Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Nanotechnology in Cancer Diagnosis and Treatment.

Traditional cancer diagnosis has been aided by the application of nanoparticles (NPs), which have made the process easier and faster. NPs possess exceptional properties such as a larger surface area, higher volume proportion, and better targeting capabilities. Additionally, their low toxic effect on healthy cells enhances their bioavailability and t-half by allowing them to functionally penetrate the fenestration of epithelium and tissues. These particles have attracted attention in multidisciplinary areas, making them the most promising materials in many biomedical applications, especially in the treatment and diagnosis of various diseases. Today, many drugs are presented or coated with nanoparticles for the direct targeting of tumors or diseased organs without harming normal tissues/cells. Many types of nanoparticles, such as metallic, magnetic, polymeric, metal oxide, quantum dots, graphene, fullerene, liposomes, carbon nanotubes, and dendrimers, have potential applications in cancer treatment and diagnosis. In many studies, nanoparticles have been reported to show intrinsic anticancer activity due to their antioxidant action and cause an inhibitory effect on the growth of tumors. Moreover, nanoparticles can facilitate the controlled release of drugs and increase drug release efficiency with fewer side effects. Nanomaterials such as microbubbles are used as molecular imaging agents for ultrasound imaging. This review discusses the various types of nanoparticles that are commonly used in cancer diagnosis and treatment.

Therapeutic Intervention for Various Hospital Setting Strains of Biofilm Forming Candida auris with Multiple Drug Resistance Mutations Using Nanomaterial Ag-Silicalite-1 Zeolite.

Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam, identified by 18S rRNA gene and ITS region sequencing. Drug-resistance-associated mutations in ERG11, TAC1B and FUR1 genes were screened to gain insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug-resistance-associated missense variants identified in the ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains, grouped into 3 clades. The prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial was tested against the 3 clades of clinical C. auris strains. 4wt%Ag/TiZSM-5 prepared using conventional impregnation technique was used for comparative study, and nano formulations were characterized using different techniques. The antibiofilm activity of nanomaterials was tested by cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the clades of C. auris strains, 4 wt%Ag/TiZSM-5 and Ag-silicalite-1 demonstrated a significant (p = 1.1102 × 10-16) inhibitory effect on the biofilm's survival rate: the lowest inhibition value was (10%) with Ag-silicalite-1 at 24 and 48 h incubation. A profound change in morphogenesis in addition to the reduction in the number of C.auris cells was shown by SEM and light microscopy. The presence of a high surface area and the uniform dispersion of nanosized Ag species displays enhanced anti-Candida activity, and therefore it has great potential against the emerging multidrug-resistant C. auris.

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases.

The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells. It acts through two main receptors: AdipoR1 and AdipoR2, forming the "Adiponectin system" which effectively exerts its cellular mechanisms and responses in target cells. It regulates various metabolic processes, while adiponectin is the adipocyte hormone known for its cardioprotective impact in clinical and experimental research. It is also a well-effector metabolic adipokine, since weight loss or diet restriction show a link with rises in adiponectin concentrations, which is accompanied with increasing insulin sensitivity, glucose, and lipids-regulation via adiponectin's antioxidant, anti-inflammatory, anti-fibrotic actions. The high adiponectin level made it an attractive player in developing therapeutical treatments for metabolic syndromes and cardiovascular disease. The elevated plasma levels of adiponectin are mostly attributed to its benefits on cardio-metabolism. In some cases, adiponectin has been paradoxically accompanied with elevated risk of cardiovascular disease, so higher adiponectin concentration is a marker of poor prediction. Thus, the adiponectin system is attractive to researchers as a biomarker of heart disease advancement and a predictor of prognosis during the term of some cardiovascular diseases and its mechanical functions in Hypertension and diabetic patients. This review highlights the physiological roles of adiponectin as an anti-inflammatory and cardioprotective hormone as well as how it plays as a biomarker and potential therapeutic tool in the cardiovascular system in adult, children, and adolescents. The adiponectin system may be seen as a rescue hormone aiding in remodeling of the cardiovascular system on both cellular and molecular levels. The paradox role of adiponectin relevant to cardiovascular mortality should be taken into consideration.

Emerging trends in the delivery of nanoformulated oxytocin across Blood-Brain barrier.

Neurological diseases are related to the central nervous system disorders and considered as serious cases. Several drugs are used to treat neurological diseases; however, to date the main issue is to design a therapeutic model which can cross the blood-brain-barrier (BBB) easily. The delivery of neuropeptides into the brain lays as one of the important routes for treating neurological disorders. Neuropeptides have been demonstrated as potential therapeutics for neurological disorders. Among numerous neuropeptides, the oxytocin (OT) hormone is of particular interest as it serves as a neurotransmitter in the brain as well as its role as a hormone. OT has a wide-range of activities in the brain and has a key role in cognitive, neuroendocrine, and social functions. However, OT does not cross the BBB readily coupled with its half-life in the blood being too short. The current literature reveals that the delivery of OT by nanoparticle-based drug delivery system (DDS) improves its efficacy. Nanoparticle based DDS are considered important tools for the targeted delivery of drugs to the brain as they lower toxicity of the drug and improve the drug efficacy. Nanoparticles are advantageous candidates for biomedical applications due to their distinctive characteristics such as quantum effects, large surface area and their ability to carry and transport the drug to its target site. OT can be delivered through oral and intranasal routes, but the bioavailability of OT inside the brain can further be enhanced by the delivery using nanoparticles. The application of nano-based delivery system not only improves the penetration of OT inside brain but also increases its half-life by the application of encapsulation and extended release. The aim of current review is to provide an overview of nanoparticle-based drug-delivery systems for the delivery of OT inside brain.

Polysaccharide Chemistry in Drug Delivery, Endocrinology, and Vaccines.

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non-exposure of active moieties to the harsh gastric environment and first-pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development.

Nanotechnology, in silico and endocrine-based strategy for delivering paclitaxel and miRNA: Prospects for the therapeutic management of breast cancer.

Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.

Endocrine roles of vitamin K-dependent- osteocalcin in the relation between bone metabolism and metabolic disorders.

Obesity and diabetes are important metabolic diseases and a major public health problem among the world, they have serious health and economic complications. Overweight and obesity are increased risk for deficiency of vitamin particularly shortage of fat soluble-vitamins. Studies reported that vitamin K supplementation reduces oxidative stress and metabolic risk biomarkers for diabetes, as well as reduces progression of insulin resistance. Vitamin K-dependent-protein osteocalcin (bone derived hormone) plays crucial roles in energy metabolism. There is a clear association between circulating vitamin k and dependent-osteocalcin concentrations with obesity and risk of Type 2 diabetes. Osteocalcin through molecular mechanisms improves insulin resistance, lipid and glucose profile, and mediate vitamin K positive effects. Insulin also signals osteocalcin to regulate bone mineralization. Normal carboxylation of vitamin K-dependent proteins/ hormones is a key step in preventing apoptosis and calcification of vascular endothelial cells. A missing relationship between bone, glucose and fat metabolism could clarify and manage many metabolic mechanisms. This review focuses on the physiological relationship between vitamin K-dependent-osteocalcin, metabolic and cardiovascular diseases through some molecular proteins and hormones including adipokines. A better understanding of the mechanism of action of osteocalcin modulated by vitamin K could help in implementing therapeutic drugs to cure metabolic diseases.

Hepatoprotective and immunological functions of Nigella sativa seed oil against hypervitaminosis A in adult male rats.

PURPOSE: The toxic effects of excess vitamin A (VA) intake deserve increased attention. Nigella sativa (NS) seed possesses physiological and pharmacological actions and protects against toxic agents. This work investigated the availability of NS seed oil as a protective agent against the effects of hypervitaminosis A (HVA) on liver function and immunity. METHODS: Fifty adult albino rats were used and divided into five groups: (G1) control; (G2) experimental HVA rats administered extreme doses (10,000 IU/kg body weight) of VA oil orally, daily for 6 weeks; (G3) rats treated with NS seed oil (800 mg/kg) orally, daily for 6 weeks; (G4) HVA rats simultaneously treated with NS seed oil at the same doses and periods; and (G5) HVA recovery group. Liver function, immunoglobulin (IgG and IgM) levels, and lysosome activity were measured in serum. RESULTS: HVA rats revealed marked elevations in alanine aminotransferase and aspartate aminotransferase activities. This is the first study to demonstrate that NS seed oil possesses significant hepatoprotective activity against HVA. NS seed oil was a potent inducer of IgG and IgM in rat serum either alone or with high doses of VA. CONCLUSIONS: These findings may be considered the initial steps of the physiological and humoral immune responses for NS seed oil against HVA, but further studies examining longer periods are needed prior to recommending the use of NS seed oil as an alternative medicine for hepatic and immune diseases.