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<i>Spilanthes filicaulis</i> (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy

by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Christopher Oloruntoba Akintayo, Olaoluwa Sesan Olukiran, Juliana Bunmi Adetunji, Omolola Adenike Ajayi-Odoko, Theophilus Oghenenyoreme Ogwa, Olorunfemi Raphael Molehin, Omolara Olajumoke Ojo, Ramzi A. Mothana, Abdullah R. Alanzi

Background and objective

Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway.

Methods

Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined.

Results

We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine).

Conclusion

Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.

Kinetics and mechanical work done to move the body centre of mass along a curve

by Raphael M. Mesquita, Patrick A. Willems, Arthur H. Dewolf, Giovanna Catavitello

When running on a curve, the lower limbs interact with the ground to redirect the trajectory of the centre of mass of the body (CoM). The goal of this paper is to understand how the trajectory of the CoM and the work done to maintain its movements relative to the surroundings (Wcom) are modified as a function of running speed and radius of curvature. Eleven participants ran at different speeds on a straight line and on circular curves with a 6 m and 18 m curvature. The trajectory of the CoM and Wcom were calculated using force-platforms measuring the ground reaction forces and infrared cameras recording the movements of the pelvis. To follow a circular path, runners overcompensate the rotation of their trajectory during contact phases. The deviation from the circular path increases when the radius of curvature decreases and speed increases. Interestingly, an asymmetry between the inner and outer lower limbs emerges as speed increases. The method to evaluate Wcom on a straight-line was adapted using a referential that rotates at heel strike and remains fixed during the whole step cycle. In an 18 m radius curve and at low speeds on a 6 m radius, Wcom changes little compared to a straight-line run. Whereas at 6 m s-1 on a 6 m radius, Wcom increases by ~25%, due to an augmentation in the work to move the CoM laterally. Understanding these adaptations provides valuable insight for sports sciences, aiding in optimizing training and performance in sports with multidirectional movements.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with <i>Pneumocystis jirovecii</i> pneumonia

by Alexandre Perret, Marion Le Marechal, Raphaele Germi, Daniele Maubon, Cécile Garnaud, Johan Noble, Aude Boignard, Loïc Falque, Mathieu Meunier, Théophile Gerster, Olivier Epaulard

Objectives

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection.

Methods

We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission.

Results

The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p Conclusions

PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Investigating trial design variability in trials of disease-modifying therapies in Parkinsons disease: a scoping review protocol

Por: Zeissler · M.-L. · Boey · T. · Chapman · D. · Rafaloff · G. · Dominey · T. · Raphael · K. G. · Buff · S. · Pai · H. V. · King · E. · Sharpe · P. · OBrien · F. · Carroll · C. B.
Introduction

Parkinson’s disease (PD) is a debilitating neurological disorder for which the identification of disease-modifying interventions represents a major unmet need. Diverse trial designs have attempted to mitigate challenges of population heterogeneity, efficacious symptomatic therapy and lack of outcome measures that are objective and sensitive to change in a disease modification setting. It is not clear whether consensus is emerging regarding trial design choices. Here, we report the protocol of a scoping review that will provide a contemporary update on trial design variability for disease-modifying interventions in PD.

Methods and analysis

The Population, Intervention, Comparator, Outcome and Study design (PICOS) framework will be used to structure the review, inform study selection and analysis. The databases MEDLINE, Web of Science, Cochrane and the trial registry ClinicalTrials.gov will be systematically searched to identify published studies and registry entries in English. Two independent reviewers will screen study titles, abstracts and full text for eligibility, with disagreements being resolved through discussion or by a third reviewer where necessary. Data on general study information, eligibility criteria, outcome measures, trial design, retention and statistically significant findings will be extracted into a standardised form. Extracted data will be presented in a descriptive analysis. We will report our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension.

Ethics and dissemination

This work will provide an overview of variation and emerging trends in trial design choices for disease-modifying trials of PD. Due to the nature of this study, there are no ethical or safety considerations. We plan to publish our findings in a peer-reviewed journal.

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