Metastatic tumours to the parotid: A 20-year single institutional experience with an emphasis on 14 unusual presentations.

The parotid gland is a rare site for distant metastasis. We aim to provide an overview of metastatic tumours to the parotid over the past 20 years, focusing on clinicopathological analysis of 14 rare diagnoses. To the best of our knowledge, we are the first group to present the most up-to-date and largest case series on unusual metastases to the parotid. A total of 93 metastatic cases were identified from 2004 to 2023, on the pathology information system at North West London Pathology, with squamous cell carcinoma (n = 45, 48.4 %) as the most common primary, followed by malignant melanoma (n = 29, 31.2 %) and Merkel cell carcinoma (n = 4, 4.3 %). We came across 14 rare tumours that had metastasised to the parotid, including metastatic adenocarcinoma from kidney (n = 3, 3.2 %), lung (n = 3, 3.2 %) and breast (n = 1, 1.1 %), olfactory neuroblastoma (n = 3, 3.2 %), soft tissue sarcoma (n = 2, 2.2 %), small cell carcinoma (n = 1, 1,1 %) and hidradenocarcinoma (n = 1, 1.1 %). Half of all secondary neoplastic lesions (50.5 %) were found in intra-parotid nodes, while the other half (49.5 %) were found in parotid parenchyma. Our study offers valuable insights into the various tumour types that can metastasise to the parotid across a wide age range. It underscores the necessity of maintaining a broad differential diagnosis. Keeping an open mind regarding the potential primary sources of the tumour is imperative for accurate diagnosis and effective treatment planning.

Association between frailty and overall survival among older adults with hepatocellular carcinoma.

INTRODUCTION: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years. MATERIALS AND METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders. RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04). DISCUSSION: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

Folate-conjugated carbon nanotubes as a promising therapeutic approach for targeted cancer therapy.

Conventional systemic cancer therapy often causes numerous adverse events. However, discovering overexpressed folate receptors in solid tumours has paved the way for targeted chemotherapy. Folic acid (FA), a ligand for these receptors, is frequently combined with chemotherapeutic drugs to improve their effectiveness. Carbon nanotubes have emerged as a versatile and promising method for delivering these folate-conjugated nano-systems, ensuring targeted delivery of therapeutic agents to cancerous cells. When FA-conjugated nanotubes dissociate, they release the drug-loaded nanotubes inside the malignant cells, reducing off-target effects. These nanotubes can also be used for combination therapies, producing synergistic effects. This review aims to comprehensively gather and critically evaluate the latest methods for delivering therapeutics using FA-conjugated nanovehicles. Additionally, it seeks to enhance our comprehension of the pertinent chemistry and biochemical pathways involved in this approach.

A recent insight of applications of gold nanoparticles in glioblastoma multiforme therapy.

The application of gold nanoparticles (AuNPs) in cancer therapy, particularly targeted therapy of glioblastoma multiforme (GBM), is an up-and-coming field of research that has gained much interest in recent years. GBM is a life-threatening malignant tumour of the brain that currently has a 95 % death rate with an average of 15 months of survival. AuNPs have proven to have wide clinical implications and compelling therapeutic potential in many researches, specifically in GBM treatment. It was found that the reason why AuNPs were highly desired for GBM treatment was due to their unique properties that diversified the applications of AuNPs further to include imaging, diagnosis, and photothermal therapy. These properties include easy synthesis, biocompatibility, and surface functionalization. Various studies also underscored the ability of AuNPs to cross the blood-brain-barrier and selectively target tumour cells while displaying no major safety concerns which resulted in better therapy results. We attempt to bring together some of these studies in this review and provide a comprehensive overview of safety evaluations and current and potential applications of AuNPs in GBM therapy that may result in AuNP-mediated therapy to be the new gold standard for GBM treatment.

Advancements in liposomal formulations: A comprehensive exploration of industrial production techniques.

Liposomes are nanosized, spherical vesicles consisting of an aqueous core encircled by one or more phospholipid bilayer shells. Liposomes have found extensive use in numerous biomedicine and nanomedicine applications due to their excellent biocompatibility, adaptable chemical composition, ease of preparation, and diverse structural characteristics. These applications include nanocarriers for drug delivery, immunoassays, nutraceuticals, tissue engineering, clinical diagnostics, and theranostics formulations. These applications stimulated significant efforts toward scaling up formation processes in anticipation of appropriate industrial advancement. Despite the advancements in conventional methods and the emergence of new approaches for liposome production, their inherent susceptibility to chemical and mechanical influences contributes to critical challenges, including limited colloidal stability and decreased efficiency in encapsulating cargo molecules. With this context, the current review provides brief insights into liposomes conventional and novel industrial production techniques. With a special focus on the structural parameters, and pivotal elements influencing the synthesis of an appropriate and stable formulation, followed by the various regulatory aspects of industrial production.

Optimizing MSW incineration bottom ash reuse: A study on treated wastewater washing and leaching control.

The current study introduces an innovative methodology by utilizing treated wastewater (TWW) from an effluent treatment plant as a washing agent to enhance the characteristics of incineration bottom ash (IBA). This approach addresses sustainability concerns and promotes the circular economy by reusing wastewater generated in municipal solid waste incineration facilities. Previous research has underscored the challenges of open IBA reuse due to elevated leaching of chlorides, sulfates, and trace metal(loid)s. Thus, the experimental setup explores various combinations of washing, with or without screening, to optimize the properties of soil-like material (SLM < 4.75 mm) and overall material (OM < 31.5 mm) fractions of IBA for unrestricted applications. Batch leaching tests were conducted on treated samples, and leaching characteristics were evaluated in accordance with regulatory standards, primarily the Dutch standard for unrestricted IBA reuse. The findings reveal that washing in isolation proves insufficient to enhance IBA properties; however, washing followed by screening, specifically for removing fines (<0.15 mm), proves effective in reducing contamination. The study identifies that multiple steps of washing and screening (with recirculation) process render OM and SLM fractions suitable for unrestricted reuse with a cumulative liquid-to-solid ratio of 6 L/kg and a total washing time of 15 min. The multi-step treatment was found effective in reducing sulfate contamination by 65-74 % and chloride contamination by 83-89 % in IBA fractions. This approach offers a promising solution for overcoming the limitations associated with IBA leaching, thereby promoting sustainable waste reuse practices.

Motion of Two-Dimensional Excitons in Momentum Space Leads to Pseudospin Distribution Narrowing on the Bloch Sphere.

Motional narrowing implies narrowing induced by motion; for example, in nuclear magnetic resonance, the thermally induced random motion of the nuclei in an inhomogeneous environment leads to a counterintuitive narrowing of the resonance line. Similarly, the excitons in monolayer semiconductors experience magnetic inhomogeneity: the electron-hole spin-exchange interaction manifests as an in-plane pseudomagnetic field with a periodically varying orientation inside the exciton band. The excitons undergo random momentum scattering and pseudospin precession repeatedly in this inhomogeneous magnetic environment, typically resulting in fast exciton depolarization. On the contrary, we show that such magnetic inhomogeneity averages out at high scattering rates due to motional narrowing. Physically, a faster exciton scattering leads to a narrower pseudospin distribution on the Bloch sphere, implying a nontrivial improvement in exciton polarization. The in-plane nature of the pseudomagnetic field enforces a contrasting scattering dependence between the circularly and linearly polarized excitons, providing a spectroscopic way to gauge the sample quality.

Prospects of probiotics in beekeeping: a review for sustainable approach to boost honeybee health.

Honeybees are vital for global crop pollination, making indispensable contributions to agricultural productivity. However, these vital insects are currently facing escalating colony losses on a global scale, primarily attributed to parasitic and pathogenic attacks. The prevalent response to combat these infections may involve the use of antibiotics. Nevertheless, the application of antibiotics raises concerns regarding potential adverse effects such as antibiotic resistance and imbalances in the gut microbiota of bees. In response to these challenges, this study reviews the utilization of a probiotic-supplemented pollen substitute diet to promote honeybee gut health, enhance immunity, and overall well-being. We systematically explore various probiotic strains and their impacts on critical parameters, including survival rate, colony strength, honey and royal jelly production, and the immune response of bees. By doing so, we emphasize the significance of maintaining a balanced gut microbial community in honeybees. The review also scrutinizes the factors influencing the gut microbial communities of bees, elucidates the consequences of dysbiosis, and evaluates the potential of probiotics to mitigate these challenges. Additionally, it delineates different delivery mechanisms for probiotic supplementation and elucidates their positive effects on diverse health parameters of honeybees. Given the alarming decline in honeybee populations and the consequential threat to global food security, this study provides valuable insights into sustainable practices aimed at supporting honeybee populations and enhancing agricultural productivity.

Secretory molecules from secretion systems fine-tune the host-beneficial bacteria (PGPRs) interaction.

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate and involves the secretion of multiple biochemical substances through dedicated protein systems called secretion systems SS. Eleven SS pathways deliver protein factors and enzymes in their immediate environment or host cells, as well as in competing microbial cells in a contact-dependent or independent fashion. These SS are instrumental in competition, initiation of infection, colonization, and establishment of association (positive or negative) with host organisms. The role of SS in infection and pathogenesis has been demonstrated for several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, and Pseudomonas. Since there is overlap in mechanisms of establishing association with host plants, several studies have investigated the role of SSs in the interaction of plant and beneficial bacteria, including symbiotic rhizobia and plant growth bacteria (PGPB). Therefore, the present review updates the role of different SSs required for the colonization of beneficial bacteria such as rhizobia, Burkholderia, Pseudomonas, Herbaspirillum, etc., on or inside plants, which can lead to a long-term association. Most SS like T3SS, T4SS, T5SS, and T6SS are required for the antagonistic activity needed to prevent competing microbes, including phytopathogens, ameliorate biotic stress in plants, and produce substances for successful colonization. Others are required for chemotaxis, adherence, niche formation, and suppression of immune response to establish mutualistic association with host plants.

Advances in the polymeric nanoparticulate delivery systems for RNA therapeutics.

RNA therapeutics have emerged as potential treatments for genetic disorders, infectious diseases, and cancer. RNA delivery to target cells for efficient therapeutic applications remains challenging due to instability and poor uptake. Polymeric nanoparticulate delivery systems offer stability, protection, and controlled release. These systems shield RNA from degradation, enabling efficient uptake and extended circulation. Various polymeric nanoparticle platforms have been explored, including lipid-based nanoparticles, polymeric micelles, dendrimers, and polymer-drug conjugates. This review outlines recent breakthroughs of recent advances, design principles, characterization techniques, and performance evaluation of these delivery systems. It highlights their potential in translating preclinical studies into clinical applications. Additionally, the review discusses the application of polymeric nanoparticles in ophthalmic drug delivery, particularly for medications that dissolve poorly in water, and the progress made in siRNA-based therapies for viral infections, autoimmune diseases, and cancers. SiRNA holds great promise for precision medicine and therapeutic intervention, with the ability to target specific genes and modulate disease-associated pathways. The versatility and potency of siRNA-based drugs offer a broader scope for therapeutic intervention compared to traditional biological drugs. As research in RNA therapeutics continues to advance, these technologies hold tremendous potential to revolutionize the treatment of various diseases and improve patient outcomes.

Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of unknown significance: A case report.

Monoclonal gammopathy of uncertain significance associated acquired von Willebrand syndrome is a serious bleeding condition driven by immunological clearance of von Willebrand factor and has limited treatment options. We present a patient who achieved durable remission through eradication of the monoclonal paraprotein with clonal directed therapy with bortezomib.

PLGA nanomedical consignation: A novel approach for the management of prostate cancer.

The malignancy of the prostate is a complicated ailment which impacts millions of male populations around the globe. Despite the multitude of endeavour accomplished within this domain, modalities that are involved in the ameliorative management of predisposed infirmity are still relent upon non-specific and invasive procedures, thus imposing a detrimental mark on the living standard of the individual. Also, the orchestrated therapeutic interventions are still incompetent in substantiating a robust and unabridged therapeutic end point owing to their inadequate solubility, low bioavailability, limited cell assimilation, and swift deterioration, thereby muffling the clinical application of these existing treatment modalities. Nanotechnology has been employed in an array of modalities for the medical management of malignancies. Among the assortment of available nano-scaffolds, nanocarriers composed of a bio-decomposable and hybrid polymeric material like PLGA hold an opportunity to advance as standard chemotherapeutic modalities. PLGA-based nanocarriers have the prospect to address the drawbacks associated with conventional cancer interventions, owing to their versatility, durability, nontoxic nature, and their ability to facilitate prolonged drug release. This review intends to describe the plethora of evidence-based studies performed to validate the applicability of PLGA nanosystem in the amelioration of prostate malignancies, in conjunction with PLGA focused nano-scaffold in the clinical management of prostate carcinoma. This review seeks to explore numerous evidence-based studies confirming the applicability of PLGA nanosystems in ameliorating prostate malignancies. It also delves into the role of PLGA-focused nano-scaffolds in the clinical management of prostate carcinoma, aiming to provide a comprehensive perspective on these advancements.

Effect of Multifactorial Balance Rehabilitation Program on Risk of Falls and Functional Fitness in Older Adults with Diabetic Peripheral Neuropathy.

BACKGROUND: Increasing age and the added disadvantage of diabetic peripheral neuropathy (DPN) put the individual at a higher risk of falls and reduced functional fitness. However, there is a dearth of literature on multifactorial balance intervention, especially targeting the needs of older adults with DPN. OBJECTIVE: The current study aimed to determine the effect of a multifactorial balance rehabilitation program on fall risk and functional fitness in older adults with DPN. METHODS: In this pre-post experimental study, 30 independently ambulating older adults (71.2 ± 4.70 years) with DPN, who were at risk of falling (timed up and go score ≥ 9.4 seconds), were recruited. Along with the standard care, all the participants received 12 weeks of the multifactorial balance rehabilitation program. RESULTS: Fall risk using the Fullerton Advanced Balance scale and functional fitness using the Senior Fitness Test were measured at baseline and after 12 weeks of the intervention. The intervention reduced the risk of falling score significantly (MD = 6.17, p < .001). All six parameters of functional fitness improved after 12 weeks of intervention. The improvement in lower limb strength (MD = 1.53 times), upper limb strength (MD = 2.48 times), endurance (MD = 16.07 seconds), lower limb flexibility (MD = 2.02 inches), upper limb flexibility (MD = 1.47 inches), and dynamic balance (MD = 1.53 seconds) was statistically significant at p < 0.05. CONCLUSION: This study provided encouraging evidence about the potential of multifactorial balance rehabilitation to reduce the risk of falling and improve functional fitness in older adults with DPN.

Observation of ~100% valley-coherent excitons in monolayer MoS2 through giant enhancement of valley coherence time.

In monolayer transition metal dichalcogenide semiconductors, valley coherence degrades rapidly due to a combination of fast scattering and inter-valley exchange interaction. This leads to a sub-picosecond valley coherence time, making coherent manipulation of exciton a highly challenging task. Using monolayer MoS2 sandwiched between top and bottom graphene, here we demonstrate fully valley-coherent excitons by observing ~100% degree of linear polarization in steady state photoluminescence. This is achieved in this unique design through a combined effect of (a) suppression in exchange interaction due to enhanced dielectric screening, (b) reduction in exciton lifetime due to a fast inter-layer transfer to graphene, and (c) operating in the motional narrowing regime. We disentangle the role of the key parameters affecting valley coherence by using a combination of calculation (solutions of Bethe-Salpeter and Maialle-Silva-Sham equations) and a careful choice of design of experiments using four different stacks with systematic variation of screening and exciton lifetime. To the best of our knowledge, this is the first report in which the excitons are found to be valley coherent in the entire lifetime in monolayer semiconductors, allowing optical readout of valley coherence possible.

Assessment of risk factors in pyogenic liver abscesses in children.

Background: Pyogenic liver abscess (LA) is a significant contributor to morbidity and mortality in developing countries like India. The risk factors predisposing to the LA specifically in children are not known. Studies done in the past largely remain inconclusive and have identified only probable causes. The cause of LA in children with no coexisting illness remains unknown. Methodology: This prospective observational study was conducted at a tertiary teaching hospital located in New Delhi, India. All children between 2 months and 12 years of age with sonographically confirmed LA presenting to the hospital were included and managed with appropriate intravenous antibiotics and relevant investigations. Results: A total of 52 children were included. The mean age was 6 years and 4 months, and the male: female ratio was 1.4:1. Around 50% of the patients were malnourished. Fever, abdominal pain and loss of appetite were the most common symptoms. Nine patients (17%) were managed conservatively, 13 (25%) needed percutaneous needle aspiration and 30 (57.69%) required drainage using a pigtail catheter. Poor socioeconomic status and anaemia were found to be the most commonly associated risk factors. Selective immunoglobulin A (IgA) deficiency was the most common primary immunodeficiency disorder followed by T-cell defect. On multivariate analysis, it was seen that in those with clinical icterus, gamma-glutamyl transferases >350 IU/m, and those with impending rupture, the time to defervescence was significantly different (P = 0.05). Conclusion: Poor socioeconomic status causing malnutrition emerged as a significant risk factor for LA in children. Selective IgA deficiency was the most common immunodeficiency seen in a few children. Adopting a conservative approach like aspiration and percutaneous drainage led to lower mortality and good recovery rates.

Characterization of MSW incineration bottom ash for use as structural fill in reinforced soil structures: Geoenvironmental, geotechnical and economical assessment.

The study presents the geoenvironmental and geotechnical characterization of MSW incineration bottom ash (IBA) and examines its reuse as structural fill in reinforced soil structures (RSS).The suitability of reuse has been assessed with regard to international regulatory standards. The prime focus of the work remains on evaluating the pullout response of geosynthetic reinforcements through IBA fill to determine the interaction coefficient, which has never been addressed in the literature. The economic viability of using IBA instead of locally available river sand for a 12 m high MSE wall is also established. The column leaching test results confirm that IBA can be utilized in RSS with suitable design measures. The geotechnical investigation shows that IBA is a well-graded, non-plastic lightweight material with adequate drainage and high shear strength. The pullout test results demonstrate that the interaction coefficient of polymeric strips and geogrid in IBA (0.73-1.53 and 0.79-1.91, respectively) is comparable or higher to materials conventionally used as structural fill in RSS, indicating adequate bondage between IBA and geosynthetic reinforcement. Further, it is estimated that using IBA as a substitute for available river sand in the vicinity can potentially reduce the overall RSS project cost by 15-20%, even if IBA has to be transported 50 km away from the project site.

Biosensor Assays Types and Their Roles Toward Ligand-Receptor Interactions in Drug Discovery.

Ligand-receptor interactions (LRIs) are the basis for all the biological processes taking place in living cells and have been exploited to develop and implement in medical field a number of highly sensitive biosensors for the detection of various biomarkers in complex biological fluids. Drug-target interactions, one of the LRIs, are important to understand the biological processes that further help in developing new and better therapeutic molecules. Biosensors based on these interactions give us an idea for the need of modification of existing drugs or to develop new drugs. Common approach to develop biosensors requires the labeling; however, label-free systems provide advantages in avoiding the chances of conformational changes, off-site labeling, and labeling-based hindrances, thus saving time and effort toward assay development. Preliminary drug screening assays are carried out in two-dimensional (2D) models, followed by animal models, which require huge capital investment to reach from bench-top to clinical trials, where only 21% of new compounds make way to phase-1 clinical trials. Three-dimensional culture or organoid culture or organ-on-chip technology has made way for predictive and complex in vitro approach that recapitulates human physiology and represents more similar in vivo behavior than 2D. Multiplexing and nanotechnology have remarkably enhanced the efficacy of biosensors and might lead to a generation of miniaturized biosensors and more than just point-of-care kits. This review provides in-depth analysis of different types of biosensor assays based on drug-target interactions, their advantages, and limitations based on cost, sensitivity, and selectivity and industrial applications.

Effect of Covid-19 lockdown/ compulsory work from home (WFH) situation on musculoskeletal disorders in India.

OBJECTIVE: To estimate self-reported musculoskeletal disorders among Indian population in work from home COVID-19 lockdown and its association on various socio-demographic and occupational factors among them. METHODS: The present cross-sectional study was conducted on working Indian professionals, through an online self-reported survey during the COVID-19 work from the home situation. Details about the perceived musculoskeletal discomforts, weight gain or loss, physical activity profile, number of working hours, total sedentary time, and satisfaction perceived with working from home were recorded from the participant responses and thereafter analyzed. RESULTS: A total of 281 responses were analyzed. 47.6% of respondents reported musculoskeletal disorders before lockdown, whereas 53.6% reported them during the lockdown period. 10% of respondents reported declination in physical activity. Finding of the chi-square for association and Spearman's rho correlation analysis suggested that gender, pre-existing musculoskeletal discomforts, current sedentary time, and long working hours are significantly associated with musculoskeletal discomforts during work from home COVID-19 lockdown. CONCLUSION: This study concluded the increment in the self-reported musculoskeletal disorders among working Indian professionals during work from home COVID-19 lockdown. The study also found the significant association between MSD and gender, working hours, sedentary time and pre-existing musculoskeletal discomforts.

Synthesis and evaluation of carbamate derivatives as fatty acid amide hydrolase and monoacylglycerol lipase inhibitors.

Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are the primary catabolic enzymes for endocannabinoids, anandamide (AEA), and 2-arachidonoyl glycerol. Numerous studies have shown that FAAH and MAGL play an important role in modulating various central nervous system activities; hence, the development of small molecule FAAH/MAGL inhibitors is an active area of research. Several small molecules possessing the carbamate scaffold are documented as potential FAAH/MAGL inhibitors. Here, we designed and synthesized a series of open chain and cyclic carbamates and evaluated their dual FAAH-MAGL inhibition properties. Phenyl [4-(piperidin-1-ylmethyl)phenyl]carbamate (2e) emerged as the most potent MAGL inhibitor (IC50 = 19 nM), benzyl (1H-benzo[d]imidazol-2-yl)carbamate (3h) was the most potent FAAH inhibitor (IC50 = 55 nM), and phenyl (6-fluorobenzo[d]thiazol-2-yl)carbamate (2i) egressed as a nonselective dual FAAH-MAGL inhibitor (FAAH: 82 nM, MAGL: 72 nM). The enzyme kinetics experiments revealed that the compounds inhibit FAAH/MAGL in a covalent-reversible manner, with a mixed binding mode of action. Moreover, the lead compounds were found suitable for blood-brain permeation in the parallel artificial membrane permeation assay. Furthermore, docking simulation experiments suggested that the potency of the lead compounds was governed by hydrogen bonds and hydrophobic interactions with the enzyme active sites. In silico drug-likeness and ADMETox prediction studies provided useful information on the compounds' oral absorption, metabolism, and toxicity profiles. In summary, this study afforded potent multifunctional carbamates with appreciable pharmacokinetic profiles meriting further investigation.