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Human health is experiencing several obstacles in the modern medical era, particularly cancer. As a result, the cancer therapeutic arsenal should be continually expanded with innovative small molecules that preferentially target tumour cells. In this study, we describe the development of two small molecule series (7a–d and 12a–e) based on the 1-benzyl-5-bromoindolin-2-one scaffold that connected through a hydrazone linker to a 4-arylthiazole (7a–d) or 4-methyl-5-(aryldiazenyl)thiazole (12a–e) moiety. The anticancer activity of all the reported indolin-2-one derivatives was assessed against breast (MCF-7) and lung (A-549) cancer cell lines. The 4-arylthiazole-bearing derivatives 7c and 7d revealed the best anticancer activity toward MCF-7 cells (IC50 = 7.17 ± 0.94 and 2.93 ± 0.47, respectively). Furthermore, the VEGFR-2 inhibitory activity for 7c and 7d was evaluated. Both molecules disclosed good inhibitory activity, and their IC50 values were equal to 0.728 µM and 0.503 µM, respectively. Additionally, the impacts of 7d on the cell cycle phases as well as on the levels of different apoptotic markers (caspase-3, caspase-9, Bax, and Bcl-2) were assessed. Molecular docking and dynamic simulations are carried out to explore the binding mode of 7d within the VEGFR-2 active site.

Biomedical engineering is the application of the principles and problem-solving methods of engineering to biology along with medicine. Computation intelligence is the study of design of intelligent agents which are systems acting perceptively. The computation intelligence paradigm offers more advantages to the enhancement and maintenance of the field of biomedical engineering. Liver cancer is the major reason of mortality worldwide. Earlier-stage diagnosis and treatment might increase the survival rate of liver cancer patients. Manual recognition of the cancer tissue is a time-consuming and difficult task. Hence, a computer-aided diagnosis (CAD) is employed in decision making procedures for accurate diagnosis and effective treatment. In contrast to classical image-dependent “semantic” feature evaluation from human expertise, deep learning techniques could learn feature representation automatically from sample images using convolutional neural network (CNN). This study introduces a Hybrid Rider Optimization with Deep Learning Driven Biomedical Liver Cancer Detection and Classification (HRO-DLBLCC) model. The proposed HRO-DLBLCC model majorly focuses on the identification of liver cancer in the medical images. To do so, the proposed HRO-DLBLCC model employs preprocessing in two stages, namely, Gabor filtering (GF) based noise removal and watershed transform based segmentation. In addition, the proposed HRO-DLBLCC model involves NAdam optimizer with DenseNet-201 based feature extractor to generate an optimal set of feature vectors. Finally, the HRO algorithm with recurrent neural network–long short-term memory (RNN-LSTM) model is applied for liver cancer classification, in which the hyperparameters of the RNN-LSTM model are tuned by the use of HRO algorithm. The HRO-DLBLCC model is experimentally validated and compared with existing models. The experimental results assured the promising performance of the HRO-DLBLCC model over recent approaches.

Till now, no definite clinical or laboratory marker can predict the recurrence or progression of T1 G3 urothelial carcinoma (UC). Genetic aberrations of the chromatin remodeling genes and sister chromatid cohesion and segregation (SCCS) were identified in UC. Here we investigated the impact of novel miRNAs and their targeted expressed SCCS and chromatin remodeling genes on T1G3 UC response to Bacillus Calmette-Guérin (BCG) therapy.One hundred tissue samples were obtained from NMIBC patients. Gene expression and immunohistochemical assay of STAG2, ARID1A, NCOR1and UTX were assessed. MiRNA analysis for their targeting miRNAs (miR-21, miR-31, Let7a and miR-199a) was carried out. Assessed genes were compared between responders and no responders to BCG. Univariate and multivariate analysis of predictors of disease recurrence and progression were performed using cox regression analysis.Thirty-two and 22 patients developed recurrence and progression to MIBC (BCG non-responders). BCG non-responders showed statistically significant higher expression of miR-21 and their targeted STAG2, miR-199a and NCOR1 gene (P.001), and lower expression of miR-31, Let7a, ARID1A and UTX genes (P.001). Higher miR-199a (P = .006) and lower miR-31 (P = .01), ARID1A (P = .008) and UTX (P = .03) were independent predictor of higher tumor recurrence. Recurrent disease (P = .003), higher expression of STAG2 (P = .01), NCOR1 (P = .01) and miR-21 (P = .03) genes and lower expression of miR-31 (P = .02), Let7a (P = .04) and ARID1A (P = .04) genes were the independent predictor of disease progression.Upregulation of STAG2 and NCOR1 and down regulation of ARID1A and UTX genes and their targeting miRNAs were associated with UC non-response to BCG.

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin AC, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.

Obstructive sleep apnea (OSA) was estimated to affect 15% to 30% of males and 5% to 15% of females with prevalence increasing with progressive tooth loss and its early identification can reduce the sequalae of OSA. Apnea-hypopnea index is confirmatory but unsuitable for clinical settings to detect OSA and concise screening tools are required to detect OSA in edentulous patients.To evaluate the impact of soft palate visibility and tongue position on incidence of OSA among edentulous patients.Thirty two edentulous participants aged between 30 and 65 years were grouped as partially edentulous (PE) and completely edentulous (CE). STOP-BANG Questionnaire (SBQ) was used to assess the scores in OSA risk factors. Mallampati score assessed soft palate visibility. Wright's Classification graded tongue position. Spearmann test evaluated the correlation between the soft palate visibility and tongue position on the OSA scores. Mann-Whitney U test evaluated influence of tooth loss and gender on OSA scores.Positive correlation existed between Mallampati scores, Wright's classification and OSA scores (p .05). CE participants and male participants had more OSA scores at (p .05) and (p .01).SBQ and Mallampati score can assist in chairside screening of OSA. Early screening for OSA in edentulous patients will direct for early intervention and prevent unforeseen sequalae.

Background: Social emotional development is imperative to young children’s long-term psychological and physical health. Physical activity (PA) may be important for young children’s social emotional development. The association between preschooler PA duration and intensity and social emotional development was investigated.Methods: Data from six hundred and fifty-one 2- to 4-year-olds in the Play Spaces and Environments for Children’s Physical Activity (PLAYCE) study were analyzed. PA was measured using ActiGraph-GT3X accelerometers worn over 7 days. Social emotional development was measured using the parent-completed Strengths and Difficulties Questionnaire. Multilevel linear regression models examined the association between PA duration and intensity and Strengths and Difficulties Questionnaire subscales.Results: Preschoolers did 158.2 (SD = 40.2) minutes per day of PA with 27% meeting the Australian Physical Activity Guidelines for the Early Years. There was a 1.74 point decrease in the total Strengths and Difficulties Questionnaire score for each additional hour of moderate-intensity PA per day (P Conclusions: These findings highlight the potential importance of PA, especially moderate-intensity play-based PA, for different aspects of preschool children’s social emotional development. Longitudinal and intervention research is required to confirm whether promoting PA in the early years provides developmental benefit.

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.

Circuit training that combines aerobic and resisted training is reported to reduce body fat, weight, and improve exercise capacity than performing either type of exercise independently. There is no study evaluating the combined effect of circuit training exercise (CTE) and dietary intervention (low-carbohydrate [LC] diet) among young males with obesity.A randomized control trial was conducted to explore the effects of a combined program of CTE and a LC diet for adults with mild or moderate obesity. Seventy adults with obesity were allocated randomly into 2 groups. The experimental group (group 1) received circuit training with LC diet intervention, whereas the control (group 2) received only circuit training. The study variables such as exercise capacity, body composition, and cardiometabolic indices were measured at the baseline and the end of 60 days of intervention.The participants of group 1 showed significant improvements in body composition (body weight, body mass index, waist circumference, waist hip circumference, and body fat percentage), exercise capacity (maximal oxygen consumption), and cardiometabolic indices (high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol) with a P.05 for all the variables, when compared with group 2.The combined structured CTE with controlled LC diet intervention in obese adults caused significant reduction in body composition and cardiometabolic indices variables and an increase in exercise capacity.

Human infections in Egypt with highly pathogenic avian influenza (HPAI) likely due to airborne transmission of HPAI virus (HPAIV) during home slaughter of poultry predominately affect women and children, who are the primary caregivers of household poultry. This study developed a safe contained poultry slaughter procedure to reduce airborne HPAIV and zoonotic infections and simultaneously created an educational outreach tool for teaching the modified procedure. The tool designed for limited literacy audiences used two illustrated posters and handouts for teaching the safe contained poultry slaughter procedure. The posters were developed with advice of animal health professionals and then refined by target audience women's focus groups. These women's focus groups proved to be the critical step for assuring the understanding, acceptance, effectiveness and accuracy of the outreach tool. The safe contained poultry slaughter procedure was designed to be low or no cost, sustainable by using a universal implement found in village households and designed as a minor variation of standard poultry halal slaughter. It was crafted to be culturally appropriate and religiously acceptable.

Lactobacilli probiotics have been suggested to reduce cholesterol with low side effects to host. Bacteriocins and exopolysaccharides (EPSs) production are two meaningful examples of functional applications of lactobacilli in the food industry. Eight Lactobacillus strains were isolated from some Egyptian fermented food and tested for their probiotic properties. Analysis of the monosaccharide composition by thin layer chromatography showed the presence of glucose, galactose and unknown sugar. The main functional groups of EPSs were elucidated by Fourier-Transform Infrared Spectroscopy. Their fermentation cultures displayed powerful antioxidant activities extending from 97.5 to 99%, 40–75% for their EPSs and free cells, respectively, and exhibited in vitro cholesterol downgrading from 48 to 82% and 72 to 91% after 48 and 120 h, respectively. Their EPSs showed good anticancer activities against carcinoma cells with low IC50 values for HCT–116, PC–3 and HepG–2 cells. To the best of our knowledge, there have been no previous reports on the potential of Lactobacillus EPSs activity against PC–3. The selected strains, L. plantarum KU985433 and L. rhamnosus KU985436 produced two different bacteriocins as detected by gel permeation chromatography with good antimicrobial activities. In vivo study demonstrated that feeding Westar rats with fermented milk exhibited greater cholesterol, LDL and blood triglyceride reduction for both strains. Whereas, HDL was increased by about 43 and 38%, respectively, and the atherogenic indices decreased.

Valve-sparing root replacement using reimplantation techniques is increasingly applied to bicuspid aortopathy. Long-term durability of cusp repair is unclear. We analyze midterm results using a conservative approach to cusp repair.From 2006 to 2018, 327 patients underwent valve-sparing reimplantation, 66 with bicuspid valves. Leaflets were analyzed after reimplantation. A majority (51/66) required no cusp repair. Fifteen patients had cusp repair limited to closure of unfused raphe or central plication. Patients were followed by echocardiography.Mean age of patients was 44.7 ± 12.3 years. The cusp repair group had a higher incidence of preoperative moderate (10% vs 40%) or severe (4% vs 33.3%) aortic insufficiency (P .001). There was no operative mortality or major complication. Mean follow-up was 51.6 ± 40.8 months. On postoperative echocardiography, incidence of none, trace, or mild aortic insufficiency was 41.3% (19/46), 43.5% (20/46), and 15.2% (7/46) in the no cusp repair group and 40% (6/15), 40% (6/15), and 20% (3/15) in the cusp repair group, respectively (P = .907). Few patients progressed in degree of aortic insufficiency. No patients required reoperation. At 5 years, freedom from any aortic insufficiency was 46.9% versus 15.8% (P = .013), and freedom from greater than trace aortic insufficiency was 59.1% versus 36.9% (P = .002) due to the higher rate of postoperative trace and mild aortic insufficiency with cusp repair. There was no difference in freedom from greater than mild aortic insufficiency (92.1% vs 100%; P = .33).Valve-sparing root replacement is reliably performed with bicuspid aortic valves whether or not cusp reconstruction is necessary. Few patients progress to greater than mild aortic insufficiency. Need for reoperation is rare in midterm follow-up.

Background: Medullary thyroid carcinoma (MTC) comprises 1–2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. Methods: Relevant articles were identified using a systematic PubMed and Google Scholar search. Results: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. Conclusion: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.

Taxane is a family of front-line chemotherapeutic agents against ovarian cancer (OC). The therapeutic efficacy is frequently counteracted by the development of chemoresistance, leading to high rates of relapse in OC patients. The role(s) of microRNAs (miRNAs) in cancer chemoresistance had been supported by many evidences Epigenetic regulation by miRNAs has been reported to influence cancer development and response to therapeutics, however, their role in OC resistance to paclitaxel (PTX) is unclear. Here, we conducted miRNA profiling in the responsive and PTX-resistant OC cell lines before and after treatment with epigenetic modulators. We reveal 157 miRNAs to be downregulated in the PTX-resistant cells compared to parental controls. The expression of five miRNAs (miRNA-7-5p, -204-3p, -501-5p, -3652 and -4286) was restored after epigenetic modulation, which was further confirmed by qPCR. In silico analysis of the signaling pathways targeted by the selected miRNAs identified the PI3K-AKT pathway as the primary target. Subsequent cDNA array analysis confirmed multiple PI3K-AKT pathway members such as AKT2, PIK3R3, CDKN1A, CCND2 and FGF2 to be upregulated in PTX-resistant cells. STRING analysis showed the deregulated genes in PTX-resistant cells to be primarily involved in cell cycle progression and survival. Thus, high throughput miRNA and cDNA profiling coupled with pathway analysis and data mining provide evidence for epigenetically regulated miRNAs-induced modulation of signaling pathways in PTX resistant OC cells. It paves the way to more in-depth mechanistic studies and new therapeutic strategies to combat chemoresistance.

The current article describes an 11-year-old male who has aplastic anemia with an extremely rare condition, that is, concomitant posterior fossa SDH and spinal SDH.This is a case report and review of literature.This case presents an 11-year-old male known to have aplastic anemia complained of neck and back pain, headache, and persistent vomiting for 3 days. He had no history of head or spine trauma at all. His parents are relatives "positive consanguinity," and his sister suffers from aplastic anemia. Clinical examination revealed severe pallor at the time of presentation, with no neurologic or locomotor deficit and positive Kernig's sign.Patients with aplastic anemia or any bleeding disorder conditions should be investigated thoroughly if symptoms denoted a CNS pathology. Concomitant cranial and spinal SDH rarely occurs, and more studies are advocated to be structured to investigate the specific pathophysiology and etiologies of this condition.

Management is clear-cut-yet many patients don't reach treatment goals. To optimize quality of life, master the fine points of T4 replacement and address the impact of comorbidities.

Most patients with non–small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)–induced cell death (NICD) of P2X7 receptor (P2X7R)–expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono–adenosine 5′-diphosphate (ADP)–ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R + CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R + CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD + -degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell–dependent manner. This was associated with increased infiltration of activated P2X7R + CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.

Megaplasmids in Campylobacter spp. likely play important roles in antibiotic resistance, virulence, and horizontal gene transfer. In this study, megaplasmids pCJDM202 (119 kb) and pCJDM67L (116 kb) from C. jejuni strains WP2-202 and OD2-67, respectively, were sequenced and characterized. These megaplasmids contained genes for tetracycline resistance [tet(O)], the Type IV secretion system, conjugative transfer and the Type VI secretion system (T6SS). The T6SS genes in Campylobacter plasmids encoded genes and proteins that were similar to those identified in Campylobacter chromosomal DNA. When the megaplasmid pCJDM202 from C. jejuni WP2-202 was transferred via conjugation to C. jejuni NCTC11168 Nal+, transconconjugants acquired tetracycline resistance and enhanced cytotoxicity towards red blood cells. A T6SS mutant of strain WP2-202 was generated and designated Δhcp3; the mutant was significantly impaired in its ability to lyse red blood cells and survive in defibrinated blood. The cytotoxicity of Campylobacter strains towards the human embryonic kidney cell line HEK 293 was not impacted by the T6SS. In summary, the T6SS encoded by Campylobacter megaplasmids mediates lysis of RBCs and likely contributes to survival on retail meats where blood cells are abundant.

Background Stapling across lung parenchyma may lead to tissue granulation, which could be confused radiographically with recurrence. We sought to define the time course and radiographic characteristics of such thickening and to determine their association with recurrence. Methods Patients who underwent limited resection for non-small cell lung cancer were included. Surveillance computed tomography scans were reviewed to characterize the morphology and size of staple line granulation tissue. Radiological and clinical findings were analyzed and univariate predictors of recurrence were examined. Results We characterized 78 patients for tissue granulation a total of 314 times in serial scans. On initial postoperative scans, 3.8% (n = 3) of staple lines showed no thickening and 17.9% (n = 14) showed thickening less than 2 mm, whereas 78.2% (n = 61) showed thickening 2 mm or greater. Of the 75 staple lines with thickening, soft tissue was characterized as linear in 32.0% (n = 24), focal along the pleura, hilum, or parenchyma in 24.0% (n = 18), and nodular in 44.0% (n = 33). Subsequent scans revealed that 25.3% of these areas (n = 19) did not change in shape or size over time, 58.7% (n = 44) showed regressive changes, and 16.0% (n = 12) showed progressive changes, the thickening of which in all 12 of these patients showed an increase in the largest dimension by 2 mm or greater. Among the 78 patients, 7.7% (n = 6) had biopsy-proven recurrence along the staple line. An increase in the largest dimension by 2 mm or greater (83.3% versus 9.7%; P = .001) and radiologic concern for malignancy (66.7% versus 11.1%; P = .001) predicted staple line recurrence. Conclusions Staple line thickening is a frequent occurrence after pulmonary limited resection, but rarely indicative of recurrence. The characteristics and initial size of granulation tissue do not predict recurrence. Increases in tissue 2 mm or greater at the staple line over time predict local recurrence, which typically occurs after a prolonged time interval.

Background The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Introduction: Multiple sclerosis (MS) is an immune-mediated disorder. Long noncoding RNAs (lncRNAs, LncR, Linc RNA) have role in many autoimmune and inflammatory disorders, including MS. LincR-Gng2...

The growing risk of antimicrobial resistance besides the continuous increase in the number of cancer patients represents a great threat to global health, which requires intensified efforts to discover new bioactive compounds to use as antimicrobial and anticancer agents. Thus, a new set of pyridothienopyrimidine derivatives 2a,b–9a,b was synthesized via cyclization reactions of 3-amino-thieno[2,3-b]pyridine-2-carboxamides 1a,b with different reagents. All new compounds were evaluated against five bacterial and five fungal strains. Many of the target compounds showed significant antimicrobial activity. In addition, the new derivatives were further subjected to cytotoxicity evaluation against HepG-2 and MCF-7 cancer cell lines. The most potent cytotoxic candidates (3a, 4a, 5a, 6b, 8b and 9b) were examined as EGFR kinase inhibitors. Molecular docking study was also performed to explore the binding modes of these derivatives at the active site of EGFR-PK. Compounds 3a, 5a and 9b displayed broad spectrum antimicrobial activity with MIC ranges of 4–16 µg/mL and potent cytotoxic activity with IC50 ranges of 1.17–2.79 µM. In addition, they provided suppressing activity against EGFR with IC50 ranges of 7.27–17.29 nM, higher than that of erlotinib, IC50 = 27.01 nM.

One of the major health concerns for human society is skin cancer. When the pigments producing skin color turn carcinogenic, this disease gets contracted. A skin cancer diagnosis is a challenging process for dermatologists as many skin cancer pigments may appear similar in appearance. Hence, early detection of lesions (which form the base of skin cancer) is definitely critical and useful to completely cure the patients suffering from skin cancer. Significant progress has been made in developing automated tools for the diagnosis of skin cancer to assist dermatologists. The worldwide acceptance of artificial intelligence-supported tools has permitted usage of the enormous collection of images of lesions and benevolent sores approved by histopathology. This paper performs a comparative analysis of six different transfer learning nets for multi-class skin cancer classification by taking the HAM10000 dataset. We used replication of images of classes with low frequencies to counter the imbalance in the dataset. The transfer learning nets that were used in the analysis were VGG19, InceptionV3, InceptionResNetV2, ResNet50, Xception, and MobileNet. Results demonstrate that replication is suitable for this task, achieving high classification accuracies and F-measures with lower false negatives. It is inferred that Xception Net outperforms the rest of the transfer learning nets used for the study, with an accuracy of 90.48. It also has the highest recall, precision, and F-Measure values.

COVID-19 (SARS-CoV-2) was declared as a global pandemic by the World Health Organization (WHO) in February 2020. This led to previously unforeseen measures that aimed to curb its spread, such as the lockdown of cities, districts, and international travel. Various researchers and institutions have focused on multidimensional opportunities and solutions in encountering the COVID-19 pandemic. This study focuses on mental health and sentiment validations caused by the global lockdowns across the countries, resulting in a mental disability among individuals. This paper discusses a technique for identifying the mental state of an individual by sentiment analysis of feelings such as anxiety, depression, and loneliness caused by isolation and pauses to the normal chains of operations in daily life. The research uses a Neural Network (NN) to resolve and extract patterns and validate threshold trained datasets for decision making. This technique was used to validate 2,173 global speech samples, and the resulting accuracy of mental state and sentiments are identified with 93.5% accuracy in classifying the behavioral patterns of patients suffering from COVID-19 and pandemic-influenced depression.

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

Cancers are a major challenge to health worldwide. Spinel ferrites have attracted attention due to their broad theranostic applications. This study aimed at investigating the antimicrobial, antibiofilm, and anticancer activities of ebselen (Eb) and cerium-nanoparticles (Ce-NPs) in the form of ZnCexFe2−XO4 on human breast and colon cancer cell lines. Bioassays of the cytotoxic concentrations of Eb and ZnCexFe2−XO4, oxidative stress and inflammatory milieu, autophagy, apoptosis, related signalling effectors, the distribution of cells through the cell-cycle phases, and the percentage of cells with apoptosis were evaluated in cancer cell lines. Additionally, the antimicrobial and antibiofilm potential have been investigated against different pathogenic microbes. The ZOI, and MIC results indicated that ZnCexFe2−XO4, X = 0.06 specimen reduced the activity of a wide range of bacteria and unicellular fungi at low concentration including P. aeruginosa (9.5 mm, 6.250 µg/mL), S. aureus (13.2 mm, 0.390 µg/mL), and Candida albicans (13.5 mm, 0.195 µg/mL). Reaction mechanism determination indicated that after ZnCexFe2−xO4, X = 0.06 treatment, morphological differences in S. aureus&nbsp, were apparent with complete lysis of bacterial cells, a concomitant decrease in the viable number, and the growth of biofilm was inhibited. The combination of Eb with ZFO or ZnCexFe2−XO4 with γ-radiation exposure showed marked anti-proliferative efficacy in both cell lines, through modulating the oxidant/antioxidant machinery imbalance, restoring the fine-tuning of redox status, and promoting an anti-inflammatory milieu to prevent cancer progression, which may be a valuable therapeutic approach to cancer therapy and as a promising antimicrobial agent to reduce the pathogenic potential of the invading microbes.

A paucity of data exists on the national use of robotic hepatectomy. We assessed national trends and perioperative outcomes of robotic hepatectomy in the USA. In addition, factors associated with use of the robotic approach were analyzed.The National Cancer Database (NCDB) was queried for patients undergoing hepatectomy from 2010 to 2016. Patients undergoing total hepatectomy for transplant were excluded. Factors associated with the use of the robotic approach were assessed using logistic regression multivariable analysis. Propensity-score analysis was performed (robotic vs. laparoscopic and robotic vs. open approaches), and perioperative outcomes were compared between the matched groups.The robotic approach was used in 287 patients (110 hospitals). Utilization of the robotic approach increased significantly on the national level from 0.8% in 2010 to 4.1% in 2016 (P0.001). The number of hospitals performing a minimum of one robotic hepatectomy per year increased from 8 in 2010 to 35 in 2016. The median hospital length of stay was 4 days (IQR 3-6), 30-day readmission rate was 5%, and 30-day/90-day mortality rates were 3%/4%. Factors associated with using robotic approach were African-American race (95% CI 1.02-2.11), recent year of surgery (95% CI 1.11-1.32), HCC histology (95% CI 1.01-52.03), tumor size (95% CI 0.87-0.96), and early-stage tumor (Stage I-II, 95% CI 1.27-3.99). On propensity-matched analysis, there were no differences between robotic and open approaches (n=184 each group) in 30-day readmission (5% vs. 7%, P=0.651), 30-day mortality (2% vs. 4%, P=0.106), 90-day mortality (3% vs. 7%, P=0.080), or 5-year overall survival (58% vs. 43%, P=0.211). However, the robotic approach was associated with a significantly shorter hospital stay (median: 4 vs. 6 days, P0.001). There were no differences between matched groups of patients undergoing robotic and laparoscopic approaches (n=182 in each group) in perioperative outcomes or length of hospital stay.National use of robotic-assisted hepatectomy has increased by fivefold over the seven-year study period. It was associated with a shorter hospital length of stay compared to the open approach without compromising perioperative outcomes or survival.

The effective segmentation of lesion(s) from dermoscopic skin images assists the Computer-Aided Diagnosis (CAD) systems in improving the diagnosing rate of skin cancer. The results of the existing skin lesion segmentation techniques are not up to the mark for dermoscopic images with artifacts like varying size corner borders with color similar to lesion(s) and/or hairs having low contrast with surrounding background. To improve the results of the existing skin lesion segmentation techniques for such kinds of dermoscopic images, an effective skin lesion segmentation method is proposed in this research work. The proposed method searches for the presence of corner borders in the given dermoscopc image and removes them if found otherwise it starts searching for the presence of hairs on it and eliminate them if present. Next, it enhances the resultant image using state-of-the-art image enhancement method and segments lesion from it using machine learning technique namely, GrabCut method. The proposed method was tested on PH2 and ISIC 2018 datasets containing 200 images each and its accuracy was measured with two evaluation metrics, i.e., Jaccard index, and Dice index. The evaluation results show that our proposed skin lesion segmentation method obtained Jaccard Index of 0.77, 0.80 and Dice index of 0.87, 0.82 values on PH2, and ISIC2018 datasets, respectively, which are better than state-of-the-art skin lesion segmentation techniques.

Background Pediatric atlantoaxial instability (AAI) is not common and could be a serious clinical condition. The Goel-Harms technique is one of the most used techniques in adults and needs more evaluation in pediatric populations. This study reports the feasibility and safety of the Goel-Harms technique in the treatment of pediatric reducible AAI. Methods In this retrospective cohort study we reported all pediatric patients who underwent Goel-Harms technique for AAI with a minimum 1-year follow up. Patients were clinically assessed using the Japanese Orthopedic Association (JOA) score and radiologically with plain radiographs, computed tomography scan, and magnetic resonance imaging of the craniocervical region. Postoperatively, patients were followed up according to our clinical and radiographic imaging protocol. The following parameters were recorded: JOA score, construct stability, fusion, and abnormal events. Results A total of 25 patients have completed a 1-year follow-up and fulfilled our criteria. The mean age was 10.68 ± 4.47 (range, 3–17) years. Fifteen patients were male and 10 were female. The final diagnosis included Down syndrome (DS) in 8, type II dens fracture in 7, os odontoideum in 3, and atlantoaxial rotatory fixation in 7. The mean follow-up was 21.76 ± 8.22 months. The preoperative JOA score improved from 15.96 ± 1.46 to 16.76 ± 1.92 at the last follow-up. Sound bone fusion was reported in 92% of patients. Conclusions Our data suggest that the Goel-Harms technique is a safe, feasible, and effective procedure in managing pediatric reducible AAI. Special perioperative care should be offered to young AAI patients with DS.

In retail meat products, Campylobacter jejuni, C. coli, and Staphylococcus aureus have been reported in high prevalence. The polymicrobial interaction between Campylobacter and other bacteria could enhance Campylobacter survival during the adverse conditions encountered during retail meat processing and storage. This study was designed to investigate the potential role of S. aureus from retail meats in enhancing the survival of Campylobacter exposed to low temperature, aerobic conditions, and biofilm formation. Results indicated that viable S. aureus cells and filter-sterilized cell-free media obtained from S. aureus prolonged the survival of Campylobacter at low temperature and during aerobic conditions. Biofilm formation of Campylobacter strains was significantly enhanced in the presence of viable S. aureus cells, but the results were inconclusive when extracts from cell-free media were used. In conclusion, the presence of S. aureus cells enhances survivability of Campylobacter strains in adverse conditions such as low temperature and aerobic conditions. Further investigations are warranted to understand the interaction between Campylobacter and S. aureus, and effective intervention strategies are needed to reduce the incidence of both foodborne pathogens in retail meat products.

Purpose Polysorbate excipients are commonly used as surfactants to stabilize therapeutic proteins in formulations. Degradation of polysorbates could lead to particle formation and instability of the drug formulation. We investigated how the fatty acid composition of polysorbate 80 impacts the degradation profile, particle formation, and product stability under stress conditions. Methods Two polysorbate 80-containing therapeutic protein formulations were reformulated with either Polysorbate 80 NF synthesized from a fatty acid mixture that contains mainly oleic acid (≥58%) or a version of polysorbate 80 synthesized with high oleic acid (>98%). Stress conditions, including high temperature and esterase spiking, were applied and changes to both the polysorbate and the therapeutic protein product were investigated for stability, purity, innate immune response and biological activity. Results The addition of esterase and storage at 37°C led to significant hydrolysis of the polysorbate and increases in sub-visible particle formation for both polysorbates tested. The fatty acid composition of polysorbate 80 did not directly alter the stability profile of either therapeutic protein as measured by size exclusion chromatography, or significantly impact innate immune response or biological activity. However, formulations with Polysorbate 80 NF showed greater propensity for sub-visible particle formation under stress conditions. Conclusions These results suggest that composition of fatty acids in polysorbate 80 may be a promoter for sub-visible particulate formation under the stress conditions tested but may not impact protein aggregation or biological activity.

Background Ultra-fast pseudo-alignment approaches are the tool of choice in transcript-level RNA sequencing (RNA-seq) analyses. Unfortunately, these methods couple the tasks of pseudo-alignment and transcript quantification. This coupling precludes the direct usage of pseudo-alignment to other expression analyses, including alternative splicing or differential gene expression analysis, without including a non-essential transcript quantification step. Results In this paper, we introduce a transcriptome segmentation approach to decouple these two tasks. We propose an efficient algorithm to generate maximal disjoint segments given a transcriptome reference library on which ultra-fast pseudo-alignment can be used to produce per-sample segment counts. We show how to apply these maximally unambiguous count statistics in two specific expression analyses – alternative splicing and gene differential expression – without the need of a transcript quantification step. Our experiments based on simulated and experimental data showed that the use of segment counts, like other methods that rely on local coverage statistics, provides an advantage over approaches that rely on transcript quantification in detecting and correctly estimating local splicing in the case of incomplete transcript annotations. Conclusions The transcriptome segmentation approach implemented in Yanagi exploits the computational and space efficiency of pseudo-alignment approaches. It significantly expands their applicability and interpretability in a variety of RNA-seq analyses by providing the means to model and capture local coverage variation in these analyses. Electronic supplementary material The online version of this article (10.1186/s12859-019-2947-6) contains supplementary material, which is available to authorized users.

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy “(n = 2631 patients)”. No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

OBJECTIVES: Despite the recent increased rate of adoption of robotic approaches for the resection of thymic tumours, their use is still limited to large-volume academic centres. To date, a large-scale analysis of the robotic approach has not been performed. We assessed the recent trends and outcomes of robotic thymectomies in the United States compared to those of open and video-assisted thoracoscopic surgical (VATS) approaches. METHODS: The National Cancer Database was queried for patients who underwent resection for thymic tumours (2010–2014). Predictors of using the robotic approach were estimated by logistic regression analysis. Propensity matching analysis (robotic versus open and robotic versus VATS) was done (1:1—caliper 0.05), controlling for age, gender, comorbidity index, induction treatment, tumour size and tumour extension. RESULTS: A total of 2558 thymectomies were performed (robotic = 300, VATS = 280, open = 1978). The use of a robotic approach increased from 6% (2010) to 14% (2014). The number of hospitals performing at least 1 robotic thymectomy increased from 22 (2010) to 52 (2014). Independent predictors influencing the choice of a robotic approach included an academic research/integrated cancer programme [odds ratio (OR) 1.66, confidence interval (CI) 1.22–2.27], later year of diagnosis (2014; OR 2.23, CI 1.31–3.80) and a patient’s race (Asian) (OR 1.68, CI 1.05–2.69). A robotic approach was less likely to be utilized in midwestern hospitals (OR 0.65, CI 0.42–0.99), in larger tumours (cm) (OR 0.85, CI 0.80–0.90), with invasion of adjacent organs (OR 0.55, CI 0.37–0.82), thymic carcinoma (OR 0.62, CI 0.40–0.97) and following induction chemotherapy (OR 0.22, CI 0.08–0.61). In a propensity-matched analysis, there were no differences in the incidence of positive margins, nodal dissection, 30-day readmission rates and 30-/90-day mortality rates between the groups. However, a robotic approach was associated with fewer conversions compared to VATS, with a trend towards a shorter length of stay compared to an open approach. There were no differences in the 5-year overall survival rate between the matched groups (robotic 93% vs VATS 94%; P = 0.571; robotic 91% vs open 80%; P = 0.094). CONCLUSIONS: Over a 4-year study period, there was a significant increase in robotic utilization for thymectomies and an increase in the number of hospitals performing the procedure. In a matched analysis, a robotic approach was comparable to a VATS or an open approach. Current trends demonstrate increased robotic utilization for small thymomas with excellent perioperative results.

Fine needle aspiration cytology (FNAC) of mediastinal masses allows for rapid on-site evaluation and the triaging of material for ancillary studies. However, surgical pathology is often considered to be the gold standard for diagnosis. This study examines the sensitivity and specificity of FNAC compared to a concurrent or subsequent surgical pathology specimen in 77 mediastinal lesions. The overall sensitivity for mediastinal mass FNAC was 78% and the overall specificity was 98%. For individual categories the sensitivity and specificity of FNAC was respectively as follows: inflammatory/infectious (33%, 99%), metastatic carcinoma (93%, 100%), lymphoma (84%, 97%), cysts (25%, 100%), soft tissue tumors (100%, 100%), paraganglioma (50%, 100%), germ cell tumor (100%, 99%), thymoma (87%, 94%), thymic carcinoma (60%, 100%), benign thymus (0%, 100%), and indeterminate (100%, 90%). For different locations within the mediastinum the sensitivity and specificity of FNAC was respectively as follows: anterosuperior mediastinum (80%, 98%), posterior mediastinum (33%, 95%), middle mediastinum (100%, 100%), and mediastinum, NOS (79%, 99%). Thus, mediastinal FNAC is fairly sensitive, very specific, and is a valuable technique in the diagnosis of mediastinal masses.

OBJECTIVES: Minimum volume standards for thoracic surgical procedures have been advocated to improve outcomes. However, such standards are controversial within the thoracic surgery literature, and the methodology to determine cut points between high- and low-volume hospitals has been criticized. Furthermore, while multiple studies have examined hospital volume and its relationship with outcomes, there have been very few attempts to study this issue from the perspective of the individual thoracic surgeon. The aim of this study was to determine if surgeon volume is associated with differences in outcomes using a large state-wide database. METHODS: The study utilized the New York State Department of Health Statewide Planning and Research Cooperative (SPARCS) data for analysis. Patients who underwent major lung resections including sublobar resection, lobectomy and pneumonectomy from 1995 to 2014 were included and were categorized into 3 subgroups based on the extent of resection. Patient characteristics included age, gender, race, insurance and comorbidities. Surgeon information was obtained by using a unique identifier. Average annual surgical volumes of sublobar resection, lobectomy and pneumonectomy were calculated separately and grouped into 3 categories based on the tertiles. Demographic data and comorbidities were compared between the various volume groups to analyse the resulting complications. Primary outcomes were in-hospital mortality and 30-day readmission. RESULTS: There were a total of 99 576 major lung resections performed between 1995 and 2014 in the SPARCS database. Among these, the majority were wedge or segmental resections (n = 54 953, 55.2%) followed by lobectomy (n = 40 421, 40.6%) and pneumonectomy (n = 4202, 4.2%). In-hospital mortality was significantly greater for low-volume surgeons compared to high-volume surgeons for all resection groups. Additionally, low-volume surgeons had higher 30-day readmission rates for patients undergoing lobectomy and pneumonectomy. However, low-volume surgeons as a group were more likely to operate on black patients and patients with Medicaid, and black race was an independent predictor of mortality across all resection groups. The vast majority of surgeons performing lobectomy (89.5%) were in the low-volume group. CONCLUSIONS: Low-volume surgeons had higher rates of in-hospital mortality compared to their high-volume counterparts. However, the vast majority of surgeons performing lobectomy (89.5%) were in the low-volume group, and low-volume surgeons operated on higher percentages of black patients. These findings suggest that minimal volume standards would significantly impact the current delivery of thoracic surgery in the US.

With the aim of studying their in vitro and in vivo pharmacokinetics, new chromatographic methods were developed for the determination of three new roflumilast synthetic analogs (I-III) as PDE-4B inhibitors in rat liver S9 fraction, phosphate buffered saline, pH 7.4, and human and rat plasma. The developed high performance liquid chromatography-ultra violet (HPLC-UV) methods were performed on a Zorbax Eclipse C8 column and UV detection was carried out at 215 nm. The three compounds were tested for their metabolic stability and were found to be metabolically more stable than roflumilast especially the 2-mercaptobenzothiazol-6-yl analog (III) which displayed an in vitro half-life time (247.55 minutes) higher than that of roflumilast (12.29 minutes) and a low in vitro clearance of 5.67 mL/min./kg. Possible phase I metabolites were investigated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showing hydroxylation of the unsubstituted benzothiazol-2-yl (I) and benzothiazole-6-yl (II) analogs and a cleaved benzothiazole metabolite of the 2-mercaptobenzothiazol-6-yl analog (III). Plasma protein binding affinity was tested using equilibrium membrane dialysis method showing a very high percentage (more than 95%) of plasma protein binding of compounds I and II where compound III exhibited lower percentage (53.71%) demonstrating its accessibility for tissue distribution. Also, a UPLC-MS/MS method was developed using an Acquity UPLC BEH shield RP C18 column to be applied to an in vivo pharmacokinetic study in rats following a subcutaneous dose (1 mg/kg). Compounds I-III showed improved in vivo pharmacokinetic parameters especially compound III which displayed a half-life 3-fold greater than roflumilast (21 hours) and a Cmax value of 113.958 ng/mL. Accordingly, this new chemical entity should be subjected to further investigation as it can be a good drug candidate for treating chronic obstructive pulmonary disease.

A new diphenyl (aryl) (Ǹ-quinazolin-4-yl-hydrazino) methylphosphonates 3a-3d was synthesized via anhydrous zinc chloride catalyzed Kabachnic-Fields reaction. The structure of the synthesized compounds was confirmed by elemental analysis, FT-IR, 1H NMR, 13C NMR, 31P NMR and MS spectral data. The synthesized compounds showed significant antimicrobial and also remarkable cytotoxicity anticancer activities against breast carcinoma cell line (MCF7). The quantum chemical calculations were performed using density functional theory (DFT) to study the effect of the changes of molecular and electronic structures on the biological activity of the investigated compounds. Also, NBO and theoretical FT-IR were calculated. The experimental results were validated by molecular docking simulation of compound 3b in the active pocket of the enzyme. The important binding interactions with the key residues in the active site were revealed. A good correlation was found between the quantum chemical parameters and experimental data.

Objective: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT). Methods: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight. Results: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% (P = .005), 70.7% (P = .004) and 87.90% (P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium (P = .015), phosphate (P = .016), and intact PTH (P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates. Conclusion: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed. Abbreviations: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi

To examine the association between uropathogens and pyuria in children24 months of age.A retrospective study of children24 months of age evaluated in the emergency department for suspected urinary tract infection (UTI) with paired urinalysis and urine culture during a 6-year period. Bagged urine specimens or urine culture growing mixed/multiple urogenital organisms were excluded. Analysis was limited to children with positive urine culture as defined by the American Academy of Pediatrics clinical practice guideline culture thresholds.Of 30 462 children, 1916 had microscopic urinalysis and positive urine culture. Urine was obtained by transurethral in-and-out catheterization in 98.3% of cases. Pyuria (≥5 white blood cells per high-powered field) and positive leukocyte esterase (small or more) on the urine dipstick were present in 1690 (88.2%) and 1692 (88.3%) of the children respectively. Children with non-Escherichia coli species were less likely to exhibit microscopic pyuria than children with E coli (OR 0.24, 95% CI 0.17-0.34) with more pronounced effect on Enterococcus and Klebsiella (OR 0.08, 95% CI 0.03-0.18 and OR 0.18, 95% CI 0.11-0.27 respectively). Similarly, positive leukocyte esterase was less frequently seen in non-E coli uropathogens compared with E coli.Pyuria and leukocyte esterase are not sensitive markers to identify non-E coli UTI in young children. More sensitive screening biomarkers are needed to identify UTI with these uropathogens.

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.

Introduction Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients. Methodology Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect. Results Serum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component). Conclusions As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.

To compare visual outcomes, incidence of cystoid macular edema (CME), and rate of repeat epiretinal membrane (ERM) surgery following phacovitrectomy for primary and secondary ERM.Retrospective review of 178,856 cataract surgeries from 2003 to 2015. Eyes that underwent cataract surgery combined with ERM peel were included (n = 708). Eyes were divided into primary (n = 538) and secondary (n = 170) ERM groups. Patient demographics, visual acuity (VA), and postoperative CME were recorded.Patients with secondary ERM had worse preoperative VA, 0.9 ± 0.6 logMAR (20/160 Snellen equivalent) as compared to patients with primary ERM, 0.6 ± 0.3 (20/80), respectively (p 0.0001). There was no difference between the secondary and primary ERM groups in postoperative vision (0.5 ± 0.4 logMAR vs. 0.5 ± 0.3; p = 0.9962) or proportion with VA ≥ 20/40 (46.4% vs. 43.1%; p = 0.6744) at 12-24 weeks. Postoperative CME was twice as likely in the secondary ERM group (16.5%) compared to the primary ERM group (7.8%) (p = 0.0018). There was no difference in the rate of repeat ERM surgery between the secondary ERM group (1.8%) and the primary ERM group (1.5%) (p = 0.7308).Eyes with secondary ERM had significant postoperative improvement in VA. They had worse preoperative VA and had a twofold increase in postoperative CME than primary ERM.

Sublobar resection is frequently offered to patients with small, peripheral lung cancers, despite the lack of outcome data from ongoing randomized clinical trials. Sublobar resection may be a particularly attractive surgical strategy for screen-detected lung cancers, which have been suggested to be less biologically aggressive than cancers detected by other means. Using prospective data collected from patients undergoing surgery in the National Lung Screening Trial, we sought to determine whether extent of resection affected survival for patients with screen-detected lung cancer.The National Lung Screening Trial database was queried for patients who underwent surgical resection for confirmed lung cancer. Propensity score matching analysis (lobectomy vs sublobar resection) was done (nearest neighbor, 1:1, matching with no replacement, caliper 0.2). Demographics, clinicopathologic and perioperative outcomes, and long-term survival were compared in the entire cohort and in the propensity-matched groups. Multivariable logistic regression analysis was done to identify factors associated with increased postoperative morbidity or mortality.We identified 1029 patients who underwent resection for lung cancer in the National Lung Screening Trial, including 821 patients (80%) who had lobectomy and 166 patients (16%) who had sublobar resection, predominantly wedge resection (n = 114, 69% of sublobar resection). Patients who underwent sublobar resection were more likely to be female (53% vs 41%, P = .004) and had smaller tumors (1.5 cm vs 2 cm, P .001). The sublobar resection group had fewer postoperative complications (22% vs 32%, P = .010) and fewer cardiac complications (4% vs 9%, P = .033). For stage I patients undergoing sublobar resection, there was no difference in 5-year overall survival (77% for both groups, P = .89) or cancer-specific survival (83% for both groups, P = .96) compared with patients undergoing lobectomy. On multivariable logistic regression analysis, sublobar resection was the only factor associated with lower postoperative morbidity/mortality (odds ratio, 0.63; 95% confidence interval, 0.40-0.98). To compare surgical strategies in balanced patient populations, we propensity matched 127 patients from each group undergoing sublobar resection and lobectomy. There were no differences in demographics or clinical and tumor characteristics among matched groups. There was again no difference in 5-year overall survival (71% vs 65%, P = .40) or cancer-specific survival (75% vs 73%, P = .89) for patients undergoing lobectomy and sublobar resection, respectively.For patients with screen-detected lung cancer, sublobar resection confers survival similar to lobectomy. By decreasing perioperative complications and potentially preserving lung function, sublobar resection may provide distinct advantages in a screened patient cohort.

One pitfall in 24-hour urine collection is the input of incorrect urinary volume by the reference laboratory. This may lead to an incorrect diagnosis of pheochromocytoma or paraganglioma. A 48-year-old African-American woman was seen in the clinic for an elevated 24-hour urine metanephrine screen during workup for secondary hypertension. Urine volume was found to be incorrectly inputted by the lab as 9750 mL rather than 975 mL. The urinary metanephrines were then recalculated and the 24-hour urinary metanephrines resulted within normal limits. This case highlights this unique and potentially under-recognised error in testing with 24-hour urine volume collection.

Due to the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2), an efficient COVID-19 screening strategy is required for patients undergoing cardiac surgery. The objective of this prospective observational study was to evaluate the role of preoperative computed tomography (CT) screening for COVID-19 in a population of COVID-19 asymptomatic patients scheduled for cardiac surgery. Between the 29th of March and the 26th of May 2020, patients asymptomatic for COVID-19 underwent a CT-scan the day before surgery, with reverse-transcriptase polymerase-chain reaction (RT-PCR) reserved for abnormal scan results. The primary endpoint was the prevalence of abnormal scans, which was evaluated using the CO-RADS score, a COVID-19 specific grading system. In a secondary analysis, the rate of abnormal scans was compared between the screening cohort and matched historical controls who underwent routine preoperative CT-screening prior to the SARS-Cov-2 outbreak. Of the 109 patients that underwent CT-screening, an abnormal scan result was observed in 7.3% (95% confidence interval: 3.2-14.0%). One patient, with a normal screening CT, was tested positive for COVID-19, with the first positive RT-PCR on the ninth day after surgery. A rate of preoperative CT-scan abnormalities of 8% (n = 8) was found in the unexposed historical controls (P0.999). In asymptomatic patients undergoing cardiac surgery, preoperative screening for COVID-19 using computed tomography will identify pulmonary abnormalities in a small percentage of patients that do not seem to have COVID-19. Depending on the prevalence of COVID-19, this results in an unfavorable positive predictive value of CT screening. Care should be taken when considering CT as a screening tool prior to cardiac surgery.

Scorpions constitute a charismatic lineage of arthropods and comprise more than 2500 described species. Found throughout various tropical and temperate habitats, these predatory arachnids have a long evolutionary history, with a fossil record that began in the Silurian. While all scorpions are venomous, the asymmetrically diverse family Buthidae harbors nearly half the diversity of extant scorpions, and all but one of the 58 species that are medically significant to humans. However, the lack of a densely sampled scorpion phylogeny has hindered broader inferences of the diversification dynamics of scorpion toxins. To redress this gap, we assembled a phylogenomic data set of 100 scorpion venom gland transcriptomes and genomes, emphasizing the sampling of highly toxic buthid genera. To infer divergence times of venom gene families, we applied a phylogenomic node dating approach for the species tree in tandem with phylostratigraphic bracketing to estimate the minimum ages of mammal-specific toxins. Our analyses establish a robustly supported phylogeny of scorpions, particularly with regard to relationships between medically significant taxa. Analysis of venom gene families shows that mammal-active sodium channel toxins (NaTx) have independently evolved in five lineages within Buthidae. Temporal windows of mammal-targeting toxin origins are correlated with the basal diversification of major scorpion mammal predators such as shrews, bats, and rodents. These results suggest an evolutionary model of relatively recent diversification of buthid NaTx homologs in response to the diversification of scorpion predators. [Adaptation; arachnids; phylogenomic dating; phylostratigraphy; venom.]