In vivo antiplasmodial properties of fractions and flavonoids of Pseudarthria hooheri Wight & Arn. (Fabaceae)

Malaria is regarded as one of the most lethal diseases. Resistance to artemisinin and its derivatives jeopardises effective malaria treatment. Finding novel antimalarial chemicals is critical given the existing treatment situation. This work aimed to examine the antiplasmodial capabilities of <i>Pseudarthria hookeri</i> fractions and flavonoids in vivo. The fractions and compounds antiplasmodial activity were evaluated on male Swiss albino mice infected with <i>Plasmodium berghei</i>, and on healthy female Swiss albino mice, the crude extract's acute toxicity was assessed. The EtOAc fraction had significant antiplasmodial activity (32.53 percent suppression at 500 mg/kg BW) and considerably prolonged the survival period of infected mice (9.8 days) compared to control mice (7.8 days). Parasitaemia was dramatically reduced (85.01, 59.41, and 70.39 percent), and the mean survival time extended (11.33, 10.00, and 9.33 days) with 15, 20 and 35 mg/kg of quercetin (<b>1</b>), 7-O-benzyl-6-prenylpinocembrin (<b>6</b>) and 6,8-diprenyleriodictyol (<b>11</b>) (isolates of the EtOAc fraction), respectively. BW loss and PCV reduction were also averted. Moreover, at 2500 mg/kg, the crude extract of <i>P. hookeri</i> showed no acute toxicity in mice. LC-MS analysis of the EtOAc fraction enabled the identification of nine flavonoids, with <b>8</b> and <b>11</b> being the main components. The present investigation confirmed <i>P. hookeri</i>'s antiplasmodial action, substantiating its ethnomedicinal application for malaria treatment.

Splenic Infarction in a COVID-19 Patient without Respiratory Symptoms

High rates of thromboembolic events have been seen in cases of COVID-19. Here, we report a case of 23-year-old previously healthy female presented with left-sided abdominal pain associated with vomiting. The computed tomography scan showed multiple ill-defined wedge-shaped low attenuating areas of the spleen, suggesting splenic infarction. In the absence of other thromboembolic contributing factors, we believe this was a thromboembolic event in splenic circulation in relation to COVID-19 infection. Our case adds to the evidence of an arterial thrombotic event in a noncritical COVID-19 patient, emphasizing the importance of addressing thromboembolism diagnosis and management measures to avoid potentially deadly consequences.

Xanthogranulomatous Pyelonephritis Caused by Stenotrophomonas maltophilia—The First Case Report and Brief Review

Xanthogranulomatous pyelonephritis (XGP) represents a rare and severe pathology secondary to chronic urinary obstruction and recurrent infections. Commonly, this condition leads to loss of kidney function, and frequently, surgical approach is the only optional treatment. Proteus mirabilis and Escherichia coli are the most frequent pathogens associated with XGP. The actual changes in the pathogen’s characteristics increased the risk of newly acquired infections once considered opportunistic. Stenotrophomonas malthophilia is one of those agents more related to immunocompromised patients, presenting an increased incidence and modified antibiotic resistance profile in the modern era. This case report presents a healthy female patient with an underlying renal stone pathology diagnosed with XGP related to S. maltophilia urinary infection. After a complete biological and imagistic evaluation, the case was treated as pyonephrosis. Empirical antibiotic administration and a surgical approach were considered. A total nephrectomy was performed, but the patient’s condition did not improve. The patient’s status improved when specific antibiotics were administered based on the bacterial identification and antibiotic susceptibility pattern of drained perinephric fluid. Levofloxacin and Vancomycin were considered the optimal combination in this case. The histopathological examination revealed XGP secondary to chronic renal stone. The present study describes the first case of XGP related to an aerobic Gram-negative pathogen such as S. maltophilia, once considered opportunistic, in an apparently healthy female adult.

Evaluation of The Food Effect On a Drospirenone Only Contraceptive Containing 4 mg Administered With and Without High-Fat Breakfast

Background:The objective of the present trial was to assess the difference in pharmacokinetics of an oral test preparation containing 4 mg drospirenone. under fasting conditions compared to food intake after single dose administration.Methods:Open label, single centre, two-treatment, two-sequence, crossover study in 24 healthy female volunteers, with duration of 1 day per sequence and with a real wash-out period of 14 days to investigate the relative bioavailability of DRSP with both forms of administration. The 90% confidence intervals were calculated for the intra-individual ratio (test with food vs. without food) of the pharmacokinetic endpoints AUC(0-72h) and Cmax of drospirenone. Results:The 90% CI calculated by means of ANOVA-log for the endpoint, intra-individual ratio (Test ‘A’ = with food intake) vs. Test ‘B’ = without food intake) of AUC(0-72h) of drospirenone was between 104.72% and 111.36%. The 90% CI calculated by means of ANOVA- log for the endpoint intra-individual ratio (Test ‘A’ vs. Test ‘B’) of Cmax of drospirenone was between 118.58% and 141.10%.The mean relative bioavailability of the Test with food ‘A’ compared to the Test without food ‘B’ after single dose administration based on the endpoints AUC(0-72h) was 107.99%; for the endpoint Cmax it was 129.35%.Conclusions:The rate of absorption, based on the endpoint Cmax of drospirenone was increased by about 30% under fed conditions which differs to a COC containing 0,02 mg EE and 3 mg drospirenone in a 24/4 regimen where the rate of absorption was reduced by about 40% for both components. Implications: Our results suggest that the food intake has no impact on the absorption of 4 mg drospirenone in the management for contraception.This raises up the contraceptive efficacy as no interference with food is expected in real life use when consuming the oral formulation

Vectorial analysis of the electrocardiogram from conventional limb leads in healthy adult Nepalese females

Introduction: ECG interpretation plays a vital role in the initial evaluation of patients presenting with cardiac complaints. Assessment of degree of cardiac vector is one of the important parameters to be studied in ECG. Methods: A prospective cross-sectional study was carried out among 84 female subjects, aged 18- 40 years of age, including students and staff of Gandaki Medical College Teaching hospital and Research Center, Pokhara, Nepal over a period of one month from 1st Oct to 1st Nov 2021. A Standard ECG machine was used and the ECG was recorded using the conventional limb leads. The individual mean electrical axis of the heart was plotted using the net voltage of QRS complex of Lead-I and Lead-III. The possible correlation between cardiac vector and physical measurements like height weight BSA and BMI were analyzed. The data were analyzed in SPSS version 27. Results: The normal mean electrical axis of the healthy female subjects was observed as 61.7±23.51°. There was a significant positive correlation of cardiac vector with height (p< 0.05), whereas a negative correlation was observed with weight and BMI (p< 0.01). However, there was no significant correlation with BSA. In our study, we observed the maximum left axis cardiac vector as -2° and right axis as 98° among 84 female subjects. Conclusion: Documentation of cardiac vector was made using standard bipolar limb leads in normal healthy female subjects. BMI is involved in the deviation of cardiac vector with a negative correlation. This observation could make it quite attractive for use in clinical practice.

Magnesium supplementation and iron status among female students: the intervention study

Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated in the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxy- and oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and the percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached a significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.

Efficacy of open-label counterconditioning for reducing nocebo effects on pressure pain

Nocebo effects can adversely affect the experience of physical symptoms, such as pain and itch. Nocebo effects on itch and pain have shown to be induced by conditioning with thermal heat stimuli and reduced by counterconditioning. However, open-label counterconditioning, in which participants are informed about the placebo content of the treatment, has not been investigated, while this can be highly relevant for clinical practice. Furthermore, (open-label) conditioning and counterconditioning has not been investigated for pain modalities relevant to musculoskeletal disorders, such as pressure pain. In a randomized controlled trial, we investigated in 110 healthy female participants whether nocebo effects on pressure pain combined with open-label verbal suggestions can be 1) induced via conditioning and 2) reduced via counterconditioning. Participants were allocated to either a nocebo or sham conditioning group. Next, the nocebo group was allocated to either counterconditioning, extinction, or continued nocebo conditioning; sham conditioning was followed by placebo conditioning. Nocebo effects were significantly larger after nocebo conditioning than sham conditioning (d = 1.27). Subsequently, a larger reduction of the nocebo effect was found after counterconditioning than after extinction (d = .99) and continued nocebo conditioning (d = 1.63), with effects similar to placebo conditioning (following sham conditioning). These results show that (counter)conditioning combined with open-label suggestions can modulate nocebo effects on pressure pain, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders, particularly for musculoskeletal disorders.

Sexual Dimorphism in Extracellular Matrix Composition and Viscoelasticity of the Healthy and Inflamed Mouse Brain

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p &lt; 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p &lt; 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p &lt; 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

Oxytocin modulates neural reactivity in women to emotional stimuli of children depending on childhood emotional neglect

Sensitivity for rewarding cues and distress signals from children are fundamental to human caregiving, and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging (fMRI) study we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo controlled within-subject design we measured neural responses to positive, negative and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) vs. placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence specific effects, positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex and right putamen, and images of children in distress the bilateral amygdala, hippocampus and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self-reported neglect interacted with oxytocin administration in the amygdala, hippocampus and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to OXT administration.