Three-dimensional modeling for colloid-facilitated contaminant transport with the effect of mobile and immobile sorbents.

A conceptual equilibrium-based mathematical model for colloid-associated contaminant transport has been developed to study the impact of the subsurface environment on contaminant transport through a three-dimensional, saturated, and homogeneous groundwater flow system with uniform flow. The kinetic model's critical limitation is dealing with the more significant number of parameters utilized upon application to larger scales in three-dimensional regions when a series of transport mechanisms are incorporated. Therefore, the present study is the first attempt to study the equilibrium approach in three-dimensional regions to avoid complexities in the model. The current study, however, shows that the mere existence of colloids does not indicate that contaminants will move more quickly; rather, it also depends on how the aqueous phase interacts with the static solid matrix, captured colloid particles, and mobile colloids as well as how colloids interact with stationary solid matrix phase. We noticed that the affinity of contaminants to immobile sorbents (stationary solid matrix and captured colloids) can reduce the transport even in the presence of colloids. Three-dimensional numerical experiments reveal that contaminants infiltrate more in the downward direction in the absence of colloids and can be distributed more in the longitudinal direction and less in the downward direction when colloids are present. The dual nature of colloids is espied here: first, colloids can remove pollutants from a specific area more quickly, and second, in a similar manner, colloids can pollute a specific region more quickly.

Anti-Inflammatory and Anti-Arthritis Activity of Quercetin: A Comprehensive Review.

This comprehensive exploration delves into the multifaceted attributes of quercetin, a flavonoid with extensive health-promoting potential. The review navigates through its fundamental properties, encompassing its chemical structure, classification as a flavonoid, and its natural prevalence in various sources. Addressing solubility, stability, and bioavailability challenges, the investigation delves into innovative isolation techniques, including solvent extraction, solid-phase extraction, natural deep eutectic solvents, supercritical fluid extraction, microwave-assisted extraction, column chromatography, and high-performance thin-layer chromatography. Transitioning into pharmacological implications, the study unveils quercetin's roles in anti-inflammatory pathways, antioxidant effects, and immune modulation, reflecting its versatile significance in health management. The review highlights its impact on wound healing processes and its potential to mitigate arthritis, elucidating its holistic contributions. Culminating in an exploration of recent studies, the analysis underscores quercetin's remarkable anti-inflammatory and anti-arthritis activities, reflecting its substantial potential across various ailments. The review concludes by projecting future trajectories, emphasizing prospects for an advanced understanding of quercetin's mechanisms, sustainable extraction techniques, clinical integration, and exploration of synergistic combinations. Collectively, this review investigation underscores quercetin's dynamic role at the intersection of natural compounds and medicinal applications, offering profound implications for well- being and health enhancement.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Evolution of the atomic and electronic structures of CuO clusters: a comprehensive study using the DFT approach.

One of the most fundamental aspects of cluster science is to understand the structural evolution at the atomic scale. In this connection, here we report a comprehensive study of the atomic and electronic structures of (CuO)n clusters for n = 1 to 12 using DFT-based formalisms. Both the plane wave-based pseudo-potential approach and LCAO-MO-based method have been employed to obtain the ground state geometries of neutral, cation and anion copper oxide clusters. The results reveal that neutral copper oxide clusters favor a planar ring structure up to heptamer and from octamer onwards they adopt a three-dimensional motif with (CuO)9 and (CuO)12 forming a barrel-shaped layered structure. Detailed electronic structure analysis reveals that the transition of the atomic structure from 2D to 3D is guided by the energy balance of the Cu-O (d-p) and Cu-Cu (d-d) bonds. The removal of one electron from the cluster (cation) results in slightly stretched bonds while the addition of one electron (anion) showed compression in the overall geometries. The thermodynamic and electronic stability of these clusters has been analyzed by estimating their binding energy, ionization energy and electron affinity as a function of size. Remarkably, among these clusters, the octamer (CuO)8 and dodecamer (CuO)12 show higher binding energy and electron affinity (∼6.5 eV) with lower ionization energy (5.5-6.0 eV). This unique feature of the octamer and dodecamer indicates that they are very promising candidates for both oxidizing and reducing agents in different important chemical reactions.

Ultrasound-guided procedures for postoperative pain management in pediatric patients undergoing abdominal surgeries: A systematic review.

Many ultrasound-guided procedures are available for administering analgesia via peripheral nerve blockade. This systematic review aims to compare different ultrasound-guided procedures to determine which procedure is better suited for pediatric abdominal surgeries. The objective is to understand the efficacy of ultrasound-guided procedures for postoperative pain management in children undergoing abdominal surgeries and to identify which procedure takes less time and is better suited for a particular surgery. A systematic literature search was performed in PubMed, SCOPUS, Central Cochrane Registry of Controlled Trials (The Cochrane Library), and ScienceDirect databases for pediatric abdominal surgeries conducted with ultrasound-guided procedures for administering analgesia. We included studies involving randomized controlled trials (RCTs). Quasi-randomized controlled studies, prospective, retrospective observational studies, case series, case reports, letters, editorials, comments, animal studies, and studies from non-English literature were excluded. We reviewed 13 articles with 910 patients included. Age groups varied from 6 months to 21 years. The most common block used was the transversus abdominis block (47.76%), and the most common surgery performed was hernia and hydrocele (52.10%). Quadratus lumborum block was used in 26.92%, erector spinae block in 8.97%, modified transversus abdominus block and rectus sheath block in 9.62%, and ilioinguinal block in 6.73% of the patients. No complications were reported in any of the studies. Transversus abdominus block is less effective in two of the studies. Each procedure for pediatric postoperative analgesia has specific advantages and limitations, highlighting the complexity of tailoring interventions. Our review focuses on the advancements in ultrasound-guided analgesia for lower abdominal surgeries in pediatric patients while also emphasizing the need for future randomized controlled trials (RCTs) to compare efficacy, standardize practices, and improve patient outcomes.

Advances in Aerosol Formulation for Targeted Delivery of Therapeutic Agents from Nose to Brain.

The intricate anatomical and physiological barriers that prohibit pharmaceuticals from entering the brain continue to provide a noteworthy hurdle to the efficient distribution of medications to brain tissues. These barriers prevent the movement of active therapeutic agents into the brain. The present manuscript aims to describe the various aspects of brain-targeted drug delivery through the nasal route. The primary transport mechanism for drug absorption from the nose to the brain is the paracellular/extracellular mechanism, which allows for rapid drug transfer. The transcellular/intracellular pathway involves the transfer across a lipoidal channel, which regulates the entry or exit of anions, organic cations, and peptides. Spectroscopy and PET (positron emission tomography) are two common methods used for assessing drug distribution. MRI (Magnetic resonance imaging) is another imaging method used to assess the efficacy of aerosol drug delivery from nose to brain. It can identify emphysema, drug-induced harm, mucus discharge, oedema, and vascular remodeling. The olfactory epithelium's position in the nasal cavity makes it difficult for drugs to reach the desired target. Bi-directional aerosol systems and tools like the "OptiNose" can help decrease extranasal particle deposition and increase particle deposition efficiency in the primary nasal pathway. Direct medicine administration from N-T-B, however, can reduce the dose administered and make it easier to attain an effective concentration at the site of activity, and it has the potential to be commercialized.

The analgesic efficacy of ultrasound-guided erector spinae plane block versus ultrasound-guided caudal epidural block for abdominal surgery in pediatric patients - A patient and assessor-blind, randomized controlled study.

Background: Literature on the efficacy and safety of erector spinae plane block (ESPB) in pediatric patients is limited. Hence, we aimed to compare ESPB versus caudal epidural block (CEB) in children undergoing abdominal surgery. Methods: In this patient and assessor-blind study, fifty-two ASA I-II patients, between 1 to 9 years of age, were randomized into groups of 26 each. ESPB group received unilateral or bilateral ultrasound (USG)-guided ESPB with 0.5 ml/kg of 0.25% bupivacaine per side. CEB group received USG-guided CEB with 1 ml/kg of 0.25% bupivacaine. The primary objective was to estimate the proportion of patients requiring postoperative rescue analgesia. The secondary objectives were to assess postoperative Face, Legs, Activity, Cry and Consolability (FLACC) scale scores, duration of analgesia, and consumption of rescue analgesic drugs. Results: More patients in the ESPB group (88.4%), compared to the CEB group (42.3%), required rescue analgesics (P value <0.001). FLACC scores in the ESPB group, though satisfactory, were inferior, to the CEB group. The duration of postoperative analgesia was shorter in the ESPB group by 9.54 h (95% CI: 4.51 to 14.57 h, P value <0.001). The median (IQR) consumption of rescue paracetamol was significantly higher in the ESPB group (20 mg/kg (10,20) compared to the CEB group (0.0 mg/kg (0.0,10) P value <0.001)). No adverse effects were reported. Conclusion: In children undergoing abdominal surgery, both ESPB and CEB were safe and efficacious. CEB provided a longer duration and better quality of analgesia. ESPB may be considered when CEB is contraindicated or difficult.

Advances in Aerogels Formulations for Pulmonary Targeted Delivery of Therapeutic Agents: Safety, Efficacy and Regulatory Aspects.

Aerogels are the 3D network of organic, inorganic, composite, layered, or hybrid-type materials that are used to increase the solubility of Class 1 (low solubility and high permeability) and Class 4 (poor solubility and low permeability) molecules. This approach improves systemic drug absorption due to the alveoli's broad surface area, thin epithelial layer, and high vascularization. Local therapies are more effective and have fewer side effects than systemic distribution because inhalation treatment targets the specific location and raises drug concentration in the lungs. The present manuscript aims to explore various aspects of aerogel formulations for pulmonary targeted delivery of active pharmaceutical agents. The manuscript also discusses the safety, efficacy, and regulatory aspects of aerogel formulations. According to projections, the global respiratory drug market is growing 4-6% annually, with short-term development potential. The proliferation of literature on pulmonary medicine delivery, especially in recent years, shows increased interest. Aerogels come in various technologies and compositions, but any aerogel used in a biological system must be constructed of a material that is biocompatible and, ideally, biodegradable. Aerogels are made via "supercritical processing". After many liquid phase iterations using organic solvents, supercritical extraction, and drying are performed. Moreover, the sol-gel polymerization process makes inorganic aerogels from TMOS or TEOS, the less hazardous silane. The resulting aerogels were shown to be mostly loaded with pharmaceutically active chemicals, such as furosemide-sodium, penbutolol-hemisulfate, and methylprednisolone. For biotechnology, pharmaceutical sciences, biosensors, and diagnostics, these aerogels have mostly been researched. Although aerogels are made of many different materials and methods, any aerogel utilized in a biological system needs to be made of a substance that is both biocompatible and, preferably, biodegradable. In conclusion, aerogel-based pulmonary drug delivery systems can be used in biomedicine and non-biomedicine applications for improved sustainability, mechanical properties, biodegradability, and biocompatibility. This covers scaffolds, aerogels, and nanoparticles. Furthermore, biopolymers have been described, including cellulose nanocrystals (CNC) and MXenes. A safety regulatory database is necessary to offer direction on the commercialization potential of aerogelbased formulations. After that, enormous efforts are discovered to be performed to synthesize an effective aerogel, particularly to shorten the drying period, which ultimately modifies the efficacy. As a result, there is an urgent need to enhance the performance going forward.

Carbon Nanotubes for Targeted Therapy: Safety, Efficacy, Feasibility and Regulatory Aspects.

It is crucial that novel and efficient drug delivery techniques be created in order to improve the pharmacological profiles of a wide variety of classes of medicinal compounds. Carbon nanotubes (CNTs) have recently come to the forefront as an innovative and very effective technique for transporting and translocating medicinal compounds. CNTs were suggested and aggressively researched as multifunctional novel transporters designed for targeted pharmaceutical distribution and used in diagnosis. CNTs can act as vectors for direct administration of pharmaceuticals, particularly chemotherapeutic medications. Multi-walled CNTs make up the great majority of CNT transporters, and these CNTs were used in techniques to target cancerous cells. It is possible to employ Carbon nanotubes (CNTs) to transport bioactive peptides, proteins, nucleic acids, and medicines by functionalizing them with these substances. Due to their low toxicity and absence of immunogenicity, carbon nanotubes are not immunogenic. Ammonium-functionalized carbon nanotubes are also attractive vectors for gene-encoding nucleic acids. CNTs that have been coupled with antigenic peptides have the potential to be developed into a novel and efficient approach for the use of synthetic vaccines. CNTs bring up an enormous number of new avenues for future medicine development depending on targets within cells, which have until now been difficult to access. This review focuses on the numerous applications of various CNT types used as medicine transport systems and on the utilization of CNTs for therapeutical purposes.

Cracking the Code of Lumpy Skin Disease: Identifying Causes, Symptoms and Treatment Options for Livestock Farmers.

The novel bovine viral infection known as lumpy skin disease is common in most African and Middle Eastern countries, with a significant likelihood of disease transfer to Asia and Europe. Recent rapid disease spread in formerly disease-free zones highlights the need of understanding disease limits and distribution mechanisms. Capripox virus, the causal agent, may also cause sheeppox and Goatpox. Even though the virus is expelled through several bodily fluids and excretions, the most common causes of infection include sperm and skin sores. Thus, vulnerable hosts are mostly infected mechanically by hematophagous arthropods such as biting flies, mosquitoes, and ticks. As a result, milk production lowers, abortions, permanent or temporary sterility, hide damage, and mortality occur, contributing to a massive financial loss for countries that raise cattle. These illnesses are economically significant because they affect international trade. The spread of Capripox viruses appears to be spreading because to a lack of effectual vaccinations and poverty in rural areas. Lumpy skin disease has reached historic levels; as a consequence, vaccination remains the only viable option to keep the illness from spreading in endemic as well as newly impacted areas. This study is intended to offer a full update on existing knowledge of the disease's pathological characteristics, mechanisms of spread, transmission, control measures, and available vaccinations.

Review on Mucormycosis: Pathogenesis, Epidemiology, Microbiology and Diagnosis.

Mucormycosis is a serious and invasive fungal infection caused by Mucorales fungi. This review article provides a concise overview of the pathogenesis, epidemiology, microbiology, and diagnosis of mucormycosis. The introduction section highlights the key microbiological properties of the pathogen and delves into the underlying mechanisms of mucormycosis pathogenesis, including the invasion and proliferation of the fungus within the host. The description of the disease section focuses on the epidemiology of mucormycosis, including its incidence, risk factors, and geographical distribution. It also explores the specific context of mucormycosis infection about COVID-19 and diabetes mellitus, highlighting the increased susceptibility observed in individuals with these conditions. A case study illustrates the clinical manifestations and challenges associated with mucormycosis, emphasizing the importance of early detection. Additionally, the review discusses the diagnosis of mucormycosis, emphasizing the significance of clinical assessment, radiological imaging, and microbiological tests for accurate and timely detection of the infection. Regarding treatment, the article covers the various therapeutic approaches, including antifungal therapy, surgical interventions, and management of underlying predisposing conditions. The limitations and challenges associated with treatment options are also addressed. This review aims to provide a comprehensive understanding of mucormycosis, equipping healthcare professionals with valuable insights into its pathogenesis, epidemiology, microbiology, and diagnostic strategies. By enhancing knowledge and awareness of this fungal infection, this review can improve patient outcomes through early diagnosis and appropriate management.

A review on marine source as anticancer agents.

This review investigates the potential of natural compounds obtained from marine sources for the treatment of cancer. The oceans are believed to contain physiologically active compounds, such as alkaloids, nucleosides, macrolides, and polyketides, which have shown promising effects in slowing human tumor cells both in vivo and in vitro. Various marine species, including algae, mollusks, actinomycetes, fungi, sponges, and soft corals, have been studied for their bioactive metabolites with diverse chemical structures. The review explores the therapeutic potential of various marine-derived substances and discusses their possible applications in cancer treatment.

The Potential of Stem Cells in Treating Breast Cancer.

There has been a lot of interest in stem cell therapy as a means of curing disease in recent years. Despite extensive usage of stem cell therapy in the treatment of a wide range of medical diseases, it has been hypothesized that it plays a key part in the progression of cancer. Breast cancer is still the most frequent malignancy in women globally. However, the latest treatments, such as stem cell targeted therapy, are considered to be more effective in preventing recurrence, metastasis, and chemoresistance of breast cancer than older methods like chemotherapy and radiation. This review discusses the characteristics of stem cells and how stem cells may be used to treat breast cancer.

Effect of experimental modulation of mood on exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually-induced mood shifts on exertional dyspnoea in individuals with COPD. METHODS: Following familiarization, 20 participants with mild to severe COPD (age 57-79 years) attended three experimental sessions on separate days, performing two 5-min treadmill exercise tests separated by a 30-min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0-10). Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were measured at 1-min intervals during each test. Mood valence ratings were obtained using Self-Assessment Manikin (SAM) scale (1-9). RESULTS: Mood valence ratings were significantly higher when viewing positive (end-exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty-five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. CONCLUSION: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD.

Examining the role of mood in pain-limited treadmill walking duration in young healthy individuals.

PURPOSE: The purpose of the study was to examine the effects of acute mood modulation on treadmill walking duration during experimental pain application. METHODS: This was a repeated measure, within-subject study design. 30 healthy individuals (Males: Females 16:14; age 22.9 ± 2.5 years; height 170.9 ± 9.5 cm; body mass 68.4 ± 14.6 kg) attended a familiarization session and three experimental sessions, whereby they simultaneously viewed emotionally evoking stimulus from the International Affective Picture System (IAPS) and performed two treadmill walking tests (maximum 10 min duration) with a fixed nociceptive input applied to the thigh (pressure cuff). The primary outcome was treadmill walking duration during pain application to achieve a fixed pain score. During walking, mood (Self-Assessment Manikin: SAM 0-9) and pain (numerical rating scale: NRS 0-10) were measured. RESULTS: Mood valence scores were significantly different in all conditions (p < 0.001), negative (2.4 ± 0.3), neutral (4.9 ± 0.6) and positive (6.6 ± 0.3). There was a significant difference (p = 0.04) in the treadmill walking duration for different mood states. For the primary outcome, post hoc analysis found differences between the negative and positive mood conditions for the treadmill walking durations to reach pain scores of 3 (negative: 224 ± 49 s; positive: 259 ± 60s, effect size [ES]: 0.80), 4 (negative: 262 ± 59 s; positive: 326 ± 90s, ES: 0.92), 5 (negative: 313 ± 86 s; positive: 385 ± 113 s, ES: 0.90), 6 (negative: 367 ± 106 s; positive: 447 ± 113 s, ES: 1.04) and 7 (negative: 423 ± 114 s; positive: 521 ± 110 s, ES: 1.02). There was no significant difference in the treadmill walking duration between the neutral vs negative mood and neutral vs positive mood conditions. CONCLUSION: These results highlight the potential psychophysiological impacts on the pain experience in healthy individuals and encourages pursuit in strategies to minimize pain-limited exercise, a highly prevalent issue in the chronic pain population. SIGNIFICANCE: Walking-based rehabilitation, designed to improve physical activity, has been shown to improve pain and disability. However active participation and adherence in walking-based rehabilitation has shown to be jeopardized by pain and pain-related cognitive and behavioural adaptations. This study examined the effect of a shift in mood on pain perception and treadmill walking tolerance. We found that with a worse mood, individuals were less tolerant of pain and walked on the treadmill for a shorter duration. These results suggest that factors which improve mood should be combined with walking-based training to improve tolerance.

Confidence Interval: Advantages, Disadvantages and the Dilemma of Interpretation.

Confidence interval (CI) is one of the important reporting tools for research data as it not only provides valuable information about the effect size along with its width but also possible clinical significance. Unfortunately, this approach is not being utilized to its fullest extent. Determining point estimate always includes an element of uncertainty due to associated sampling error. A confidence interval may be an appropriate tool to measure this uncertainty. Further, the P value does not convey information about the magnitude of an effect and the error associated with it. Thus, in an ideal situation effect size should preferably be associated with a confidence interval to assess precision. Not only does CI let us assess likely effects but also decides whether the intervention applied could have clinical utility. In contrast, the p-value limits our option to either reject any differences that are not significant or accept those that are. However, confidence intervals are commonly misinterpreted. It is imperative to understand that the CI is not the range of effects that 95% of patients in the population exhibit. Moreover, it would also be erroneous to say that there is a 95% probability that the CI includes the true population effect. Interpretation is usually based on the context in which the confidence interval is being looked at. From a utility point of view and like other statistical tools confidence interval approach does have several advantages as well as disadvantages and is far beyond being a perfect statistical tool.

Unveiling the potential of proteomic and genetic signatures for precision therapeutics in lung cancer management.

Lung cancer's enduring global significance necessitates ongoing advancements in diagnostics and therapeutics. Recent spotlight on proteomic and genetic biomarker research offers a promising avenue for understanding lung cancer biology and guiding treatments. This review elucidates genetic and proteomic lung cancer biomarker progress and their treatment implications. Technological strides in mass spectrometry-based proteomics and next-generation sequencing enable pinpointing of genetic abnormalities and abnormal protein expressions, furnishing vital data for precise diagnosis, patient classification, and customized treatments. Biomarker-driven personalized medicine yields substantial treatment improvements, elevating survival rates and minimizing adverse effects. Integrating omics data (genomics, proteomics, etc.) enhances understanding of lung cancer's intricate biological milieu, identifying novel treatment targets and biomarkers, fostering precision medicine. Liquid biopsies, non-invasive tools for real-time treatment monitoring and early resistance detection, gain popularity, promising enhanced management and personalized therapy. Despite advancements, biomarker repeatability and validation challenges persist, necessitating interdisciplinary efforts and large-scale clinical trials. Integrating artificial intelligence and machine learning aids analyzing vast omics datasets and predicting treatment responses. Single-cell omics reveal cellular connections and intratumoral heterogeneity, valuable for combination treatments. Biomarkers enable accurate diagnosis, tailored medicines, and treatment response tracking, significantly impacting personalized lung cancer care. This approach spurs patient-centered trials, empowering active patient engagement. Lung cancer proteomic and genetic biomarkers illuminate disease biology and treatment prospects. Progressing towards individualized efficient therapies is imminent, alleviating lung cancer's burden through ongoing research, omics integration, and technological strides.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Ocular manifestations in HIV patients attending a tertiary care hospital in Eastern India and correlation of posterior segment lesions with CD4+ counts.

PURPOSE: We aimed to study the ocular manifestations in human immunodeficiency virus (HIV)-infected patients and the correlation of posterior segment lesions with CD4+ counts. METHODS: This hospital-based, cross-sectional study enrolled HIV-positive patients attending the ophthalmology department of a tertiary care hospital in Eastern India. Complete demographic information was obtained for each patient. Comprehensive ophthalmic evaluation was done in each case. RESULTS: A total of 184 HIV-positive patients were enrolled in the study. Ocular manifestations were detected in 62 cases. The prevalence of ocular manifestations in the present study was 33.69%. Mean age of patients included in the study was 34.8 ± 10.77 years. Prevalence of ocular manifestations was highest in the age group of 30-39 years (41.93%). Highest prevalence of ocular manifestations was noted in patients with low level of education and poor socioeconomic status. Sexual transmission was the major route of HIV transmission (in 92% of cases). Posterior segment lesions were seen in 69.35% of cases. HIV retinopathy was the most common posterior segment manifestation noted in 25 eyes. Significant positive correlation was noted between severities of posterior segment findings and CD4+ counts, which we found to increase with decrease in CD4+ counts (P < 0.001). CONCLUSION: Detailed ophthalmic evaluation including fundus examination is must in all cases of HIV/acquired immunodeficiency syndrome (AIDS) patients as it may help in early diagnosis, treatment, and prevention of sight-threatening complications due to opportunistic infections.