Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

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Associations of Dietary Patterns and Nutrients with Glycated Hemoglobin in Participants with and without Type 1 Diabetes

Background: Diet has been associated with poor glycemic control in diabetes. Few studies have examined this association in people with type 1 diabetes (T1D), who are at a higher risk for cardiovascular disease than people without diabetes. Methods: We report data from cross-sectional and longitudinal analyses from a coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; non-diabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Dietary patterns based on variations in food group intake were created with principal components analysis. Linear regression was used to examine the associations of dietary patterns, macronutrients, and food groups with HbA1c in a model adjusted for relevant covariates and stratified by diabetes status. Results: Three dietary patterns were identified: “fruits, veggies, meats, cereal”, “baked desserts” and “convenience foods and alcohol” patterns. At baseline, a higher intake of the “baked dessert” pattern was significantly associated with higher HbA1c in T1D at baseline as well at year 6 of the study when adjusted for age, sex, BMI, total calories, and diabetes duration. No such associations were observed in the case of non-diabetic controls. Dietary saturated fats and animal fats were also positively associated with HbA1c in adults with T1D at baseline and/or at year 6. Conclusions: The habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts, may increase risks of poor glycemic control in T1D.     

Kidney recipients with allograft failure,transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.     

Aluminium Induced Glutathione is Essential for Developing Resistance Against Fusarium Infection in Wheat

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Pre-treatment of wheat seedlings with 50 μM concentration of aluminium sulphate (Al) induces...     

Assessment of Genetic Fidelity Using Random Amplified Polymorphic DNA and Inter Simple Sequence Repeats Markers of <Emphasis Type="Italic">Lawsonia inermis</Emphasis> L. Plants Regenerated by Axillary Shoot Proliferation

An efficient, reliable and reproducible plant regeneration protocol was developed for Lawsonia inermis L. using mature nodal explants. Shoot proliferation (81.6 %) with 7.8 shoots/explant was achieved on Murashige and Skoog’s (MS) medium supplemented with 1.0 mg l^?1 6-benzyladenine. Shoot numbers were up-scaled by inducing multiple shoots from axenic nodal segments derived from the primary shoots on the shoot regeneration medium. Thus the authors could achieve ca. 129–134 shoots from single nodal explant. Ninety-three percent rooting of in vitro regenerated shoots was achieved on growth regulator free half-strength MS medium. Regenerated plantlets were successfully transferred to soil with 85 % survival rate. Genetic stability analyses of the in vitro regenerated plants using random amplified polymorphic DNA and inter simple sequence repeat markers revealed a homogeneous amplification profile for all micropropagated plants. This is the first report that evaluates the use of molecular markers to establish genetic fidelity of micropropagated L. inermis for the rapid clonal multiplication and true-to-type production of plant for attaining the ever increasing demand in pharmaceutical industries.     

Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani

Simple, cost-effective approach for routine surveillance of parasite susceptibility to antileishmanial drug miltefosine (MIL) is highly desirable for controlling emergence of drug resistance in visceral leishmaniasis (VL). We validated a simple resazurin-based fluorimetric assay using promastigotes to track natural MIL tolerance in Leishmania donovani parasites from VL cases (n?=?17) against standard amastigote assay, in two different labs in India. The inter-stage MIL susceptibility correlated strongly (r?=?0.70, p?=?0.0018) using J774.A.1 macrophage cell line-based amastigote assay and fluorescence-based resazurin assay for promastigotes. Investigation of inter-stage MIL susceptibility for the same set of clinical isolates in another lab also showed a strong correlation (r?=?0.72, p?=?0.0012) using mouse peritoneal macrophages for amastigote assay and resazurin-based alamar blue assay for promastigotes. Additionally, parasites from post-kala-azar dermal leishmaniasis (PKDL) lesions (n?=?7, r?=?0.78, p?=?0.046) and MIL-induced parasites (r?=?0.92, p?=?0.0001; n?=?3) also exhibited a strongly correlated inter-stage miltefosine susceptibility. Thus, our results support the utility of resazurin assay as a simplified biological tool for MIL susceptibility monitoring in clinical isolates from MIL-treated VL/PKDL patients.     

Evaluating the image quality of cone beam CT acquired during rotational delivery

Objective:

The aim of this work was to evaluate the quality of kilovoltage (kV) cone beam CT (CBCT) images acquired during arc delivery.

Methods:

Arc plans were delivered on a Catphan^® 600 phantom (The Phantom Laboratory Inc., Salem, NY), and kV CBCT images were acquired during the treatment. The megavoltage (MV) scatter effect on kV CBCT image quality was evaluated using parameters such as Hounsfield unit (HU) accuracy, spatial resolution, contrast-to-noise ratio (CNR) and spatial non-uniformity (SNU). These CBCT images were compared with reference scans acquired with the same acquisition parameters without MV “beam on”. This evaluation was carried out for different photon beams (6 and 15 MV), arc types (half vs full arc), static field sizes (10 × 10 and 25 × 25 cm²) and source-to-imager distances (SID) (150 and 170 cm).

Results and Conclusion:

HU accuracy, CNR and SNU were considerably affected by MV scatter, and this effect was increased with increasing field size and decreasing photon energy, whereas the spatial resolution was almost unchanged. The MV scatter effect was observed to be more for full-rotation arc delivery than for half-arc delivery. In addition, increasing the SID resulted in decreased MV scatter effect and improved the image quality.

Advances in knowledge:

Nowadays, volumetric modulated arc therapy (VMAT) is increasingly used in clinics, and this arc therapy enables us to acquire CBCT imaging simultaneously. But, the main issue of concurrent imaging is the “MV scatter” effect on CBCT imaging. This study aims to experimentally quantify the effect of MV scatter on CBCT image quality.     

Probing chelation motifs in HIV integrase inhibitors

A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.