A large sequenced mutant library - valuable reverse genetic resource that covers 98% of sorghum genes.

Mutant populations are crucial for functional genomics and discovering novel traits for crop breeding. Sorghum, a drought and heat-tolerant C4 species, requires a vast, large-scale, annotated, and sequenced mutant resource to enhance crop improvement through functional genomics research. Here, we report a sorghum large-scale sequenced mutant population with 9.5 million ethyl methane sulfonate (EMS)-induced mutations that covered 98% of sorghum's annotated genes using inbred line BTx623. Remarkably, a total of 610 320 mutations within the promoter and enhancer regions of 18 000 and 11 790 genes, respectively, can be leveraged for novel research of cis-regulatory elements. A comparison of the distribution of mutations in the large-scale mutant library and sorghum association panel (SAP) provides insights into the influence of selection. EMS-induced mutations appeared to be random across different regions of the genome without significant enrichment in different sections of a gene, including the 5' UTR, gene body, and 3'-UTR. In contrast, there were low variation density in the coding and UTR regions in the SAP. Based on the Ka /Ks value, the mutant library (~1) experienced little selection, unlike the SAP (0.40), which has been strongly selected through breeding. All mutation data are publicly searchable through SorbMutDB (https://www.depts.ttu.edu/igcast/sorbmutdb.php) and SorghumBase (https://sorghumbase.org/). This current large-scale sequence-indexed sorghum mutant population is a crucial resource that enriched the sorghum gene pool with novel diversity and a highly valuable tool for the Poaceae family, that will advance plant biology research and crop breeding.

A leucine-rich repeat receptor kinase as a regulator in the cuticular wax deposition in sorghum.

Cuticular wax (CW) is the first defensive barrier of plants that forms a waterproof barrier, protects the plant from desiccation, and defends against insects, pathogens, and UV radiation. Sorghum, an important grass crop with high heat and drought tolerance, exhibits a much higher wax load than other grasses and the model plant Arabidopsis. In this study, we explored the regulation of sorghum CW biosynthesis using a bloomless mutant. The CW on leaf sheaths of bloomless 41 (bm41) mutant showed significantly reduced very long-chain fatty acids (VLCFAs), triterpenoids, alcohols, and other wax components, with an overall 86% decrease in total wax content compared to the wild-type. Notably, the 28-carbon and 30-carbon VLCFAs were decreased in the mutants. Using bulk segregant analysis, we identified the causal gene of the bloomless phenotype as a leucine-rich repeat transmembrane protein kinase. Transcriptome analysis of the wild-type and bm41 mutant leaf sheaths revealed BM41 as a positive regulator of lipid biosynthesis and steroid metabolism. BM41 may regulate CW biosynthesis by regulating the expression of the gene encoding 3-ketoacyl-CoA synthase 6. Identification of BM41 as a new regulator of CW biosynthesis provides fundamental knowledge for improving grass crops' heat and drought tolerance by increasing CW.

Leading report of molecular prevalence of tick borne Anaplasma marginale and Theileria ovis in yaks (Bos grunniens) from Pakistan.

Domestic yak (Bos grunniens) is an economically important feature of the mountainous region of Gilgit-Baltistan in Pakistan where agriculture is restricted and yaks play multiple roles which includes being a source of milk, meat, hides, fuel and power. However little is known about the parasitic infections in Pakistani yaks. Aim of this research was to report the prevalence and genetic diversity of protozoa parasite (Theileria ovis, 18 S rDNA gene was targeted) and an obligate bacterium (Anaplasma marginale, msp-1 gene was amplified) in the blood that was sampled from 202 yaks collected from four districts in Gilgit-Baltistan during January 2023 till January 2024. Results revealed that 6/202 (3%) yaks were of Theileria ovis while 8/202 (4%) were Anaplasma marginale infected. Positive PCR products of both parasites were confirmed by DNA sequencing and their similarity with previously available pathogen sequences was determined by BLAST analysis. Phylogenetic tree indicated that isolates of both parasites displayed genetic. Anaplasma marginale infection varied with the sampling districts and Shigar district had the highest rate of bacterial infection. Cows were significantly more prone to Theileria ovis infection than bulls. Calf and hybrid yaks were more prone to Anaplasma marginale infection. In conclusion, this is the first report that yaks residing the Gilgit-Baltistan region in Pakistan are infected with Theileria ovis and Anaplasma marginale. Similar larger scales studies are recommended in various regions of Gilgit-Baltistan to document the infection rates of these parasites to formulate strategies that will lead to the effective control of these pathogens.

Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Not all marketed skin cleansers' pH is optimal for atopic dermatitis.

Background: The normally acidic skin pH changes in atopic dermatitis (AD) to alkaline, which contributes to the associated skin-barrier dysfunction. Hence, acidic cleansers would be preferred, but such information is scarce. Objective: Guiding health-care providers and patients on selecting skin cleansers with a pH optimal for AD. Methods: A total of 250 products were tested: 37 soaps (32 bars, 5 liquid) and 213 syndets (14 bars, 199 liquid); 10% solutions were tested for pH by using a pH meter; pH values 6.65-7.35 were considered neutral. Results: The pH of the tested skin cleansers varied widely (3.59-10.83). All 37 soaps were highly alkaline. In the 14 syndet bars, the pH was neutral in 6, alkaline in 8, and acidic in none. In the 199 syndet liquids, the pH was acidic in 84.9%, neutral in 11.1%, and alkaline in 4.0%. The product's pH was disclosed in none of the 37 soaps and in only 32 syndets (15%) , of which 9 bars were labeled "balanced," whose measured pH was neutral in 6 and alkaline in 3. Of the other 23 syndets, the labeled pH was referred to as "balanced" in 20 whose measured pH was neutral in 2 (6.80, 6.88) and acidic in 18 (3.59-6.59). The pH in the other three syndets was 4.25-6.00. Conclusion: All tested soaps had undesirable pH, whereas 84.9% of the liquid syndets were acidic (which is desirable) and 11.1% were neutral (which could be acceptable). Only 12.8% of the products disclosed the pH, an issue in need of improvement.

Comparison of the modified Masood's scoring index versus international academy of cytology Yokohama system in the categorization of breast fine needle aspirates.

CONTEXT: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system. AIMS: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system. CONCLUSION: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases.

Exposure to Imidacloprid under variable conditions disturbs the muscle fatty acid profile of a fresh water non target fish: Labeo rohita.

Economy of Pakistan is heavily dependent upon agriculture and extensive use of pesticide is quiet common to enhance the crop yield. Imidacloprid is among the first choice pesticides in Pakistan and it has been reported that through run off along with water it ends up in water bodies affecting non target aquatic fauna. Through the present investigation, we are reporting the effects of Imidacloprid on the fatty acids composition of a non-target, commercially important carp: Labeo rohita. Fish were exposed to sub lethal concentration of Imidacloprid (120 mgL1) for 2, 4 and 8 days (short term) as well as for 16, 32 and 64 days (long term experimental conditions). Pesticide untreated controls were also maintained for each treatment. Following the specific Imidacloprid exposure, fatty acid composition (%) was determined in the muscle of all experimental groups by using gas chromatography. Fish exposed to Imidacloprid for 8 days had reduced Palmitic acid (p = 0.02) and elevated muscle Arachidic acid (p < 0.001) than control group. Labeo rohita exposed to the pesticide for 32 days had elevated muscle Oleic (p = 0.02) and Linoleic acid (p = 0.02) while fish exposed to Imidacloprid to 64 days had reduced muscle Palmitic (p = 0.04) and Oleic acid (p = 0.03). In conclusion, we are reporting that the exposure to sub lethal concentration of Imidacloprid disturb the muscle fatty acid composition of Labeo rohita that may affect its food quality. The effects were more pronounced under long term experimental conditions and were probably due to potentiating lipid peroxidation and disturbed fish metabolism upon Imidacloprid exposure.

Obstructive Sleep Apnea and Short-Term Outcomes After Pediatric Cardiac Surgery.

Obstructive sleep apnea (OSA) has been associated with negative cardiovascular effects and negative outcomes following cardiovascular surgery in the adult population. Our objective was to evaluate if there is a similar association in children. Single center retrospective matched cohort study, we collected data on patients aged 1-18 who were admitted to the cardiac intensive care unit (CICU) between Jan 2012 and Dec 2021. We used a 3:1 propensity score matching for cases not diagnosed with OSA. Primary outcome was a composite variable: "adverse outcome," consisting of prolonged hospital and CICU stay, prolonged duration of mechanical ventilation, need for extracorporeal membrane oxygenation, and death. The study comprised 80 patients diagnosed with OSA and 240 patients without a diagnosis of OSA before cardiac surgery. The median age was 5.3 years (IQR 2.7-11.2). There were 184 (57.5%) males, and 102 (31.9%) had chromosomal and genetic abnormalities. There was a difference in "adverse outcome" between the OSA and non-OSA groups [34 (42.50%) vs 68 (28.33%), p = 0.027]. Moreover, bivariate analysis revealed that CICU length of stay, and chromosomal anomalies were statistically different between the groups. By logistic regression the composite variable "adverse outcome" remained associated to the OSA group (p = 0.009) with an adjusted odds ratio (OR) of 4.09 (1.83-9.18), p < 0.001. Children diagnosed with OSA had a higher risk of "adverse outcome" following cardiac surgery. The risk disappeared if the patient had Tonsillectomy and Adenoidectomy before cardiac surgery. Further studies should explore a proactive treatment for OSA in pediatric patients who need cardiac surgery.

Current perspectives and difficulties in the design of acaricides and repellents from plant-derived compounds for tick control.

Ticks and tick-borne diseases have gained increasing attention in recent years due to their impact on public health and significant losses in livestock production. The use of synthetic compounds for tick control is becoming problematic, mainly due to the resistance to commercially available products as well as their toxicity. Therefore, new alternative control methods are required. For this purpose, plant-derived extracts may be considered as effective repellents and/or acaricides. The present literature review focuses on studies evaluating the acaricidal and repellent activity of plant-derived extracts and plant secondary metabolites. We also noted recent advances in protein-ligand-docking simulation to examine the possible toxic effect of natural chemical compounds on ticks. In conclusion, plant-derived repellents/acaricides can be effective against ticks, especially in rural areas and livestock farms.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinaemia: A cross-sectional study in outpatient gastroenterology clinics.

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.

Point-of-care testing performed by healthcare professionals outside the hospital setting: consensus based recommendations from the IFCC Committee on Point-of-Care Testing (IFCC C-POCT).

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Point-of-Care Testing (C-POCT) supports the use of point-of-care testing (POCT) outside of the hospital setting performed by healthcare professionals without formal laboratory education because of its numerous benefits. However, these benefits are associated with risks that must be managed, to ensure the provision of reliable test results and minimize harm to the patient. Healthcare professionals, local regulatory bodies, accredited laboratories as well as manufacturers should actively be engaged in education, oversight and advice to ensure that the healthcare professional selects the appropriate equipment and is able to analyze, troubleshoot and correctly interpret the point-of-care (POC) test results.

A rare case of primary neuroendocrine carcinoma of the central nervous system.

Primary neuroendocrine carcinoma (NEC) of the brain is an extremely rare presentation, with only a few previous case reports. We describe a primary NEC arising from the left parieto-occipital lobe. The 55-year-old patient presented with complaints of headache and dizziness for the preceding 7 months. Magnetic resonance imaging revealed a large ill-defined mass in the left parieto-occipital lobe, with possible differential diagnosis of meningioma. A craniotomy was performed, and a firm vascular tumor was removed. Histopathological examination revealed a large cell NEC. Immunohistochemistry was performed to exclude the possibility of an extracranial primary. Based on the immunohistochemical expression and absence of any extracranial tumor on positron emission tomography, the diagnosis of primary NEC of the brain was made. It is important to differentiate between primary and metastatic neuroendocrine tumors because they show a significant difference in prognosis and treatment.

Pituitary tuberculoma with panhypopituitarism masquerading as a pituitary adenoma.

Tuberculosis of the hypothalamo-pituitary axis is extremely uncommon. The presentation of panhypopituitarism in a case of sellar tuberculosis is an even rarer occurrence. We present a case of a 44-year-old man who presented with complaints of headache and right-sided diminution of vision for six months. A hormone profile showed abnormal anterior pituitary assay suggestive of panhypopituitarism. Magnetic Resonance imaging of the brain showed a sellar mass measuring 1.8 × 1.5 × 1.3 cm with suprasellar extension suggestive of a pituitary adenoma. Histopathological examination showed multiple epithelioid cell granulomas along with Langhans giant cells and mixed inflammatory infiltrates against a necrotic background. Zeihl Neelson stain demonstrated the presence of acid-fast bacilli. Thus, a final diagnosis of pituitary tuberculoma was made, and the patient started on antitubercular therapy. It is extremely important to correctly diagnose sellar tuberculosis as the treatment is entirely different, and the patient usually responds well to therapy.

Gaussian-Filtered High-Frequency-Feature Trained Optimized BiLSTM Network for Spoofed-Speech Classification.

Voice-controlled devices are in demand due to their hands-free controls. However, using voice-controlled devices in sensitive scenarios like smartphone applications and financial transactions requires protection against fraudulent attacks referred to as "speech spoofing". The algorithms used in spoof attacks are practically unknown; hence, further analysis and development of spoof-detection models for improving spoof classification are required. A study of the spoofed-speech spectrum suggests that high-frequency features are able to discriminate genuine speech from spoofed speech well. Typically, linear or triangular filter banks are used to obtain high-frequency features. However, a Gaussian filter can extract more global information than a triangular filter. In addition, MFCC features are preferable among other speech features because of their lower covariance. Therefore, in this study, the use of a Gaussian filter is proposed for the extraction of inverted MFCC (iMFCC) features, providing high-frequency features. Complementary features are integrated with iMFCC to strengthen the features that aid in the discrimination of spoof speech. Deep learning has been proven to be efficient in classification applications, but the selection of its hyper-parameters and architecture is crucial and directly affects performance. Therefore, a Bayesian algorithm is used to optimize the BiLSTM network. Thus, in this study, we build a high-frequency-based optimized BiLSTM network to classify the spoofed-speech signal, and we present an extensive investigation using the ASVSpoof 2017 dataset. The optimized BiLSTM model is successfully trained with the least epoch and achieved a 99.58% validation accuracy. The proposed algorithm achieved a 6.58% EER on the evaluation dataset, with a relative improvement of 78% on a baseline spoof-identification system.

Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus.

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-ß-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.

Integrating In Vitro and In Silico Approaches to Assess Monotheca buxifolia Plant Extract against Rhipicephalus (Boophilus) microplus and Sarcoptes scabiei.

Tick and mite infestations pose significant challenges to animal health, agriculture, and public health worldwide. The search for effective and environmentally friendly acaricidal agents has led researchers to explore natural alternatives. In this study, we investigated the acaricidal potential of the Monotheca buxifolia plant extract against Rhipicephalus microplus ticks and Sarcoptes scabiei mites. Additionally, we employed a computational approach to identify phytochemicals from the extract that could serve as drug candidates against these ectoparasites. The contact bioassay results demonstrated that the M. buxifolia plant extract exhibited significant efficacy against R. microplus and S. scabiei, with higher concentrations outperforming the positive control acaricide permethrin in terms of mite mortality. Time exposure to the extract also showed a positive correlation with better lethal concentration (LC50 and LC90) values. Similarly, the adult immersion test revealed a notable inhibition of tick oviposition via the plant extract, especially at higher concentrations. The two-protein primary structure, secondary structure and stability were predicted using the Expasy's ProtParam server, SOPMA and SUSUI server, respectively. Using Homology modeling, the 3D structure of the protein was obtained and validated through the ERRAT server, and active sites were determined through the CASTp server. The docking analysis revealed that Alpha-Amyrenyl acetate and alpha-Tocopherol exhibited the highest docking scores for S. scabiei and R. microplus aspartic protease proteins, respectively. These phytochemicals demonstrated strong binding interactions, suggesting their potential as acaricidal drug candidates. In conclusion, the M. buxifolia plant extract displayed significant acaricidal activity against R. microplus and S. scabiei. Moreover, the computational approach identified promising phytochemicals that could serve as potential drug candidates for controlling these ectoparasites.

Comparison of Blood Pressure Measurements by Currently Available Multiparameter Monitors and Mercury Column Sphygmomanometer in Patients Admitted in Pediatric Intensive Care Unit.

Background: The multiparameter monitor (MPM) is replacing mercury column sphygmomanometers (MCS) in acute care settings. However, data on the former's accuracy in critically ill children are scarce and mostly extrapolated from adults. We compared non-invasive blood pressure (NIBP) measurements by MPMs with MCS in pediatric intensive care unit (PICU). Patients: Adequately sedated and hemodynamically stabilized children (age, 1-144 months) were prospectively enrolled. Materials and methods: Three NIBP measurements were obtained from MCS (Diamond®, India) and MPM (Intellivue MX800® or Ultraview SL®) in rapid succession in the upper limb resting in supine position. Respective three measurements were averaged to obtain a paired set of NIBP readings, one each from MCS and MPM. Such readings were obtained thrice a day. NIBP readings were then compared, and agreement was assessed. Results: From 39 children [median age (IQR), 30 (10-72) months], 1,690 sets of NIBP readings were obtained. A-third of readings were from infants and children >96 months, while 383 (22.6%) readings were from patients on inotropes. Multiparameter monitors gave significantly higher NIBP readings compared to MCS [median systolic blood pressure (SBP), 6.5 (6.4-6.7 mm Hg); diastolic blood pressure (DBP), 4.5 (4.3-4.6 mm Hg); mean arterial pressure (MAP), 5.3 (5.1-5.4 mm Hg); p < 0.05]. It was consistent across age, gender, and critical care characteristics. Multiparameter monitors overestimated SBP in 80% of readings beyond the maximal clinically acceptable difference (MCAD). Conclusions: Non-invasive blood pressure readings from MCS and MPMs are not interchangeable; SBP was 6-7 mm Hg higher with the latter. Overestimation beyond MCAD was overwhelming. Caution is required while classifying systolic hypotension with MPMs. Confirmation with auscultatory methods is advisable. More studies are required to evaluate currently available MPMs in different pediatric age groups. How to cite this article: Khan AA, Gupta PK, Baranwal AK, Jayashree M, Sahoo T. Comparison of Blood Pressure Measurements by Currently Available Multiparameter Monitors and Mercury Column Sphygmomanometer in Patients Admitted in Pediatric Intensive Care Unit. Indian J Crit Care Med 2023;27(3):212-221.

Synchronous ipsilateral adrenal cortical adenoma and ganglioneuroma: A case report.

Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two independent neoplasms arising from the cortex and the medulla without any histological admixture. Adrenal cortico-medullary mixed tumors are rare tumors comprising of adrenal cortical and chromaffin cells intermixed with each other. Ganglioneuroma is a rare benign tumor originating from the paravertebral sympathetic ganglia and is rarely seen in the adrenal medulla. The presence of a synchronous ganglioneuroma with an adrenal cortical adenoma in the ipsilateral adrenal gland is exceedingly rare. We report a collision tumor comprising of an adrenal cortical adenoma and a ganglioneuroma detected as an incidental finding in a pediatric patient who presented with hypertension and palpitations.

Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short- and Long-term Oncologic Outcomes.

OBJECTIVE: To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. SUMMARY OF BACKGROUND DATA: Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. METHODS: Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. RESULTS: Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates ( P = 0.05) but had similar incidence of positive CRM ( P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. CONCLUSION: In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.

Structure-based in silico design and in vitro acaricidal activity assessment of Acacia nilotica and Psidium guajava extracts against Sarcoptes scabiei var. cuniculi.

Infestation by Sarcoptes scabiei var. cuniculi mite causes scabies in humans and mange in animals. Alternative methods for developing environmentally friendly and effective plant-based acaricides are now a priority. The purpose of this research was the in silico design and in vitro evaluation of the efficacy of ethanol extracts of Acacia nilotica and Psidium guajava plant leaves against S. scabiei. Chem-Draw ultra-software (v. 12.0.2.1076.2010) was used to draw 36 distinct compounds from these plants that were employed as ligands in docking tests against S. scabiei Aspartic protease (SsAP). With docking scores of - 6.50993 and - 6.16359, respectively, clionasterol (PubChem CID 457801) and mangiferin (PubChem CID 5281647) from A. nilotica inhibited the targeted protein SsAP, while only beta-sitosterol (PubChem CID 222284) from P. guajava interacted with the SsAP active site with a docking score of - 6.20532. Mortality in contact bioassay at concentrations of 0.25, 0.5, 1.0, and 2.0 g/ml was determined to calculate median lethal time (LT50) and median lethal concentration (LC50) values. Acacia nilotica extract had an LC50 value of 0.218 g/ml compared to P. guajava extract, which had an LC50 value of 0.829 g/ml at 6 h. These results suggest that A. nilotica extract is more effective in killing mites, and these plants may have novel acaricidal properties against S. scabiei. Further research should focus on A. nilotica as a potential substitute for clinically available acaricides against resistant mites.