-onset multiple sclerosis Portuguese cohort.

BACKGROUND: Late-onset multiple sclerosis (LOMS) is defined as the onset of symptoms above 50 years, corresponding to an increasingly recognized subset of MS. This study aimed at comparing demographic and clinical data of patients with LOMS to those of early-onset MS (EOMS) from a Portuguese cohort. METHODS: Retrospective chart review of an MS cohort from a Portuguese tertiary center. RESULTS: From 746 patients with MS (61.7% female), we identified 39 cases with presentation after 50 years of age (22 males and 17 females), corresponding to 5.3%. The mean age at onset was 55.4 (±5.0) for LOMS and 29.5 (±8.9) for EOMS. There was no significant difference in disease duration. The most common type was relapsing-remitting MS, accounting for 51.5% and 83.9% of LOMS and EOMS patients, respectively. Primary-progressive MS (PPMS) was significantly more represented in the LOMS group (41.0%) (p < 0.01). The median EDSS was significantly higher in the LOMS group (4.75, 0.0-7.5) when compared to the EOMS group (2.0, 0.0-9,0). The most frequent presenting feature was myelitis in both LOMS (48.7%) and EOMS patients (47.4%), resulting in significantly higher EDSS (p = 0.003). CONCLUSIONS: LOMS is associated with higher EDSS when considering the same disease duration, translating into increased disability.

Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.

Predictors of cognitive dysfunction in hereditary transthyretin amyloidosis with liver transplant.

BACKGROUND: Cognitive dysfunction is part of the broad spectrum of clinical manifestations in older untreated hereditary transthyretin amyloidosis patients with peripheral polyneuropathy. OBJECTIVE: The objective of this study is to systematically explore cognitive dysfunction in ATTRV30M amyloidosis patients whose disease course was modified by liver transplant (LT). METHODS: A series of 269 carriers of TTRVal30Met mutation treated with LT underwent a neuropsychological assessment. Clinical charts were reviewed to identify focal neurological episodes (FNEs), cognitive complaints and laboratory results. Chi-square and Mann-Whitney tests explored potential predictors of cognitive dysfunction. RESULTS: Cognitive dysfunction was identified in 35 patients (13%)-14 (5%) had mild and 21 (8%) had moderate dysfunction. In comparison to normal cognition, both mild and moderate cognitive dysfunction patients had older age, higher mPND score and elevated NT-proBNP and Cystatin C values. Mild cognitive dysfunction was associated with longer disease duration and history of FNEs, whereas moderate dysfunction was related to older age at disease onset and more cognitive complaints and depression symptoms. CONCLUSIONS: Consistent with the natural history of the disease, older age and higher severity of the disease are significantly associated and potentially predictors of cognitive dysfunction in ATTRV30M patients treated with LT. The level of cognitive dysfunction may depend on some clinical variables.

Immediate puerperium during the pandemic: women's oral history in the light of obstetric care models / Puerperio inmediato en la pandemia: historia oral de mujeres a la luz de modelos de atención obstétrica / Puerpério imediato na pandemia: história oral de mulheres à luz dos modelos de assistência obstétrica

ABSTRACT Objective: To describe the immediate puerperium experience of women during the COVID-19 pandemic in a public maternity hospital in Curitiba/PR in southern Brazil. Method: A qualitative study, following the Thematic Oral History methodological framework. The setting was a high-risk maternity-school. Data collection took place through a semi-structured, audio-recorded, on-site interview, from October to December 2021, with analysis of results following the Thematic Oral History method, which comprises the phases of transcription, textualization and transcreation. Results: Nine women in immediate puerperium participated, with varied professions and aged between 25 and 34 years. Relevant topics were: "Maternity in a context of risk", which deals with emotional aspects related to the pandemic, health care during the pandemic and care actions against COVID-19; "Physical and symbolic perceptions of breastfeeding", which involves feelings, manifestations in the body and the symbolic of breastfeeding; "Achieve: direct and indirect transitive verb", which talks about women's power of personal transformation; and "Nuances of care", which addresses the (in)delicacies of the care received. Conclusion: The experience of immediate puerperium in hospital environments during the pandemic transversely went beyond aspects of pregnancy, childbirth and the puerperium, revealing elements not related to the pandemic and others, such as fear of contamination specific to the pandemic context. Talking about their experience is an opportunity to expose feelings and align thoughts about their reality. Characteristics of childbirth care models orbiting between technocratic and humanized were observed, demonstrating aspects to be overcome by health professionals and worked with women.

RESUMEN Objetivo: Describir la experiencia del posparto inmediato de mujeres durante la pandemia de COVID-19 en una maternidad pública de Curitiba/PR en el sur de Brasil. Método: Estudio cualitativo, siguiendo el marco metodológico de la Historia Oral Temática. El escenario era una maternidad-escuela de alto riesgo. La recolección de datos se realizó a través de una entrevista semiestructurada, grabada en audio, cara a cara, de octubre a diciembre de 2021, con análisis de los resultados siguiendo el método de Historia Oral Temática, que comprende las fases de transcripción, textualización y transcreación. Resultados: Participaron nueve mujeres en puerperio inmediato, con variadas profesiones y con edades entre 25 y 34 años. Los temas relevantes fueron: "Maternidad en contexto de riesgo", que trata aspectos emocionales relacionados con la pandemia, la atención a la salud en la pandemia y las acciones de atención frente al COVID-19; "Percepciones físicas y simbólicas de la lactancia materna", que involucra sentimientos, manifestaciones en el cuerpo y lo simbólico de la lactancia materna; "Conseguir: verbo transitivo directo e indirecto", que habla del poder de transformación personal de la mujer; y "Matices del cuidado", que aborda las (in)delicadezas del cuidado recibido. Conclusión: La vivencia del puerperio inmediato en el ambiente hospitalario durante la pandemia permeó transversalmente aspectos del embarazo, parto y puerperio, revelando elementos no relacionados con la pandemia y otros, como el miedo a la contaminación, propios del contexto pandémico. Hablar de tu experiencia es una oportunidad para exponer sentimientos y alinear pensamientos sobre tu realidad. Se observaron características de modelos de atención al parto que orbitan entre tecnocráticos y humanizados, evidenciando aspectos a ser superados por profesionales de la salud y trabajados con mujeres.

RESUMO Objetivo: descrever a experiência de puerpério imediato de mulheres na pandemia da COVID-19 em maternidade pública de Curitiba/PR, no Sul do Brasil. Método: estudo qualitativo, seguindo referencial metodológico da História Oral Temática; o local foi uma maternidade-escola de alto risco; a coleta de dados deu-se por entrevista semiestruturada, audiogravada, presencial, de outubro a dezembro de 2021, com análise dos resultados seguindo o método História Oral Temática, que compreende as fases de transcrição, textualização e transcriação. Resultados: participaram nove mulheres no puerpério imediato, com profissões variadas e idade entre 25 e 34 anos. Os Temas Relevantes foram: "Maternar em um contexto de risco", que versa sobre aspectos emocionais relativos à pandemia, assistência à saúde na pandemia e ações de cuidado contra COVID-19; "Percepções físicas e simbólicas do aleitamento materno", que envolve sentimentos, manifestações no corpo e o simbólico do amamentar; "Conseguir: verbo transitivo direto e indireto", que fala sobre o poder de transformação pessoal das mulheres; e "Nuances do cuidar", que aborda (in)delicadezas do cuidado recebido. Conclusão: A experiência de puerpério imediato no ambiente hospitalar na pandemia perpassou transversalmente aspectos da gestação, parto e puerpério, revelando elementos não relacionados à pandemia e outros, como o medo da contaminação, específicos do contexto pandêmico. Falar sobre sua experiência é oportunidade de expor sentimentos e alinhar pensamentos sobre sua realidade. Foram observadas características dos modelos de assistência ao parto orbitando entre tecnocrático e humanizado, demonstrando aspectos a serem superados por profissionais de saúde e trabalhados com as mulheres.