Cerebral microbleeds in patients with Parkinson’s disease

Cerebral microbleeds (CMBs) are known to be associated with cognitive impairments in the elderly and in patients with various diseases; however, the nature of this association has not yet been evaluated in Parkinson’s disease (PD). In the present study, we analyzed the incidence of CMBs in PD according to cognitive status, and the impact of CMBs on cognitive performance was also evaluated. The CMBs in PD with dementia (n = 36), mild cognitive impairment (MCI, n = 46), or cognitively normal (n = 41) were analyzed using conventional T2*-weighted gradient-recalled echo images. Additionally, the relationship between the presence of CMBs and cognitive performance on individual tests of cognitive subdomains was analyzed using a detailed neuropsychological test. CMBs occurred more frequently in PD patients with dementia (36.1 %) compared to those with MCI (15.2 %), those who are cognitively normal (14.6 %), and normal controls (12.2 %, p = 0.025). However, the significant association of CMBs with PD dementia disappeared after adjusting white matter hyperintensities (WMHs) as a covariate. The frequencies of deep, lobar, and infratentorial CMBs did not differ among the four groups. After adjusting for age, sex, years of education, and WMHs, PD patients with CMBs had poorer performance in attention domain compared with those without CMBs (34.9 vs 42.6, p = 0.018). The present data demonstrate that even though CMBs were inseparably associated with the presence of WMHs, CMBs occur more commonly in PD patients with dementia than in those without dementia. Additionally, the burden of CMBs may contribute to further cognitive impairment in PD.     

Fractional Exhaled Nitric Oxide and Impulse Oscillometry in Children With Allergic Rhinitis

Purpose

Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS).

Methods

This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups.

Results

FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Δ X5) and reactance area (Δ AX) were compared. In the AR group, however, there was no difference in Δ X5 and Δ AX between the AR group with BHR and the AR group without.

Conclusions

Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.     

Transient lower extremity lymphedema following COVID-19 vaccination: A case report

Rationale:Complications from COVID-19 vaccines have yet to be sufficiently analyzed because they are rapidly approved without long-term data. In particular, there are no case reports of lymphedema in a healthy patient following vaccination. Herein, we report a patient who underwent transient lymphedema after vaccination with BNT16b2.Patient concerns:A 79-year-old woman with pitting edema in both lower legs after administration of a second dose of Pfizer vaccine was referred to our clinic. In the absence of clinical evidence of swelling during the laboratory evaluation, we suspected deep vein thrombosis. However, ultrasonographic findings revealed no evidence of venous thrombosis or varicose veins.Diagnosis:On the basis of lymphoscintigraphy, the patient was diagnosed with transient lymphedema with decreased lymphatic transport in both lower extremities.Intervention:The patient received intensive physiotherapy, including complex decongestive physiotherapy and pneumatic pump compression, to improve the lymphatic circulation. Furthermore, the patient was trained to apply a multilayer compressive bandage to the lower extremities.Outcomes:At 2 months follow-up after rehabilitative treatment, the patient''s symptoms improved without recurring lymphedema.Lessons:In the absence of clinical evidence of swelling during laboratory evaluation or ultrasonographic investigations suggesting deep vein thrombosis, we should consider the possibility of lymphatic disorders.     

Efficacy and Safety of Pregabalin for Muscle Cramps in Liver Cirrhosis: A Double-Blind Randomized Controlled Trial

BackgroundMuscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients.MethodsWe conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH.ResultsThis study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5–10) per week in the pregabalin group and 6.5 (4.0–10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (−36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy.ConclusionWith multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01271660","term_id":"NCT01271660"}}NCT01271660     

The question of the question: impactful implementation science to address the HIV epidemic

IntroductionQuestions about the implementation of evidence‐based intervention to treat and prevent HIV have risen to the top of the field''s scientific priorities. Despite the availability of highly efficacious treatment and prevention interventions, impact has fallen short of targets because these interventions are used with insufficient reach, consistency, sustainability and equity in diverse real‐world settings. At present, substantial excitement for implementation science — defined as research methods and strategies to improve use of evidence‐based interventions — has focused on developing and disseminating methods to conduct rigorous research. Yet, impactful answers depend on a sometimes less visible, but even more important, step: asking good questions about implementation.DiscussionIn this commentary, we offer several considerations for researchers formulating implementation research questions based on several distinctive features of the field. First, as findings are used not only by other researchers but by implementers, scientific questions must incorporate a range of stakeholder and community perspectives to be most relevant. Second, real‐world settings are contextually diverse, and the most relevant scientific questions must position answers to make sense within these contexts (whether geographical, organizational and sociological), rather than apart from them. Third, implementation is complex and dynamic; consequently, research questions must make use of emerging standards in describing implementation strategies and their effects whenever possible. Finally, the field of implementation science continues to evolve, so framing problems with a diverse disciplinary lens will enable researchers to pose insightful and impactful questions.ConclusionsWe are now at a juncture marked by both rich evidence‐based interventions and a persistent global pandemic. To achieve continued scientific progress against the HIV epidemic, asking the right questions might be part of the answer itself.     

Cellular characterization of actin gene concerned with contact‐dependent mechanisms in Naegleria fowleri

Free‐living amoeba, Naegleria fowleri, destroys target cells through contact‐dependent mechanisms, such as phagocytosis and/or trogocytosis. A previous experiment showed that the nf‐actin gene consisted of 1.2 kbp, produced a 50.1 kDa recombinant protein (Nf‐actin), and was localized on the cytoskeleton, pseudopodia and amoebastome. In this study, cellular characterization of the nf‐actin gene concerned with contact‐dependent mechanisms in N fowleri was performed. The nf‐actin gene was amplified from a gene‐cloned vector, pEXQP5‐T7/NT TOPO. The nf‐actin gene was introduced into the Ubi‐pEGFP‐C2 vector, and Ubi‐pEGFP‐C2/nf‐actin was transfected into N fowleri trophozoites. Strong GFP fluorescence was detected in N fowleri trophozoites transfected with Ubi‐pEGFP‐C2/nf‐actin. Expression of EGFP‐Nf‐actin protein was detected by Western blot analysis. The nf‐actin‐overexpressing N fowleri showed significantly increased adhesion activity against extracellular matrix components, fibronectin, collagen I and fibrinogen, compared with wild‐type N fowleri. Moreover, nf‐actin‐overexpressing N fowleri showed increased phagocytic activity and cytotoxicity in comparison with wild‐type N fowleri. In summary, the overexpressed nf‐actin gene has an important function in ability to increase cell adhesion, cytotoxicity and phagocytosis by N fowleri.     

The paradigm shift to prevention and its relationship to dental education

The past seventy-five years have witnessed an extraordinary growth of scientific knowledge related to oral health and the development of evidence-based dentistry. The centrality of prevention to the control of oral diseases and the maintenance of good oral health has become increasingly recognized by the scientific community, dental educators, dental practitioners, and the public at large. Yet, despite significant improvements in the overall oral health of Americans, important disparities exist, and large segments of the population are disproportionately burdened by oral diseases. Despite the proven effectiveness of various preventive modalities, such as fluoridation and dental sealants, these have not been universally disseminated and implemented. This review will highlight the challenges remaining in completing the decades-long paradigm shift to prevention and the important role to be played by the dental education community in this process.