Mesenchymal stem cell-derived rapid drug screening system for Alzheimer's disease for the identification of novel drugs.

A reliable and efficient in vitro model is needed to screen drugs for Alzheimer's disease (AD), as many drugs are currently in the developmental stage. To address this, we developed an in vitro model using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) to screen novel drugs for AD. We differentiated AM-MSCs into neurons and degenerated them using beta amyloid1-42 (Aß). We then tested AD drugs, which are commercially available such as donepezil, rivastigmine, memantine, citicoline, and two novel drugs, that is, probucol, an anti-hyperlipidaemic drug, and NMJ-2, a cinnamic acid analogue for their potential to protect the cells against neurodegeneration. We used gene expression and immunofluorescence staining to assess the neuroprotective ability of these drugs. We also measured the ability of these drugs to reduce lactate dehydrogenase, reactive oxygen species, and nitric oxide levels, as well as their ability to stabilize the mitochondrial membrane potential and increase acetylcholine (ACh) levels. The AD drugs and novel drugs reduced cytotoxicity and oxidative stress, stabilized mitochondrial membrane potential, and restored ACh levels. Furthermore, they reduced BACE1 expression, with a concomitant increase in the expression of cholinergic markers. This AM-MSCs-based AD-like model has immense potential to be an accurate human model and an alternative to animal models for testing a large number of lead compounds in a short time. Our results also suggest that the novel drugs probucol and NMJ-2 may protect against Aß-induced neurodegeneration.

Netrin-like domain of sFRP4, a Wnt antagonist inhibits stemness, metastatic and invasive properties by specifically blocking MMP-2 in cancer stem cells from human glioma cell line U87MG.

Rapid proliferation, high stemness potential, high invasiveness and apoptotic evasion are the distinctive hallmarks of glioma malignancy. The dysregulation of the Wnt/ß-catenin pathway is the key factor regulating glioma malignancy. Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), which has a prominent pro-apoptotic role in glioma stem cells, has two functional domains, the netrin-like domain (NLD), and cysteine-rich domain (CRD) both of which contribute to apoptotic properties of the whole protein. However, there are no reports elucidating the specific effects of individual domains of sFRP4 in inhibiting the invasive properties of glioma. This study explores the efficacy of the domains of sFRP4 in inhibiting the key hallmarks of glioblastoma such as invasion, metastasis, and stemness. We overexpressed sFRP4 and its domains in the glioblastoma cell line, U87MG cells and observed that both CRD and NLD domains played prominent roles in attenuating cancer stem cell properties. Significantly, we could demonstrate for the first time that both NLD and CRD domains negatively impacted the key driver of metastasis and migration, the matrix metalloproteinase-2 (MMP-2). Mechanistically, compared to CRD, NLD domain suppressed MMP-2 mediated invasion more effectively in glioma cells as observed in matrigel invasion assay and a function-blocking antibody assay. Fluorescent matrix degradation assay further revealed that NLD reduces matrix degradation. NLD also significantly disrupted fibronectin assembly and decreased cell adhesion in another glioma cell line LN229. In conclusion, the NLD peptide of sFRP4 could be a potent short peptide therapeutic candidate for targeting MMP-2-mediated invasion in the highly malignant glioblastoma multiforme.

Laser induced plant leaf extract mediated synthesis of CuO nanoparticles and its photocatalytic activity.

Metal nanoparticles furnished by the green synthesis approach have exhibited fascinating attributes owing to their biocompatibility with biomolecules, and their rapid environmentally friendly synthesis. On copper oxide (CuO) nanoparticles, a laser induced bio reduction work has been accomplish using Centella asiatica aqueous extract at room temperature is the pioneer in the field. This synthesis technique is easy, fruitful, eco-friendly, and counterfeit for the size-tunable synthesis of diverse shapes of stable copper nanoparticles. UV-visible spectroscopy, Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), Energy - Dispersive X-ray Spectroscopy (EDX), X-ray diffraction (XRD) and photodegradation study have astounding properties of regulating the formation, crystalline nature, and morphology of an integrated specimen. Moreover, the obtained copper oxide nanoparticle has the tendency to decrease the absorbance maximum value of methylene blue because of the catalytic activity posed by these nanoparticles on the reduction of methylene blue by Centella asiatica. It has been studied and confirmed by UV-visible spectrophotometer, and it has been recognised as an electron relay effect.

Self-assembly of CdSe 3D urchins and their photocatalytic response.

Photocatalysis is found to be one of the best suited processes that respond to the purification of water systems and the semiconductor nanomaterials are learned to be incredible materials which carry out the photocatalytic process as they readily decompose the pollutants effectively. In this present work, CdSe nanoparticles belonging to II-VI group semiconductor compounds were synthesized using a facile hydrothermal process with different precursor concentrations and were analysed for various characterization studies such as X-ray diffraction (XRD), Transmission electron microscopy (TEM), UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR) and Photoluminescence (PL) studies. The XRD study of the synthesized CdSe nanostructures revealed that the average crystallite size was ranging from 18.5 nm to 24 nm pointing out the increase in size with increase in molar concentrations. The morphological structure of synthesized CdSe samples exhibited urchin-like structure for a lower concentration with several rod-like projections appearing in diverse directions. These CdSe nano-urchins synthesized with lower concentrations are found suitable to carry out the process of photocatalytic activity. The process was carried out under visible light radiation for 180 min with aqueous solution of methylene blue (MB) as the ideal toxin to be degraded. The attained degradation efficiency was nearly 80% clearly displaying that the synthesized samples are good photocatalysts. By tuning the bandgap, through the optimization of the precursor concentrations, greater efficiency can be achieved in future.

Regeneration study of MB in recycling runs over nickel vanadium oxide by solvent extraction for photocatalytic performance for wastewater treatments.

Recently, researchers are concentrating on the synthesis of composite materials to enhance the efficiency of the materials in various applications. In this work, nickel vanadium oxide (NiV2O6) nanocomposite material is prepared via two methods and the prepared samples have been characterized with basic studies to analyse the effect of preparation method and the reaction time. The XRD studies reveal a polycrystalline growth in both the methods. The broad XRD peaks obtained for samples prepared via hydrothermal method suggests the size reduction and 1D nanostructure formation. The SEM analysis shows the formation of 1D structures in hydrothermal and 3D microsphere structures in solvothermal methods. The possible formation mechanism behind this formation has been discussed in this manuscript. The FTIR peaks in the fingerprint region confirm the formation and vibration of metal-oxygen bonds. The large optical bandgap values obtained from Tauc plot again confirms the formation of nanostructures of the synthesized samples. The photocatalytic activity of nickel vanadium oxide on methylene blue dye under halogen light were performed and, the recyclability of the sample is investigated. It was found from the photocatalytic spectrum that, the samples prepared from both the methods shows a degradation efficiency of more than 80% within 150 min. It was confirmed that the prepared NiV2O6 photocatalyst samples does not lose their degradation ability even after five cycles of repeated usage.

Photocatalytic effect of CuO nanoparticles flower-like 3D nanostructures under visible light irradiation with the degradation of methylene blue (MB) dye for environmental application.

The present research work focuses on preparing 3D transition metal doped copper oxide nanostructures through sonication method and to investigate the effect of doping different transition metal into copper oxide (CuO) on the basic properties of CuO nanoparticles and, to study the photocatalytic behaviour of the doped CuO samples. The morphological studies performed with the help of SEM revealed the formation of flower like CuO 3D nanostructures for all the doped samples. The slight shift in the position of peaks in the x-ray diffraction (XRD) pattern confirms that doping has been successfully done into CuO. Also, the sharp diffraction peaks suggest the polycrystalline nature of the sample with monoclinic structure. The UV-vis absorption analysis reveals a bandgap of 2.26, 2.12 and 2.15 eV for the CuO samples doped with nickel, zinc, and iron respectively via Tauc plot. The photocatalytic performance of the samples tested through the degradation of methylene blue (MB) dye suggests that samples doped with Zn shows better degradation. Thus, it is evident that the morphology and the optical properties of the CuO can be tailored by doping transition metal into it.

Photocatalytic degradation effect of CdSe nanoparticles for textile wastewater effluents at low cost and proves to be efficient method.

Semiconductor nanoparticles and nanocrystals have a great impact due to its contribution in the diverse fields including electronics, solar energy, biological imaging, and photonics. Among these semiconductor nanoparticles, cadmium selenide of II-VI group binary semiconductor nanoparticles were synthesized using solvothermal process for the different reaction temperatures. The XRD pattern of the synthesized samples confirms the crystalline nature of the samples and showed increase in its crystallite size with rise in temperature. The morphology of the samples was analysed with TEM images and found that the nanoparticles synthesized at different temperatures were varied in size and shape indicating the increase in the size of the particles with the raise in temperature. The optical properties of the samples pointed out that they exhibit a blue shift owing to quantum confinement. Photocatalytic activity was carried out for the synthesized samples under visible light radiation using methylene blue (MB) as a model pollutant and it proved to be a good photocatalyst achieving the efficiency of 75% which is promising for future application with good optimization. The efficiency could be increased when these semiconductor CdSe nanoparticles are doped with metal particles due to an increase in the absorption edge wavelength and a decrease in bandgap energy were reported in detail.

Supplementation of the diets with hydroponic maize fodder affects digestibility, puberty, sexual behavior, and semen characteristics in buck kids.

Hydroponics is one of the widely adopted technologies for fodder production in arid and semi-arid regions. In addition to the benefits such as shorter growth period and minimal water and land use, it also produces nutritious fodder that contains essential nutrients required for the growth and reproduction of livestock. This study was conducted to evaluate the effect of feeding hydroponic maize fodder on the reproductive performance of buck kids. Twenty-four Tellicherry buck kids aged around 3 months were randomly selected and allocated into three treatment groups, namely, control, treatment 1 (T1), and treatment 2 (T2). Experimental diets were formulated by replacing the concentrate with hydroponic maize fodder at 0% (control), 25% (T1), and 50% (T2) level. The buck kids supplemented with hydroponic maize fodder attained puberty earlier (T1, 246.50 ± 2.61 days; T2, 241.00 ± 2.06 days) (P < 0.05); had higher (P < 0.05) scrotal circumference, testicular volume, and fresh semen characteristics; and exhibited intense sexual behaviors than the non-supplemented kids. Furthermore, hydroponic maize fodder supplementation improved the digestibility of dry matter (DM) (P < 0.01), organic matter (OM) (P < 0.01), crude fiber (CF) (P < 0.05), ether extract (EE) (P < 0.01), and nitrogen-free extract (NFE) (P < 0.01) in the kids. In conclusion, hydroponic maize fodder feeding did not have any negative impact on the reproductive performance of kids. Furthermore, the hydroponic maize fodder supplementation enhanced the kids' nutrient digestibility and reproductive performance.

Clinicopathological comparison of VHL expression as a prognostic tumor marker in renal cell carcinoma: A single center experience.

AIM: To assess the VHL gene expression as a prognostic marker in Renal Cell Carcinoma (RCC) and compare it with clinicopathologic features. MATERIALS AND METHODS: This retrospective observational study was conducted in the department of Urology and Renal Transplantation in Sri Ramachandra Institute of Higher Education and Research, Chennai from August 2016 to August 2018. Thirty patients who have undergone a radical/partial nephrectomy with biopsy proven histological diagnosis of RCC during the study period were included in the study. Data was analyzed using Statistical package for Social Sciences version 17. RESULTS: A complete loss and retained VHL expression were noted in 60% and 40% of the RCC specimens. Association between smoking and VHL expression was found to be statistically significant. There was no statistical significance found between age group, sex, chief complaints, BMI. ECOG score, hypertension, family history, location of tumor, calcification, venous system or lymphnode involvement. However, rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant. CONCLUSION: Complete loss of VHL expression was noted in majority of the specimens that leads to the development of RCC. Smoking has been found to be statistically significant in tumors that retain VHL expression which may contributes to more aggressive form of tumor. Association between rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant.

De novo assembly and annotation of the whole genomic analysis of Vibrio campbellii RT-1 strain, from infected shrimp: Litopenaeus vannamei.

OBJECTIVES: This study aimed to sequence the whole genome of Vibrio campbellii RT-1 strain. METHODS: V. campbellii strain was isolated from an infected shrimp, Litopenaeus vannamei collected from aquaculture ponds, India (12.1899° N, 79.9249° E). The whole genome sequencing (WGS) was performed using the Illumina Hiseq 2500 platform and assembled de novo using SPAdes and Velvet optimiser. Furthermore, the gene prediction and annotation were performed by a rapid prokaryotic genome tool-Prokka. RESULTS: The genome of V. campbellii RT-1 strain has one circular chromosome with 6327218 bp long. V. campbellii RT-1 strain contains 5787 predicted genes with an average of 45% GC content. A total of 86 known genes associated with pathogenicity were identified and 28 genes were found to be responsible for virulence factors. Furthermore, 1112 unigenes were subjected to Gene Ontology (GO) terms, and 4895 predicted proteins were annotated with Clusters of orthologous (COGs) functional groups. CONCLUSIONS: The phylogenetic position of V. campbellii RT-1 strain was established through whole genome sequencing and genomic tools which provides a strong platform to further study on genomic alterations and phenotype of V. campbellii.

Microsurgical anatomy of the superior sagittal sinus and draining veins.

BACKGROUND: The superior sagittal sinus and the draining cerebral veins are often encountered during the surgery for parasagittal and falx meningiomas and during the interhemisperic transcallosal approaches. A knowledge about the variations from the normally described anatomy helps in anticipating and avoiding problems related to these structures during surgery. AIM: The normal variations in the disposition of the superior sagittal sinus and the number and direction of the draining veins in the Indian population have been studied. SETTINGS AND DESIGN: This is an anatomical study in the fresh cadavers. MATERIALS AND METHODS: Sixty fresh cadavers were examined in the autopsy theatre of the Forensic Medicine Department of the Hospital between March 2011 and February 2013. STATISTICAL ANALYSIS USED: Epi-Info, MS-Excel, and the Statistical Package for the Social Sciences (SPSS) were used for data analysis. RESULTS: The position of the superior sagittal sinus was variable and was up to within 1cm on either side of the sagittal suture. The origin of the superior sagittal sinus varied from the level of foramen caecum to a little posterior from the foramen caecum. The total length of the superior sagittal sagitttal sinus varied from 321 mm to 357 mm (average length 338.77mm); vertical compartments of the sinus were found in three-fourth of the cases studied. Tributaries were found in the herringbone pattern and varied from 13 to 19 on the right and 14 to 19 on the left. The Rolandic vein was the largest draining vein in most of the cases. The superior sagittal sinus drained predominantly to the right transverse sinus in three-fourth of the cases studied. The position of the torcula was variable; often towards the right side and at a higher level. The central sulcus was 49.93 mm posterior to the coronal suture and 130.78 mm anterior to the lambdoid suture. CONCLUSIONS: This is the first study of its kind in Indian population studying the anatomical variations in the anatomy of the superior sagittal sinus that may have a significant bearing on the neurosurgical approaches adopted.

P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer.

BACKGROUND: Therapeutic resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) is attributed to various cellular mechanisms and signaling molecules that influence as a single factor or in combination. DESIGN: In this study, utilizing in vitro p21-activated kinase 1 (Pak1) overexpression and knockdown cell line models along with in vivo athymic mouse tumor xenograft models and clinical samples, we demonstrate that Pak1 is a crucial signaling kinase in gemcitabine resistance. RESULTS: Pak1 kindles resistance via modulation of epithelial-mesenchymal transition and activation of pancreatic stellate cells. Our results from gemcitabine-resistant and -sensitive cell line models showed that elevated Pak1 kinase activity is required to confer gemcitabine resistance. This was substantiated by elevated levels of phosphorylated Pak1 and ribonucleotide reductase M1 levels in the majority of human PDAC tumors when compared with normal. Delineation of the signaling pathway revealed that Pak1 confers resistance to gemcitabine by preventing DNA damage, inhibiting apoptosis and regulating survival signals via NF-κB. Furthermore, we found that Pak1 is an upstream interacting substrate of transforming growth factor ß-activated kinase 1-a molecule implicated in gemcitabine resistance. Molecular mechanistic studies revealed that gemcitabine docks with the active site of Pak1; furthermore, gemcitabine treatment induces Pak1 kinase activity both in vivo and in cell-free system. Finally, results from athymic mouse tumor models illustrated that Pak1 inhibition by IPA-3 enhances the cytotoxicity of gemcitabine and brings about pancreatic tumor regression. CONCLUSION: To our knowledge, this is the first study illustrating the mechanistic role of Pak1 in causing gemcitabine resistance via multiple signaling crosstalks, and hence Pak1-specific inhibitors will prove to be a better adjuvant with existing chemotherapy modality for PDAC.

Single-crystal nanopyramidal BGaN by nanoselective area growth on AlN/Si(111) and GaN templates.

We report nano-selective area growth (NSAG) of BGaN by MOCVD on AlN/Si(111) and GaN templates resulting in 150 nm single crystalline nanopyramids. This is in contrast to unmasked or micro-selective area growth, which results in a multi-crystalline structure on both substrates. Various characterization techniques were used to evaluate NSAG as a viable technique to improve BGaN material quality on AlN/Si(111) using results of GaN NSAG and unmasked BGaN growth for comparison. Evaluation of BGaN nanopyramid quality, shape and size uniformity revealed that the growth mechanism is the same on both the templates. Further STEM analysis of BGaN nanopyramids on AlN/Si (111) templates confirmed that these are single-crystalline structures without any dislocations, likely due to single nucleation occurring in the 80 nm mask opening. CL results correspond to boron content between 1.7% and 2.0% in the nanopyramids. We conclude that NSAG is promising for growth of high-quality BGaN nanostructures and complex nano-heterostructures, especially for low-cost silicon substrates.

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Universal power-law of terahertz optical properties of borosilicate, tellurite, and chalcogenide glass families.

Terahertz (THz) time-domain spectroscopy (TDS, THz-TDS) was used to measure THz optical properties, i.e., refractive indices and absorption coefficients, of borosilicate, tellurite, and chalcogenide glass families. We observe that the THz optical properties depend on glass compositions. THz refractive indices recorded an increasing trend from borosilicate to chalcogenide and to tellurite glass families. Our results demonstrate the ability to select a glass family, system, and composition to target THz optical properties for potential use in THz optical and photonic applications. We report K and ß fitting parameters for the power-law model used to describe these properties and show how it can be universally applied to several glass families.

An Overview of Ovarian Cancer: The Role of Cancer Stem Cells in Chemoresistance and a Precision Medicine Approach Targeting the Wnt Pathway with the Antagonist sFRP4.

Ovarian cancer is one of the most prevalent gynecological cancers, having a relatively high fatality rate with a low five-year chance of survival when detected in late stages. The early detection, treatment and prevention of metastasis is pertinent and a pressing research priority as many patients are diagnosed only in stage three of ovarian cancer. Despite surgical interventions, targeted immunotherapy and adjuvant chemotherapy, relapses are significantly higher than other cancers, suggesting the dire need to identify the root cause of metastasis and relapse and present more precise therapeutic options. In this review, we first describe types of ovarian cancers, the existing markers and treatment modalities. As ovarian cancer is driven and sustained by an elusive and highly chemoresistant population of cancer stem cells (CSCs), their role and the associated signature markers are exhaustively discussed. Non-invasive diagnostic markers, which can be identified early in the disease using circulating tumor cells (CTCs), are also described. The mechanism of the self-renewal, chemoresistance and metastasis of ovarian CSCs is regulated by the Wnt signaling pathway. Thus, its role in ovarian cancer in promoting stemness and metastasis is delineated. Based on our findings, we propose a novel strategy of Wnt inhibition using a well-known Wnt antagonist, secreted frizzled related protein 4 (sFRP4), wherein short micropeptides derived from the whole protein can be used as powerful inhibitors. The latest approaches to early diagnosis and novel treatment strategies emphasized in this review will help design precision medicine approaches for an effective capture and destruction of highly aggressive ovarian cancer.

Short peptide domains of the Wnt inhibitor sFRP4 target ovarian cancer stem cells by neutralizing the Wnt ß-catenin pathway, disrupting the interaction between ß-catenin and CD24 and suppressing autophagy.

AIMS: One of the hallmarks of cancer stem cells (CSC) is hyperactive Wnt ß-catenin signaling due to the decreased presence of Wnt antagonists such as secreted frizzled related protein 4 (SFRP4). Cysteine-rich domain (CRD) and netrin-like domain (NLD) are the two functional domains of SFRP4 having anti-tumor properties. In this study, we have explored the effectiveness of short micropeptides SC-301 (from CRD) and SC-401 (from NLD) on CSC properties, EMT, apoptosis and autophagy in ovarian CSCs enriched from PA-1 and SKOV-3 cell lines. MAIN METHODS: Gene expression analysis, Western blot and immunocytochemistry were performed on ovarian CSCs to evaluate the inhibitory potential of micropeptides to various CSC associated oncogenic properties. Co-immunoprecipitation was performed to detect the binding of CD24 to ß-catenin protein complex. CYTO-ID Autophagy Detection Kit 2.0 was used to monitor autophagic flux in peptide treated CSCs. KEY FINDINGS: It is clearly seen that the micropeptides derived from both the domains inhibit Wnt pathway, initiate apoptosis, inhibit migration and chemosensitize CSCs. Specifically, CD24, a defining marker of ovarian CSC was suppressed by peptide treatment. Notably, interaction between CD24 and ß-catenin was disrupted upon peptide treatment. SFRP4 peptide treatment also suppressed the autophagic process which is crucial for CSC survival. SIGNIFICANCE: The study demonstrated that although both peptides have inhibitory effects, SC-401 was emphatically more effective in targeting CSC properties and down regulating the Wnt ß-catenin machinery.

An Update to the Malthus Model for Radiotherapy Utilisation in England.

AIMS: The Malthus Programme predicts national and local radiotherapy demand by combining cancer incidence data with decision trees detailing the indications, and appropriate dose fractionation, for radiotherapy. Since the last model update in 2017, technological advancements and the COVID-19 pandemic have led to increasing hypofractionation of radiotherapy schedules. Indications for radiotherapy have also evolved, particularly in the context of oligometastatic disease. Here we present a brief update on the model for 2021. We have updated the decision trees for breast, prostate, lung and head and neck cancers, and incorporated recent cancer incidence data into our model, generating a current estimate of fraction demand for these four cancer sites across England. MATERIALS AND METHODS: The decision tree update was based on evidence from practice-changing randomised controlled trials, published guidelines, audit data and expert opinion. Site- and stage-specific incidence data were taken from the National Disease Registration Service. We used the updated model to estimate the proportion of patients who would receive radiotherapy (appropriate rate of radiotherapy) and the fraction demand per million population at a national and Clinical Commissioning Group level in 2021. RESULTS: The total predicted fraction demand has decreased by 11.4% across all four cancer sites in our new model, compared with the 2017 version. This reduction can be explained primarily by greater use of hypofractionated treatments (including stereotactic ablative radiotherapy) and a shift towards earlier stage presentation. The only large change in appropriate rate of radiotherapy was an absolute decrease of 3% for lung cancer. CONCLUSIONS: Compared with our previous model, the current version predicts a reduction in fraction demand across England. This is driven principally by hypofractionation of radiotherapy regimens, using technology that requires increasingly complex planning. Treatment complexity and local service factors need to be taken into account when translating fraction burden into linear accelerator demand or throughput.

Effect of Non-Surgical Periodontal Therapy on Systemic Inflammatory Markers, Glycemic Status and Levels of Proteinuria in Type 2 Diabetic and Non-Diabetic Patients With Chronic Periodontitis.

AIMS AND OBJECTIVES:  The present study aimed to evaluate the effect of non-surgical periodontal therapy (NSPT) on systemic inflammatory markers, glycemic status, and levels of proteinuria in Type 2 diabetic and non-diabetic individuals with chronic periodontitis. METHODOLOGY: A total of 120 patients, categorized into three groups of 40 each, were included in this randomized observational study. Group 1 comprised patients with chronic periodontitis; Group 2 had chronic periodontitis with controlled diabetes; and Group 3 represented patients with chronic periodontitis with uncontrolled diabetes based on fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) levels. Periodontal clinical parameters like plaque index, gingival index, bleeding on probing, pocket depth, and clinical attachment levels were evaluated. Blood samples and urine samples were collected and assessed for the levels of FBS, HbA1c, total protein, albumin, globulin, and proteinuria. All parameters recorded at baseline and three months after non-surgical periodontal therapy were analyzed for statistical significance at p <.05 using SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc. RESULTS: A significant reduction in the periodontal clinical parameters within the groups, except for the clinical attachment level in Group 1 patients (p = 0.05), was observed. Glycemic status revealed a significant reduction after non-surgical periodontal therapy (p < 0.001), and on intragroup comparison, the total protein, albumin, globulin, and microprotein blood and urine levels showed significance among the evaluated groups (p < 0.001). CONCLUSION: Non-surgical periodontal treatment can effectively improve the periodontal and circulating inflammatory status. Results of our study showed improved glycemic control and a reduction in systemic inflammatory markers and proteinuria after performing non-surgical periodontal treatment in patients with type 2 diabetes.