645 research outputs found
Otępienie naczyniopochodne i mieszane: znaczenie wczesnego leczenia farmakologicznego
U pacjentów z otępieniem naczyniopochodnym oraz z otępieniem
w chorobie Alzheimera (AD, Alzheimer’s disease) z towarzyszącymi
chorobami naczyniowymi mózgu obserwuje się związek otępienia
ze schorzeniami naczyniowymi mózgu. Rozpoznanie otępienia
naczyniopochodnego jest złożone i w głównej mierze opiera
się na obrazie klinicznym, w którym dominuje stopniowa progresja
otępienia ściśle związana z występowaniem udarów oraz
ogniskowych objawów neurologicznych, w powiązaniu z objawami
obejmującymi również zmiany w zakresie zaburzeń funkcji wykonawczych,
co prowadzi do obniżenia zdolności do wykonywania
instrumentalnych czynności życia codziennego. W odróżnieniu
od otępienia naczyniopochodnego u pacjentów z otępieniem
w AD z towarzyszącymi schorzeniami naczyniowymi mózgu
zwykle dochodzi do stopniowo postępujących zaburzeń w zakresie
funkcji poznawczych, która może się również wiązać ze współwystępowaniem
incydentów mózgowo-naczyniowych. Wczesne
rozpoznanie połączone z interwencją terapeutyczną przyczynia się
do zapobieżenia dalszemu postępowi choroby związanemu z możliwością
wystąpienia incydentów naczyniowych. Prawidłowe leczenie
chorób naczyniowych mózgu może ograniczyć deteriorację
poznawczą u pacjentów z otępieniem naczyniopochodnym,
a w wyniku leczenia inhibitorami cholinesterazy można uzyskać
poprawę w zakresie objawów otępienia w porównaniu z momentem
rozpoczęcia terapii. Na podstawie łącznej analizy wyników
uzyskanych w dwóch trwających 24 tygodnie badaniach klinicznych
przeprowadzonych z udziałem grupy kontrolnej przyjmującej
placebo wskazano, że u chorych z otępieniem naczyniopochodnym
leczonych donepezilem następuje poprawa w zakresie funkcji poznawczych,
globalnego funkcjonowania oraz instrumentalnych
czynności życia codziennego. Jednocześnie u pacjentów z otępieniem
w przebiegu AD z towarzyszącymi chorobami naczyniowymi
mózgu obserwuje się stopniowo narastające objawy otępienia
mimo schorzeń naczyniowych mózgu, a skutki tej terapii
należy rozpatrywać jako możliwość uzyskania początkowej poprawy,
z następującą stabilizacją lub spowolnieniem postępu objawów
otępienia w czasie. W badaniach dotyczących chorych leczonych
donepezilem u pacjentów z otępieniem w AD oraz z otępieniem
w AD z towarzyszącymi chorobami naczyniowymi mózgu obserwuje
się podobne efekty leczenia w zakresie funkcji poznawczych,
globalnego funkcjonowania oraz jakości życia. Wyniki tych badań
uzasadniają celowość prowadzenia farmakoterapii donepezilem
u osób z otępieniem naczyniopochodnym lub z otępieniem w przebiegu
AD ze współistniejącymi chorobami naczyniowymi mózgu
RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health
Auswirkungen von Antifeminismus auf Frauenverbände
AUSWIRKUNGEN VON ANTIFEMINISMUS AUF FRAUENVERBÄNDE
Auswirkungen von Antifeminismus auf Frauenverbände / Rahner, Judith (Rights reserved) ( -
Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management
Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations
A map of neurofilament light chain species in brain and cerebrospinal fluid and alterations in Alzheimer\u27s disease
Neurofilament light is a well-established marker of both acute and chronic neuronal damage and is increased in multiple neurodegenerative diseases. However, the protein is not well characterized in brain tissue or body fluids, and it is unknown what neurofilament light species are detected by commercial assays and whether additional species exist. We developed an immunoprecipitation-mass spectrometry assay using custom antibodies targeting various neurofilament light domains, including antibodies targeting Coil 1A/1B of the rod domain (HJ30.13), Coil 2B of the rod domain (HJ30.4) and the tail region (HJ30.11). We utilized our assay to characterize neurofilament light in brain tissue and CSF of individuals with Alzheimer\u27s disease dementia and healthy controls. We then validated a quantitative version of our assay and measured neurofilament light concentrations using both our quantitative immunoprecipitation-mass spectrometry assay and the commercially available immunoassay from Uman diagnostics in individuals with and without Alzheimer\u27s disease dementia. Our validation cohort included CSF samples from 30 symptomatic amyloid-positive participants, 16 asymptomatic amyloid-positive participants, 10 symptomatic amyloid-negative participants and 25 amyloid-negative controls. We identified at least three major neurofilament light species in CSF, including N-terminal and C-terminal truncations, and a C-terminal fragment containing the tail domain. No full-length neurofilament light was identified in CSF. This contrasts with brain tissue, which contained mostly full-length neurofilament and a C-terminal tail domain fragment. We observed an increase in neurofilament light concentrations in individuals with Alzheimer\u27s disease compared with healthy controls, with larger differences for some neurofilament light species than for others. The largest differences were observed for neurofilament light fragments including NfL165 (in Coil 1B), NfL324 (in Coil 2B) and NfL530 (in the C-terminal tail domain). The Uman immunoassay correlated most with NfL324. This study provides a comprehensive evaluation of neurofilament light in brain and CSF and enables future investigations of neurofilament light biology and utility as a biomarker
COVIDReady2 study protocol: cross-sectional survey of medical student volunteering and education during the COVID-19 pandemic in the United Kingdom.
BACKGROUND: The coronavirus disease 2019 pandemic has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students. METHODS: The COVIDReady2 study is a national cross-sectional study of all medical students at medical schools in the United Kingdom. The primary outcome is to explore the experiences of medical students who volunteered during the pandemic in comparison to those who did not. We will compare responses to determine the educational benefit and issues they faced. In addition to quantitative analysis, thematic analysis will be used to identify themes in qualitative responses. DISCUSSION: There is a growing body of evidence to suggest that service roles have potential to enhance medical education; yet, there is a shortage of studies able to offer practical advice for how these roles may be incorporated in future medical education. We anticipate that this study will help to identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future, and help inform medical education in a non-pandemic setting. TRIAL REGISTRATION: Not Applicable
A Cost Analysis of Postoperative Pain Management in Endometrial Cancer Patients: Robotic Department of Surgery vs. Laparoscopy Department of Surgery
Effect of race on prediction of brain amyloidosis by plasma Aβ42/Aβ40, phosphorylated tau, and neurofilament light
BACKGROUND AND OBJECTIVES: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.
METHODS: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age,
RESULTS: There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were
DISCUSSION: Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and consistent measure of brain amyloidosis across AA and NHW groups, but models based on plasma p-tau181, p-tau231, and NfL may perform inconsistently and could result in disproportionate misdiagnosis of AA individuals
Comparison of plasma and CSF biomarkers in predicting cognitive decline
OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer\u27s disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.
METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over a maximum of 6 years as predicted by the fluid biomarkers.
RESULTS: Analyses included 371 cognitively normal participants, aged 72.7 ± 5.2 years (mean ± standard deviation) with an average length of follow-up of 3.9 ± 1.6 years. Standardized concentrations of biomarkers were associated with annualized cognitive change: plasma Aβ42/Aβ40, 0.014 standard deviations (95% confidence intervals 0.002 to 0.026); CSF Aβ42/Aβ40, 0.020 (0.008 to 0.032); plasma Nfl, -0.018 (-0.030 to -0.005); and CSF NfL, -0.024 (-0.036 to -0.012). Power analyses estimated that 266 individuals in each treatment arm would be needed to detect a 50% slowing of decline if identified by abnormal plasma measures versus 229 for CSF measures.
INTERPRETATION: Both plasma and CSF measures of Aβ42/Aβ40 and NfL predicted cognitive decline. A clinical trial that enrolled individuals based on abnormal plasma Aβ42/Aβ40 and NfL levels would require only a marginally larger cohort than if CSF measures were used
Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population
BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin
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