A Randomized Prospective Survey Targeting Knowledge, Barriers, Facilitators and Readiness to Participation in Dementia Research.

BACKGROUND: While the U.S. National Institute on Aging has developed a strategy for recruitment of minority populations in dementia research, including increasing awareness and engagement, minority populations remain under-represented, and the evidence-base is limited. We tested a conceptually driven communication approach targeting barriers and facilitators to research participation vs. standard education. METHODS: In this 2-phase project, input from the minority advisory board of the Cleveland Alzheimer's Disease Research Center informed development of 2 brief health communication videos which differentially focused on research barriers and facilitators (POWER) versus an education control (Phase 1). In Phase 2, a randomized prospective survey compared POWER vs. an active comparator control on pre/post video change in dementia knowledge, cumulative barriers, and facilitators to dementia research, and change in research readiness measured by the Transtheoretical behavior change model. Changes in outcomes were evaluated using two group by two time points repeated measure analysis of variance (RMANOVA) controlling for age, gender, race, and education. RESULTS: The pre-video sample (n=242) had mean age of 57.6 (SD17.2) years, mostly female (n=181, 74.8%), 42.6% non-white. The analyzable sample who completed both pre and post assessments comprised n=102 in the POWER and n=105 in the control group. Non-white participants made up 41.1% of the analyzable POWER (n=51) and 44.1% (n= 52) of controls. Adjusted for age, gender, race and education, controls had a greater increase in dementia knowledge (p=0.004). There was a significant reduction in barriers for POWER (p=.044) vs. control. There were no differences in research facilitators and research readiness between POWER vs. control. Among African Americans (n=59, 28.5% of the analyzable sample) there was a trend for improved dementia knowledge (p=.059) favoring control and in research readiness (p=.051), favoring POWER. CONCLUSIONS: Targeting barriers and attitudes towards research could inform development of approaches with potential to improve dementia research participation across diverse communities.

The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.

Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson's disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature of PD. They are also involved in the formation and maintenance of the blood-brain barrier (BBB), but barrier integrity is compromised in people with PD. This study focuses on an unexplored area of PD pathogenesis by characterizing the interplay between astrocytes, inflammation and BBB integrity, and by combining patient-derived induced pluripotent stem cells with microfluidic technologies to generate a 3D human BBB chip. Here we report that astrocytes derived from female donors harboring the PD-related LRRK2 G2019S mutation are pro-inflammatory and fail to support the formation of a functional capillary in vitro. We show that inhibition of MEK1/2 signaling attenuates the inflammatory profile of mutant astrocytes and rescues BBB formation, providing insights into mechanisms regulating barrier integrity in PD. Lastly, we confirm that vascular changes are also observed in the human postmortem substantia nigra of both males and females with PD.

Isolation and characterization of KDML105 aromatic rice rhizobacteria producing indole-3-acetic acid: impact of organic and conventional paddy rice practices.

Indole-3-acetic acid (IAA) synthesis is a major property of rhizosphere bacteria. The IAA-producing ability of rhizobacteria may be influenced by agricultural management. We therefore evaluated the IAA-producing potential of rhizobacteria isolated during organic rice farming (ORF) and conventional rice farming (CRF) in Thung Kula Rong Hai areas of Thailand. The results indicated that ORF gave a significantly higher percentage of IAA producers (95·8%) than CRF (69·9%). The average IAA values of the ORF isolates were around two times higher than those of the CRF isolates both in the absence (12·8 and 5·8 µg IAA ml-1 , respectively) and presence of L-tryptophan (L-Trp) (35·2 and 17·2 µg IAA ml-1 , respectively). The 16S rRNA gene sequence analysis indicated that the 23 selected isolates belonged to 8 different genera-Sinomonas sp., Micrococcus sp., Microbacterium sp., Fictibacillus sp., Bacillus sp., Burkholderia sp., Leclercia sp. and Enterobacter sp. Interestingly, only three ORF isolates, i.e. ORF15-20 (Micrococcus sp.), ORF15-21 (Sinomonas sp.) and ORF15-23 (Sinomonas sp.), exhibited high IAA production ability without L-Trp (128·5, 160·8 and 174·7 µg IAA ml-1 , respectively). Meanwhile, a slight decrease in IAA production with L-Trp was noticed, suggesting that the L-Trp was not used for the IAA synthesis of these isolates. Biopriming with rhizobacterial isolates significantly enhanced the rate of germination of KDML 105 rice seeds compared to the control.

Individual Treatment Progress Predicts Satisfaction With Transition-Related Care for Youth With Gender Dysphoria: A Prospective Clinical Cohort Study.

BACKGROUND: The number of adolescents presenting with gender dysphoria (GD) in healthcare services has increased significantly, yet specialized services offering transition-related care (TRC) for trans youth is lacking. AIM: To investigate satisfaction with TRC, regret, and reasons for (dis)satisfaction with transition-related medical interventions (TRMIs) in trans adolescents who had presented to the Hamburg Gender Identity Service for children and adolescents (Hamburg GIS). METHODS: Data were collected from a clinical cohort sample of 75 adolescents and young adults diagnosed with GD (81% assigned female at birth) aged 11 to 21 years (M = 17.4) at baseline and follow-up (on a spectrum of ongoing care, on average 2 years after initial consultation). To determine progress of the youth's medical transitions, an individual treatment progress score (ITPS) was calculated based on number of desired vs received TRMIs. OUTCOMES: Main outcome measures were satisfaction with TRC at the time of follow-up, ITPS, social support, reasons for regret and termination of TRC, and (dis)satisfaction with TRMIs. RESULTS: Participants underwent different stages of TRMIs, such as gender-affirming hormone treatment or surgeries, and showed overall high satisfaction with TRC received at the Hamburg GIS. Regression analysis indicated that a higher ITPS (an advanced transition treatment stage) was predictive of higher satisfaction with TRC. Sex assigned at birth, age, and time since initial consultation at the clinic showed no significant effects for satisfaction with TRC, while degree of social support showed a trend. No adolescents regretted undergoing treatment at follow-up. Additional analysis of free-text answers highlighted satisfaction mostly with the physical results of TRMI. CLINICAL IMPLICATIONS: Because youth were more satisfied with TRC when their individual transition (ITPS) was more progressed, treatment should start in a timely manner to avoid distress from puberty or long waiting lists. STRENGTHS AND LIMITATIONS: This study is one of the first to report on treatment satisfaction among youth with GD from Europe. The ITPS allowed for a more detailed evaluation of TRMI wishes and experiences in relation to satisfaction with TRC and may close a gap in research on these treatments in adolescent populations. However, all participants were from the same clinic, and strict treatment eligibility criteria may have excluded certain trans adolescents from the study. Low identification rates with non-binary identities prevented comparisons between non-binary and binary genders. CONCLUSION: The study highlights the role of TRMI and individual treatment or transition progress for youth's overall high satisfaction with TRC received at the Hamburg GIS. Nieder TO, Mayer TK, Hinz S, et al. Individual Treatment Progress Predicts Satisfaction With Transition-Related Care for Youth With Gender Dysphoria: A Prospective Clinical Cohort Study. J Sex Med 2021;18:632-645.

Impaired cognitive self-awareness mediates the association between alexithymia and excitation/inhibition balance in the pgACC.

BACKGROUND: Previous research showed that automatic emotion regulation is associated with activation of subcortical areas and subsequent feedforward processes to cortical areas. In contrast, cognitive awareness of emotions is mediated by negative feedback from cortical to subcortical areas. Pregenual anterior cingulate cortex (pgACC) is essential in the modulation of both affect and alexithymia. We considered the interplay between these two mechanisms in the pgACC and their relationship with alexithymia. METHOD: In 68 healthy participants (30 women, age = 26.15 ± 4.22) we tested associations of emotion processing and alexithymia with excitation/inhibition (E/I) balance represented as glutamate (Glu)/GABA in the pgACC measured via magnetic resonance spectroscopy in 7 T. RESULTS: Alexithymia was positively correlated with the Glu/GABA ratio (N = 41, p = 0.0393). Further, cognitive self-awareness showed an association with Glu/GABA (N = 52, p = 0.003), which was driven by a correlation with GABA. In contrast, emotion regulation was only correlated with glutamate levels in the pgACC (N = 49, p = 0.008). CONCLUSION: Our results corroborate the importance of the pgACC as a mediating region of alexithymia, reflected in an altered E/I balance. Furthermore, we could specify that this altered balance is linked to a GABA-related modulation of cognitive self-awareness of emotions.

Are medical students interested in sexual health education? A nationwide survey.

The majority of medical students and medical healthcare providers do not feel comfortable when addressing sexual problems. It was suggested that more courses in sexual health are needed at medical schools to overcome this shortcoming. To assess medical students' interest in and attitude about sexual health education at medical schools in Germany, a 13-item online questionnaire was developed. The link to the questionnaire was distributed at all medical schools in Germany. In total, 3264 medical students (69.9% female) from all 37 medical schools in Germany participated. Students from all universities indicated that contents related to sexual health are taught at their university. The majority (n=1809; 62.1%) answered that courses in sexual health should be mandatory. The types of educational experiences that were viewed as most appropriate were lectures (n=2281, 78.3%) and seminars without patient contact (n=1414, 48.5%). Students were most interested in child sexual abuse and sexually transmitted infections. It should be ensured that all medical students have acquired basic knowledge in diagnosing and treating frequent sexual problems at the end of their medical studies. Suggestions are made about how to improve current efforts of sexual health education at medical schools.

Polyelectrolyte assisted charge titration spectrometry: Applications to latex and oxide nanoparticles.

The electrostatic charge density of particles is of paramount importance for the control of the dispersion stability. Conventional methods use potentiometric, conductometric or turbidity titration but require large amount of samples. Here we report a simple and cost-effective method called polyelectrolyte assisted charge titration spectrometry or PACTS. The technique takes advantage of the propensity of oppositely charged polymers and particles to assemble upon mixing, leading to aggregation or phase separation. The mixed dispersions exhibit a maximum in light scattering as a function of the volumetric ratio X, and the peak position XMax is linked to the particle charge density according to σ∼D0XMax where D0 is the particle diameter. The PACTS is successfully applied to organic latex, aluminum and silicon oxide particles of positive or negative charge using poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate). The protocol is also optimized with respect to important parameters such as pH and concentration, and to the polyelectrolyte molecular weight. The advantages of the PACTS technique are that it requires minute amounts of sample and that it is suitable to a broad variety of charged nano-objects.

Self-sifting of chain plasmons: the complex optics of Au nanoparticle clusters.

The strong enhancement of electrical fields in subnanometer gaps of self-assembled gold nanoparticle clusters holds great promise for large scale fabrication of sensitive optical sensing substrates. Due to the large number of involved nanoparticles, however, their optical response is complex and not easily accessible through numerical simulations. Here, we use hyperspectral supercontinuum spectroscopy to demonstrate how confined optical modes of well defined energies are supported by different areas of the cluster. Due to the strong resonant coupling in those regions, the cluster essentially acts as a nanoscale optical sieve which sorts incident light according to its wavelength.

Exploring the pattern and neural correlates of neuropsychological impairment in late-life depression.

BACKGROUND: Neuropsychological impairment is a key feature of late-life depression, with deficits observed across multiple domains. However, it is unclear whether deficits in multiple domains represent relatively independent processes with specific neural correlates or whether they can be explained by cognitive deficits in executive function or processing speed. METHOD: We examined group differences across five domains (episodic memory; executive function; language skills; processing speed; visuospatial skills) in a sample of 36 depressed participants and 25 control participants, all aged ≥ 60 years. The influence of executive function and processing speed deficits on other neuropsychological domains was also investigated. Magnetic resonance imaging correlates of executive function, processing speed and episodic memory were explored in the late-life depression group. RESULTS: Relative to controls, the late-life depression group performed significantly worse in the domains of executive function, processing speed, episodic memory and language skills. Impairments in executive function or processing speed were sufficient to explain differences in episodic memory and language skills. Executive function was correlated with anisotropy of the anterior thalamic radiation and uncinate fasciculus; processing speed was correlated with anisotropy of genu of the corpus callosum. Episodic memory was correlated with anisotropy of the anterior thalamic radiation, the genu and body of the corpus callosum and the fornix. CONCLUSIONS: Executive function and processing speed appear to represent important cognitive deficits in late-life depression, which contribute to deficits in other domains, and are related to reductions in anisotropy in frontal tracts.

Carbon nanotubes as cooper-pair beam splitters.

We report on conductance measurements in carbon nanotube based double quantum dots connected to two normal electrodes and a central superconducting finger. By operating our devices as beam splitters, we provide evidence for crossed Andreev reflections tunable in situ. This opens an avenue to more sophisticated quantum opticslike experiments with spin entangled electrons.

Dual task performance in early Alzheimer's disease, amnestic mild cognitive impairment and depression.

BACKGROUND: The dual task paradigm (Baddeley et al. 1986; Della Sala et al. 1995) has been proposed as a sensitive measure of Alzheimer's dementia, early in the disease process. METHOD: We investigated this claim by administering the modified dual task paradigm (utilising a pencil-and-paper version of a tracking task) to 33 patients with amnestic mild cognitive impairment (aMCI) and 10 with very early Alzheimer's disease, as well as 21 healthy elderly subjects and 17 controls with depressive symptoms. All groups were closely matched for age and pre-morbid intellectual ability. RESULTS: There were no group differences in dual task performance, despite poor performance in episodic memory tests of the aMCI and early Alzheimer's disease groups. In contrast, the Alzheimer patients were specifically impaired in the trail-making test B, another commonly used test of divided attention. CONCLUSIONS: The dual task paradigm lacks sensitivity for use in the early differential diagnosis of Alzheimer's disease.

White matter hyperintensities in late life depression: a systematic review.

BACKGROUND: White matter hyperintensities in MRI scans are age related but appear to be more prevalent in depressed patients. They may be more pronounced in late onset depression. This finding, if confirmed, would potentially illuminate the heterogeneity of depression in elderly subjects. METHODS: We conducted a systematic literature search of studies investigating white matter changes in late life depression, identifying 98 studies. The 30 remaining eligible studies were scrutinised for the presence and severity measures of periventricular and deep white matter changes in late life, late onset and, if available, early onset depression as well as in controls. Comparisons between groups were entered into random effects meta-analyses using odds ratios and Cohen's d, as appropriate. Correlations with potential confounders, such as age difference between groups, were explored. RESULTS: Late life depression and, to a greater extent, late onset depression in late life were characterised by more frequent and intense white matter abnormalities. In particular, the odds of having white matter changes were over 4 for late compared with early onset depression. Similarly, on severity scales, late onset depression had scores of 0.7-0.8 standard deviations above early onset patients. CONCLUSIONS: Significant differences between early and late onset depression suggest different aetiological mechanisms, in accordance with a theory of "cerebrovascular" depression of late onset. Greater duration of depressive symptoms, signs and treatment does not appear to have a measurable impact on white matter signal in MRI scans.

Shot noise in Fabry-Perot interferometers based on carbon nanotubes.

We report on shot noise measurements in carbon nanotube based Fabry-Perot electronic interferometers. As a consequence of quantum interference, the noise power spectral density oscillates as a function of the voltage applied to the gate electrode. The quantum shot noise theory accounts for the data quantitatively and allows us to determine directly the transmissions of the two channels characterizing the nanotube. In the weak backscattering regime, the dependence of the noise on the backscattering current is found weaker than expected, pointing either to electron-electron interactions or to weak decoherence.

Cavernous malformation within a schwannoma: review of the literature and hypothesis of a common genetic etiology.

The finding of cavernous malformations within tumors of the central or peripheral nervous system is a rare occurrence. We report a case of a histologically proven cavernous malformation found within an eighth cranial nerve schwannoma in a 76-year-old man. The patient presented with progressive loss of hearing on the left, facial pain and dysesthesia. Symptoms improved significantly after the tumor was subtotally resected through a left retrosigmoid craniotomy. Including the present report, 34 cases of cavernous malformations associated with tumors of nervous system origin, 24 cases (71%) involving tumors of Schwann cell origin, and 9 cases (26%) involving gliomas have been published. The cases were classified into two forms based on the type of association. Conjoined association, in which the cavernous malformation is located within the tissue of the nervous system tumor, and discrete association, in which the cavernous malformation and nervous system tumor are in separate locations. We explore the etiology of this association and hypothesize that a common genetic pathway may be involved in a majority of these cases.

Frequency of Norovirus in stool samples from patients with gastrointestinal symptoms in Switzerland.

To determine the frequency of sporadic community-acquired Norovirus (NV) infection in the German-speaking part of Switzerland, an evaluation of gastroenteritis cases seen in physicians' practices between July 2001 and July 2003 was conducted. A total of 699 stool specimens documented to be free of common bacterial pathogens was screened for the presence of NV by RT-PCR. NV was detected in 125 (17.9%) of these specimens. In the seasonal analysis, the highest rate of NV-positive samples (38.3%) was found between January and March 2002. After July 2002, the study was expanded to additionally test for NV in stool samples containing a known bacterial pathogen. Among 132 such specimens, NV was detected in only one. This suggests that NV mixed-infections are playing a marginal role in Switzerland.

Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95.

Semaphorins are a family of secreted and membrane-associated proteins involved in growth cone guidance during development. Here, we describe the interaction of Semaphorin4F (Sema4F) with the post-synaptic density protein SAP90/PSD-95. Using the yeast two-hybrid system and coprecipitation assays we were able to show an interaction between the extreme C-terminus of Sema4F and the PDZ domains of SAP90/PSD-95. Heterologous coexpression of a chimeric EphrinB1/Semaphorin4F protein with SAP90/PSD-95 in COS cells leads to translocation of SAP90/PSD-95 from the cytosol to the membrane. Deletion analysis shows that this translocation activity of Sema4F is completely dependent on the presence of the last three C-terminal amino acids. In addition, Sema4F immunoreactivity is present in synaptosome fractions and enriched in post-synaptic density fractions. Consistently, in cultured hippocampal neurons, we demonstrate punctate colocalization of Sema4F and SAP90/PSD-95 in dendrites, furthermore we found colocalization of Sema4F with synapsin1 suggesting a synaptic localization. Our data implicate a new functional context for semaphorins at glutamatergic synapses.

Cellular prion protein is expressed on peripheral blood mononuclear cells but not platelets of normal and scrapie-infected sheep.

BACKGROUND AND OBJECTIVES: Transmissible spongiform encephalopathies (TSEs) including sheep scrapie are characterized by the conversion of a normal, cellular prion protein (PrPc) to an abnormal protease-resistant form (PrPSc). Like human peripheral blood, the peripheral blood of scrapie-infected sheep remains one possible source of disease transmission. As a first step in understanding the disease requirements in the natural scrapie host, the presence of PrPc was evaluated in peripheral blood cells from five normal and five scrapie-infected Suffolk sheep. DESIGN AND METHODS: Live peripheral blood cells from normal and scrapie-infected sheep were analyzed for the presence of PrP using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: PrP mRNA was detected in peripheral blood mononuclear cells (PBMC) but not in platelets or granulocytes. Consistent with PrP mRNA expression, cell-surface expressed PrP was detected on PBMC, but was not detected on granulocytes, platelets, or erythrocytes. Two-color flow cytometric analysis of PBMC specific phenotypes revealed that regardless of scrapie-status, expression of PrP was significantly higher on B2 positive B-lymphocytes than on CD4, CD8, WC1 positive T-lymphocytes or CD14 positive monocytes. In addition, PrP expressed on PBMC from normal and scrapie-infected sheep was sensitive to proteinase K (PK)and phosphatidylinositol-specific phospholipase C (PIPLC). INTERPRETATION AND CONCLUSIONS: Regardless of the scrapie-status of the sheep, resting PBMC transcribe PrPc and express PrPc as a cell-surface protein sensitive to both PK and PIPLC. Because of the abundance of PrPc on PBMC, future diagnostic tests using PK and PIPLC to discriminate between protease sensitive and resistant PrP must be carefully evaluated.

PrP(c) mRNA, but not PrP(Sc) is found in the salivary glands of scrapie-infected sheep.

Transmission studies in transmissible spongiform encephalopathies (TSEs) have become increasingly important due to the possible transmission of bovine spongiform encephalopathy to humans resulting in new variant Creutzfeldt-Jacob disease. The horizontal transmission of scrapie, a TSE of sheep, is poorly understood. Possible sources of horizontal transmission are the submandibular and parotid salivary glands. TSEs like natural sheep scrapie are characterized by the conversion of a normal protease sensitive prion protein, PrP(c), to an abnormal protease resistant prion protein, PrP(Sc). Since the presence of PrP(Sc) is an indicator of disease, the salivary glands of scrapie-infected sheep were examined for the presence of PrP(Sc). Although PrP(c) mRNA was detected in the salivary glands, PrP(Sc) was not found in the salivary glands of scrapie-infected sheep. These data suggest that the salivary glands are unlikely sources of horizontal transmission of natural sheep scrapie.