Awareness and Risk Assessment of Breast Cancer Among Women in Saudi Arabia: A Cross-Sectional Study.

Background Breast cancer is the most common female cancer worldwide including in Saudi Arabia. As a result, many cases are diagnosed at an advanced stage, leading to a poor outcome. Understanding risk perception is a significant component of awareness of breast cancer risks. It can be helpful to reduce the mortality of breast cancer via increasing awareness of the risk factors. Objective Our study was designed to assess the level of awareness among women in Saudi Arabia regarding breast cancer, including knowledge about risk factors, symptoms, and the importance of early detection. Methods A cross-sectional study was conducted, and participants were randomly selected. The target population in this study is all women in Saudi Arabia. Data was collected via an online questionnaire. The collected data was analyzed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 21.0, Armonk, NY). Results About 713 women were enrolled in this study. Most of them (69%) were within the age group of 35-45 years old. Age at menarche was found to be 12-13 years old in 313 (43.9%) of the participants and age at first live birth was found to be 20-24 in about 360 (50.5%). The number of population with first-degree relatives that have a history of breast cancer is one relative in 126 (17.7%) of the participants and about 36 (5%) had breast biopsy. About 76 (10.7%) of the participants were considered as having a high risk of breast cancer according to the estimated five-year breast cancer-risk assessment (had a five-year breast cancer risk >1.66%). The mean knowledge score of the participants about breast cancer was found to be 4.62 ± 1.86 out of 8. About 509 (71.4%) of the participants were considered to be having a good level of knowledge about breast cancer. Long-term hormone contraceptive use and older age can increase the chance of developing breast cancer as agreed on by 363 (50.9%) and 287 (40.3%) of the participants respectively. A total of 677 (95%) of the participants mentioned that early detection is important to survive breast cancer. And 639 (89.6%) of the participants think that breast cancer is treatable and about 288 (40.4%) think that the suitable age to start mammography is above 30 years old. Conclusion There is a good general knowledge and awareness about breast cancer among study participants. There were few knowledge gaps regarding the effect of obesity, hormonal contraceptives and older age on the association with breast cancer. About 10% of the participants were found to be having high five-year breast cancer risk.

Gingerols and shogaols: A multi-faceted review of their extraction, formulation, and analysis in drugs and biofluids to maximize their nutraceutical and pharmaceutical applications.

Gingerols represent the main bioactive compounds in ginger drugs mostly Zinigiber officinale (F. Zingebraceae) and account for the biological activities and the strong/pungent flavor in ginger. Ginger (Z. officinale) rhizome is one of the most valued herbal drugs for ailments' treatment in many ayurvedic medicine asides from its culinary applications as a spice. Gingerols and their dehydrated products shogaols are phenolic phytochemicals found in members of the Zingiberaceae family and account for most of their effects including anti-inflammatory and anticancer activities. This review entails most of the novel trends related to the extraction, optimization, and formulations of gingerols and shogaols to insure best recoveries and efficacies from their natural resources. Further, it presents a comprehensive overview of the different analytical approaches for the determination of gingerols/shogaols' levels in nutraceuticals to ensure highest quality and for their detection in body fluids for proof of efficacy.

Application of Automated External Defibrillators Among the Public: A Cross-Sectional Study of Knowledge, Attitude, Practice, and Barriers of Use in Saudi Arabia.

Background: The likelihood of survival of an out-of-hospital cardiac arrest quadruples with the rapid application of basic life support (BLS). The public's ability to perform cardiopulmonary resuscitation (CPR) and use automated external defibrillators (AEDs) is extremely important. This study aimed to assess the public knowledge, attitudes, and practices (KAP) of utilizing AEDs and to understand barriers to AED application. Methods: We conducted a cross-sectional study from March 1-30, 2022. An electronic questionnaire was constructed and validated to measure the KAP for public AED utilization and its barriers. Results: Of the 406 participants, 244 (60.10%) were males. Male respondents had 17% less knowledge and poorer attitude towards using an AED as compared to female respondents. Knowledge and attitudes on using AEDs were low (70.7%) among Saudi nationals compared to those of foreign nationals. Those who were BLS/CPR trained had a 2.5 times greater understanding and willingness to use AEDs in public than those who were not. Barriers to AEDs in CPR/BLS-trained participants were: (1) accidentally hurting the victim (14.3%), (2) duty as a bystander to just call the ambulance and wait for help (12.1%), (3) never taught what to do (n = 41, 18.4%), (4) did not want to be scolded if performed wrong (3.1%), and (5) never witnessed such a situation (51.6%). Conclusion: There is a strong association between knowledge of and willingness to use AEDs in emergency situations among the public. Misconceptions about AEDs hinder their use. This calls for urgent training programs through accessible technology to reach the public.

ABCC2 brush-border expression predicts outcome in papillary renal cell carcinoma: a multi-institutional study of 254 cases.

AIMS: Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC. In this study we evaluated the prognostic significance of ABCC2 IHC staining patterns in a large, multi-institutional PRCC cohort and assessed the association of these patterns with ABCC2 mRNA expression. METHODS AND RESULTS: We assessed 254 PRCCs for ABCC2 IHC reactivity patterns that were stratified into negative, cytoplasmic, brush-border <50%, and brush-border ≥50%. RNA in situ hybridization (ISH) was used to determine the transcript level of each group. Survival analysis was performed with SPSS and GraphPad software. RNA-ISH showed that the ABCC2 group with any brush-border staining was associated with a significant increase in the transcript level, when compared to the negative/cytoplasmic group (P = 0.034). Both ABCC2 groups with brush-border <50% (P = 0.024) and brush-border ≥50% (P < 0.001) were also associated with worse disease-free survival (DFS) in univariate analysis. Multivariate analysis showed that only ABCC2 IHC brush-border (<50% and ≥50%) reactivity groups (P = 0.037 and P = 0.003, respectively), and high-stage disease (P < 0.001) had a DFS of prognostic significance. In addition, ABCC2 brush-border showed significantly worse DFS in pT1a (P = 0.014), pT1 (P = 0.013), ≤4 cm tumour (P = 0.041) and high stage (P = 0.014) groups, while a similar analysis with high WHO/ISUP grade in these groups was not significant. CONCLUSION: ABCC2 IHC brush-border expression in PRCC correlates with significantly higher gene expression and also independently predicts survival outcomes.

Molecular Characterization of Community- and Hospital- Acquired Methicillin-Resistant Staphylococcus aureus Isolates during COVID-19 Pandemic.

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant superbug that causes various types of community- and hospital-acquired infectious diseases. The current study was aimed to see the genetic characteristics and gene expression of MRSA isolates of nosocomial origin. A total of 221 MRSA isolates were identified from 2965 clinical samples. To identify the bacterial isolates, the clinical samples were inoculated on blood agar media plates first and incubated at 37 °C for 18-24 h. For further identification, the Gram staining and various biochemical tests were performed once the colonies appeared on the inoculated agar plates. The phenotypic identification of antibiotic susceptibility patterns was carried out using Kirby-Bauer disk diffusion method by following the Clinical and Laboratory Standards Institute (CLSI) 2019 guidelines. The biofilm-producing potentials of MRSA were checked quantitatively using a spectrophotometric assay. All strains were characterized genotypically by SCCmec and agr typing using the specific gene primers. Furthermore, a total of twelve adhesion genes were amplified in all MRSA isolates. MRSA was a frequently isolated pathogen (44% community acquired (CA)-MRSA and 56% hospital acquired (HA)-MRSA), respectively. Most of the MRSA isolates were weak biofilm producers (78%), followed by moderate (25%) and strong (7%) biofilm producers, respectively. Prominent adhesion genes were clfB (100%), icaAD (91%), fib (91%), sdrC (91%) followed by eno (89%), fnbA (77%), sdrE (67%), icaBC (65%), clfA (65%), fnbB (57%), sdrD (57%), and cna (48%), respectively. The results of the current study will help to understand and manage the spectrum of biofilm-producing MRSA-associated hospital-acquired infections and to provide potential molecular candidates for the identification of biofilm-producing MRSA.

A Novel Approach to Detect IDH Point Mutations in Gliomas Using Nanopore Sequencing: Test Validation for the Clinical Laboratory.

The use of standard next-generation sequencing technologies to detect key mutations in IDH genes for glioma diagnosis imposes several challenges, including high capital cost and turnaround delays associated with the need for batch testing. For both glioma testing and testing in other tumor types where highly specific mutation identification is required, the high-throughput nature of next-generation sequencing limits the feasibility of using it as a primary approach in clinical laboratories. We hypothesized that third-generation nanopore sequencing by Oxford Nanopore Technologies has the capability to overcome these limitations. This study aimed to develop and validate a nanopore-based IDH mutation detection assay for clinical practice using glioma formalin-fixed, paraffin-embedded (FFPE) tissue. Glioma FFPE (n = 66) samples with confirmed IDH gene mutational status were sequenced on the MinION device using an amplicon-based approach. All cases were concordant when compared with the reference results. Limit of blank and limit of detection for the variant allele fraction were 1.5% and 3.3%, respectively, at 500× read depth per gene. Total sequencing cost per sample was CAD$50 to CAD$134 with results being available in 9 to 15 hours. These findings demonstrate that nanopore-sequencing technology can be leveraged to develop low-cost, high-performance clinical sequencing-based assays with quick turnaround times to support the detection of targeted mutations in FFPE tumor tissue.

Ethyl lauroyl arginate-based hydrophobic ion pair complex in lipid nanocapsules: A novel oral delivery approach of rosmarinic acid for enhanced permeability and bioavailability.

Limited oral bioavailability due to high hydrophilicity restricts the beneficial use of Rosmaranic acid (RM) that is characterized by many biological and pharmacological effects. The present work was addressed to extract RM from Rosmarinus officinalis L. leaves and then increase its lipophilicity and permeability through the application of hydrophobic ion pair (HIP) approach using ethyl lauroyl arginate (ELA) as a novel counter-ion. Different RM:ELA ratios were screened to optimize HIP formation process. The encapsulation of the optimized HIP into lipid nanocapsules (LNCs) was then achieved to facilitate oral administration. The results of % transmittance, % complexation efficiency (87.32 ± 0.19%) and partition coefficient revealed the successful formation of the HIP complex occurred at RM:ELA molar ratio of 1:2. The formed HIP was successfully loaded into spherical small sized (39.32 ± 0.18 nm) LNCs. The ex vivo permeability studies across porcine intestine showed that the cumulative RM amount permeated/area after 6 h from HIP and LNCs were 3.79 ± 0.57 and 5.71 ± 0.32 µg/cm2, respectively. Pharmacokinetic study results showed that the maximum RM concentrations in plasma (Cmax) can be arranged in a descending manner as follows; 61.33 ± 8.89 < 42.13 ± 11.22 < 20.96 ± 3.12 ng/ml attained after 4.80, 8.00 and 10.40 h in case of LNC, HIP and solution, respectively. Moreover, the HIP and LNC formulae showed higher total drug amounts in plasma reaching 1.46 and 1.88-fold relative to RM solution, respectively. In conclusion, the HIP complex and HIP loaded LNCs prosper in enhancing the permeability and absorption of the low permeable drugs.

Is Parental Rating of Child's Oral Health Associated with Caries Experience in Children? A Cross-Sectional Study.

Aim: The Parents' view to the oral health of their children is a significant factor that can impact oral health practices and behaviors. The aim of this research was to investigate how parental assessment of their child's oral health associates with caries experience in children receiving dental treatment at the hospital of Taibah University Dental College. Materials and Methods: This cross-sectional study enrolled 127 children who underwent dental treatment at Taibah University Dental College and Hospital during 2020-2021. Dental caries experience was assessed using the dmft/DMFT index, and parental rating of oral health was obtained through a questionnaire. Three logistic regression models were used to assess the correlation between dental caries experience and parental rating of oral health while controlling for sociodemographic and behavioral factors. Results: Most parents rated the oral health of their child as good (60.4%), followed by excellent (18.8%) and very good (15.6%). The mean dmft/DMFT score was 3.47 ± 3.46, with 43.8% of children having high/very high dental caries experience. Logistic regression analysis showed that children whose parents rated their oral health as poor were more likely to have high/very high dental caries experience compared to those rated as excellent/very good/good/fair (adjusted odds ratio = 4.45, 95% confidence interval 1.23-16.07). Conclusion: This study suggests a link between parental assessment of their child's oral health and an elevated prevalence of dental caries in children. The study found that children whose parents rated their oral health as suboptimal had higher odds of having high dental caries experience. These findings emphasize the significance of parental perception of their child's oral health and suggest a necessity for customized interventions to enhance parental knowledge and practices concerning children's oral health.

Unveiling major ethnopharmacological aspects of genus Diospyros in context to its chemical diversity: A comprehensive overview.

Diospyros species (DS), "Ebenaceae," were known for their therapeutic uses in folk medicine since days of yore. Thereafter, scientific evidence related their health benefits to a myriad of chemical classes, for instance, naphthoquinones, flavonoids, tannins, coumarins, norbergenin derivatives, sterols, secoiridoids, sesquiterpenes, diterpenoids, triterpenoids, volatile organic compounds (VOCs), and carotenoids. The available literature showed that more than 200 compounds were isolated and identified via spectroscopic techniques. Many pharmacological activities of DS have been previously described, such as antioxidant, neuroprotective, antibacterial, antiviral, antiprotozoal, antifungal, antiinflammatory, analgesic, antipyretic and cosmeceutical, investigated, and confirmed through versatile in vitro and in vivo assays. Previous studies proved that genus Diospyros is a rich reservoir of valuable bioactive compounds. However, further comparative studies among its different species are recommended for more precise natural source-based drug discovery and clinical application. Accordingly, this review is to recall the chemical abundance and diversity among different members of genus Diospyros and their ethnopharmacological and pharmacological uses. PRACTICAL APPLICATIONS: Practically, providing sufficient background on both secondary metabolites divergence and pharmacological properties of genus Diospyros has many fruitful aspects. As demonstrated below, extracts and many isolated compounds have significant curative properties, which can lead to the discovery of pharmaceutically relevant alternative substitutes to conventional medicine. Consequently, molecular docking on various receptors can be applied. On the grounds, Naoxinqing tablets, a standardized herbal product containing D. kaki leaves extract, have been patented and recorded in Chinese Pharmacopeia as an approved Traditional Chinese Medicine (TCM) for the treatment of cerebro- and cardiovascular diseases, although the underlying mechanism remains under advisement. Moreover, the antimicrobial applications of DS are of considerable concern; since the widespread use of antibiotics resulted in different forms of bacterial resistance, hence, limiting and compromising effective treatment. In addition, as a result of contemporary rampant memory disorders, neuroprotective activities of different extracts of DS became of great emphasis.

Recurrent KRAS mutations are early events in the development of papillary renal neoplasm with reverse polarity.

We evaluated the clinicopathologic and molecular characteristics of mostly incidentally detected, small, papillary renal neoplasms with reverse polarity (PRNRP). The cohort comprised 50 PRNRP from 46 patients, divided into 2 groups. The clinically undetected (<5 mm) neoplasms (n = 34; 68%) had a median size of 1.1 mm (range 0.2-4.3 mm; mean 1.4 mm), and the clinically detected (≥5 mm) neoplasms (n = 16; 32%) which had a median size of 13 mm (range 9-30 mm; mean 16 mm). Neoplasms were positive for GATA3 (n = 47; 100%) and L1CAM (n = 34/38; 89%) and were negative for vimentin (n = 0/44; 0%) and, to a lesser extent, AMACR [(n = 12/46; 26%; weak = 9, weak/moderate = 3)]. KRAS mutations were found in 44% (n = 15/34) of the clinically undetected PRNRP and 88% of the clinically detected PRNRP (n = 14/16). The two clinically detected PRNRP with wild-type KRAS gene were markedly cystic and contained microscopic intracystic tumors. In the clinically undetected PRNRP, the detected KRAS mutations rate was higher in those measuring ≥1 mm vs <1 mm [n = 14/19 (74%) vs n = 1/15 (7%)]. Overall, the KRAS mutations were present in exon 2-codon 12: c.35 G > T (n = 21), c.34 G > T (n = 3), c.35 G > A (n = 2), c.34 G > C (n = 2) resulting in p.Gly12Val, p. Gly12Asp, p.Gly12Cys and p.Gly12Arg, respectively. One PRNRP had a G12A/V/D complex mutation. Twenty-six PRNRP were concurrently present with other tumors of different histologic subtypes in the ipsilateral kidney; molecular testing of 8 of the latter showed wild-type KRAS gene despite the presence of KRAS mutations in 5 concurrent PRNRP. On follow up, no adverse pathologic events were seen (range 1-160 months; mean 44 months). In conclusion, the presence of KRAS mutations in small, clinically undetected PRNRP provides a unique finding to this entity and supports its being an early event in the development of these neoplasms.

Insights into the neuroprotective effects of Salvia officinalis L. and Salvia microphylla Kunth in the memory impairment rat model.

Salvia species have a longstanding traditional culinary use, mostly being consumed in the Mediterranean diet as a common herb added to food. Salvia is commonly consumed as a herbal tea for memory enhancement. Alzheimer's disease (AD) is the most prevalent form of dementia affecting people worldwide Therefore, the current research aimed to investigate potential therapeutic benefits of Salvia officinalis (SOL) cultivated in Jordan and Salvia microphylla (SML) cultivated in Egypt with regard to acetylcholinesterase activity, ß-amyloid deposition and oxidative stress associated with scopolamine-induced AD. Metabolite profiling of the ethanol extracts of SOL and SML was performed using UPLC-ESI-MS/MS analysis. Methyl carnosate, carnosic acid, carnosol, rosmanol and salvianolic acids were the major secondary metabolites identified in SOL and SML extracts. In our study, scopolamine (1.14 mg kg-1, i.p.) was administered for 7 consecutive days to induce memory impairment in rats. SML and SOL (150 and 300 mg kg-1, p.o.) were tested for their effects to reduce the scopolamine-induced deficits. Donepezil (0.5 mg kg-1, i.p.) was used as a positive control. Scopolamine induced histopathological changes in rats' prefrontal cortex and hippocampus in addition to ß-amyloid plaque deposition. Furthermore, scopolamine treatment promoted oxidative stress and acetylcholinesterase activity. On the other hand, treatment with Salvia extracts corrected the histological changes induced by scopolamine and significantly reduced ß-amyloid deposition. Moreover, both oxidative stress markers and acetylcholinesterase activity were ameliorated by Salvia treatment. Using virtual docking to the active sites of the human acetylcholinesterase crystal structure, salvianolic acid K, rosmarinic acid and salvianolic acid C showed the best fitting binding modes to active sites of acetylcholinesterase. Accordingly, the present study demonstrates the beneficial effects of Salvia species from Egypt and Jordan against scopolamine-induced AD-like disorder.

Protective effects of Brownea grandiceps (Jacq.) against ϒ-radiation-induced enteritis in rats in relation to its secondary metabolome fingerprint.

Radiation enteritis is the most common complication of radiotherapy in patients with pelvic malignancies. Thus, the radioprotective activity of the total hydro-alcoholic extract (BGE) and the ethyl acetate soluble fraction (EAF) of Brownea grandiceps leaves was evaluated against ϒ-radiation-induced enteritis in rats. (BGE) and (EAF) were characterized using HPLC-PDA-ESI-MS/MS analysis. The total phenolic and flavonoid contents were also quantified. In vivo administration of (BGE) (400 mg/kg) and (EAF) (200 & 400 mg/kg) prevented intestinal injury and maintained the mucosal integrity of irradiated rats through increasing villi length and promoting crypt regeneration. Also, (EAF) showed more potent antioxidant activity than (BGE) through reduction of MDA level and enhancement of GSH content and catalase enzyme activity. (BGE) and (EAF) down-regulated intestinal NF-κB expression leading to diminished expression of downstream inflammatory cytokine TNF-α. Moreover, (EAF) markedly reduced the expression of profibrotic marker TGF-ß1. Seventy-nine compounds were tentatively identified, including flavonoids, proanthocyanidins, polar lipids and phenolic acids. (EAF) showed significantly higher total phenolic and flavonoid contents, as compared to (BGE). Results revealed remarkable radioprotective activity of (BGE) and (EAF), with significantly higher activity for (EAF). The chemical constituents of (BGE) and (EAF) strongly supported their radioprotective activity. To the best of our knowledge, the present study describes for the first time the radioprotective activity of B. grandiceps leaves in relation to its secondary metabolome fingerprint; emphasizing the great promise of B. grandiceps leaves, especially (EAF), to be used as natural radio-protective agent.

ABCC2 expression in papillary renal cell carcinoma provides better prognostic stratification than WHO/ISUP nucleolar grade.

Papillary renal cell carcinoma (PRCC) classification has traditionally been divided into two histologic types, type 1 and type 2. A new biological stratification system has recently been proposed based on comprehensive morphologic and genomic analysis. The predominant molecular marker in this 4-tiered stratification is the renal drug transporter ABCC2. In this study, we assessed and validated the value of the biological grouping in a PRCC cohort of 176 patients and provided a comprehensive assessment of clinicopathological variables. Tissue microarrays (TMAs) were constructed from nephrectomy specimens. The TMAs were stained with ABCC2 and GATA3 antibodies, and the PRCC cohort was stratified into four groups PRCC1-PRCC4: PRCC1 25%, PRCC2 37%, PRCC3 36%, and PRCC4 2%. PRCC1 demonstrated lower disease stage (p = 0.041) than PRCC2 and PRCC3. The biological stratification was significant on univariate analysis when analyzing both overall survival (p = 0.039) and disease-free survival (p = 0.011). The biological groups maintained the significance of predicting overall survival after adjusting for WHO/ISUP grade, age, pathological stage, and necrosis (p = 0.049, hazard ratio: 5.008, 95% confidence interval: 1.007 to 24.909). In contrast, WHO/ISUP grade did not maintain its significance on multivariate survival analysis. ABCC2 expression profile also separated cases ≤ 4 cm, based on disease-free survival (p = 0.038). None of the patients in the PRCC1 group died of disease during the follow-up period. The proposed biologic stratification adds molecular markers to the traditional morphologic assessment to better stratify patients' prognosis. ABCC2 expression can also potentially serve as a predictive biomarker owing to its known implication in cancer biology and drug resistance.

Metabolomic Profiles of Essential Oils from Selected Rosa Varieties and Their Antimicrobial Activities.

This study aimed to analyze the essential oils of the aerial parts (A) and flowers (F) of Rosa banksiae var. banksiae Ait. (RBW), Rosa polyantha Thunb. "orange fairy" (RPO) and Rosa polyantha Thunb. "white fairy" (RPW), family Rosaceae, and perform multivariate data analyses and antimicrobial activity evaluations. The essential oil analyses were performed by GC/FID and GC/MS. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and clustered heat map were used for the multivariate analyses. The antimicrobial activity was evaluated by the well-diffusion method against four bacteria and four fungi. Two hundred fifty-three compounds were identified from the six oil samples. The major components in RBW-A, RPO-A, and RPW-A were n-undecane (14.40, 19.36, and 9.21%) n-dodecane (14.54, 22.13, and 8.39%), and yomogi alcohol (8.41, 10.53, and 6.28%), respectively, whereas RBW-F, RPO-F and RPW-F contained n-heptadecane (16.70%), n-undecane (7.98%), and ß-phellandrene (22.78%), respectively. The tested essential oils showed moderate antifungal activity against Aspergillus fumigatus compared to amphotericin B. PCA and HCA revealed five main clusters. The six samples carried close chemical profiles and can be regarded as fruitful sources of safe antifungal agents.

Pimenta dioica and Pimenta racemosa: GC-based metabolomics for the assessment of seasonal and organ variation in their volatile components, in silico and in vitro cytotoxic activity estimation.

Volatile constituents isolated from the stems (S) and leaves (L) of Pimenta dioica (PD) and Pimenta racemosa (PR) during the four seasons were analyzed using GLC/FID (Gas liquid chromatography - flame ionization detector) and GLC/MS (Gas liquid chromatography - mass spectrometry). Eighty-nine compounds were identified in all samples, in which oxygenated monoterpene represented by eugenol was the major constituent in PDS-S3 (autumn) (88.71%) and PDS-S2 (summer) (88.41%). Discrimination between P. dioica and P. racemosa leaves and stems in different seasons was achieved by applying chemometrics analysis comprising Principal Component Analysis (PCA) and Hierarchal Cluster Analysis (HCA). For P. dioica, they were partially segregated where leaves collected from spring and autumn were superimposed, and similarly for P. dioica stems collected in summer and autumn. For P. racemosa leaves, the PCA score plot showed that all seasons were completely segregated from each other, with the winter and autumn samples being in very close distance to each other. P. racemosa stems collected in autumn and spring exhibited significant variation, as they were completely detached from each other. Moreover, summer and winter fell in a near distance to each other. An in vitro cell viability assay was done to evaluate the variation in the cytotoxicity of the isolated essential oils against breast (MCF-7), hepatic (HepG-2), and cervical (HeLa-2) cancer cell lines using the MTT assay. The maximum cytotoxic effect was observed by PDL against HeLa, HepG-2 and MCF-7 cells with IC50 values equal to 122.1, 139.6, and 178.7 µg mL-1, respectively. An in silico study was done to assess the cytotoxic effect of the major compounds detected in the oils by determining their inhibitory effect on human DNA topoisomerase II (TOP-2), human cyclin-dependent kinase 2 (CDK-2) and matrix metalloproteinase 13 (MMP-13). o-Cymene followed by eugenol showed the highest fitting with all of the examined proteins approaching doxorubicin. It can be concluded that GC coupled with chemometrics provide a strong tool for the discrimination of samples, while Pimenta could afford a natural drug that could alleviate cancer.

New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in renal neoplasia, particularly focusing on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. In the era of evolving histo-molecular classification of renal neoplasia, morphology is still key. However, entities (or groups of entities) are increasingly characterized by specific molecular features, often associated either with recognizable, specific morphologies or constellations of morphologies and corresponding immunohistochemical profiles. The correct diagnosis has clinical implications leading to better prognosis, potential clinical management with targeted therapies, may identify hereditary or syndromic associations, which may necessitate appropriate genetic testing. We hope that this undertaking will further facilitate the identification of these entities in practice. We also hope that this update will bring more clarity regarding the evolving classification of renal neoplasia and will further reduce the category of "unclassifiable renal carcinomas/tumors". We propose three categories of novel entities: (1) "Novel entity", validated by multiple independent studies; (2) "Emerging entity", good compelling data available from at least two or more independent studies, but additional validation is needed; and (3) "Provisional entity", limited data available from one or two studies, with more work required to validate them. For some entities initially described using different names, we propose new terminologies, to facilitate their recognition and to avoid further diagnostic dilemmas. Following these criteria, we propose as novel entities: eosinophilic solid and cystic renal cell carcinoma (ESC RCC), renal cell carcinoma with fibromyomatous stroma (RCC FMS) (formerly RCC with leiomyomatous or smooth muscle stroma), and anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC). Emerging entities include: eosinophilic vacuolated tumor (EVT) and thyroid-like follicular renal cell carcinoma (TLFRCC). Finally, as provisional entities, we propose low-grade oncocytic tumor (LOT), atrophic kidney-like lesion (AKLL), and biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC).

Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. essential oil-loaded chitosan topical preparations.

The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing.