The polyphenolic phytoalexin polydatin inhibits amyloid aggregation of recombinant human prion protein

Prion diseases involve misfolded and highly infectious aggregates of prion protein (PrP^Sc) which forms amyloid plaques leading to fatal neurodegeneration. The absence of clinically proven therapeutics makes the discovery of effective remedial interventions a prime concern. Herein, we report novel prion intervention by the polyphenolic phytoalexin, polydatin which binds with moderate affinity to the recombinant protease resistant core of human prion protein, encompassing the sequence 90–231 (rPrP^res) and inhibits its conversion into the highly neurotoxic forms. An extensive evaluation using biophysical techniques revealed that polydatin incubated rPrP^res samples generate off-pathway oligomers having reduced cross-β sheet signature, and relatively smaller in size than the native rPrP^res oligomers. The detailed structural analysis using molecular dynamics simulations elucidated the induction of antagonistic mobilities in the β2–α2 loop, α3 helix and the N-terminal amyloidogenic region of prions. This study puts forward novel prion fibrillogenesis inhibitory potential of polydatin, specifically by stabilizing the N-terminal amyloidogenic region. Collectively our results affirm the importance of polydatin in crippling the prion pathogenesis and may serve as a structural scaffold for designing novel therapeutic agents targeting amyloidogenic transition in prions.

Polydatin is found to be a pharmacologically-significant scaffold that can bind to the rPrP^res repertoire and inhibit its conversion to the highly infectious and neurotoxic PrP^Sc-like form, thus acting like a promising anti-prion drug lead.     

Extraction of polyoxotantalate by Mg–Fe layered double hydroxides: elucidation of sorption mechanisms

The extraction of Ta(v) as polyoxometallate species (H_xTa₆O₁₉^(8−x)−) using Mg–Fe based Layered Double Hydroxide (LDH) was evaluated using pristine material or after different pre-treatments. Thus, the uptake increased from 100 ± 5 mg g⁻¹ to 604 ± 30 mg g⁻¹, for respectively the carbonated LDH and after calcination at 400 °C. The uptake with calcined solid after its reconstruction with Cl⁻ or NO₃⁻ anions has also been studied. However, the expected exchange mechanism was not found by X-ray Diffraction analysis. On the contrary, an adsorption mechanism of Ta(v) on LDH was consistent with measurements of zeta potential, characterized by very negative values for a wide pH range. Moreover, another mechanism was identified as the main contributor to the uptake by calcinated LDH, even after its reconstruction with Cl⁻ or NO₃⁻: the precipitation of Ta(v) with magnesium cations released from MgO formed by calcination of the LDH. This latter reaction has been confirmed by the comparison of the uptake of Ta(v) in dedicated experiments with solids characterized by a higher magnesium solubility (MgO and MgCl₂). The obtained precipitate has been analyzed by X-ray diffraction (XRD) and would correspond to a magnesium (polyoxo)tantalate phase not yet referenced in the powder diffraction databases.

Reaction of polyoxotantalate ions and MgFe Layered Double Hydroxide leads to magnesium polyoxotantalate precipitate.     

Shedding the light on Pharmacists’ roles during COVID-19 global pandemic

Introduction(Background)The role of pharmacists revolves around providing the highest levels of care to society and ensuring the provision of medicine to all patients. However, with the spread of coronavirus disease 2019 (COVID −19), pharmacists as a very important part of healthcare professionals’ team are responsible for fighting against the disease regardless of their setting of practice. The role of pharmacists will undergo a little change to extend and include other roles in order to ensure the safety of the community and limit the virus spread. Also, they will be required to obtain information from reliable sources, and to be up to date, so they can be reliable advisors to the community and raise their awareness.ObjectivesThe purpose of this review is to highlight community and hospital pharmacists’ roles during (COVID-19) global pandemic, and to clearly illustrate how they are contributing to maintain pharmacy services continuity, supporting other healthcare professionals, and facilitating the patient’s education.SummaryClinical pharmacists provide direct patient care through monitoring adverse drug reactions, ensuring individualized treatment, performing evidence-based practice, and evaluating drugs in clinical trials. On the other hand, community pharmacists which are the most accessible healthcare providers by the community increase their awareness regarding the preventive measures, balance medicines supply and demand, provide drive-thru and home delivery services, offer telehealth counselling, psychological support, refer suspected COVID-19 patients, and provide vaccination when available.ConclusionInnovative pharmacists’ roles have emerged to adapt to changes during COVID-19 pandemic, however, they may be needed in the post COVID-19 world as well.     

Longitudinal Associations of Plasma Phospholipid Fatty Acids in Pregnancy with Neonatal Anthropometry: Results from the NICHD Fetal Growth Studies—Singleton Cohort

Despite increasing interest in the health effects of polyunsaturated FAs (PUFAs), their roles in fetal and neonatal growth remain understudied. Within the NICHD Fetal Growth Studies—Singleton Cohort, we prospectively investigated the associations of individual and subclasses of plasma phospholipid PUFAs at gestational weeks (GW) 10–14, 15–26, 23–31, and 33–39 with neonatal anthropometric measures as surrogates for fetal growth among 107 women with gestational diabetes mellitus (GDM) and 214 non-GDM controls. Multivariable weighted linear regression models estimated the associations between plasma phospholipid PUFAs and neonatal anthropometric measures. Adjusted beta coefficients for phospholipid docosahexaenoic acid (DHA) per standard deviation (SD) increase at GW 23–31 in association with birthweight z-score, neonatal length, and neonatal fat mass were 0.25 (95% CI: 0.08–0.41), 0.57 (0.11–1.03) cm, and 54.99 (23.57–86.42) g, respectively; all false discovery rates (FDRs) < 0.05. Estimated Δ5-desaturase activity per SD increase at GW 33–39 but not at other time points was positively associated with birthweight z-score: 0.29 (95% CI: 0.08–0.33); neonatal length: 0.61 (0.29–0.94) cm; and neonatal fat mass: 32.59 (8.21–56.96) g; all FDRs < 0.05. Longitudinal analysis showed consistent results. Our findings suggest that mid-to-late pregnancy presented as critical windows for primarily diet-derived DHA and Δ5-desaturase activity in relation to neonatal anthropometric measures.     

CHA2DS2‐VASc and PESI scores are associated with right ventricular dysfunction on computed tomography pulmonary angiography in patients with acute pulmonary thromboembolism

BackgroundAccurate risk stratification is the most important step in the management of patients with acute pulmonary thromboembolism (PTE). Pulmonary embolism severity index (PESI) is a clinical tool for PTE risk stratification. CHA₂DS₂‐VASc score, a risk assessment tool in patients with atrial fibrillation, is recently considered for acute PTE. The presence of right ventricular (RV) dysfunction in imaging is more efficient in acute PTE risk evaluation.HypothesisThis study aims to evaluate the association between CHA₂DS₂‐VASc and PESI score and each of them with RV dysfunction on computed tomography pulmonary angiography (CTPA).MethodsOne hundred eighteen patients with a definite diagnosis of PTE were entered. The CHA₂DS₂‐VASc and PESI scores were calculated for all of them. RV dysfunction including an increase in RV to left ventricular diameter ratio, interventricular septal bowing, and reflux of contrast medium into the inferior vena cava was examined by CTPA.ResultsPESI and CHA₂DS₂‐VASc scores were significantly associated with RV dysfunction. In addition, different classes of PESI scores were correlated with RV dysfunction. Moreover, this study showed that the CHA₂DS₂‐VASc score and PESI score had a positive correlation. The area under the curve value for the CHA₂DS₂‐VASc score was 0.625 with 61.54% sensitivity and 60.0% specificity for predicting RV dysfunction while for PESI score was 0.635 with 66.7% sensitivity and 60.0% specificity.ConclusionThis study showed that not only CHA₂DS₂‐VASc and PESI scores are positively correlated, but they are both associated with RV dysfunction diagnosed by CTPA. CHA₂DS₂‐VASc and PESI scores are able to predict RV dysfunction.     

Nutritional Status of Indian Children with Cerebral Palsy: A Cross-sectional Study

Indian Journal of Pediatrics -     

Associative thinking in schizophrenia: A contextualist approach

Explored the question of whether responses that appeared to be highly pathological on the basis of the word association test did indeed reflect an underlying aberrant associative process or whether the associations actually had a greater degree of meaning than was evident from the test (N = 60). Utilizing contextualist techniques designed by the authors, which were analogous to the word association test but yet measured schizophrenic associative thinking in specific contexts that more closely approximated natural language situations, the quality and purposiveness of the schizophrenics' associations were examined. The word association test technique was judged to be inadequate by itself to account for underlying associative processes involved in schizophrenic associative thought disorder. A majority of responses (70% schizophrenic, 81% nonschizophrenic) judged to be pathological on the basis of the word association test alone became meaningful in the context of a sentence created by the Ss to explain purposively their associations. The schizophrenics' experience of a stimulus word and consequent associations to that word became clearer when placed within an appropriate context (i.e., a sentence), rather than examined as isolated semantic features (as in the word association test).