ABSTRACT
Personalized medicine, which involves modifying treatment strategies/drug dosages based on massive laboratory/imaging data, faces large statistical and study design problems. The authors believe that the use of continuous multidimensional data, such as those regarding gut microbiota, or binary multidimensional systems properly transformed into a continuous variable, such as the epigenetic clock, offer an advantageous scenario for the design of trials of personalized medicine. We will discuss examples focusing on kidney diseases, specifically on IgA nephropathy. While gut dysbiosis can provide a treatment strategy to restore the standard gut microbiota using probiotics, transforming epigenetic omics data into epigenetic clocks offers a promising tool for personalized acute and chronic kidney disease care. Epigenetic clocks involve a complex transformation of DNA methylome data into estimated biological age. These clocks can identify people at high risk of developing kidney problems even before symptoms appear. Some of the effects of both the epigenetic clock and microbiota on kidney diseases seem to be mediated by endothelial dysfunction. These "big data" (epigenetic clocks and microbiota) can help tailor treatment plans by pinpointing patients likely to experience rapid declines or those who might not need overly aggressive therapies.
Subject(s)
Epigenesis, Genetic , Gastrointestinal Microbiome , Kidney Diseases , Precision Medicine , Humans , Precision Medicine/methods , Gastrointestinal Microbiome/genetics , Kidney Diseases/microbiology , Kidney Diseases/genetics , Kidney Diseases/therapy , Microbiota , DNA Methylation , Epigenomics/methods , Dysbiosis/microbiology , AnimalsABSTRACT
Leiomyoma of the urinary bladder in the pediatric age group is one of the rarest tumors with only 2 case reports in the English literature. Rhabdomyosarcoma is the commonest tumor at this site in this age group. It needs to be distinguished from rhabdomyosarcoma by histomorphology for appropriate treatment and management. We report the third case of urinary bladder leiomyoma arising in a 6-year-old boy with a short review of the literature.
Subject(s)
Leiomyoma , Rhabdomyosarcoma , Urinary Bladder Neoplasms , Child , Humans , Leiomyoma/metabolism , Leiomyoma/pathology , Male , Rhabdomyosarcoma/metabolism , Rhabdomyosarcoma/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Patient safety is the major concern in providing quality care. Medication errors have been identified as the most common type of preventable errors. This study aimed to assess the knowledge and perception regarding medication error among nurses. METHODS: A quantitative cross-sectional research design was used. The study was conducted in four different private hospitals in Lalitpur. A total enumerative sampling technique was used to select 302 nurses from these hospitals. Descriptive statistical methods were used to assess socio-demographic variables and inferential statistics methods such as the chi-squared test was used to analyse the association between knowledge, perception, and its socio-demographic characteristics. RESULTS: Most of the respondents 244 (80.8%) agreed the cause of medication error occurs due to unclear handwriting and 217 (71.9%) agreed prescribing the wrong route or dose and time. Mostly respondents 126 (41.7%) had inadequate knowledge, 101 (33.4%) had adequate knowledge and 75 (24.8%) had moderate knowledge on medication error. Mostly respondents 273 (90.4%) had positive perception and 26 (8.6 %) had negative perception. CONCLUSIONS: Most of the nurses had inadequate knowledge but has positive perception on medication error. Appropriate strategies for reducing nurses' workload, barriers to reporting, and sensitization workshops in a regular basis by the administrator should be developed to address medication errors and enhance patient safety in hospital settings.
Subject(s)
Medication Errors , Patient Safety , Humans , Cross-Sectional Studies , Nepal , Medication Errors/prevention & control , PerceptionABSTRACT
[This corrects the article DOI: 10.1016/j.ekir.2024.02.1344.].
ABSTRACT
Cancer is among the leading causes of mortality and morbidity in the world. Metallic nanoparticles, especially gold nanoparticles (AuNPs) have emerged to be attractive systems to circumvent the associated adverse effects. By the virtue of their unique properties of tunable size, shape, composition, optical properties, biocompatibility, minimal toxicity, multivalency, fluorescence-luminescence property and surface plasmon resonance; AuNPs have the potential to be used as drug delivery systems. It is vital to ensure that the drug reaches the target site of action for selective kill of cancer cells without harm to healthy cells. These AuNPs can be easily functionalized with a wide array of ligands like peptides, oligonucleotides, polymers, carbohydrates for active targeting to ensure site specific delivery and reduced systemic effects. AuNPs have been in-vestigated as carriers for gene delivery, drug delivery with or without photothermal therapy, in diagnosis based on radiation or spectroscopy. They have emerged as attractive theranostic approach in the overall management of cancer with superior benefit to risk features. In this review, we have discussed synthesis of different AuNPs (nanorods, spherical nanoparticles, and hollow AuNPs), their functionalization strategies and their applications in biomedical domain. Various research studies and clinical trials on application of AuNPs in diagnosis and therapeutics are highlighted.
Subject(s)
Drug Delivery Systems , Gold , Metal Nanoparticles , Neoplasms , Theranostic Nanomedicine , Gold/chemistry , Gold/administration & dosage , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/administration & dosage , Neoplasms/therapy , Neoplasms/drug therapy , Theranostic Nanomedicine/methods , Animals , Drug Delivery Systems/methods , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Drug Carriers/chemistryABSTRACT
Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolytes, such as calcium and hydrogen ions, potassium, and sodium, as well as other osmotic substances, affect the swelling of mitochondria. Intracellular glucose levels may also affect mitochondrial swelling, although the relationship between mitochondrial ion homeostasis and intracellular glucose is poorly understood. This article reviews what is currently known about how the Sodium-Glucose transporter (SGLT) may impact mitochondrial sodium (Na+) homeostasis. SGLTs regulate intracellular glucose and sodium levels and, therefore, interfere with mitochondrial ion homeostasis because mitochondrial Na+ is closely linked to cytoplasmic calcium and sodium dynamics. Recently, a large amount of data has been available on the effects of SGLT2 inhibitors on mitochondria in different cell types, including renal proximal tubule cells, endothelial cells, mesangial cells, podocytes, neuronal cells, and cardiac cells. The current evidence suggests that SGLT inhibitors (SGLTi) may affect mitochondrial dynamics regarding intracellular Sodium and hydrogen ions. Although the regulation of mitochondrial ion channels by SGLTs is still in its infancy, the evidence accumulated thus far of the effect of SGLTi on mitochondrial functions certainly will foster further research in this direction.
Subject(s)
Mitochondria , Mitochondria/metabolism , Humans , Animals , Sodium/metabolism , Sodium-Glucose Transporter 2/metabolism , Glucose/metabolism , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , HomeostasisABSTRACT
Biliary adenofibroma (BAF) is an uncommon liver tumor with a high propensity for malignant transformation. The histomorphology of BAF with malignant transformation can show a spectrum of changes ranging from benign, dysplastic to frank malignancy. Thus, the diagnosis of BAF imposes the pursuit of dysplasia/ malignancy focus. We presented a case of intrahepatic cholangiocarcinoma arising from BAF in a 49-year-old woman with detailed histomorphology. We also performed a PubMed database search and tabulated all previously reported cases of BAF with dysplasia/ malignant transformation. A statistic comparison of age, sex ratio, size of the tumor, and survival following complete resection between BAFs with and without dysplasia/ malignancy from the retrieved data is presented. Our analysis did not highlight any statistically significant difference between BAFs with and without dysplasia/ malignancy in age, sex ratio, tumor size, and survival following complete surgical resection. Our study highlights the histopathology and immunohistochemistry of a case of BAF with malignant transformation and highlights the importance of this diagnosis in management. Further longitudinal studies on a larger cohort of patients are required to validate our findings.
ABSTRACT
Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.
ABSTRACT
Deoxyglucose conjugated nanoparticles with persistent luminescence have shown theragnostic potential. In this study, deoxyglucose-conjugated nano-particles with persistent luminescence properties were synthesized, and their theragnostic potential was evaluated in fibrosarcoma cancer cells and a tumor model. The uptake of nano-formulation was found to be higher in mouse fibrosarcoma (WEHI-164) cells cultured in a medium without glucose. Nanoparticles showed a higher killing ability for cancer cells compared to normal cells. A significant accumulation of nanoparticles to the tumor site in mice was evident by the increased tumor/normal leg ratio, resulting in a significant decrease in tumor volume and weight. Histopathological studies showed a significant decrease in the number of dividing mitotic cells but a greater number of apoptotic/necrotic cells in nanoparticle-treated tumor tissues, which was correlated with a lower magnitude of Ki-67 expression (a proliferation marker). Consequently, our results showed the potential of our nano-formulation for cancer theragnosis.
ABSTRACT
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age with increased incidence of emotional disturbances and other psychopathology. We undertook this research to study the prevalence and severity of depression and anxiety as well as understand body image disturbances and self-esteem of the women of PCOS. We studied the relationship of depressive symptoms with self-esteem and body image disturbances. METHOD: A total of 105 patients diagnosed as PCOS were recruited from gynecology OPD after informed consent and ethics approval. A proforma along with Beck's Depression Inventory, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Body Image Concern Inventory and Rosenberg' s Self-Esteem Scale were administered to patients for further assessment. RESULTS: In total, 54 (51.43%) patients of PCOS had depression on BDI, 12( 11.43%) patients had body image disturbances an d 23 (21.90%) patients had a low self-esteem. A total of 21 patients( 20%) had mild and moderate depression while 5% had severe depression. Majority 53 (50.48%) of our patients had mild anxiety whereas severe to extreme anxiety was seen in about 31% of patients. Body image disturbances were seen in only 12(11.43%) patients and low self-esteem was present in 23 patients. No statistically significant correlation of depression was seen with body image or self-esteem. CONCLUSIONS: The results of this study indicate that there is a high prevalence of depression and anxiety in patients of PCOS than body image concerns and low self-esteem. Prognosis for patients would improve by liaison between gynecologist and psychiatrist.
ABSTRACT
The nonhomologous end-joining pathway is a primary DNA double-strand break repair pathway in eukaryotes. DNA ligase IV (Lig4) catalyzes the final step of DNA end ligation in this pathway. Partial loss of Lig4 in mammals causes Lig4 syndrome, while complete loss is embryonically lethal. DNA ligase 4 (DNAlig4) null Drosophila melanogaster is viable, but sensitive to ionizing radiation during early development. We proposed to explore if DNAlig4 loss induced other long-term sensitivities and defects in D. melanogaster. We demonstrated that DNAlig4 mutant strains had decreased lifespan and lower resistance to nutrient deprivation, indicating Lig4 is required for maintaining health and longevity in D. melanogaster.
Subject(s)
Drosophila melanogaster , Longevity , Animals , DNA End-Joining Repair , DNA Ligase ATP/genetics , DNA Ligase ATP/metabolism , DNA Ligases/genetics , DNA Ligases/metabolism , DNA Repair/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Longevity/genetics , Mutation , NutrientsABSTRACT
Monodispersed core@shell γ-Fe2O3@MnxOy nanoparticles have been prepared through thermolysis of iron and manganese oleate. Further, these prepared nanoparticles are coated with biocompatible substances such as silica and polyethylene glycol. These particles are highly biocompatible for different cell lines such as normal and cancer cell lines. The nanoparticles are used as hyperthermia agents, and successful hyperthermia treatment in cancer cells is carried out. As compared to γ-Fe2O3@SiO2, γ-Fe2O3@MnxOy@SiO2 shows the enhanced killing of cancer cells through hyperthermia. In order to make them potential candidates for targeting to cancer cells, folic acid (FA) is tagged to the nanoparticles. Fluorescein isothiocyanate (FITC) is also tagged onto these nanoparticles for imaging. The developed γ-Fe2O3@MnxOy@SiO2 nanoparticle can act as a single entity for therapy through AC magnetic field, imaging through FITC and targeting through folic acid simultaneously. This is the first report on this material, which is highly biocompatible for hyperthermia, imaging, and targeting.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Humans , Silicon Dioxide , Fluorescein-5-isothiocyanate , Hyperthermia , Nanoparticles/therapeutic use , Folic Acid , FluoresceinABSTRACT
The oncogene Ras and the tumor suppressor gene p53 are frequently co-mutated in human cancer and mutations in Ras and p53 can cooperate to generate a more malignant cell state. To discover novel druggable targets for cancers carrying co-mutations in Ras and p53, we performed arrayed, kinome focused siRNA and oncology drug phenotypic screening utilizing a set of syngeneic Ras mutant squamous cell carcinoma (SCC) cell lines that also carried co-mutations in selected p53 pathway genes. These cell lines were derived from SCCs from carcinogen-treated inbred mice which harbored germline deletions or mutations in Trp53, p19Arf, Atm, or Prkdc. Both siRNA and drug phenotypic screening converge to implicate the phosphoinositol kinases, receptor tyrosine kinases, MAP kinases, as well as cell cycle and DNA damage response genes as targetable dependencies in SCC. Differences in functional kinome profiles between Ras mutant cell lines reflect incomplete penetrance of Ras synthetic lethal kinases and indicate that co-mutations cause a rewiring of survival pathways in Ras mutant tumors. This study describes the functional kinomic landscape of Ras/p53 mutant chemically-induced squamous cell carcinoma in both the baseline unperturbed state and following DNA damage and nominates candidate therapeutic targets, including the Nek4 kinase, for further development.
Subject(s)
Carcinoma, Squamous Cell , Tumor Suppressor Protein p53 , ras Proteins , Animals , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16/genetics , Humans , Mice , Mutation , RNA, Small Interfering , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , ras Proteins/geneticsABSTRACT
YVO4:Ho3+/Yb3+ nanophosphors prepared by an effective polyol-mediated route show dual-mode behavior in photoluminescence. Upon 980 nm excitation, the upconversion red emission spectrum exhibits a bright red peak at â¼650 nm, characteristic of the electronic transition of the Ho3+ ion via involvement of two-photon absorption, which has been confirmed by the power-dependent luminescence study. Moreover, at 300 nm excitation, downconversion emission peaks are observed at 550, 650, and â¼755 nm. The nonradiative resonant energy transfer occurs from the V-O charge transfer band to Ho3+ ions, resulting in an improved emission of Ho3+ ions. Moreover, polyethylene glycol-coated nanoparticles make it suitable for water dispersibility; and these particles are conjugated with Fe3O4 nanoparticles to form magnetic-luminescent hybrid nanoparticles. Highly water-dispersible magnetic-luminescent hybrid material attained the hyperthermia temperature (â¼42 °C) under an applied AC magnetic field. The specific absorption rate value is found to be high (138 W/g), which is more than that of pure superparamagnetic Fe3O4 nanoparticles. At 300 nm excitation, the high quantum yield value of â¼27% is obtained from YVO4:Ho3+/Yb3+, which suggests that it is a good phosphor material. By employing the neutron activation analysis technique, it is shown that nanophosphor particles can absorb Au3+ up to the ppm level. Interestingly, such nanophosphor also shows the potentiality for anticounterfeiting applications.
ABSTRACT
Nanocrystals having single-band red emission under near-infrared (NIR) excitation through the upconversion process offer great advantages in terms of enhanced cellular imaging in in vitro and in vivo experiments in the biological window (600-900 nm), as a security ink, in photothermal therapy (PTT), in photodynamic therapy (PDT), and so forth but are challenging for materials scientists. In this work, we report for the first time the preparation of a super bright red emitter at 655 nm from monodispersed NaErF4:0.5%Tm@NaYF4:20%Yb nanocrystals (core@active shell). This phosphor exhibits 35 times stronger photoluminescence as compared to NaErF4:0.5%Tm@NaYF4 (core@inactive shell). Here, an Er3+-enriched host matrix works simultaneously as an activator and a sensitizer under NIR excitation. Upconversion red emission at 655 nm arises due to the electronic transition of Er3+ via the involvement of a three-photon absorption (expected to be a two-photon absorption), which has been confirmed via a power-dependent luminescence study. Tm3+ ions incorporated into the core with the active shell act as trapping centers, which promote the red band emission via the back-energy transfer process. Moreover, the active shell containing Yb3+ ions efficiently transfers the energy to the Er3+-enriched core, which suppresses the nonradiative channel rate, and Tm3+ ions act as trapping centers, which reduce the luminescence quenching via reduction of energy migration to the surface of the host lattice. Also, we have shown the potential applications of these nanocrystals: cellular imaging through downconversion and upconversion processes and security ink.
Subject(s)
Erbium/chemistry , Fluorides/chemistry , Luminescent Agents/chemistry , Nanoparticles/chemistry , Ytterbium/chemistry , Yttrium/chemistry , A549 Cells , Energy Transfer , Humans , Luminescence , Luminescent Measurements , MCF-7 Cells , Optical ImagingABSTRACT
UNLABELLED: Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War. METHODS AND MATERIALS: Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure. RESULTS: A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene. DISCUSSION: The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.
Subject(s)
Chemical Warfare Agents/toxicity , Lung Neoplasms/chemically induced , Mustard Gas/toxicity , Adult , Aged , Genes, p53 , Humans , Inhalation Exposure , Lung Neoplasms/genetics , Male , Middle Aged , MutationABSTRACT
DNA damage is a hallmark of cancer, and mutation and misregulation of proteins that maintain genomic fidelity are associated with the development of multiple cancers. DNA double strand breaks are arguably considered the most deleterious type of DNA damage. The nonhomologous end-joining (NHEJ) pathway is one mechanism to repair DNA double strand breaks, and proteins involved in NHEJ may also regulate DNA replication. We previously established that DNA-PKcs, a NHEJ protein, promotes genomic stability and cell viability following cellular exposure to replication stress; we wanted to discern whether another NHEJ protein, DNA ligase IV (Lig4), shares this phenotype. Our investigations focused on triple negative breast cancer cells, as, compared to nonbasal breast cancer, LIG4 is frequently amplified, and an increased gene dose is associated with higher Lig4 expression. We depleted Lig4 using siRNA and confirmed our knockdown by qPCR and western blotting. Cell survival diminished with Lig4 depletion alone, and this was associated with increased replication fork stalling. Checkpoint protein Chk1 activation and dephosphorylation were unchanged in Lig4-depleted cells. Lig4 depletion resulted in sustained DNA-PKcs phosphorylation following hydroxyurea exposure. Understanding the effect of Lig4 on genomic replication and the replication stress response will clarify the biological ramifications of inhibiting Lig4 activity. In addition, Lig4 is an attractive clinical target for directing CRISPR/Cas9-mediated repair towards homology-directed repair and away from NHEJ, thus understanding of how diminishing Lig4 impacts cell biology is critical.
ABSTRACT
ABSTRACT Biliary adenofibroma (BAF) is an uncommon liver tumor with a high propensity for malignant transformation. The histomorphology of BAF with malignant transformation can show a spectrum of changes ranging from benign, dysplastic to frank malignancy. Thus, the diagnosis of BAF imposes the pursuit of dysplasia/ malignancy focus. We presented a case of intrahepatic cholangiocarcinoma arising from BAF in a 49-year-old woman with detailed histomorphology. We also performed a PubMed database search and tabulated all previously reported cases of BAF with dysplasia/ malignant transformation. A statistic comparison of age, sex ratio, size of the tumor, and survival following complete resection between BAFs with and without dysplasia/ malignancy from the retrieved data is presented. Our analysis did not highlight any statistically significant difference between BAFs with and without dysplasia/ malignancy in age, sex ratio, tumor size, and survival following complete surgical resection. Our study highlights the histopathology and immunohistochemistry of a case of BAF with malignant transformation and highlights the importance of this diagnosis in management. Further longitudinal studies on a larger cohort of patients are required to validate our findings.
ABSTRACT
ABSTRACT Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.