An insight into biosensing platforms used for the diagnosis of various lung diseases: A review.

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model.

AIM: The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. METHOD: Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. RESULT: The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, -27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. CONCLUSION: Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

The Impact of Polymerase Chain Reaction Urine Testing on Clinical Decision-Making in the Management of Complex Urinary Tract Infections.

While urinary polymerase chain reaction (PCR) testing is effective in organism identification in patients with complex urinary tract infections (cUTI), limited data exists on the clinical usefulness of this test. We serially surveyed physicians treating symptomatic patients with cUTI both at presentation and after PCR, and urine culture (UC) results were available to ascertain how the test results modified the therapy. A total of 96 unique surveys completed by 21 providers were included in the data analysis. The mean age for female and male patients was 69.4 ± 15.5 and 71.6 ± 12.7 years, respectively. The test positivity and line-item concordance for UC and PCR were consistent with prior reports. The PCR results modified or confirmed treatment in 59/96 (61.5%) and 25/96 (26.0%) of the cases, respectively, with 12/29 (41.4%) and 47/67 (70.1%) having negative and positive PCR results, respectively, resulting in treatment change (difference 28.7%, p < 0.01). Of these, 55/59 (57.3%) were alterations in the antibiotic regimen. PCR use to modify treatment was similar across providers and not statistically different when stratified by patient age, gender, or prior empiric therapy. In 31/59 (52.5%) of the cases, the PCR results modified the treatment where UC would not; conversely, UC would have modified the treatment in 3/37 (8.1%) of the cases where PCR did not (difference 44.4%, p < 0.01). We find that PCR test results are used by clinicians in managing cUTI, and use of this test provides an opportunity to improve antibiotic stewardship in this difficult-to-treat subset of patients.

Experimental design approach for development of carboplatin loaded chitosan modified liposomal formulation with improved topical vaginal therapeutic potential.

One of the most prevalent cancers affecting women globally is cervical cancer. Cervical cancer is thought to cause 570 000 new cases annually, and standard treatments can have serious side effects. In this work, the main aim is to design, fabrication, and evaluation of carboplatin loaded chitosan coated liposomal formulation (CCLF-I) for vaginal delivery in the treatment of cervical cancer. The particle size and polydispersity index of the CCLF-1 were observed at 269.33 ± 1.15 and 0.40 ± 0.002 nm, respectively. The in vitro mucin binding studies showed good adhesiveness of CCLF-I as compared to plain liposomes (CPLF-I), which was found at 23.49 and 10.80%, respectively. The ex-vivo percent drug permeation from plain liposomal formulation (CPLF-I) was found to be higher in comparison to chitosan coated liposomal formulation which was 56.33% while in CCLF-I it was observed 47.32% this is due to, higher retainability of delivery system (CCLF-I) on targeted site attained by coating of mucoadhesive polymer on liposomes. Ex vivo tissue retention studies exhibited 24.2% of CCLF-I in comparison to 10.34% from plain drug formulation (CPLF-I). The in vivo vaginal retention studies exhibited 14% of drug retention after 24 h from the novel formulation in comparison to 6% from the plain formulation. The developed CCLF-I formulation would open a new avenue in the cervical treatment.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

The Essential Role of PCR and PCR Panel Size in Comparison with Urine Culture in Identification of Polymicrobial and Fastidious Organisms in Patients with Complicated Urinary Tract Infections.

Complicated urinary tract infections (cUTIs) are difficult to treat, consume substantial resources, and cause increased patient morbidity. Data suggest that cUTI may be caused by polymicrobial and fastidious organisms (PMOs and FOs, respectively); as such, urine culture (UC) may be an unreliable diagnostic tool for detecting cUTIs. We sought to determine the utility of PCR testing for patients presumed to have a cUTI and determine the impact of PCR panel size on organism detection. We reviewed 36,586 specimens from patients with presumptive cUTIs who received both UC and PCR testing. Overall positivity rate for PCR and UC was 52.3% and 33.9%, respectively (p < 0.01). PCR detected more PMO and FO than UC (PMO: 46.2% vs. 3.6%; FO: 31.3% vs. 0.7%, respectively, both p < 0.01). Line-item concordance showed that PCR detected 90.2% of organisms identified by UC whereas UC discovered 31.9% of organisms detected by PCR (p < 0.01). Organism detection increased with expansion in PCR panel size from 5-25 organisms (p < 0.01). Our data show that overall positivity rate and the detection of individual organisms, PMO and FO are significantly with PCR testing and that these advantages are ideally realized with a PCR panel size of 25 or greater.

Nanomaterials and Their Impact on the Immune System.

Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.

Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review.

Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.

Utility of the HAS-BLED Score in Risk Stratifying Patients on Dual Antiplatelet Therapy Post 12 Months After Drug-Eluting Stent Placement.

INTRODUCTION: Current guidelines recommend continuation of dual anti-platelet therapy (DAPT) for 12 months after percutaneous coronary intervention (PCI). Recent studies have shown benefit in continuing DAPT beyond 12 months but at the risk of increase bleeding. To date, there has been little data on risk stratifying patients to determine who can continue DAPT beyond 12 months at minimal bleeding risk. METHODS: All patients who underwent drug-eluting stent (DES) placement from January 1, 2013 to September 30, 2014 were reviewed. Patients who had follow-up for at least 12 months, placement of 2nd generation everolimus-coated DES, and were on DAPT for at least 12 months were included. Patients with a history of atrial fibrillation, follow-up time less than 12 months, or were on concurrent oral anticoagulation therapy were excluded. RESULTS: Five hundred thirty-one patients were analyzed as described above. Two hundred two patients included in our study with 7 patients in the bleeding cohort and 195 patients in no-bleed cohort. The HAS-BLED score in patients who had a bleeding episode vs. those who did not was 3.29 vs. 2.24 (P value of 0.0009). Although not statistically significant, patients who had a bleeding episode were more likely to have renal dysfunction, alcohol use, be on prasugrel, and be on 325mg of aspirin. CONCLUSION: The study shows that the HAS-BLED score can be of utility in risk stratifying patients in determining who can continue DAPT beyond 12 months. Furthermore, a HAS-BLED score of less than 2 may help guide extended DAPT beyond 12 months at minimal bleeding risk. © 2016 Wiley Periodicals, Inc.

Factors associated with emotional distress in newly diagnosed prostate cancer patients.

OBJECTIVE: Early identification and intervention have been recommended for newly diagnosed prostate cancer patients who experience significant emotional distress; however, there is little empirical basis for designing or selecting interventions for these men. We sought to identify factors that are associated with distress in these men as a basis for identifying suitable intervention strategies. METHODS: Using cross-sectional data and validated scales, we investigated the extent to which clinical, demographic, belief, and personality characteristics are associated with emotional distress assessed with the Distress Thermometer in 1425 men newly diagnosed with clinically localized prostate cancer (pretreatment). RESULTS: Beliefs potentially amenable to psychoeducational interventions [low self-efficacy for decision-making (B =-0.11, p = 0.02), low confidence in cancer control (B =-0.03, p < 0.001), and masculine identity threat (B =-0.26, p = 0.001)] were associated with higher emotional distress, as well as personality factors [low optimism (B =-0.04, p = 0.052) and low resilience (B =-0.83, p < 0.001)]. CONCLUSIONS: Findings provide a framework for the development of interventions for prostate cancer patients with elevated emotional distress. These may include improving provider communication about prostate cancer prognosis for those with low confidence in cancer control, providing decision-making support to increase decision-making self-efficacy, or referral to brief cognitive behavioral interventions to help patients reframe masculine identity threat or for those with low optimism or resilience reframe and adjust to the health threat.

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems.

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract.

Comparison of Polymerase Chain Reaction and Urine Culture in the Evaluation of Patients with Complex Urinary Tract Infections.

To compare organism identification using polymerase chain reaction (PCR) and urine culture (UC) in patients with complex urinary tract infections (cUTIs), we reviewed the results of 3395 patients seen during 2022 with cUTI who underwent concomitant PCR and UC testing. We compared the overall positivity rates as well as the ability of each test to identify fastidious organisms (FOs) and the presence of polymicrobial infections (PMOs) and conducted concordance analysis between the tests. PCR detected 36.4% more organisms than UC and was 20 and nearly 36 times more likely to detect PMOs and FOs, respectively. PCR identified 90.6% of organisms found in UC, whereas UC identified 40.7% of organisms found in PCR testing. We found that 62.4% of organisms found in PCR were not found in urine culture, while UC found 9.4% of organisms not identified in polymerase chain reaction. All these differences were statistically significant (p < 0.05). Although we found that PCR was superior to UC in overall pathogen detection, and detection of both PMOs and FOs, both identified potentially pathogenic organisms not found in the corresponding test. Our data strongly suggest that the evaluation of patients with cUTI is best accomplished using PCR in conjunction with UC.

Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases.

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.

Mineralization of fluoropolymers from combustion in a pilot plant under representative European municipal and hazardous waste combustor conditions.

The goal of this study was to provide data to support mineralization of fluoropolymer waste and insignificant generation of PFAS as products of incomplete combustion (PIC) during incineration of fluoropolymer applications at their end-of-life. Destruction efficiency is not an acceptable metric to indicate mineralization and therefore we need to look for and measure products of incomplete destruction. A mixed sample of fluoropolymers representing 80% of commercial fluoropolymers was combusted at conditions representative of municipal and industrial waste incinerators operating in EU. State-of-the-art emission sampling and analytical methods (UPLC-MS/MS, GC-MS) were used for identifying and quantifying those PFAS whose standards were available. Statistical analysis of the results confirmed non-detect to negligible levels of PFAS evidencing mineralization of fluoropolymers.

Current perspectives on Vaxinia virus: an immuno-oncolytic vector in cancer therapy.

Viruses are being researched as cutting-edge therapeutic agents in cancer due to their selective oncolytic action against malignancies. Immuno-oncolytic viruses are a potential category of anticancer treatments because they have natural features that allow viruses to efficiently infect, replicate, and destroy cancer cells. Oncolytic viruses may be genetically modified; engineers can use them as a platform to develop additional therapy modalities that overcome the limitations of current treatment approaches. In recent years, researchers have made great strides in the understanding relationship between cancer and the immune system. An increasing corpus of research is functioning on the immunomodulatory functions of oncolytic virus (OVs). Several clinical studies are currently underway to determine the efficacy of these immuno-oncolytic viruses. These studies are exploring the design of these platforms to elicit the desired immune response and to supplement the available immunotherapeutic modalities to render immune-resistant malignancies amenable to treatment. This review will discuss current research and clinical developments on Vaxinia immuno-oncolytic virus.

PROTACs: Promising approach for anticancer therapy.

Proteolysis-targeting chimeras (PROTACs) are being developed as an effective method for degrading cancer-related proteins by modifying the endogenous ubiquitin-proteasome system. To investigate the dynamics between an E3 ligase and target protein, researchers have developed a wide variety of bifunctional PROTACs by combining small molecule ligands. These PROTACs employ numerous ligands, some of which are reversible, some of which are irreversible, some attach to orthosteric sites, while others bind to allosteric sites. Some are agonists, while others are antagonists, and the target protein may be activated in either a positive or negative manner. A variety of targeted ligand approaches can be used to enhance PROTAC properties, including tumor selectivity and drug delivery, and to overcome drug resistance. The processes and behaviors of small molecule-based PROTACs and targeted proteolysis approaches as anticancer therapeutic molecules have been introduced in this mini-review.