Proximie in the operating theatre: evaluation of a virtual operating platform for medical student education.

INTRODUCTION: Medical students often hesitate to enter the operating theatre because of poor visibility of the surgical field and anxiety about the theatre environment. In addition, ear, nose and throat (ENT) surgery is underrepresented in many medical curricula. Virtual systems like Proximie offer flexible viewing of surgeries with surgeon commentary, potentially addressing these issues. METHODS: This descriptive survey study aimed to evaluate the use of Proximie as a surgical education tool for delivering ENT teaching to medical students. Live ENT procedures were recorded at the ENT Department of the John Radcliffe Hospital and shared with interested clinical medical students through Proximie accounts. Students were added to a private group chat to ask questions and provided feedback through structured forms, assessing procedural effectiveness and the platform's technology. Live-streaming and recording of procedures were facilitated by ENT surgeons providing commentary. RESULTS: Conducted over four virtual theatre days, the study gathered 52 responses: 96% of students rated Proximie's educational value as 4 of 5 or higher; 57% preferred the virtual experience over physical attendance because of its convenience and the improved view of the surgical field. Students valued the live commentary and showed interest in using Proximie for a broader range of surgeries. Suggested improvements included fixing technical issues, better communication of theatre lists, and expanding surgical specialty coverage. CONCLUSIONS: Proximie has been highly rated by medical students for its effective and engaging approach in the instruction of surgical skills, underscoring its value as an educational tool. Future research is needed to formally assess knowledge acquisition and retention across multiple surgical subspecialties. This work is the first step towards evaluating the utility of virtual operating theatre platforms for medical student education.

Garlic oil improves small intestinal motility in experimentally induced type II diabetes mellitus in female Wistar rats.

Diabetes mellitus adversely affects the contractile ability of the small intestine. However, there is a paucity of studies investigating the impact of garlic oil on small intestinal motility. This study aimed to evaluate the potential beneficial effects of garlic oil on type 2 diabetes mellitus in rats. Thirty-six adult female Wistar rats (n = 36) were divided into four groups: control, non-diabetic rats supplemented with garlic oil, diabetic rats, and diabetic rats treated with garlic oil. The rats were anesthetized using pentobarbitone (40 mg/kg BW); various motility parameters and oxidative markers were determined in small intestinal segments. Measurements were taken for naso-anal length, waist circumference, fasting blood glucose level (FBG), and plasma insulin level. Compared to the control group, the diabetic rats exhibited a reduction in the average force of contraction and motility index in all small intestinal segments. Furthermore, the rats exhibited a reduction in the average duration of muscle contraction only in the jejunum. The rats also exhibited hyperglycemia, insulin resistance, significant oxidative stress, and obesity. This was proven by changes in motility parameters, fasting blood glucose levels, HOMA-IR values, intestinal MDA levels, and waist circumference. The non-diabetic rats supplemented with garlic oil also exhibited a decrease in the average force of contraction and motility index in all small intestinal segments, despite having consistently higher Lee index and waist circumference values. However, the diabetic rats treated with garlic oil demonstrated improved small intestinal motility in nearly all small intestinal segments and a reduction in oxidative stress. In conclusion, rats with diabetes mellitus experienced a decrease in small intestinal motility, which is primarily driven by oxidative stress. Normal rats administered with garlic oil supplements exhibited similar effects. In contrast, garlic oil treatment in diabetic rats led to enhanced small intestinal motility and a notable anti-hyperglycemic effect, which can be attributed to the potent antioxidant properties of garlic oil.

Nurse-led renal cell carcinoma clinic: a single center review.

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

Intragastric balloons for obesity: critical review of device design, efficacy, tolerability, and unmet clinical needs.

INTRODUCTION: Sustaining a healthy weight is a challenge and obesity, with associated risk of co-morbidities, is a major public health concern. Bariatric surgery has shown a great promise for many where pharmacological and lifestyle interventions failed to work. However, challenges and limitations associated with bariatric surgery has pushed the demand for less invasive, reversible (anatomically) interventions, such as intragastric balloons (IGBs). AREAS COVERED: This review critically appraises IGBs used in the past, present, and those in clinical trials, discussing the device designs, limitations, placement and removal techniques, patient eligibility, efficacy, and safety issues. EXPERT OPINION: Several intragastric balloons were developed over the years that brought excitement to patients and healthcare professionals alike. Albeit good efficacy, there had been several safety issues reported with IGBs such as spontaneous deflation, intestinal occlusion, gut perforation, and mucosal ulcerations. This led to evolution of IGBs design; device material, filling mechanism, fluid type, inflation volume, and further innovations to ease ingestion and removal of device. There are some IGB devices under development aimed to swallow like a conventional pill and excrete naturally through defecation, however, how successful they will be in clinical practice in terms of their efficacy and tolerability remains to be seen in the future.

Cellular signaling in the hypoxic cancer microenvironment: Implications for drug resistance and therapeutic targeting.

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.

A Phytobezoar Causing Terminal Ileal Obstruction Following Revision Bariatric Surgery: A Case Report.

Bezoars are a rare complication causing small bowel obstruction. A phytobezoar causing terminal ileum obstruction following a Roux-en-Y gastric bypass (RYGB) is extremely rare. A middle-aged woman with post-sleeve gastrectomy weight regain, converted to RYGB, presented 17 months after surgery with obstructive symptoms due to an impacted phytobezoar in the terminal ileum. Diagnostic laparoscopy, enterotomy, and extraction of the large impacted phytobezoar from the terminal ileum relieved the obstruction. Swallowing improperly masticated food in altered gastrointestinal anatomy due to RYGB can cause a phytobezoar in any part of the gastrointestinal tract. These patients need proper nutritional counseling and psychological evaluation to prevent this rare complication.

Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

A comparative study of acetyl-l-carnitine and caloric restriction impact on hippocampal autophagy, apoptosis, neurogenesis, and astroglial function in AlCl3-induced Alzheimer's in rats.

Alzheimer's disease (AD) is a worldwide chronic progressive neurodegenerative disease. We aimed to investigate and compare the neuroprotective impact of acetyl-l-carnitine and caloric restriction (CR) on AlCl3-induced AD to explore the pathogenesis and therapeutic strategies of AD. Sixty-seven adult male Wistar rats were allocated into Control, AlCl3, AlCl3-acetyl-l-carnitine, and AlCl3-CR groups. Each of AlCl3 and acetyl-l-carnitine were given by gavage in a daily dose of 100 mg/kg and CR was conducted by giving 70% of the daily average caloric intake of the control group. Rats were subjected to behavioral assessment using open field test, Y maze, novel object recognition test and passive avoidance test, biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate-activated protein kinase, Beclin-1, Bcl-2-associated X protein, and B cell lymphoma 2 (Bcl2) as well as hippocampal Ki-67 and glial fibrillary acidic protein immunohistochemistry. AlCl3-induced cognitive and behavioral deficits coincident with impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Acetyl-l-carnitine and CR partially protect against AlCl3-induced behavioral, cognitive, biochemical, and histological changes, with more ameliorative effect of acetyl-l-carnitine on hippocampal apoptotic markers, and more obvious behavioral and histological improvement with CR.

Sex-specific effects of excipients on oral drug bioavailability.

The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.

Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways.

Angiogenesis and metastasis play pivotal roles in the progression of cancer. We recently discovered that crocin, a dietary carotenoid derived from the Himalayan crocus, inhibited the growth of colon cancer cells. However, the exact role of crocin on the angiogenesis and metastasis in colorectal cancer remains unclear. In the present study, we demonstrated that crocin significantly reduces the viability of colon cancer cells (HT-29, Caco-2) and human umbilical vein endothelial cells (HUVEC), but was not toxic to human colon epithelial (HCEC) cells. Furthermore, pre-treatment of human carcinoma cells (HT-29 and Caco-2) with crocin inhibited cell migration, invasion, and angiogenesis in concentration -dependent manner. Further studies demonstrated that crocin inhibited TNF-α, NF-κB and VEGF pathways in colon carcinoma cell angiogenesis and metastasis. Crocin also inhibited cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVEC) in a concentration -dependent manner. We also observed that crocin significantly reduced the secretion of VEGF and TNF-α induced activation of NF-kB by human colon carcinoma cells. In the absence of TNF-α, a concentration-dependent reduction in NF-kB was observed. Many of these observations were confirmed by in vivo angiogenesis models, which showed that crocin significantly reduced the progression of tumour growth. Collectively, these finding suggest that crocin inhibits angiogenesis and colorectal cancer cell metastasis by targeting NF-kB and blocking TNF-α/NF-κB/VEGF pathways.

Synthesis, Characterization, and Assessment of Anti-Cancer Potential of ZnO Nanoparticles in an In Vitro Model of Breast Cancer.

Advanced innovations for combating variants of aggressive breast cancer and overcoming drug resistance are desired. In cancer treatment, ZnO nanoparticles (NPs) have the capacity to specifically and compellingly activate apoptosis of cancer cells. There is also a pressing need to develop innovative anti-cancer therapeutics, and recent research suggests that ZnO nanoparticles hold great potential. Here, the in vitro chemical effectiveness of ZnO NPs has been tested. Zinc oxide (ZnO) nanoparticles were synthesized using Citrullus colocynthis (L.) Schrad by green methods approach. The generated ZnO was observed to have a hexagonal wurtzite crystal arrangement. The generated nanomaterials were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-visible spectroscopy. The crystallinity of ZnO was reported to be in the range 50-60 nm. The NPs morphology showed a strong absorbance at 374 nm with an estimated gap band of 3.20 eV to 3.32 eV. Microscopy analysis proved the morphology and distribution of the generated nanoparticles to be around 50 nm, with the elemental studies showing the elemental composition of ZnO and further confirming the purity of ZnO NPs. The cytotoxic effect of ZnO NPs was evaluated against wild-type and doxorubicin-resistant MCF-7 and MDA-MB-231 breast cancer cell lines. The results showed the ability of ZnO NPs to inhibit the prefoliation of MCF-7 and MDA-MB-231 prefoliation through the induction of apoptosis without significant differences in both wild-type and resistance to doxorubicin.

A medical image enhancement based on generalized class of fractional partial differential equations.

BACKGROUND: The interest in using fractional calculus operators has grown in the field of image processing. Image enhancement is one of image processing tools that aims to improve the details of an image. The enhancement of medical images is a challenging task due to the unforeseeable variation in the quality of the captured images. METHODS: In this study, we present a mathematical model based on the class of fractional partial differential equations (FPDEs). The class is formulated by the proportional-Caputo hybrid operator (PCHO). Moreover, some properties of the geometric functions in the unit disk are applied to determine the upper bound solutions for this class of FPDEs. The upper bound solution is indicated in the relations of the general hypergeometric functions. The main advantage of FPDE lies in its capability to enhance the low contrast intensities through the proposed fractional enhanced operator. RESULTS: The proposed image enhancement algorithm is tested against brain and lungs computed tomography (CT) scans datasets of different qualities to show that it is robust and can withstand dramatic variations in quality. The quantitative results of Brisque, Piqe, SSEQ, and SAMGVG were 40.93%, 41.13%, 66.09%, and 31.04%, respectively for brain magnetic resonance imaging (MRI) images and 39.07, 41.33, 30.97, and 159.24 respectively for the CT lungs images. The comparative results show that the proposed image enhancement model achieves the best image quality assessments. CONCLUSIONS: Overall, this model significantly improves the details of the given datasets, and could potentially help the medical staff during the diagnosis process.

Potential applications and performance of machine learning techniques and algorithms in clinical practice: A systematic review.

PURPOSE: The advent of clinically adapted machine learning algorithms can solve numerous problems ranging from disease diagnosis and prognosis to therapy recommendations. This systematic review examines the performance of machine learning (ML) algorithms and evaluates the progress made to date towards their implementation in clinical practice. METHODS: Systematic searching of databases (PubMed, MEDLINE, Scopus, Google Scholar, Cochrane Library and WHO Covid-19 database) to identify original articles published between January 2011 and October 2021. Studies reporting ML techniques in clinical practice involving humans and ML algorithms with a performance metric were considered. RESULTS: Of 873 unique articles identified, 36 studies were eligible for inclusion. The XGBoost (extreme gradient boosting) algorithm showed the highest potential for clinical applications (n = 7 studies); this was followed jointly by random forest algorithm, logistic regression, and the support vector machine, respectively (n = 5 studies). Prediction of outcomes (n = 33), in particular Inflammatory diseases (n = 7) received the most attention followed by cancer and neuropsychiatric disorders (n = 5 for each) and Covid-19 (n = 4). Thirty-three out of the thirty-six included studies passed more than 50% of the selected quality assessment criteria in the TRIPOD checklist. In contrast, none of the studies could achieve an ideal overall bias rating of 'low' based on the PROBAST checklist. In contrast, only three studies showed evidence of the deployment of ML algorithm(s) in clinical practice. CONCLUSIONS: ML is potentially a reliable tool for clinical decision support. Although advocated widely in clinical practice, work is still in progress to validate clinically adapted ML algorithms. Improving quality standards, transparency, and interpretability of ML models will further lower the barriers to acceptability.

Anti-proliferative, Anti-angiogenic and Anti-inflammatory Effects of Moringa peregrina Leaf Extracts on Testosterone- Induced Benign Prostatic Hyperplasia in Rats.

AIM: To investigate the potential anti-inflammatory and biochemical effects of Moringa peregrina leaf extracts on testosterone-induced benign prostatic hyperplasia (BPH) in rats. METHODS: Six groups of rats (each group included 5 rats) were included in this study. The groups included: 1) the control group, 2) the testosterone-induced BPH group, 3) with 50 mg/kg bwt (bodyweight) oil-treated BPH, 4) with 100 mg/kg bwt. oil-treated BPH, 5) with 500mg/kg bwt. ethanol treated BPH and 6) with 1,000 mg/kg bwt. aqueous treated BPH group. Biochemical markers were measured to evaluate the effect of M. peregrina leaf extracts. RESULTS: Our results showed a significant improvement in the thickness of epithelial cells of the BPH glandular tissues when treated with different M. peregrina extracts (p < 0.05). In addition, M. peregrina extracts showed anti-inflammatory, anti-proliferative and anti-angiogenesis effects on the BPH tissues by reduction of IL-6, PCNA and VEGF-A, respectively. CONCLUSION: Our preclinical study concluded that M. peregrina leaf extracts showed a significant effect on BPH by reducing inflammation, proliferation, and angiogenic processes with no signs of toxicity.

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index < 0.7), nano-range (~357.4 ± 2% nm), transmittance (> 90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris.

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne.

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management.

Comparative Morphological and Morphometric Study between Medial and Lateral Menisci in Aged Male and Female Human Cadavers.

Background: The meniscal cartilages are fibrous discs that are important for knee structures and have the ability to bear weight and stabilize joints. However, morphological and standard data for the meniscus are limited. Therefore, this work will compare anatomical and histological parameters of meniscal cartilages. The results will be important for the different measurements that are necessary for knee joint surgery. Materials and Methods: A total of 24 aged cadavers (12 males and 12 females) were included. Knee joints were dissected and the menisci were excised and labeled as medial or lateral, right or left, male or female. Then, the menisci were kept in 10% formalin solution. Morphological variations of the meniscal shapes were macroscopically categorized. Different measurements, including the distance between anterior and posterior horns, outer and inner circumferences, width (breadth), and thickness, were done using a digital Vernier caliper and recorded manually. Results: 48 medial menisci (MMi) cartilages were studied, they were 54.6% crescent-shaped, 34.6% V-shaped, and 10.8% U-shaped. 48 lateral menisci (LMi) cartilages were studied, 41.6% were crescent-shaped, 56.4% were C-shaped, and 2% were disc-shaped articular cartilage. Findings included differences in their lengths and thickness. Conclusion: The findings of this study were significant in providing new information on various morphological and morphometric parameters of the MMi and LMi in aged males and females, which are necessary to require more precise and comprehensive fundamental data that will be helpful for many specialists for better diagnostic and therapeutic approaches; aiming to restore normal joint conditions in senile people complaining of different meniscal pathologies.