Hybrid versus Conventional Colorectal Endoscopic Submucosal Dissection: A Multi-Center Randomized Controlled Trial (SHORT-ESD).

BACKGROUND: Hybrid endoscopic submucosal dissection (H-ESD) which utilizes ESD knife along with snare-based resection, has been developed to overcome the technical complexity of conventional ESD (C-ESD). This study aimed to compare the therapeutic outcomes of H-ESD vs. C-ESD for non-pedunculated colorectal lesions ≥20 mm in size. METHODS: We conducted a multicenter randomized controlled trial to compare H-ESD and C-ESD (Short-ESD trial). Patients with colorectal lesions between 20-50 mm in size were randomly assigned (1:1) to H-ESD or C-ESD. Primary outcome was procedure time/speed. Secondary outcomes were en-bloc and complete (R0) resection rates and adverse event rates. RESULTS: A total of 89 patients (median age 63 years; 49.3% women) with median polyp size 30 mm underwent H-ESD (n=40) and C-ESD (n=49). The mean procedure time of H-ESD was significantly shorter than that of C-ESD (41.1±16.3 vs. 54.3±28.2 minutes; p=0.007). The en-bloc and R0 resection rates trended lower in the H-ESD vs C-ESD groups (77.5% vs. 87.8%; p=0.26 and 72.5% vs. 79.6%; p=0.46) without reaching statistical significance. Adverse event rate was similar between H-ESD and C-ESD (10% vs 8.2%; p=1.00). CONCLUSION: Both H-ESD and C-ESD were safe and effective for resection of large colorectal lesions. H-ESD was associated with a shorter procedure time. H-ESD may represent a viable alternative to C-ESD, with the main advantage being easy applicability of a snare-based technique for colorectal lesions. Future studies are needed to further define the most suitable lesions for H-ESD, as to optimize efficiency and safety without compromising resection outcomes. ClinicaTrials.gov NCT NCT05347446.

Diagnostic Accuracy of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): An Institution Experience.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a standardized system which is used to classify results of thyroid fine-needle aspiration (FNA). This system is used to evaluate and determine which patients should get thyroid surgery. It was created in order to reduce the number of patients requiring surgery. The question remains as to whether this reporting system is accurate in determining those nodules that have malignant potential and those that do not. This study is a retrospective analysis of patients in one institution who have undergone FNA and then thyroid surgery based on TBSRTC. The outcome of the pathology reports after surgery was analyzed to determine the accuracy of TBSRTC in our institution (Lourdes Hospital, Binghamton, NY). The results from our institution were compared with similar studies in other institutions to determine accuracy and reproducibility. Our results indicated that the risk of malignancy in each Bethesda category was similar to the risk percentages described for most categories in the 2017 TBSRTC update.

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma.

MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA+ NB remains poorly understood. Here, we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B (MYO1B) as being highly expressed in MNA+ NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA+ NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA+ NB and independently of MYCN.

Classification and Locoregional Treatment of Rectal Neuroendocrine Tumors.

A 43-year-old male presented to his primary care physician's office with a complaint of painless rectal bleeding with a concomitant weight loss of 10-15 pounds and intermittent abdominal pain. Endoscopic evaluation was remarkable for a 5 mm rectal polyp roughly 10 cm from the anal verge. Resection was performed and the pathology was consistent with a low-grade neuroendocrine/carcinoid tumor. Immunostaining for synaptophysin, chromogranin, CD56, and CAM5.2 were positive while staining for CK20 was negative. Given the absence of metastasis on radiographic and endoscopic evaluation, the patient was managed conservatively thereafter with observation. Despite having an indolent clinical course, resection is recommended for all rectal neuroendocrine tumors. Locoregional endoscopic resection versus radical resection can be used for adequate tissue removal depending on the characteristics of the tumor and the degree of invasion.

Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity.

The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1 H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp-EXE-MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp-EXE-MMs showed sustained release behavior as compared to EXE-suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase-3, p53, and CYP19A1 in MCF-7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp-EXE-MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.

Sulphur Containing Heterocyclic Compounds as Anticancer Agents.

After cardiovascular disease, cancer is the most common cause of death worldwide. Due to their versatility, heterocyclic compounds play an important role in drug discovery. Medical remedies are constantly being discovered, especially for catastrophic disorders such as cancer. Here, this review is focused on sulphur containing heterocyclic compounds as anticancer agents. Sulphur is found in a variety of vitamin cofactors, sugars, and nucleic acids, and it also plays a function in controlling translation by sulphurating transfer RNA. Sulphur has obtained a lot of interest in the anticancer research medicinal fields. Thiophene derivatives were tested for anti-proliferative activity against breast cancer cells in a recent screening study, and the bulk of chemicals exhibited potent inhibitory effects. In recent years, azoles such as thiazole and thiadiazole structures have gained prominence in cancer research.

Marine-derived Natural Products as Anticancer Agents.

Cancer is a deadly human disease on the rise due to changes in lifestyle, nutrition, and global warming. Cancer is characterized by uncontrolled, disordered, and undesired cell division. About 60% of cancer medicines approved by the FDA are made from natural ingredients. Intensive efforts over the last decade to better understand the vast chemical diversity provided by marine life have resulted in an intriguing "marine pipeline" of potential anticancer clinical and preclinical treatments. The molecular targets of marine products as anticancer drugs, as well as different reported compounds acting on distinct targets, are the topic of this review.

Impact of COVID-19 on Student's Dental Education and Life.

Objectives: We sought to identify the impact of the COVID-19 pandemic on the Oman Dental College (ODC) students' management of their educational and student life. Methods: We conducted a quantitative cross-sectional online survey study using SurveyMonkey. During the 2019-2020 academic year, 383 ODC students across six levels of education were invited to participate in the survey. Descriptive statistics were applied to the students' demographic profiles, and other characteristics of the participants' data were analyzed. Cronbach's alpha was calculated for internal consistency. A univariate analysis was carried out to identify the differences between genders and between the Bachelor of Dental Surgery levels in relation to the questionnaire themes. A Pearson's correlation test evaluated the association between students' perception of risks due to the pandemic and the other relevant themes. Results: A 50.9% response rate revealed that five of the themes showed internal reliability ranging from excellent to acceptable, namely: performance of exercise, effect of the pandemic on their families, use of a facemask, college's online services, and students' mental health (0.51, 0.59, 0.70, 0.78, and 0.90, respectively). More than half of the participants felt encouraged to engage in self-directed learning using online resources. They felt some level of nervousness, worry, anxiety, or tension as well as stress during the pandemic. Statistical differences between levels of education were noted in the ODC's-online teaching services (p < 0.001) and students' mental health (p = 0.03). There was no difference between female and male students. The ODC's online services theme positively related to the students' mental health theme (r = 0.22, p < 0.001). Conclusions: ODC students experienced some mental health issues during the pandemic, including anxiety, stress, and sleeping issues. However, the majority of them were healthy. Most students were satisfied with the online teaching provided by ODC. It was also evident that faculty were always connected with the students. A positive relationship was noted between the management of online lectures and students' mental health.

March of the Eosinophils: A Case of Eosinophilic Gastroenteritis, Immune Thrombocytopenia, and Iron Deficiency Anemia.

Eosinophilic gastrointestinal disorders (EGIDs) refer to eosinophilic infiltration of various sections of the gastrointestinal tract in the absence of secondary causes. Diagnosis of EGID requires histological evidence of eosinophilic infiltration of the GI tract. Here, we present a case of a young male with biopsy-proven eosinophilic gastroenteritis with a concomitant established diagnosis of immune thrombocytopenic purpura (ITP).  Presently, EGIDs remain an underexplored clinical entity. While its pathophysiology is not fully understood at this time, TH2 mediated activation of B-cells and subsequent stimulation of eosinophils locally appears to be at play. This is in contrast to the TH1 predominant cytokine profile underlying ITP, which this patient also has. Treatment typically involves dietary modifications and glucocorticoids.

In situ Hydrogels for Effective Treatment of Cancer: Strategies and Polymers Used.

Cancer is a worldwide health ailment with no known boundaries in terms of mortality and occurrence rates, thus is one of the biggest threats to humankind. Hence, there is an absolute need to develop novel therapeutics to bridge the infirmities associated with chemotherapy and conventional surgical methodologies including impairment of normal tissue, compromised drug efficiency and an escalation in side effects. In lieu of this, there's been a surge in curiosity towards development of injectable hydrogels for cancer therapy because local administration of the active pharmaceutical agent offers encouraging advantages such as providing higher effective dose at target site, prolonged retention time of drug, ease of administration, mitigation of dose in vivo ,improved patient compliance. Furthermore, due to its biocompatible nature such systems can significantly reduce the side effects that occur on long-term exposure to chemotherapy. The present review details the most recent advancements in in-situ gel forming polymers (natural and synthetic), polymeric cross-linking methodologies and in-situ gelling mechanisms, focusing on their clinical benefits in cancer therapy.

DNA intercalators as anticancer agents.

Cancer is one of the most prevailing disease conditions, which occurs due to uncontrolled cell division either due to natural mutation to the genes or due to changes induced by physical, chemical, or biological carcinogens. According to WHO, it is the second leading cause of death worldwide and has reported 10 million deaths in 2020. Hence, there arises the need for better chemotherapies and DNA intercalators are one such emerging therapy for cancer. DNA intercalating agents reversibly intercalate with the double-helical structure of DNA by interacting with adjacent base pairs and disrupting the structure of DNA and thereby causing cell death. Here, we discuss the different classes of organo-intercalators used in cancer therapy describing their anticancer and intercalation ability by different methods along with their structure-activity relationship and mechanism of action.

RANBP2 and USP9x regulate nuclear import of adenovirus minor coat protein IIIa.

As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus outbreaks are associated with severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy available. An adenoviral vaccine based on human adenovirus species D (HAdV-D) is currently in use for COVID-19. Herein, we investigate host interactions of HAdV-D type 37 (HAdV-D37) protein IIIa (pIIIa), identified by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2). USP9x binding did not invoke its signature deubiquitination function but rather deregulated pIIIa-RANBP2 interactions. In USP9x-knockout cells, viral genome replication and viral protein expression increased compared to wild type cells, supporting a host-favored mechanism for USP9x. Conversely, RANBP2-knock down reduced pIIIa transport to the nucleus, viral genome replication, and viral protein expression. Also, RANBP2-siRNA pretreated cells appeared to contain fewer mature viral particles. Transmission electron microscopy of USP9x-siRNA pretreated, virus-infected cells revealed larger than typical paracrystalline viral arrays. RANBP2-siRNA pretreatment led to the accumulation of defective assembly products at an early maturation stage. CRM1 nuclear export blockade by leptomycin B led to the retention of pIIIa within cell nuclei and hindered pIIIa-RANBP2 interactions. In-vitro binding analyses indicated that USP9x and RANBP2 bind to C-terminus of pIIIa amino acids 386-563 and 386-510, respectively. Surface plasmon resonance testing showed direct pIIIa interaction with recombinant USP9x and RANBP2 proteins, without competition. Using an alternative and genetically disparate adenovirus type (HAdV-C5), we show that the demonstrated pIIIa interaction is also important for a severe respiratory pathogen. Together, our results suggest that pIIIa hijacks RANBP2 for nuclear import and subsequent virion assembly. USP9x counteracts this interaction and negatively regulates virion synthesis. This analysis extends the scope of known adenovirus-host interactions and has potential implications in designing new antiviral therapeutics.

Testicular Sarcoidosis: An Underdiagnosed Manifestation That Poses Unique Challenges.

Testicular involvement is a rarely encountered complication of sarcoidosis. There are unique challenges involved when sarcoidosis affects the genitourinary system. These include differentiating the findings from testicular cancer, which often results in invasive procedures such as orchiectomies. It can also be a cause of secondary infertility in men. Additionally, it may also be underdiagnosed. Here, we describe a case where a patient showed a constellation of findings suggestive of sarcoidosis, along with testicular involvement at initial presentation. In this case, the diagnosis was made clinically with supporting laboratory, pathology, and ultrasound findings. The testicular findings were not biopsied, as the patient had easily accessible skin findings to confirm sarcoidosis. His testicular findings are continued to be monitored via ultrasound.

Graves' Disease Following COVID-19 Vaccination.

Autoimmune endocrine diseases have been reported after influenza and the human papillomavirus vaccine, but there is limited data on autoimmune diseases after coronavirus disease 2019 (COVID-19) vaccination. Our report is about a 42-year-old Caucasian male and a 68-year-old Caucasian female who developed Graves' disease after receiving Moderna (Moderna, Inc., Cambridge, Massachusetts, United States) and Johnson & Johnson (Johnson & Johnson, New Brunswick, New Jersey, United States) vaccines, respectively. Both patients had no previous autoimmune thyroiditis and had normal thyroid function but developed hyperthyroidism characterized by suppressed thyroid-stimulating hormone (TSH), elevated free T4 level, and TSH receptor antibodies after vaccination. COVID-19 vaccines, either mRNA-based (Moderna) or non-mRNA-based (Johnson & Johnson), can cause Graves' disease. The clinical manifestations are similar to Graves' disease but without ocular manifestations.

Human health risk assessment in PM10 -bound trace elements, seasonal patterns, and source apportionment study in a critically polluted coking coalfield area of India.

Jharia Coalfield (JCF) has been affected by coalmine fire and subsidence problems for several years. The emission of particulate pollutants is due to the history of unscientific and unregulated coal mining in the JCF area. In the present study (conducted in the year 2019), seasonal variations, possible causes, and human health hazards of particulate matter (PM10 )-bound trace metals like Cd, Cu, Fe, Cr, Ni, Mn, Co, Pb, Zn, and As were estimated. The mean concentration of PM10 (418 ± 67 µg/m3 ) exceeded the limit of NAAQS (National Ambient Air Quality Standards India, 2009) by a factor of 4.18. PM10 -bound trace metal concentrations were found in the order of Fe > Mn > Cu > Zn > Cr > Pb > Co > Ni > Cd > As. The maximum trace metal concentrations of all the metals studied were observed at the mining areas of JCF affected by coalmine fire. Human health carcinogenic and noncarcinogenic risks in children and adults were estimated through exposure pathways, ingestion, dermal contact, and inhalation. The cancer risk was evaluated as excess cancer risk (ECR). Noncancer risk estimates were evaluated as the hazard index (HI) and the hazard quotient (HQ). The HI and HQ values for Cr, Cu, Cd, As, and Pb at coalmine-fire-affected areas were observed to be higher than the value of safe dose (≤1), showing a possible noncarcinogenic risk to the inhabitants as a result of multielemental toxicity. The ECR values (>10-6) in JCF areas suggested a carcinogenic risk to the populace of the area, owing to inhalation of PM10 -linked Cd. Active mine fire (related to mining activities), higher transportation load, and resuspended particulate matter from road transportation were identified as the possible causes of the estimated risks based on principal component analysis and Pearson correlation analyses. Integr Environ Assess Manag 2022;18:469-478. © 2021 SETAC.

Wegovy (semaglutide): a new weight loss drug for chronic weight management.

Obesity is a growing epidemic within the USA. Because weight gain is associated with an increased risk of developing life-threatening comorbidities, such as hypertension or type 2 diabetes, there is great interest in developing non-invasive pharmacotherapeutics to help combat obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic medications that have shown promise in encouraging glycemic control and promoting weight loss in patients with or without type 2 diabetes. This literature review summarizes and discusses the weight loss results from the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), PIONEER (Peptide Innovation for Early Diabetes Treatment), and STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial programs. The SUSTAIN and PIONEER clinical trials studied the use of 1.0 mg, once-weekly, subcutaneous and oral semaglutide (a new GLP-1 homolog), respectively, on participants with type 2 diabetes. The STEP trial examined the effects of 2.4 mg, once-weekly, subcutaneous semaglutide on patients with obesity. Trial data and other pertinent articles were obtained via database search through the US National Library of Medicine Clinical Trials and the National Center for Biotechnology Information. All three clinical trials demonstrated that semaglutide (injected or oral) has superior efficacy compared with placebo and other antidiabetic medications in weight reduction, which led to Food and Drug Administration approval of Wegovy (semaglutide) for weight loss.

Recent Advances in the Local Drug Delivery Systems for Improvement of Anticancer Therapy

The conventional anticancer chemotherapies not only cause serious toxic effects but also produce resistance in tumor cells exposed to long-term therapy. Usually, the selective killing of metastasized cancer cells requires long-term therapy with higher drug doses because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist in delivering drug molecules at the specific target site and reduce undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver a small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in drug delivery systems and their application in treating different cancer types in humans.

Development and optimization of nanoparticles loaded with erucin, a dietary isothiocyanate isolated from Eruca sativa: Antioxidant and antiproliferative activities in ehrlich-ascites carcinoma cell line.

The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER.

PM2.5-bound trace elements in a critically polluted industrial coal belt of India: seasonal patterns, source identification, and human health risk assessment.

The concentration of trace elements like Fe, Mn, Cu, Zn, Ni, Pb, Cd, Cr, Co, and As in atmospheric particulate matter (PM2.5) was estimated to investigate their seasonal variation, potential sources, and health risk at Jharia coalfield, India, during May 2018 to April 2019. Measured PM2.5 (170 ± 45 µg/m3) exceeded the National Ambient Air Quality Standards (2009) by a factor of 4.25, the Clean Air Act, National Ambient Air Quality Standards (40 CFR part 50) by a factor of 11, and Air Quality Guidelines of World Health Organization (2005) by a factor of 16. Mean concentration of the trace elements were observed in the order of Fe > Mn > Cu > Zn > Cr > Pb > Co > Ni > Cd > As, highest being perceived at the monitoring sites affected by coal mine fire. The significantly higher HQ values posed by PM2.5-bound Cd, Cr, Cu, Pb, and As and higher HI values (multi-elemental exposure) indicated potential non-carcinogenic risk to the residents of Dhanbad. Higher ECR values in the coal mining areas of JCF indicated higher carcinogenic risk to the population (adults > children) of Dhanbad due to inhalation of PM2.5-bound Cr. Spontaneous combustion of coal in the mines, active mine fire, associated mining activities, heavy vehicular emission, and re-suspended road dust were recognized as the potential sources of the trace elements from the results of PCA and Pearson correlation analysis.

Pollution evaluation, human health effect and tracing source of trace elements on road dust of Dhanbad, a highly polluted industrial coal belt of India.

Dust samples were collected from roads of five distinct types of land use zones (National Highway, residential areas, sensitive areas, mining areas, and busy traffic areas) of Dhanbad to determine the pollution characteristics, health risk, and identifying the source of trace elements. The dust samples were segregated into ≤ 60 µm and trace elements like Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn were analysed. Concentrations of Cd, Cr, Cu, Fe, and Mn were observed highest in the mining areas, whereas Ni, Pb, and Zn presented higher concentration values at National Highway and busy traffic zones. Cd showed highest geo-accumulation index (Igeo), contamination factor (Cf), and ecological risk (ER) among all the trace elements. The health risk assessment model was performed to assess the health effects of carcinogenic and non-carcinogenic pollutants caused due to multi-elemental exposure on adults and children. The significantly higher HQ (Hazard Quotient) and HI (Hazard Index) values posed by Cr, Fe, and Mn indicated potential non-carcinogenic risks to the people of Dhanbad. Similarly, values of CR (Cancer Risk) for Cd, Cr and Ni were within the range of 10-6-10-4, which indicated to cause carcinogenic risk to the population by the exposure of road dust. Principal Component Analysis (PCA) and Pearson correlation showed that coal mining activities in Jharia coalfield, coal-based industries like coke-oven plants, coal washeries and heavy vehicular load in the roads of Dhanbad were the major causes of emission of these trace elements.