Explore the vast range of titles available.

Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson’s disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or ‘enhancer/suppressor’ screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo , we used a mutation in the Drosophila vesicular monoamine transporter ( dVMAT ) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems.

Advances in communication technologies offer new opportunities for the conduct of qualitative research. Among these, Zoom—an innovative videoconferencing platform—has a number of unique features that enhance its potential appeal to qualitative and mixed-methods researchers. Although studies have explored the use of information and communication technologies for conducting research, few have explored both researcher and participant perspectives on the use of web and videoconferencing platforms. Further, data are lacking on the benefits and challenges of using Zoom as a data collection method. In this study, we explore the feasibility and acceptability of using Zoom to collect qualitative interview data within a health research context in order to better understand its suitability for qualitative and mixed-methods researchers. We asked 16 practice nurses who participated in online qualitative interviews about their experiences of using Zoom and concurrently recorded researcher observations. Although several participants experienced technical difficulties, most described their interview experience as highly satisfactory and generally rated Zoom above alternative interviewing mediums such as face-to-face, telephone, and other videoconferencing services, platforms, and products. Findings suggest the viability of Zoom as a tool for collection of qualitative data because of its relative ease of use, cost-effectiveness, data management features, and security options. Further research exploring the utility of Zoom is recommended in order to critically assess and advance innovations in online methods.

To provide the poultry industry with effective mitigation strategies, the effects of cetylpyridinium chloride (CPC) on the reduction of Salmonella Infantis, hilA expression, and chicken skin microbiota were evaluated. Chicken breast skins (4×4 cm; N = 100, n = 10, k = 5) were inoculated with Salmonella (Typhimurium or Infantis) at 4°C (30min) to obtain 10 8 CFU/g attachment. Skins were shaken (30s), with remaining bacteria being considered firmly attached. Treatments were applied as 30s dips in 50 mL: no inocula-no-treatment control (NINTC), no treatment control (NTC), tap water (TW), TW+600 ppm PAA (PAA), or TW+0.5% CPC (CPC). Excess fluid was shaken off (30s). Samples were homogenized in nBPW (1 min). Samples were discarded. Salmonella was enumerated and Log 10 transformed. Reverse transcriptase-qPCR (rt-qPCR) was performed targeting hilA gene and normalized using the 2 -ΔΔCt method. Data were analyzed using one-way ANOVA in RStudio with means separated by Tukey’s HSD (P≤0.05). Genomic DNA of rinsates was extracted, 16S rRNA gene (V4) was sequenced (MiSeq), and data analyzed in QIIME2 (P≤0.05 and Q≤0.05). CPC and PAA affected Salmonella levels differently with CPC being effective against S . Infantis compared to TW (P<0.05). Treatment with CPC on S . Infantis-infected skin altered the hilA expression compared to TW (P<0.05). When inoculated with S . Typhimurium, there was no difference between the microbiota diversity of skins treated with PAA and CPC; however, when inoculated with S . Infantis, there was a difference in the Shannon’s Entropy and Jaccard Dissimilarity between the two treatments (P<0.05). Using ANCOM at the genus level, Brochothrix was significant (W = 118) among skin inoculated with S . Typhimurium. Among S . Infantis inoculated, Yersiniaceae , Enterobacterales , Lachnospiraceae CHKCI001 , Clostridia vadinBB60 group , Leuconostoc , Campylobacter , and bacteria were significant (408). CPC and PAA-treated skins had lowest relative abundance of the genera. In conclusion, CPC mitigated Salmonella Infantis, altered hilA expression, and influenced the chicken skin microbiota.

•We propose a bipartite graph model to quantify WM-GM FC network and its properties.•We assessed age effects on WM-GM FC network properties (N=1492, age=22–96y).•We found heterogeneous FC changes in lifespan but mainly declines in later years.•We found declined global efficiencies of major networks in lifespan or later years. The effects of normal aging on functional connectivity (FC) within various brain networks of gray matter (GM) have been well-documented. However, the age effects on the networks of FC between white matter (WM) and GM, namely WM-GM FC, remains unclear. Evaluating crucial properties, such as global efficiency (GE), for a WM-GM FC network poses a challenge due to the absence of closed triangle paths which are essential for assessing network properties in traditional graph models. In this study, we propose a bipartite graph model to characterize the WM-GM FC network and quantify these challenging network properties. Leveraging this model, we assessed the WM-GM FC network properties at multiple scales across 1,462 cognitively normal subjects aged 22–96 years from three repositories (ADNI, BLSA and OASIS-3) and investigated the age effects on these properties throughout adulthood and during late adulthood (age ≥70 years). Our findings reveal that (1) heterogeneous alterations occurred in region-specific WM-GM FC over the adulthood and decline predominated during late adulthood; (2) the FC density of WM bundles engaged in memory, executive function and processing speed declined with age over adulthood, particularly in later years; and (3) the GE of attention, default, somatomotor, frontoparietal and limbic networks reduced with age over adulthood, and GE of visual network declined during late adulthood. These findings provide unpresented insights into multi-scale alterations in networks of WM-GM functional synchronizations during normal aging. Furthermore, our bipartite graph model offers an extendable framework for quantifying WM-engaged networks, which may contribute to a wide range of neuroscience research.

Background Mitral valve failure can require repair or replacement. Replacement bioprosthetic valves are treated with glutaraldehyde prior to implantation. The aim of this study was to determine the changes in mechanical properties following glutaraldehyde fixation of mitral valve chordae. Methods To investigate the impact of glutaraldehyde on mitral valve chordae, 24 basal chordae were dissected from four porcine hearts. Anterior and posterior basal (including strut) chordae were used. All 24 chordae were subjected to a sinusoidally varying load (mean level 2N, dynamic amplitude 2N) over a frequency range of 0.5–10 Hz before and after glutaraldehyde treatment. Results The storage and loss modulus of all chordal types decreased following glutaraldehyde fixation. The storage modulus ranged from: 108 to 119 MPa before fixation and 67.3–87.4 MPa following fixation for basal chordae; 52.3–58.4 MPa before fixation and 47.9–53.5 MPa following fixation for strut chordae. Similarly, the loss modulus ranged from: 5.47 to 6.25 MPa before fixation and 3.63–4.94 MPa following fixation for basal chordae; 2.60–2.97 MPa before fixation and 2.31–2.93 MPa following fixation for strut chordae. Conclusion The viscoelastic properties of mitral valve chordae are affected by glutaraldehyde fixation; in particular, the reduction in storage moduli decreased with an increase in chordal diameter.

There are thousands of known cellular phosphorylation sites, but the paucity of ways to identify kinases for particular phosphorylation events remains a major roadblock for understanding kinase signaling. To address this, we here develop a generally applicable method that exploits the large number of kinase inhibitors that have been profiled on near-kinome-wide panels of protein kinases. The inhibition profile for each kinase provides a fingerprint that allows identification of unknown kinases acting on target phosphosites in cell extracts. We validate the method on diverse known kinase-phosphosite pairs, including histone kinases, EGFR autophosphorylation, and Integrin β1 phosphorylation by Src-family kinases. We also use our approach to identify the previously unknown kinases responsible for phosphorylation of INCENP at a site within a commonly phosphorylated motif in mitosis (a non-canonical target of Cyclin B-Cdk1), and of BCL9L at S915 (PKA). We show that the method has clear advantages over in silico and genetic screening. Identifying kinases responsible for specific phosphorylation events remains challenging. Here, the authors leverage kinase inhibitor profiles for the identification of kinase-substrate site pairs in cell extracts, developing a method that can identify the enzymes responsible for unassigned phosphorylation events.

Injecting proteins into the central nervous system that stimulate neuronal growth can lead to beneficial effects in animal models of disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has shown promise in animal and cell models of Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). Here, systemic AAV9-GDNF was delivered via tail vein injections to young rats to determine whether this could be a safe and functional strategy to treat the SOD1 rat model of ALS and, therefore, translated to a therapy for ALS patients. We found that GDNF administration in this manner resulted in modest functional improvement, whereby grip strength was maintained for longer and the onset of forelimb paralysis was delayed compared to non-treated rats. This did not, however, translate into an extension in survival. In addition, ALS rats receiving GDNF exhibited slower weight gain, reduced activity levels and decreased working memory. Collectively, these results confirm that caution should be applied when applying growth factors such as GDNF systemically to multiple tissues.

OBJECTIVE:--To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population. RESEARCH DESIGN AND METHODS--Five public clinics in Chicago, Illinois, participated in the study with computer kiosks installed in waiting room areas. Two hundred forty-four subjects with diabetes were randomized to receive either supplemental computer multimedia use (intervention) or standard of care only (control). The intervention includes audio/video sequences to communicate information, provide psychological support, and promote diabetes self-management skills without extensive text or complex navigation. HbA[subscript 1c] (A1C), BMI, blood pressure, diabetes knowledge, self-efficacy, self-reported medical care, and perceived susceptibility of complications were evaluated at baseline and 1 year. Computer usage patterns and implementation barriers were also examined. RESULTS:--Complete 1-year data were available for 183 subjects (75%). Overall, there were no significant differences in change in A1C, weight, blood pressure, knowledge, self-efficacy, or self-reported medical care between intervention and control groups. However, there was an increase in perceived susceptibility to diabetes complications in the intervention group. This effect was greatest among subjects with lower health literacy. Within the intervention group, time spent on the computer was greater for subjects with higher health literacy. CONCLUSIONS:--Access to multimedia lessons resulted in an increase in perceived susceptibility to diabetes complications, particularly in subjects with lower health literacy. Despite measures to improve informational access for individuals with lower health literacy, there was relatively less use of the computer among these participants.

Background and Purpose. The use of locomotor training with a body-weight–support systemand treadmill (BWST) and manual assistance has increased in rehabilitation. The purpose of this case report isto describe the process for retraining walking in a person with an incomplete spinal cord injury (SCI) using the BWST and transferring skills from the BWST to overground assessment and community ambulation. Case Description. Following discharge from rehabilitation, a man with an incomplete SCI at C5–6 and an American Spinal Injury Association (ASIA) Impairment Scale classification of D participated in 45sessions of locomotor training. Outcomes. Walking speed and independence improved from 0.19 m/s as a home ambulator using a rolling walker and a right ankle-foot orthosis to 1.01 m/s as a full-time ambulator using a cane only for communitymobility. Walking activity (X̄±SD) per 24 hours increased from 1,054±543 steps to 3,924±1,629 steps. Discussion. In a person with an incomplete SCI, walking ability improved after locomotor trainingthat used a decision-making algorithm and progression across training environments.

Masks reduce transmission of SARS-CoV2 and other respiratory pathogens. Comparative studies of the fitted filtration efficiency of different types of masks are scarce. To describe the fitted filtration efficiency against small aerosols (0.02-1 µm) of medical and non-medical masks and respirators when worn, and how this is affected by user modifications (hacks) and by overmasking with a cloth mask. We tested a 2-layer woven-cotton cloth mask of a consensus design, ASTM-certified level 1 and level 3 masks, a non-certified mask, KF94s, KN95s, an N95 and a CaN99. Closed rooms with ambient particles supplemented by salt particles. 12 total participants; 21-55 years, 68% female, 77% white, NIOSH 1-10. Using standard methods and a PortaCount 8038, we counted 0.02-1 µm particles inside and outside masks and respirators, expressing results as the percentage filtered by each mask. We also studied level 1 and level 3 masks with earguards, scrub caps, the knot-and-tuck method, and the effects of braces or overmasking with a cloth mask. Filtration efficiency for the cloth mask was 47-55%, for level 1 masks 52-60%, for level 3 masks 60-77%. A non-certified KN95 look-alike, two KF94s, and three KN95s filtered 57-77%, and the N95 and CaN99 97-98% without fit testing. External braces and overmasking with a well-fitting cloth mask increased filtration, but earguards, scrub caps, and the knot-and-tuck method did not. Limited number of masks of each type sampled; no adjustment for multiple comparisons. Well-fitting 2-layer cotton masks filter in the same range as level 1 masks when worn: around 50%. Level 3 masks and KN95s/KF94s filter around 70%. Over a level 1 mask, external braces or overmasking with a cloth-mask-on-ties produced filtration around 90%. Only N95s and CaN99s, both of which have overhead elastic, performed close to the occupational health and safety standards for fit tested PPE (>99%), filtering at 97-99% when worn, without formal fit testing. These findings inform public health messaging about relative protection from aerosols afforded by different mask types and explain the effectiveness of cloth masks observed in numerous epidemiologic studies conducted in the first year of the pandemic. A plain language summary of these findings is available at https://maskevidence.org/masks-compared.