Upfront boost to gross disease followed by elective pelvic radiation improves compliance to radiation therapy delivery metrics in locally advanced vulvar cancer.

Locally advanced cancer of the vulva (LACV) is commonly diagnosed in older women (>65 years), and is treated using combined multimodality therapy (CMT) that includes radiation therapy (RT). Compliance to optimal RT metrics, including completion of > 20 fractions, overall treatment duration of < 8 weeks (56 days), and < 1 week intra-treatment break is associated with better disease outcomes. However, published results note that a significant number of patients with LACV do not adhere to these metrics. The aim of our study is to evaluate whether a modified sequence of RT delivery, treating the localized boost volume upfront followed by the larger elective nodal volume is associated with improved compliance to optimal RT delivery metrics.

Modulation of mammary tumour progression using murine model by ethanol root extract of Saussurea costus (falc.) lipsch.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers. AIM OF THE STUDY: The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model. MATERIALS AND METHODS: The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking. RESULTS: Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract. CONCLUSIONS: The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.

Population Pharmacokinetic Analyses for Tebipenem after Oral Administration of Pro-Drug Tebipenem Pivoxil Hydrobromide.

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral (PO) carbapenem pro-drug that is converted to the active moiety tebipenem in the enterocytes. Tebipenem has activity against multidrug-resistant Gram-negative pathogens, including extended-spectrum beta lactamase-producing Enterobacterales, and is being developed for the treatment of patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). The objectives of these analyses were to develop a population pharmacokinetic (PK) model for tebipenem using data from three phase 1 studies and one phase 3 study and to identify covariates that described the variability in tebipenem PK. Following construction of the base model, a covariate analysis was conducted. The model was then qualified by performing a prediction-corrected visual predictive check and evaluated by using a sampling-importance-resampling procedure. The final population PK data set was composed of data from 746 subjects who provided 3,448 plasma concentrations, including 650 patients (1,985 concentrations) with cUTI/AP. The final population PK model that best described tebipenem PK was found to be a two-compartment model with linear, first-order elimination and two transit compartments to describe the rate of drug absorption after PO administration of TBP-PI-HBr. The relationship between renal clearance (CLR) and creatinine clearance (CLcr), the most clinically significant covariate, was described using a sigmoidal Hill-type function. No dose adjustments are warranted on the basis of age, body size, or sex as none of these covariates were associated with substantial differences in tebipenem exposure in patients with cUTI/AP. The resultant population PK model is expected to be appropriate for model-based simulations and assessment of pharmacokinetic-pharmacodynamic relationships for tebipenem.

Newly Recognized CNS Tumors in the 2021 World Health Organization Classification: Imaging Overview with Histopathologic and Genetic Correlation.

In 2021, the World Health Organization released an updated classification of CNS tumors. This update reflects the growing understanding of the importance of genetic alterations related to tumor pathogenesis, prognosis, and potential targeted treatments and introduces 22 newly recognized tumor types. Herein, we review these 22 newly recognized entities and emphasize their imaging appearance with correlation to histologic and genetic features.

Design and development of mechanical test bench for testing and calibration of multiple blood pressure measuring devices.

Blood pressure (BP) measurement is an important physiological parameter for human health monitoring, which plays a significant role in the diagnosis of many incurable diseases. However, due to inaccuracies in the different types of BP measuring devices, the calibration of these BP measuring instruments is a major concern for a medical practitioner. Currently, these devices' calibration, testing, and validation are performed using rigorous methods with complex clinical trials and following the available documentary standards. This article describes the design and development of an indigenous mechanical test bench (MTB) system for the testing and calibration of multiple BP devices, as per International Organization of Legal Metrology (OIML) recommended documents e.g., OIML R 16-1 and OIML R 16-2. The developed system can test and calibrate 20 BP devices, simultaneously. The traceability of the developed MTB is established by performing its calibration against the Air Piston Gauge, a national primary vacuum standard. The estimated expanded measurement uncertainty evaluated is found to be ±0.11 mmHg, which is almost one order better than the measurement uncertainty required for the test and calibration of BP measuring instruments as per standard. The MTB has successfully been used to test and calibrate several BP measuring instruments. The data of one such device is reported herein as an indicator of the performance process. The calibration of these BP measuring instruments was performed in the static mode, and the estimated expanded measurement uncertainty was found to be ±1.25 mmHg. The developed MTB system would prove to be an excellent instrument for calibration laboratories, hospitals, regulatory agencies, and other users to test and calibrate 20 BP measuring devices simultaneously and cost-effectively.

Edge-Enhancing Gradient-Echo MP2RAGE for Clinical Epilepsy Imaging at 7T.

The 3D edge-enhancing gradient-echo (EDGE) MR imaging sequence offers superior contrast-to-noise ratio in the detection of focal cortical dysplasia. EDGE could benefit from 7T MR imaging but also faces challenges such as image inhomogeneity and low acquisition efficiency. We propose an EDGE-MP2RAGE sequence that can provide both EDGE and T1-weighted contrast, simultaneously, improving data-acquisition efficiency. We demonstrate that with sequence optimization, EDGE images with sufficient uniformity and T1-weighted images with high gray-to-white matter contrast can be achieved.

High-Resolution 7T MR Imaging of the Trochlear Nerve.

BACKGROUND AND PURPOSE: The trochlear nerve has traditionally been difficult to identify on MR imaging. The advent of 7T MR imaging promises to greatly benefit visualization of small structures due to gains in the signal-to-noise ratio allowing improved spatial resolution. We investigated the utility of a clinically feasible ultra-high-resolution 7T MR imaging protocol for identification of the trochlear nerve, as well as assessment of normal trochlear nerve anatomy. MATERIALS AND METHODS: Coronal high-resolution 2D T2-weighted TSE images used in a 7T epilepsy protocol of 50 subjects at our institution were reviewed by 2 independent radiologists for visualization of the trochlear nerve at the nerve origin and cisternal, tentorial, and cavernous segments. The frequency of nerve visibility within these segments and their anatomy were documented, and disagreements were resolved by joint review. RESULTS: Of the 100 nerves reviewed in 50 subjects, at least 2 segments of the trochlear nerve from the brainstem to the cavernous sinus were identified in 100% of cases. The origins from the brainstem and cisternal segment were visible in 65% and 93% of nerves, respectively. The trochlear nerve was identified at the trochlear groove in 100% of cases and in the posterior wall of the cavernous sinus in 74% of cases. CONCLUSIONS: Coronal high-resolution 2D TSE at 7T reliably identified the trochlear nerve throughout its course and is a promising tool for imaging patients with suspected trochlear nerve pathology.

Association of timing of congenital diaphragmatic hernia repair with survival and morbidity for patients not requiring extra-corporeal life support.

BACKGROUND: While physiologic stabilization followed by repair has become the accepted paradigm for management of congenital diaphragmatic hernia (CDH), few studies have examined the effect of incremental changes in operative timing on patient outcomes. We hypothesized that later repair would be associated with higher morbidity and mortality. METHODS: Data were queried from the CDH Study Group (CDHSG) from 2007-2020. Patients with chromosomal or cardiac abnormalities and those who were never repaired or required pre-repair extra-corporeal life support (ECLS) were excluded. Time to repair was analyzed both as a continuous variable and by splitting the cohort into top/bottom percentiles. The primary outcome of interest was in-hospital mortality. Secondary outcomes included need for and duration of post-repair ventilatory and nutritional support. RESULTS: A total of 4,104 CDH infants were included. Median time to repair was 4 days (IQR 2-6). On multivariable analysis, high-risk (CDHSG stage C/D) defects and lower birthweight predicted later repair. Overall, in-hospital mortality was 6%. On univariate analysis, there was no difference in the number of days to repair between survivors and non-survivors. On risk-adjusted analysis, single-day changes in day of repair were not associated with increased mortality. Later repair was associated with longer time to reach full oral feeds, increased post-repair ventilator days, and increased need for tube feeds and supplementary oxygen at discharge. CONCLUSIONS: For infants with isolated CDH not requiring pre-operative ECLS, there is no difference in mortality based on timing of repair, but single-day delays in repair are associated with increased post-repair duration of ventilatory and nutritional support.

Fusarium and allied fusarioid taxa (FUSA). 1.

Seven Fusarium species complexes are treated, namely F. aywerte species complex (FASC) (two species), F. buharicum species complex (FBSC) (five species), F. burgessii species complex (FBURSC) (three species), F. camptoceras species complex (FCAMSC) (three species), F. chlamydosporum species complex (FCSC) (eight species), F. citricola species complex (FCCSC) (five species) and the F. concolor species complex (FCOSC) (four species). New species include Fusicolla elongata from soil (Zimbabwe), and Neocosmospora geoasparagicola from soil associated with Asparagus officinalis (Netherlands). New combinations include Neocosmospora akasia, N. awan, N. drepaniformis, N. duplosperma, N. geoasparagicola, N. mekan, N. papillata, N. variasi and N. warna. Newly validated taxa include Longinectria gen. nov., L. lagenoides, L. verticilliforme, Fusicolla gigas and Fusicolla guangxiensis. Furthermore, Fusarium rosicola is reduced to synonymy under N. brevis. Finally, the genome assemblies of Fusarium secorum (CBS 175.32), Microcera coccophila (CBS 310.34), Rectifusarium robinianum (CBS 430.91), Rugonectria rugulosa (CBS 126565), and Thelonectria blattea (CBS 952.68) are also announced here. Citation: Crous PW, Sandoval-Denis M, Costa MM, Groenewald JZ, van Iperen AL, Starink-Willemse M, Hernández-Restrepo M, Kandemir H, Ulaszewski B, de Boer W, Abdel-Azeem AM, Abdollahzadeh J, Akulov A, Bakhshi M, Bezerra JDP, Bhunjun CS, Câmara MPS, Chaverri P, Vieira WAS, Decock CA, Gaya E, Gené J, Guarro J, Gramaje D, Grube M, Gupta VK, Guarnaccia V, Hill R, Hirooka Y, Hyde KD, Jayawardena RS, Jeewon R, Jurjevic Z, Korsten L, Lamprecht SC, Lombard L, Maharachchikumbura SSN, Polizzi G, Rajeshkumar KC, Salgado-Salazar C, Shang Q-J, Shivas RG, Summerbell RC, Sun GY, Swart WJ, Tan YP, Vizzini A, Xia JW, Zare R, González CD, Iturriaga T, Savary O, Coton M, Coton E, Jany J-L, Liu C, Zeng Z-Q, Zhuang W-Y, Yu Z-H, Thines M (2022). Fusarium and allied fusarioid taxa (FUSA). 1. Fungal Systematics and Evolution 9: 161-200. doi: 10.3114/fuse.2022.09.08.

Brain Abnormalities and Epilepsy in Patients with Parry-Romberg Syndrome.

BACKGROUND AND PURPOSE: Parry-Romberg syndrome is a rare disorder characterized by progressive hemifacial atrophy. Concomitant brain abnormalities have been reported, frequently resulting in epilepsy, but the frequency and spectrum of brain involvement are not well-established. This study aimed to characterize brain abnormalities in Parry-Romberg syndrome and their association with epilepsy. MATERIALS AND METHODS: This is a single-center, retrospective review of patients with a clinical diagnosis of Parry-Romberg syndrome and brain MR imaging. The degree of unilateral hemispheric atrophy, white matter disease, microhemorrhage, and leptomeningeal enhancement was graded as none, mild, moderate, or severe. Other abnormalities were qualitatively reported. Findings were considered potentially Parry-Romberg syndrome-related when occurring asymmetrically on the side affected by Parry-Romberg syndrome. RESULTS: Of 80 patients, 48 (60%) had brain abnormalities identified on MR imaging, with 26 (32%) having abnormalities localized to the side of the hemifacial atrophy. Sixteen (20%) had epilepsy. MR imaging brain abnormalities were more common in the epilepsy group (100% versus 48%, P < .001) and were more frequently present ipsilateral to the hemifacial atrophy in patients with epilepsy (81% versus 20%, P < .001). Asymmetric white matter disease was the predominant finding in patients with (88%) and without (23%) epilepsy. White matter disease and hemispheric atrophy had a higher frequency and severity in patients with epilepsy (P < .001). Microhemorrhage was also more frequent in the epilepsy group (P = .015). CONCLUSIONS: Ipsilateral MR imaging brain abnormalities are common in patients with Parry-Romberg syndrome, with a higher frequency and greater severity in those with epilepsy. The most common findings in both groups are white matter disease and hemispheric atrophy, both presenting with greater severity in patients with epilepsy.

Development of a novel one-step triplex PCR assay for the simultaneous detection of porcine circovirus type 2, porcine parvovirus and classical swine fever virus in a single tube.

Co-infection of multiple pathogens complicates diagnosis, treatment and preventive measures based on clinical signs. Therefore, reliable diagnostic tool for timely reporting of suspected diseases is very much essential. A novel one-step triplex PCR assay was developed and evaluated for simultaneous detection of three important viruses namely porcine circovirus type 2 (PCV2), porcine parvovirus (PPV) and classical swine fever virus (CSFV) involved in reproductive problems in pigs. Each of the three pairs of oligonucleotide primers exclusively amplified the targeted fragment of the specific viruses. The multiplex PCR assay was found to be sensitive in detecting at least 300 pg of viral genomic DNA or RNA from a mixture of three viruses in a reaction. No amplification was obtained from other common viruses or pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), Japanese encephalitis virus (JEV), porcine group A rotavirus (PoRVA), Escherichia coli and Staphylococcus aureus thereby indicating that the developed multiplex PCR has high specificity. Because of the sensitivity and specificity, the developed multiplex PCR assay will be a useful tool for clinical diagnosis of mixed infections of DNA and RNA viruses in pigs.

Reflectance based non-destructive determination of colour and ripeness of tomato fruits.

The preference and quality of tomato fruit are primarily determined by its apparent colour and appearance. Non-destructive and rapid methods for assessment of tomato colour and ripeness are therefore of immense significance. This study was conducted to identify reflectance-based indices and to develop models for the non-destructive determination of colour and ripeness (maturity) of tomato fruits. Tomato fruits of two varieties and two hybrids, representing different ripening stages were investigated. Fruits were either harvested directly from the plants or they were picked up from the lots stored at 25 °C. Reflectance from individual fruit was recorded in a spectrum ranging from 350 to 2500 nm. These fruits at different ripening stages were ranked on a relative ripening score (0.0-8.5). Obtained data (reflectance and ripening score) were subjected to chemometric analysis. In total, six models were developed. The first-best model was based on the index R521 (reflectance at wavelength 521 nm) i.e., y (colour/ripeness) = - 2.456 ln (x) - 1.093 where x is R521. This model had a root mean standard error of prediction (RMSEP) ≥ 0.86 and biasness = - 0.09. The second-best model y = 2.582 ln (x) - 0.805 was based on the index R546 (x) and had RMSEP ≥ 0.89 and biasness = 0.10. Models could bifurcate tomatoes into basic ripening stages and also red and beyond red tomato fruits from other stages across the varieties/hybrids and ripening conditions [for plant harvested (fresh) and stored (aged) fruits]. Findings will prove useful in developing simple and thereby cost-effective tools for rapid screening/sorting of tomato fruits based on their colour or ripeness not only for basic research (phenotyping) but also for the purpose of processing, value-addition, and pharmaceutical usages. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01126-2.

Smart Heart Disease Prediction System with IoT and Fog Computing Sectors Enabled by Cascaded Deep Learning Model.

Chronic illnesses like chronic respiratory disease, cancer, heart disease, and diabetes are threats to humans around the world. Among them, heart disease with disparate features or symptoms complicates diagnosis. Because of the emergence of smart wearable gadgets, fog computing and "Internet of Things" (IoT) solutions have become necessary for diagnosis. The proposed model integrates Edge-Fog-Cloud computing for the accurate and fast delivery of outcomes. The hardware components collect data from different patients. The heart feature extraction from signals is done to get significant features. Furthermore, the feature extraction of other attributes is also gathered. All these features are gathered and subjected to the diagnostic system using an Optimized Cascaded Convolution Neural Network (CCNN). Here, the hyperparameters of CCNN are optimized by the Galactic Swarm Optimization (GSO). Through the performance analysis, the precision of the suggested GSO-CCNN is 3.7%, 3.7%, 3.6%, 7.6%, 67.9%, 48.4%, 33%, 10.9%, and 7.6% more advanced than PSO-CCNN, GWO-CCNN, WOA-CCNN, DHOA-CCNN, DNN, RNN, LSTM, CNN, and CCNN, respectively. Thus, the comparative analysis of the suggested system ensures its efficiency over the conventional models.