Analysis of Molecular Genetic Variants of Lgals4 in Esophageal Cancer: A Preliminary Report.

Esophageal cancer is the eighth most common cancer worldwide and fourth most common in developing countries. Altered glycosylation pattern of cell membrane molecules along with inflammation is a characteristic attribute of oncogenesis. Galectin-4, a tandem repeat galectin, has shown effect on cancer progression/metastasis in digestive system cancers. This role of galectin-4 can be attributed to variations in LGALS4, gene encoding galectin-4. The present case-control study was designed to analyze four intronic SNPs in LGALS4 with susceptibility toward esophageal cancer.Esophageal cancer cases and age- and gender-matched apparently healthy individuals were recruited for the present study. Genotyping of rs8113319, rs4802886, rs4802887, and rs12610990 was carried out using Sanger sequencing and PCR-RFLP. MedCalc software, SNPStats and SHEsis online platform were used for statistical analysis.Genotypic analyses revealed an overall increased heterozygosity of rs12610990, rs4802886, and rs4802887, and AA genotype of rs8113319 in the study participants. Haplotypic analyses also revealed a predominance of AAAT haplotype in the cases. Moreover, combined presence of wild alleles of rs4802886 and rs4802887 could influence protection toward disease, and combined presence of wild alleles of rs12610990 and rs8113319 could influence disease susceptibility. Furthermore, a strong linkage disequilibrium was also observed between the SNPs. Further studies are underway to validate galectin-4 and its genetic variants as blood-based biomarkers in early disease diagnosis, improving treatment outcome.

Guggulsterone protects against cigarette smoke-induced COPD linked lung inflammation.

Recently, we have shown that guggulsterone is the principal constituent responsible for protective effects of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease (COPD)-linked inflammation/emphysema. Given that cigarette smoke (CS) exposure is a primary risk factor for COPD and beneficial effects of guggulsterone have not been investigated in CS-induced COPD-linked lung inflammation. The present work was designed to validate the potential of guggulsterone in amelioration of COPD-linked lung inflammation by using a CS-based mouse model of the condition. Male BALB/c mice were exposed to 9 cigarettes/day with 1 h interval for 4 days daily. Guggulsterone was administered daily at a dose of 10 mg/kg orally for 4 consecutive days, 1 h before initiation of CS exposure. Mice were subjected to measurement of lung function followed by procurement of bronchoalveolar lavage fluid (BALF)/lung tissue. BALF was analyzed for inflammatory cells and pro-inflammatory cytokines. Lung tissue was subjected to RT-PCR for gene expression analysis. Data showed that CS exposure resulted in a significant increase in total BALF cells, predominantly neutrophils, and macrophages. Interestingly, guggulsterone administration significantly blunted CS-induced inflammation as reflected by reduced neutrophil and macrophage count. Further, the compound inhibited CS-induced gene expression of pro-inflammatory mediators TNF-α/ IL-1ß/ G-CSF/and KC in lungs along with the production of pro-inflammatory mediators TNF-α/ IL-1ß/ IL-6/ G-CSF/ KC/and MCP-1 in BALF. Further, guggulsterone improved the lung function parameters upon CS exposure. Analysis of mRNA expression of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 suggests that guggulsterone may restore the fine balance between matrix-degrading proteases and its inhibitor in lung tissue upon CS exposure, which may contribute in the development of emphysema at later stages. Overall, our data show that guggulsterone protects against CS-induced COPD-linked lung inflammation by modulating relevant molecular players. Based on the potential effects of guggulsterone in the amelioration of CS-induced lung inflammation, we speculate that guggulsterone might alter chronic CS-induced emphysema.

Underutilized fruit lasoda (Cordia myxa L.): Review on bioactive compounds, antioxidant potentiality and applications in health bioactivities and food.

Underutilized fruits are thought to be nutrient and antioxidant gold mines. Despite their high nutritive value, therapeutic properties, and ability to grow in adverse soil and climatic conditions, they have received little attention. However, these underutilized fruits are an important component of traditional foods, particularly in arid and semiarid regions of Rajasthan. Lasoda (Cordia myxa) contains numerous phytochemicals that contribute to its antioxidant potential, including tannins, flavonoids, phenolic acids, xanthones, terpenes, and saponins. The primary goal of this review is to emphasize the importance of extracting bioactive compounds from lasoda and evaluating their antioxidant potential. Furthermore, this review emphasizes the major areas for the application of lasoda and its extract as prospective positive health agents that can be used in the preparation of functional foods. The use of lasoda may also improve the value of bakery products and meat quality and prevent postharvest losses. This review is a pilot article that can aid in the nutritional profiling of Cordia fruits and seeds, and it provides information on the effective and efficient use of this underutilized fruit in the food and nutraceutical industries.

A large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information.

Resection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.

Comparison of gastric emptying time between breast-fed and formula milk-fed infants less than 6 months old, using gastric ultrasound-An observational study.

BACKGROUND: Fasting before elective anesthesia care is a standardized practice worldwide. The aim is to decrease the risk of aspiration leading to pulmonary complications such as aspiration pneumonitis during anesthesia care. There are different guidelines for elective preoperative fasting in children. However, there is insufficient literature measuring gastric emptying time after breast milk or formula milk feeding in infants. OBJECTIVE: This study used gastric ultrasound to determine the gastric emptying time for breast milk and formula milk in children below 6 months of age. We also compared the calculated gastric volumes among breast-fed and formula milk-fed based on Schmitz's and Spencer's formula. MATERIALS AND METHODS: This prospective observational study was conducted at a tertiary care center in India between November (2017-2019). A total of 52 infants less than 6 months of age were recruited. The study population was divided into two groups (breast-fed and formula milk-fed) of 26 patients each. Ultrasound was used to measure the antral cross-sectional area of the stomach and to calculate the gastric volume using the two classical formulas (Schmitz and Spencer's). Gastric emptying was reported when the bull's eye appearance of the gastric antrum was seen or when the antral cross-sectional area was less than 3.07 cm2. RESULTS: The number of breast-fed children whose antral cross-sectional was greater than 3.07 cm2 (cut-off value for aspiration risk) beyond 1 h was 14/26 (53.84%) while none (0) children went beyond 3 h. The number of formula-fed children whose antral cross-sectional was greater than 3.07 cm2 beyond 1 h was 17/26 (65.38%) while one child (3.84%) went beyond 3 h. Using Schmitz's formula, mean (SD) gastric emptying times were 0.35 ± 0.68 h (95% CI 0.35 ± 0.185, range 0.165-0.535) for breast-fed patients and 0.35 ± 0.69 h (95% CI 0.35 ± 0.188, range 0.162-0.538) for formula-fed patients, and were thus neither clinically nor statistically different (p = .73) Using Spencer's formula, the mean gastric emptying times were 0.12 ± 0.33 h (95% CI 0.12 ± 0.09, range 0.03-0.21) for breast-fed patients and 0.04 ± 0.20 h (95% CI 0.04 ± 0.05, range -0.01 to 0.09) for formula-fed patients, and were also neither clinically nor statistically different p = .13. CONCLUSION: In our series, the gastric emptying times in breast-fed and formula-fed infants less than 6 months old were similar. Our results support the fasting guidelines of the European Society of Anaesthesiology and Intensive Care 2022, that is, 3 h for breastfeeding and 4 h for formula milk feeding. In addition, this shows that the Schmitz's and Spencer's formulae used to calculate the gastric volume based on ultrasound measurement of the antral cross-sectional area are not comparable in infants less than 6 months.

Dry-air roasting impact on physicochemical, functional, antioxidant properties, phenolic profile and Maillard reaction products of flaxseed flour and cake flour.

The study investigated and compared physicochemical, functional, antioxidant properties, phenolic profile and Maillard reaction products (MRP) of flaxseed flour (FF) and flaxseed cake flour (FCF) upon dry-air roasting (DaR) of flaxseeds at 140, 160 and 180 °C for 5 and 10 min. This information on FF and FCF is limited and has considerable gaps. The raw FF exhibited higher fat, ash, antioxidant and functional properties while lower protein than the FCF. Upon increasing DaR conditions, the ash and protein increased in FCF and decreased in FF. DaR at 180 °C for 10 min augmented water solubility index, ΔE, MRP, free rutin and syringic acid, bound epicatechin, gallic acid and syringic acid while lowered moisture, L*, b*, hue, chroma, potassium, iron, selenium, emulsion indexes, caffeic acid, flavonoids and free resveratrol in FF and FCF. In conclusion, DaR improves phenolic profile, antioxidant properties, MRP, water solubility and oil absorption capacity of FF and FCF.

Comparison of volumetric and 2D-based response methods in the PNOC-001 pediatric low-grade glioma clinical trial.

Background: Although response in pediatric low-grade glioma (pLGG) includes volumetric assessment, more simplified 2D-based methods are often used in clinical trials. The study's purpose was to compare volumetric to 2D methods. Methods: An expert neuroradiologist performed solid and whole tumor (including cyst and edema) volumetric measurements on MR images using a PACS-based manual segmentation tool in 43 pLGG participants (213 total follow-up images) from the Pacific Pediatric Neuro-Oncology Consortium (PNOC-001) trial. Classification based on changes in volumetric and 2D measurements of solid tumor were compared to neuroradiologist visual response assessment using the Brain Tumor Reporting and Data System (BT-RADS) criteria for a subset of 65 images using receiver operating characteristic (ROC) analysis. Longitudinal modeling of solid tumor volume was used to predict BT-RADS classification in 54 of the 65 images. Results: There was a significant difference in ROC area under the curve between 3D solid tumor volume and 2D area (0.96 vs 0.78, P = .005) and between 3D solid and 3D whole volume (0.96 vs 0.84, P = .006) when classifying BT-RADS progressive disease (PD). Thresholds of 15-25% increase in 3D solid tumor volume had an 80% sensitivity in classifying BT-RADS PD included in their 95% confidence intervals. The longitudinal model of solid volume response had a sensitivity of 82% and a positive predictive value of 67% for detecting BT-RADS PD. Conclusions: Volumetric analysis of solid tumor was significantly better than 2D measurements in classifying tumor progression as determined by BT-RADS criteria and will enable more comprehensive clinical management.

Impact of subgingival instrumentation on systemic inflammation and serum bone resorption marker in premenopausal women with periodontitis: a prospective interventional study.

OBJECTIVES: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. METHOD AND MATERIALS: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). RESULTS: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. CONCLUSION: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health.

Assessment of Knowledge and Awareness Regarding Oro-systemic Link among General Population: A Cross-sectional Survey.

Aim: Various surveys aimed at gathering the knowledge and awareness of health practitioners as well as students, both medical and dental, regarding the link between oral health and systemic diseases have been published. However, relatively few studies have attempted to examine the awareness of such knowledge among the general population. Therefore, the current study aimed to explore the public perception regarding the oro-systemic link. Materials and methods: The present study was designed as a cross-sectional survey to be carried out in the Department of Periodontology and Oral Implantology, PGIDS, Rohtak. All survey participants were provided with a written questionnaire which was required to be completed by each participant independently. The study questionnaire was designed to collect demographic data followed by specific questions targeting the awareness and knowledge of the participants regarding the relationship between oral and systemic health. Results: A total of 240 completed questionnaires were available for analysis. Only about a quarter of the total participants (27.5 %) believed that oral health status has any effect on the rest of the body. A positive response (YES) of 25% was observed for effect of diabetes and physician prescribed medicines on systemic health. Regarding the effect of pregnancy, smoking, stress, and obesity on systemic health, less than 20% positive response was recorded. Conclusion: The findings indicate a very poor awareness regarding the impact of systemic conditions on oral status and vice versa, among the studied population. Clinical significance: Pedodontists should lay emphasis on imparting knowledge about oro-systemic connections to their patients as well accompanying guardians. This would go a long way in spreading much needed awareness among the general population as well as ensuring that children adopt healthy lifestyle habits right from childhood. How to cite this article: Sangwan A, Sangwan P, Kaur M, et al. Assessment of Knowledge and Awareness Regarding Oro-systemic Link among General Population: A Cross-sectional Survey. Int J Clin Pediatr Dent 2023;16(S-2):S202-S205.

Urinary Apolipoprotein A1 and Neutrophil Gelatinase-associated Lipocalin in Children with Idiopathic Nephrotic Syndrome.

Urinary biomarkers are a promising diagnostic modality whose role was explored in nephrotic syndrome (NS). We estimated urinary apolipoprotein A1 (Apo A1) and neutrophil gelatinase-associated lipocalin (NGAL) in children with first-episode NS (FENS) and controls with a longitudinal follow-up to see the serial changes during remission. The study groups comprised 35 children with FENS and an equal number of age- and sex-matched controls. Patients were followed up at regular intervals, and 32 patients were classified as having steroid-sensitive NS (SSNS) and 3 as having steroid-resistant NS (SRNS). The mean follow-up period was 8.7 ± 4.2 months. Three patients in the SSNS group were labeled as having frequent relapses or steroid-dependent disease during follow-up. Of the three children with SRNS, two had minimal changes in the disease and one had idiopathic membranous nephropathy. The levels of Apo A1:creatinine, NGAL:creatinine, and spot urinary protein:urinary creatinine ratios were significantly higher in children with FENS compared with controls. The levels of the urine biomarkers decreased significantly at subsequent follow-up with remission. The Apo A1 and NGAL levels in SSNS patients were significantly high compared with both the controls and FENS patients. Urinary Apo A1 levels in SRNS patients were lower at initial presentation. This longitudinal study revealed changes in the urinary Apo A1 and NGAL in NS over the course of the disease.

Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation.

BACKGROUND: Pulmonary hypertension (PH) is a chronic vascular disease characterized, among other abnormalities, by hyperproliferative smooth muscle cells and a perturbed cellular redox and metabolic balance. Oxidants induce cell cycle arrest to halt proliferation; however, little is known about the redox-regulated effector proteins that mediate these processes. Here, we report a novel kinase-inhibitory disulfide bond in cyclin D-CDK4 (cyclin-dependent kinase 4) and investigate its role in cell proliferation and PH. METHODS: Oxidative modifications of cyclin D-CDK4 were detected in human pulmonary arterial smooth muscle cells and human pulmonary arterial endothelial cells. Site-directed mutagenesis, tandem mass-spectrometry, cell-based experiments, in vitro kinase activity assays, in silico structural modeling, and a novel redox-dead constitutive knock-in mouse were utilized to investigate the nature and definitively establish the importance of CDK4 cysteine modification in pulmonary vascular cell proliferation. Furthermore, the cyclin D-CDK4 oxidation was assessed in vivo in the pulmonary arteries and isolated human pulmonary arterial smooth muscle cells of patients with pulmonary arterial hypertension and in 3 preclinical models of PH. RESULTS: Cyclin D-CDK4 forms a reversible oxidant-induced heterodimeric disulfide dimer between C7/8 and C135, respectively, in cells in vitro and in pulmonary arteries in vivo to inhibit cyclin D-CDK4 kinase activity, decrease Rb (retinoblastoma) protein phosphorylation, and induce cell cycle arrest. Mutation of CDK4 C135 causes a kinase-impaired phenotype, which decreases cell proliferation rate and alleviates disease phenotype in an experimental mouse PH model, suggesting this cysteine is indispensable for cyclin D-CDK4 kinase activity. Pulmonary arteries and human pulmonary arterial smooth muscle cells from patients with pulmonary arterial hypertension display a decreased level of CDK4 disulfide, consistent with CDK4 being hyperactive in human pulmonary arterial hypertension. Furthermore, auranofin treatment, which induces the cyclin D-CDK4 disulfide, attenuates disease severity in experimental PH models by mitigating pulmonary vascular remodeling. CONCLUSIONS: A novel disulfide bond in cyclin D-CDK4 acts as a rapid switch to inhibit kinase activity and halt cell proliferation. This oxidative modification forms at a critical cysteine residue, which is unique to CDK4, offering the potential for the design of a selective covalent inhibitor predicted to be beneficial in PH.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.

Sliding limbus-conjunctival flaps for minimizing the pterygium recurrence: a prospective tertiary care institute study.

Objective: To describe the surgical technique and long-term outcomes of sliding limbus-conjunctival flaps to treat primary pterygium. Methods: Our single-center, single-surgeon-based, prospective study (part of the postgraduate thesis) included primary pterygium patients. We included the larger pterygium in bilateral cases for our research. All patients underwent pterygium excision and reconstruction by sliding limbus-conjunctival flaps technique to minimize the recurrence rates. Similar surgical steps and drugs were used for all the enrolled patients. Two ophthalmologists (SS and MK) evaluated all cases for blinding purposes. A minimum follow-up of 12 months was ensured in all cases. Results: Fifty eyes of 50 patients underwent the sliding limbus-conjunctival flaps surgery at a mean age of 50.40 ± 15.05 years. There were 27 (54%) males and 23 (46%) females with nasal pterygium (100%), having an average horizontal size of 2.96 mm. A "with the rule" astigmatism was seen in 44 (88%) eyes with a horizontal keratometry value of 42.00 ± 2.83, which increased significantly to 42.23 ± 2.02 (p>0.05) after surgery. The visual acuity was improved by 1 Snellen's line in 21 cases, 2 lines in 4 cases, and by 3 lines in 1 case. No change in visual acuity was seen in 24 cases. The early minor postoperative complications were self-resolving. At a mean follow-up of 14.5 months, the recurrence was found in 2 patients (4%), one in the 3rd and the other in the 9th month. Conclusion: The sliding limbus-conjunctival flaps technique is a simple, safe, and efficient procedure for primary pterygium cases. Pterygium surgery positively affects the visual acuity and keratometry values in most patients, making it a cosmetic and functional ophthalmic surgical procedure.

Developing a cluster-based approach for deciphering complexity in individuals with neurodevelopmental differences.

Objective: Individuals with neurodevelopmental disorders such as global developmental delay (GDD) present both genotypic and phenotypic heterogeneity. This diversity has hampered developing of targeted interventions given the relative rarity of each individual genetic etiology. Novel approaches to clinical trials where distinct, but related diseases can be treated by a common drug, known as basket trials, which have shown benefits in oncology but have yet to be used in GDD. Nonetheless, it remains unclear how individuals with GDD could be clustered. Here, we assess two different approaches: agglomerative and divisive clustering. Methods: Using the largest cohort of individuals with GDD, which is the Deciphering Developmental Disorders (DDD), characterized using a systematic approach, we extracted genotypic and phenotypic information from 6,588 individuals with GDD. We then used a k-means clustering (divisive) and hierarchical agglomerative clustering (HAC) to identify subgroups of individuals. Next, we extracted gene network and molecular function information with regard to the clusters identified by each approach. Results: HAC based on phenotypes identified in individuals with GDD revealed 16 clusters, each presenting with one dominant phenotype displayed by most individuals in the cluster, along with other minor phenotypes. Among the most common phenotypes reported were delayed speech, absent speech, and seizure. Interestingly, each phenotypic cluster molecularly included several (3-12) gene sub-networks of more closely related genes with diverse molecular function. k-means clustering also segregated individuals harboring those phenotypes, but the genetic pathways identified were different from the ones identified from HAC. Conclusion: Our study illustrates how divisive (k-means) and agglomerative clustering can be used in order to group individuals with GDD for future basket trials. Moreover, the result of our analysis suggests that phenotypic clusters should be subdivided into molecular sub-networks for an increased likelihood of successful treatment. Finally, a combination of both agglomerative and divisive clustering may be required for developing of a comprehensive treatment.

PACS-Integrated Tools for Peritumoral Edema Volumetrics Provide Additional Information to RANO-BM-Based Assessment of Lung Cancer Brain Metastases after Stereotactic Radiotherapy: A Pilot Study.

Stereotactic radiotherapy (SRT) is the standard of care treatment for brain metastases (METS) today. Nevertheless, there is limited understanding of how posttreatment lesional volumetric changes may assist prediction of lesional outcome. This is partly due to the paucity of volumetric segmentation tools. Edema alone can cause significant clinical symptoms and, therefore, needs independent study along with standard measurements of contrast-enhancing tumors. In this study, we aimed to compare volumetric changes of edema to RANO-BM-based measurements of contrast-enhancing lesion size. Patients with NSCLC METS ≥10 mm on post-contrast T1-weighted image and treated with SRT had measurements for up to seven follow-up scans using a PACS-integrated tool segmenting the peritumoral FLAIR hyperintense volume. Two-dimensional contrast-enhancing and volumetric edema changes were compared by creating treatment response curves. Fifty NSCLC METS were included in the study. The initial median peritumoral edema volume post-SRT relative to pre-SRT baseline was 37% (IQR 8-114%). Most of the lesions with edema volume reduction post-SRT experienced no increase in edema during the study. In over 50% of METS, the pattern of edema volume change was different than the pattern of contrast-enhancing lesion change at different timepoints, which was defined as incongruent. Lesions demonstrating incongruence at the first follow-up were more likely to progress subsequently. Therefore, edema assessment of METS post-SRT provides critical additional information to RANO-BM.

A Large Open Access Dataset of Brain Metastasis 3D Segmentations with Clinical and Imaging Feature Information.

Resection and whole brain radiotherapy (WBRT) are the standards of care for the treatment of patients with brain metastases (BM) but are often associated with cognitive side effects. Stereotactic radiosurgery (SRS) involves a more targeted treatment approach and has been shown to avoid the side effects associated with WBRT. However, SRS requires precise identification and delineation of BM. While many AI algorithms have been developed for this purpose, their clinical adoption has been limited due to poor model performance in the clinical setting. Major reasons for non-generalizable algorithms are the limitations in the datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models to improve generalizability. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and whole tumor (including peritumoral edema) 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging feature information. We used a streamlined approach to database-building leveraging a PACS-integrated segmentation workflow.

OHVIRA syndrome: hysteroscopy and intraoperative sonography - a value addition in the management.

We report a postpubertal case of obstructed hemivagina and ipsilateral renal agenesis syndrome who presented with dysmenorrhoea and light menstrual flow. Imaging modalities confirmed the diagnosis after which vaginal septal incision and drainage was performed. In addition, we also performed vaginoscopy using hysteroscope, both preincision and postincision and drainage, to visualise the vagina and to exclude any communication between two hemivaginas. Completeness of drainage was ensured by performing intraoperative sonography. In a few instances, communication (fistula or microperforation) between the two hemivaginas would result in spontaneous haematocolpos decompression, mimicking normal menstrual flow and often delaying diagnosis. The role of direct visualisation under hysteroscopy should be emphasised in such cases. We postulate that hysteroscopy and intraoperative sonography may aid in better diagnostic and therapeutic management in such cases.

Association between intraoperative starch use and postoperative kidney dysfunction in patients undergoing major gastro-intestinal surgery: A propensity score-matched analysis.

BACKGROUND: The impact of intraoperative starch-based fluid therapy on postoperative kidney dysfunction in patients undergoing major abdominal surgery is uncertain. Low molecular weight starch is expected to cause less postoperative kidney dysfunction. METHODS: This retrospective study evaluated the impact of intraoperative 6% hydroxyethyl starch on postoperative renal dysfunction. The primary outcome of this study was postoperative acute kidney injury as per KDIGO definition within 72 hours of surgery. RESULTS: This study analysed data from 461 patients with a median (interquartile range) age of 45 (33-58) years, and 48.2% of all patients were female. The proportion (95% confidence interval) of patients who developed acute kidney injury was 0.18 (0.14-0.21); 62.9% of patients had acute kidney injury stage I, 32% had acute kidney injury stage II, and the rest were acute kidney injury stage III. In the propensity score-matched sample, the average treatment effect of intraoperative colloid use on postoperative serum creatinine at day 3 (p = 0.32), duration of postoperative intensive care unit stay (p = 0.97), duration of hospital stay (p = 0.37), postoperative worst international normalised ratio (p = 0.92), and postoperative transfusion requirement (p = 0.40) were not statistically significant. CONCLUSION: Intraoperative use of low molecular weight hydroxyethyl starch use was not associated with postoperative kidney dysfunction and coagulopathy in adult patients undergoing major open abdominal surgery.

The Brain Tumor Segmentation (BraTS-METS) Challenge 2023: Brain Metastasis Segmentation on Pre-treatment MRI.

Clinical monitoring of metastatic disease to the brain can be a laborious and timeconsuming process, especially in cases involving multiple metastases when the assessment is performed manually. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) guideline, which utilizes the unidimensional longest diameter, is commonly used in clinical and research settings to evaluate response to therapy in patients with brain metastases. However, accurate volumetric assessment of the lesion and surrounding peri-lesional edema holds significant importance in clinical decision-making and can greatly enhance outcome prediction. The unique challenge in performing segmentations of brain metastases lies in their common occurrence as small lesions. Detection and segmentation of lesions that are smaller than 10 mm in size has not demonstrated high accuracy in prior publications. The brain metastases challenge sets itself apart from previously conducted MICCAI challenges on glioma segmentation due to the significant variability in lesion size. Unlike gliomas, which tend to be larger on presentation scans, brain metastases exhibit a wide range of sizes and tend to include small lesions. We hope that the BraTS-METS dataset and challenge will advance the field of automated brain metastasis detection and segmentation.

Protective effect of oleo-gum resin of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease-linked lung inflammation and emphysema: Isolation and identification of key bioactive phytoconstituent.

ETHNOPHARMACOLOGICAL RELEVANCE: Oleo-gum resin of Commiphora wightii (Arnott) Bhandari of family Burseraceae, commonly known as 'guggul', is a well known Ayurvedic drug used traditionally to treat various disorders including respiratory ailments. However, role of C. wightii in chronic obstructive pulmonary disease (COPD) is not known. AIM: The present work was designed to investigate the protective potential of standardized C. wightii extract/and its fractions against elastase-induced COPD-linked lung inflammation and to identify key bioactive constituent(s). MATERIAL AND METHODS: C. wightii oleo-gum resin extract was prepared using Soxhlet extraction technique and the resultant extract was standardized on basis of guggulsterone content using HPLC. The extract was partitioned by different solvents in increasing order of polarity. Standardized extract/its partitioned fractions were orally administered to male BALB/c mice 1 h prior to intra-tracheal instillation of elastase (1U/mouse). Anti-inflammatory effect was evaluated by analyzing inflammatory cells and myeloperoxidase activity in lungs. The various fraction(s) were subjected to column chromatography to isolate bioactive compound. Isolated compound was identified using 1H and 13C-NMR and analyzed for assessment of several inflammatory mediators using techniques like ELISA, PCR, and gelatin zymography. RESULTS: C. wightii extract attenuated elastase-induced lung inflammation in dose-dependent manner and Ethyl acetate fraction (EAF) provided maximum protection. EAF was subjected to column chromatography followed by assessment of bioactivity of each sub-fraction, ultimately leading towards isolation of two compounds i.e. C1 and C2. C1 seems to be the key active principle of C. wightii, as it displayed significant anti-inflammatory activity against elastase induced lung inflammation while C2 largely remains ineffective. C1 was identified as mixture of E- and Z-guggulsterone (GS). Reduction in the elastase induced lung inflammation by GS was associated with downregulation of expression of several COPD linked pro-inflammatory factors such as IL-6/TNF-α/IL-1ß/KC/MIP-2/MCP-1/G-CSF as well as normalization of redox imbalance as indicated by levels of ROS/MDA/protein carbonyl/nitrite/GSH etc. Further, 21 days prolonged administration of GS (10 mg/kg b.wt; once daily) protected against elastase-induced emphysema by mitigating expression/activity of MMP-2/-9 and increasing TIMP-1 expression. CONCLUSION: Overall, guggulsterone seems to be the key bioactive constituent responsible for exerting beneficial effects of C. wightii against COPD.