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AbstractUbiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson’s disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it’s been recruited by USP30 viathe distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation. Although, there are reports on USP30s’ inhibitors but no study on the repurposing of inhibitors approved against MMP-9 and SGLT-2 as potential inhibitors of USP30 in PD. Thus, the highlight therein, is to repurpose approved inhibitors of MMP-9 and SGLT-2 against USP30 in PD using extensive computational modelling framework. 3D structures of Ligands and USP30 were obtained from PubChem and protein database (PDB) servers respectively, and were subjected to molecular docking, ADMET evaluation, DFT calculation, molecular dynamics simulation (MDS) and free energy calculations. Out of the 18 drugs, 2 drugs showed good binding affinity to the distal ubiquitin binding domain, moderate pharmacokinetic properties and good stability. The findings showed canagliflozin and empagliflozin as potential inhibitors of USP30. Thus, we present these drugs as repurposing candidates for the treatment of PD. However, the findings in this current study needs to be validated experimentally.Communicated by Ramaswamy H. Sarma

Background/AimsThe quadriceps angle, which depicts the quadriceps muscle's mechanical effect on the knee, is frequently used as an assessment metric when diagnosing a variety of knee-related issues. Smartphone goniometer applications have clinical assessment capabilities that can be used instead of the universal goniometer. The aim of this study was to analyse the criterion validity and inter- and intra-rater reliability of a smartphone goniometer application for measuring the quadriceps angle.MethodsA total of 50 typically healthy women were included in this study. The quadriceps angle was evaluated with the universal goniometer as the gold standard and the Angulus smartphone goniometer application on each participant. The intraclass correlation coefficient and 95% confidence intervals were used to analyse reliability, while the standard error of the mean was used to calculate precision. Bland-Altman plots and 95% limits of agreement were used to establish the levels of agreement between the smartphone goniometer application and the universal goniometer. The Pearson correlation coefficient was used to quantify the smartphone goniometer application criterion validity in comparison to the universal goniometer.ResultsThe smartphone goniometer application had good intra-rater reliability (intraclass correlation coefficient 0.99; 95% confidence interval 0.96–1) and inter-rater reliability (intraclass correlation coefficient 0.98; 95% confidence interval 0.94–1). A strong and significant correlation was found between the universal goniometer and the smartphone goniometer application, showing good criterion validity (r=0.99; 95% confidence interval 0.98–0.99; P=0.006).ConclusionsThe use of the smartphone goniometer application to measure the quadriceps angle was valid and demonstrated excellent intra- and inter-rater reliability levels.Implications for practiceThe smartphone goniometer application can be used in clinical practice as a valid and reliable quadriceps angle measurement tool.

AbstractGastric ulcer is associated with weakening of the mucous coating of the stomach and damages to the intestinal lining. It is caused by H. pyloriassisted by enzymes including VacA, which necessitates the need for inhibitors of VacA. Bioactive compounds from Cyperus rotundushave been documented to have anti-inflammatory activities. However, the mechanism of action of the phytochemicals is not characterized. This research aimed to assess, in silico, the potential of selected bioactive compounds against VacA based on the binding to its active sites. VacA and bioactive compounds structures were obtained from protein database and PubChem webserver, respectively. All compounds, including 2 controls, omeprazole and cimetidine were docked against the protein using AutoDock Vina and screened based on the binding energy. The selected complexes were subjected to pharmacokinetics and toxicity screening. Finally, molecular dynamics simulation and MMPBSA were carried out on two best compounds. 17 compounds interacted with the active site of VacA with higher binding affinities, with 7 of them – aureusidine, catechin, chlorogenic acid, isorhamnetin, isovitexin, oreintin, and vitexin having the best behaviours based on ADMET and druglikeness screening. Molecular dynamics and MMPBSA experiments of two of the hits corroborated good stability and binding energy for Ellagic Acid and Scirpusin B (ΔG = −14.38 and −13.20 kcal mol−1, respectively). These phytochemicals showed good pharmacokinetic profiles with respect to the control drugs. This study revealed that the identified compounds of C. rotundusmay serve as VacA inhibitors and may be potent candidates for novel drug formulations in gastric ulcer treatment.Communicated by Ramaswamy H. Sarma

ABSTRACTIntroductionDespite cancer treatment strides, mortality due to ovarian cancer remains high globally. While immunotherapy has proven effective in treating cancers with low cure rates, it has limitations. Growing evidence suggests that both tumoral and non-tumoral components of the tumor immune microenvironment (TIME) play a significant role in cancer growth. Therefore, developing novel and focused therapy for ovarian cancer is critical. Studies indicate that TIME is involved in developing ovarian cancer, particularly genome-, transcriptome-, and proteome-wide studies. As a result, TIME may present a prospective therapeutic target for ovarian cancer patients.Areas coveredWe examined several TIME-targeting medicines and the connection between TIME and ovarian cancer. The key protagonists and events in the TIME and therapeutic strategies that explicitly target these events in ovarian cancer are discussed.Expert opinionWe highlighted various targeted therapies against TIME in ovarian cancer, including anti-angiogenesis therapies and immune checkpoint inhibitors. While these therapies are in their infancy, they have shown promise in controlling ovarian cancer progression. The use of ‘omics’ technology is helping in better understanding of TIME in ovarian cancer and potentially identifying new therapeutic targets. TIME-targeted strategies could account for an additional treatment strategy when treating ovarian cancer.

Malaria is a major health problem in Southwestern Saudi Arabia. This study aimed to measure the level of community understanding of malaria transmission, protection, and treatment. A questionnaire-based cross-sectional study enrolled 1070 participants from 2 districts with different malaria prevalence rates in Jazan Province. The response rate was 97.27%. Of the 1070 total; 754 (70.5%) had heard about malaria. Sixty-seven percentage know that fever was the main symptom. Approximately 59.8% did not know that stagnant water is one of the most important locations for mosquito breeding. Nevertheless, we found that 50% of the participants knew that mosquitoes bite at night and 96.9% confirmed that mosquitoes did not bite during the day. The most effective sources of information were distributed leaflets (41.8%) and video awareness (31.9%). The most significant factors affecting participants knowledge were gender, residence, family members, income, and education (P< .05). Knowledge levels were satisfactory in this study, and the majority of participants exhibited adequate attitudes and practices related to malaria prevention. However, knowledge differences were observed with regard to the place of residence. Greater emphasis should be directed towards education programs in malaria-endemic areas to ensure complete eradication of malaria.

To investigate the prevalence of depressive symptoms in community-dwelling Saudi adults aged ≥50 years and the associated risk factors. Patient Health Questionnaire 9 (PHQ-9) was dichotomized as depressive symptoms when the participants scored ≥10. Risk factors included age, sex, body mass index, education, employment, marital status, number of chronic diseases and medications, fatigue severity scale (FSS), and Montreal Cognitive Assessment (MoCA). Among the 206 participants, the prevalence of depressive symptoms was 17.48%. The number of chronic diseases, medications, and fatigue symptoms were significantly higher in those with depressive symptoms, whereas cognitive functions were significantly lower. Fatigue symptoms and cognitive functions were significantly associated with depressive symptoms. The cut-off scores for risk factors were ≥42 (FSS) and ≤23 (MoCA scale). Fatigue and cognitive impairments were the only risk factors that distinguished participants with and without depressive symptoms.

For over a century, modern therapy has been at battle with malignancy, with no apparent victory in sight. Cancer therapies have come a long way, but they still need to be more targeted and have fewer systemic side effects to showcase a superior therapeutic efficacy. In such a pursuit, nanotechnology comes up to the rescue with a myriad of therapeutic benefits appended with a marginally low adverse impacts. The wide spread usage of nanotechnology over the past two decades has already led to a wide range of advancements in the therapeutic fields, with the capability to target malignant tissues either passively or actively. A potential chemotherapeutic drug, camptothecin has demonstrated notable anti-tumor action against an array of malignancies, including breast, ovarian, colon, lung, and stomach cancers. The widespread clinical usage of camptothecin is constrained by its insolubility in water, quick reversion of active to the inactive form in the biological system, high prevalence of resistance to a number of chemotherapeutics, and appended adverse effects to normal healthy tissues from extended use. However, lipid-based, polymeric and inorganic nano formulations are now being researched upon for the targeted delivery of camptothecin for an array of malignancies. This review article presents the applications of nanotools for camptothecin targeting in diverse malignancies, both actively and passively. An elaborative discussion on the hurdles for the clinical translation of the nano formulations are also discussed.

Engaging in physical activity (PA) has been proved to reduce the risk of developing cardiovascular diseases. In patients with peripheral arterial disease (PAD), diminished PA predicts high overall mortality. However, the extent of the association of participation in PA with PAD severity is unknown. Therefore, the overarching aim of this study was to investigate the association between PAD severity, PA levels and patterns using the Hispanic Community Health Study/Study of Latinos. This was a cross-sectional cohort study that included 495 participants with PAD and a total of 12,281 participants without PAD from the Hispanic Community Health Study/Study of Latinos database. The Global Physical Activity Questionnaire was administered to assess the time spent weekly in performing moderate-to-vigorous PA (MVPA) during work, leisure time, and transportation. The ankle–brachial index (ABI) was used to measure PAD. PA status was categorized on the basis of MVPA as follows: physically active and physically inactive to insufficient. In addition, all participants were classified as follows: those with normal ABI who were physically active, those with normal ABI but who were physically inactive, those with PAD but were physically active, and those with PAD who were physically inactive. Complex sample for regression models were used to investigate the association between PA and the severity of PAD. Of the participants, 235 (47.5%) were physically inactive to insufficient, and 260 participants (52.5%) engaged in at least 150 min/wk of MVPA, which is the recommended PA level according to the guidelines of World Health Organization. Compared with who were highly active, the participants who engaged in low PA were twice as likely to have moderately severe ABI and 4 times as likely to have severe ABI, after adjustment for the covariates (age, smoking status, and body mass index). Hispanic/Latino adults with sever PAD in the US showed pattern of physical inactivity. Findings of this study highlight the association between PA and severity of PAD. These findings highlight the necessity of interventions in increasing PA in these participants. Future studies are required to identify appropriate exercise regimens or home-based programs to help patients with severe PAD meet the current PA recommendations.