ABSTRACT
Rapid and accurate quantification of low-abundance protein biomarkers in biofluids can transform the diagnosis of a range of pathologies, including infectious diseases. Here, we harness ultrabright plasmonic fluors as "digital nanolabels" and demonstrate the detection and quantification of subfemtomolar concentrations of human IL-6 and SARS-CoV-2 alpha and variant proteins in clinical nasopharyngeal swab and saliva samples from COVID-19 patients. The resulting digital plasmonic fluor-linked immunosorbent assay (digital p-FLISA) enables detection of SARS-CoV-2 nucleocapsid protein, both in solution and in live virions. Digital p-FLISA outperforms the "gold standard" enzyme-linked immunosorbent assay (ELISA), having a nearly 7000-fold lower limit-of-detection, and outperforms a commercial antigen test, having over 5000-fold improvement in analytical sensitivity. Detection and quantification of very low concentrations of target proteins holds potential for early detection of pathological conditions, treatment monitoring, and personalized medicine.
Subject(s)
COVID-19 , Humans , Enzyme-Linked Immunosorbent Assay , COVID-19/diagnosis , Fluoroimmunoassay , SARS-CoV-2 , Biomarkers , Sensitivity and SpecificityABSTRACT
Introduction: The impact of the coronavirus 2 (SARS-CoV-2) pandemic and the effect of preventive health strategies on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are largely unknown. The public health model imposed during the pandemic and the lessons learnt have implications on recommending future preventive strategies for COPD care in general and exacerbations in particular. Aim: This study endeavors to assess the role of preventive strategies of COVID-19 on exacerbation rates of COPD during the lockdown period compared to similar periods the previous year and assess the compliance to preventive strategies for COVID-19 among COPD patients. Methods: This is a hospital-based descriptive cross-sectional study at a tertiary care center. AECOPD in patients during a period spanning five months in the pre-lockdown days was compared with exacerbation rates for a similar period during the national lockdown. Results: Sixty-eight patients were recruited (mean age: 67.38) among whom 47 were males and 21 were females. There were only 7 (10.3%) reported admissions during the lockdown period of 5 months compared to 50 (73.5%) during the corresponding period pre-lockdown. Mild exacerbations reported during the lockdown period were also significantly less with only 17 (25%) against 58 (85.3%) during the pre-lockdown period. Adherence to measures such as donning of masks, hand hygiene, and social distancing was observed among COPD patients with good compliance to the health practices promulgated in the pandemic. Discussion: A significant reduction in exacerbation rates among AECOPD patients during the period of lockdown was observed compared to a similar period the year prior. Noticeable were the findings that both community-based milder exacerbations and severe exacerbations necessitating hospitalizations showed a reduction during the period of lockdown. Adaptability, compliance and acceptance to usage of masks, hand hygiene measures, and norms such as physical distancing were observed in the majority of COPD patients.
Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Female , Male , Humans , Aged , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Pandemics , Cross-Sectional Studies , Communicable Disease Control , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , India/epidemiologyABSTRACT
Nanotechnology-enabled neuromodulation is a promising minimally-invasive tool in neuroscience and engineering for both fundamental studies and clinical applications. However, the nano-neuro interaction at different stages of maturation of a neural network and its implications for the nano-neuromodulation remain unclear. Here, we report heterogeneous to homogeneous transformation of neuromodulation in a progressively maturing neural network. Utilizing plasmonic-fluors as ultrabright fluorescent nanolabels, we reveal that negative surface charge of nanoparticles renders selective nano-neuro interaction with a strong correlation between the maturation stage of the individual neurons in the neural network and the density of the nanoparticles bound on the neurons. In stark contrast to homogeneous neuromodulation in a mature neural network reported so far, the maturation-dependent density of the nanoparticles bound to neurons in a developing neural network resulted in a heterogeneous optical neuromodulation (i.e., simultaneous excitation and inhibition of neural network activity). This study advances our understanding of nano-neuro interactions and nano-neuromodulation with potential applications in minimally-invasive technologies for treating neuronal disorders in parts of the mammalian brain where neurogenesis persists throughout aging.
Subject(s)
Neurology , Neurons , Animals , Neurons/metabolism , Neurogenesis/physiology , Brain/metabolism , Nanotechnology , MammalsABSTRACT
Expansion microscopy (ExM) is a rapidly emerging super-resolution microscopy technique that involves isotropic expansion of biological samples to improve spatial resolution. However, fluorescence signal dilution due to volumetric expansion is a hindrance to the widespread application of ExM. Here, we introduce plasmon-enhanced expansion microscopy (p-ExM) by harnessing an ultrabright fluorescent nanoconstruct, called plasmonic-fluor (PF), as a nanolabel. The unique structure of PFs renders nearly 15000-fold brighter fluorescence signal intensity and higher fluorescence retention following the ExM protocol (nearly 76%) compared to their conventional counterparts (<16% for IR-650). Individual PFs can be easily imaged using conventional fluorescence microscopes, making them excellent "digital" labels for ExM. We demonstrate that p-ExM enables improved tracing and decrypting of neural networks labeled with PFs, as evidenced by improved quantification of morphological markers (nearly a 2.5-fold increase in number of neurite terminal points). Overall, p-ExM complements the existing ExM techniques for probing structure-function relationships of various biological systems.
Subject(s)
Coloring Agents , Microscopy, Fluorescence/methodsABSTRACT
BACKGROUND: The infant and young child feeding practices (IYCF) decide child growth and well-being. Paternal perspectives and involvement in IYCF are of paramount importance and are grossly under-studied. AIMS: To study the experiences and opinions of fathers of infants and young children towards feeding practices. SETTINGS AND DESIGN: Two focus group discussions (FGD) were carried out in the community settings in Dakshina Kannada District, Karnataka State. METHODS AND MATERIAL: FGDs were carried out in the areas of two selected primary health centres. FGD guide was used and the discussions were audio recorded. Themes were derived from the transcript. RESULTS: Four main themes were generated from the transcripts of two FGDs. Lack of time to involve in child feeding, lack of felt need for increased involvement, sense of being complete in providing paternal care and readiness to learn were the generated themes. All participating fathers had favourable attitudes towards learning more about IYCF. CONCLUSIONS: Lack of time felt need for higher paternal involvement in IYCF and sense of being complete in providing paternal care were the themes extracted, along with favourable attitude towards increasing their involvement in IYCF.
Subject(s)
Breast Feeding , Child Nutritional Physiological Phenomena , Infant , Female , Child , Humans , Child, Preschool , Health Promotion/methods , India , Nutrition Policy , Feeding Behavior , MothersABSTRACT
Background: Tuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019. Methods: We obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Findings: There were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980. Interpretation: BRICS' actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country. Funding: National Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.
ABSTRACT
Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of proteins secreted by single cells, to study cell-to-cell heterogeneity in secretion, or to detect proteins of low abundance or incipient secretion. Here, we introduce the "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging of protein secretion. We find that plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise compared with conventional fluorescence labels. We demonstrate high-resolution imaging of different secreted cytokines in the single-plexed and spectrally multiplexed FluoroDOT assay that revealed cellular heterogeneity in secretion of multiple proteins simultaneously. Using diverse biochemical stimuli, including Mycobacterium tuberculosis infection, and a variety of immune cells such as macrophages, dendritic cells (DCs), and DC-T cell co-culture, we demonstrate that the assay is versatile, facile, and widely adaptable for enhancing biological understanding of spatial and temporal dynamics of single-cell secretome.
Subject(s)
Cytokines , Tuberculosis , Humans , Cytokines/metabolism , Tuberculosis/metabolism , Macrophages , T-Lymphocytes/metabolismABSTRACT
Background: Overall child health depends on nutrition and its related practices. At the family level, responsibility of child feeding lies with both parents. There is no uniform and systematic way to determine and assess the practices of fathers in infant and young child feeding (IYCF). Also, there is a paucity of evidence related to interventions for fathers in improving their practices and involvement in the feeding of their infant or young child (aged less than two years). Methods: This was a community-based randomized control trial, conducted among 120 fathers with infants and/or young children in Dakshina Kannada District of Karnataka. Fathers with poor level of involvement and practices towards IYCF, during the initial assessment, were included as the study participants. For the intervention, a module in the flipchart format was developed. Simple randomization technique was used to allot the participants into two groups - intervention and control. Participants in the intervention group received module intervention, in addition to the care which they received routinely, and the control group received only routine care. The participants in the intervention group were paid a monthly visit to implement the module, for six months. The post-intervention assessment was done at the end of 6 months. Results: A total of 117 participants provided post-intervention data. The mean age was 34.7 (+/- 5.48) years in the intervention group and 34.36 years (+/- 5.26) in the control group. The intervention group had a significant improvement in knowledge, attitude, and practice components at 6 months. We noted higher change scores for the intervention group (p<0.05). Conclusions: The extent of increase in practice and involvement in child feeding was clearly higher among the intervention group. The module developed was successful in improving the practices of fathers in feeding their infants and young children. Clinical Trials Registry India: CTRI/2017/06/008936 (29/06/2017).
Subject(s)
Infant Nutritional Physiological Phenomena , Nutritional Status , Adult , Child , Child, Preschool , Fathers , Humans , India , Infant , Male , ParentsABSTRACT
Novel methods that enable facile, ultrasensitive and multiplexed detection of low molecular weight organic compounds such as metabolites, drugs, additives, and organic pollutants are valuable in biomedical research, clinical diagnosis, food safety and environmental monitoring. Here, we demonstrate a simple, rapid, and ultrasensitive method for detection and quantification of small molecules by implementing a competitive immunoassay with an ultrabright fluorescent nanolabel, plasmonic fluor. Plasmonic-fluor is comprised of a polymer-coated gold nanorod and bovine serum albumin conjugated with molecular fluorophores and biotin. The synthesis steps and fluorescence emission of plasmonic-fluor was characterized by UV-vis spectroscopy, transmission electron microscopy, and fluorescence microscopy. Plasmon-enhanced competitive assay can be completed within 20 min and exhibited more than 30-fold lower limit-of-detection for cortisol compared to conventional competitive ELISA. The plasmon-enhanced competitive immunoassay when implemented as partition-free digital assay enabled further improvement in sensitivity. Further, spatially multiplexed plasmon-enhanced competitive assay enabled the simultaneous detection of two analytes (cortisol and fluorescein). This simple, rapid, and ultrasensitive method can be broadly employed for multiplexed detection of various small molecules in research, in-field and clinical settings.
Subject(s)
Biosensing Techniques , Nanotubes , Biological Assay , Gold , ImmunoassayABSTRACT
BACKGROUND: HIV is an infectious disease affecting 36.7 million people worldwide. In recent times, Antiretroviral Therapy (ART) has become accessible to the majority of People Living with HIV (PLHIV) and this has transformed the course of infection to one that is chronic, characterized by fewer diseases pathognomonic of AIDS. In view of this, there is a pressing need for better markers, apart from the routine HIV indicators, to detect comorbidities such as Neurocognitive Impairment (NCI). The aim of this study was to find out the association between Veterans Aging Cohort Study (VACS) index and Neurocognitive function in HIV positive patients. METHODS: In our study, we included 97 HIV positive patients and their Neurocognitive function was assessed using a combination of Montreal Cognitive Assessment and Grooved Pegboard Test, while VACS index was calculated using the most recent laboratory values. Binomial Logistics Regression analyses, adjusting for potential confounding variables, was performed to determine the association between VACS score and Neurocognitive Impairment. RESULTS: We found that a higher VACS Index was associated with global and domain-wise Neurocognitive impairment (p < 0.01), specifically in the domains of attention (p < 0.01) and fine motor skills (p = 0.01). Our study also showed that among all the VACS components, older age (p = 0.02) and lower hemoglobin (p < 0.01) values were associated with global NCI. After plotting an ROC curve, a VACS cut-off score of 11.00 was identified as it had good sensitivity (87.0%) and specificity (71.4%) in identifying Global NCI. CONCLUSION: Our findings extend prior research on the use of VACS Index to predict global and domain-wise NCI in HIV-positive patients. However, further research with more comprehensive neurocognitive testing is required in our setting before VACS Index can be used as a tool to screen for neurocognitive dysfunction among PLHIV.
Subject(s)
Cognition , HIV Infections , Veterans , Aging , Cohort Studies , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , India/epidemiologyABSTRACT
Context: The feeding practices during first 2 years of life determine the overall health and survival during childhood and beyond. Child nutrition is responsibility of both parents and so far emphasis has been laid mostly on mothers. Fathers' involvement toward Infant and Young child feeding (IYCF) has been proved to be of paramount importance and yet it is given limited importance. Objectives: This study aims to study the level of paternal involvement toward IYCF and its associated factors and to assess the knowledge, attitude, and practices toward IYCF in Dakshina Kannada District in South Indian State of Karnataka. Settings and Design: This community-based cross-sectional study was conducted in the coastal District of Dakshina Kannada; Karnataka State in India. Methods: The study included 450 fathers of infant and young children (aged <2 years) in five taluks of Dakshina Kannada district. They were assessed for knowledge, attitude, and practices related to IYCF. Median score for the practice component was considered cut off to classify involvement in IYCF. Data were analyzed using IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. Chi-square-test and Binary Logistic Regression with Hosmer-Lemeshow goodness-of-fit model were used. Unadjusted and adjusted odds ratios were generated. A p-value of <0.05 was considered statistically significant. Results: Mean age of the study population was 34.6 years (SD, 5.4). The practice scores median (IQR) was 34.0 (IQR, 31.0-39.0), and 40.9% of the participants had poor involvement in IYCF. This was significantly higher among fathers from predominantly urban area. Those who had education above graduation and younger fathers had better involvement in IYCF. Conclusions: Less than half of fathers had poor involvement in IYCF, and it was lower among fathers from urban areas, higher age, and lower educational levels.
Subject(s)
Fathers , Mothers , Adult , Child , Child, Preschool , Cross-Sectional Studies , Feeding Behavior , Female , Humans , India , Infant , MaleABSTRACT
Background: The major determinant to the well-being of infants and young children (IYC) is their feeding practices. These practices are the responsibility of both parents, meaning that fathers have an equal role to mothers. Fathers' involvement can have an impact on the overall health of the children. Despite this, paternal involvement towards IYC feeding (IYCF) have not been studied adequately. Methods: This randomized control trial (n=120) will be conducted among fathers of infants (children aged <1 year) and young children (children aged 12-23 months) in selected households in Dakshina Kannada District of the southern Indian State of Karnataka. The study will be conducted after an initial baseline assessment on awareness, attitude and involvement of fathers in IYCF. Fathers with scores less than the 50 th percentile in the practice component will be categorized as fathers with poor involvement and will be potential participants for the trial. A visual module will be developed and validated for improving paternal involvement in IYCF. Using a simple randomization technique, the participants will be allocated to modular intervention and control group (1:1 allocation). Each participant in the intervention arm will be visited once a month to implement the module, for six months on a one-to-one basis. Following the intervention, a post-test assessment will be done for both groups to measure the level of paternal involvement in IYCF. Ethics and dissemination: Approval has been obtained from the Institutional Ethics Committee of Kasturba Medical College, Mangalore, India. The dissemination plans include scientific conferences and publication in scientific journals. Registration: The study is registered with Clinical Trial Registry of India ( CTRI/2017/06/008936).
Subject(s)
Fathers , Mothers , Child , Child, Preschool , Educational Status , Feeding Behavior , Female , Humans , India , Infant , Male , Randomized Controlled Trials as TopicABSTRACT
The world stunned by a pandemic of such cataclysmic scale is reeling under the joint burden of health impact unleashed by the diseases and the strain on the economy. Glaring shortfalls and inconsistencies in strategies to combat the pandemic have surfaced worldwide irrespective of the country's economic and health care status. The responses have vacillated from mute to drastic. Gaps in health preparedness coupled with administrative tardiness, lack of co-ordination and foresight has heightened the impact of pandemic. Coordinated holistic approach with structured policies in place is the need of the hour. Surveillance and epidemiological models to predict the unpredictable and preempt the backlash will dictate our future successes and failures in this protracted fight against the pandemic. This article attempts to review the present status of health policy on COVID in general and with specific reference to India and their outcome thus far. We also propose a simple and practical framework on which a decisive, well-knit, reliable and acceptable policy can be framed.
Subject(s)
COVID-19/epidemiology , Health Policy/trends , Humans , India/epidemiology , Pandemics/prevention & control , SARS-CoV-2ABSTRACT
The detection and quantification of protein biomarkers in interstitial fluid is hampered by challenges in its sampling and analysis. Here we report the use of a microneedle patch for fast in vivo sampling and on-needle quantification of target protein biomarkers in interstitial fluid. We used plasmonic fluor-an ultrabright fluorescent label-to improve the limit of detection of various interstitial fluid protein biomarkers by nearly 800-fold compared with conventional fluorophores, and a magnetic backing layer to implement conventional immunoassay procedures on the patch and thus improve measurement consistency. We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum-a challenging site for biomarker detection-and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids. Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.
Subject(s)
Biomarkers/analysis , Extracellular Fluid/chemistry , Microtechnology/instrumentation , Needles , Animals , Cocaine/analysis , Cytokines/analysis , Equipment Design , Female , Fluorescent Dyes/chemistry , Immunosorbent Techniques/instrumentation , Limit of Detection , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
Herein, the recent advances in realizing highly efficient cellulose-based solar evaporators for alleviating the global water crisis are summarized. Fresh water scarcity is one of the most threatening issues for sustainable development. Solar steam generation, which harnesses the abundant sunlight, has been recognized as a sustainable approach to harvest fresh water. In contrast to synthetic polymeric materials that can pose serious negative environmental impacts, cellulose-based materials, owing to their biocompatibility, renewability, and sustainability, are highly attractive for realizing solar steam generators. The molecular and macromolecular features of cellulose and the physicochemical properties of extracted cellulose nanoparticles (cellulose nanocrystals and cellulose nanofibrils (CNF)) and natural cellulose materials (wood and bacterial nanocellulose (BNC)) that make them attractive as supporting substrate materials in solar steam generators are briefly discussed. Recent progress in designing highly efficient cellulose-based solar evaporators, including utilizing extracted cellulose nanoparticles via bottom-up assembly CNF, natural cellulose materials with intrinsic hierarchical structure (wood and BNC), and commercial planar cellulose substrates (air-laid paper, cellulose paper, and cotton fabric) is reviewed. The outstanding challenges that need to be addressed for these materials and devices to be utilized in the real-world and in overcoming global water crisis are also briefly highlighted.
ABSTRACT
Cancer immunotherapy involves a cascade of events that ultimately leads to cytotoxic immune cells effectively identifying and destroying cancer cells. Responsive nanomaterials, which enable spatiotemporal orchestration of various immunological events for mounting a highly potent and long-lasting antitumor immune response, are an attractive platform to overcome challenges associated with existing cancer immunotherapies. Here, we report a multifunctional near-infrared (NIR)-responsive core-shell nanoparticle, which enables (i) photothermal ablation of cancer cells for generating tumor-associated antigen (TAA) and (ii) triggered release of an immunomodulatory drug (gardiquimod) for starting a series of immunological events. The core of these nanostructures is composed of a polydopamine nanoparticle, which serves as a photothermal agent, and the shell is made of mesoporous silica, which serves as a drug carrier. We employed a phase-change material as a gatekeeper to achieve concurrent release of both TAA and adjuvant, thus efficiently activating the antigen-presenting cells. Photothermal immunotherapy enabled by these nanostructures resulted in regression of primary tumor and significantly improved inhibition of secondary tumor in a mouse melanoma model. These biocompatible, biodegradable, and NIR-responsive core-shell nanostructures simultaneously deliver payload and cause photothermal ablation of the cancer cells. Our results demonstrate potential of responsive nanomaterials in generating highly synergistic photothermal immunotherapeutic response.
Subject(s)
Aminoquinolines/pharmacology , Antineoplastic Agents/pharmacology , Imidazoles/pharmacology , Immunologic Factors/pharmacology , Immunotherapy , Melanoma/therapy , Photothermal Therapy , Aminoquinolines/chemistry , Animals , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Female , Imidazoles/chemistry , Immunologic Factors/chemistry , Indoles/chemistry , Melanoma/pathology , Mice , Mice, Inbred C57BL , Nanoparticles/chemistry , Particle Size , Polymers/chemistry , Silicon Dioxide/chemistry , Surface Properties , Tumor Cells, CulturedABSTRACT
BACKGROUND: Cetuximab-based chemotherapy is the standard palliative chemotherapy in head and neck cancers, but there is a limitation due to financial and logistic reasons, and where oral metronomic chemotherapy can be a successful alternate. Oral metronomic chemotherapy (MCT) can either be with Methotrexate alone or a combination of Methotrexate and Erlotinib. The study was aimed to assess the clinical outcome of oral MCT in head and neck cancer patients. MATERIALS AND METHODS: This was a retrospective review done at a tertiary cancer centre in India. The clinical outcomes of head and neck cancers patients started on palliative oral MCT from 1st August 2016 to 31st December 2017 were analyzed. The demographic details, toxicity profiles, response to MCT, disease progression status were analyzed. Univariate analysis was done to assess the factors associated with disease progression. Kaplan Meier curve was used for estimating progression free survival (PFS). RESULTS: Of the total 104 patients, the most common primary site of head and neck cancer was oral cavity (52%). MCT scheduled with Methotrexate and Erlotinib in 80 patients. Toxicity rate was 61%, with Grade 3-4 toxicity in 21%. Response rate was 56% and clinically meaningful response rate was 69%. Disease progression was observed in 55% patients. Median PFS rate was 134 Days. Oral MCT was permanently stopped in 73%, the most common reason being disease progression. DISCUSSION: Patients who underwent palliative oral MCT had a median PFS of 134 days which is considered as promising treatment method. Results confirmed more than 50% response rate with lower Grade 3-4 toxicities. CONCLUSION: Palliative oral MCT either with Methotrexate and Erlotinib or Methotrexate alone will be a feasible treatment option in patients with head and neck cancers treated with palliative intent.
Subject(s)
Administration, Metronomic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Administration, Oral , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Disease Progression , Female , Humans , India , Male , Middle Aged , Retrospective Studies , Tertiary Care CentersABSTRACT
In India, under the National Tuberculosis Elimination Programme, the government provides free treatment for multidrug-resistant tuberculosis; however, many patients seek care elsewhere, which is costly. To determine those out-of-pocket expenses, we interviewed 40 presumptive patients and found that they spent more than their median annual income before registering for the government program.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Antitubercular Agents/therapeutic use , Health Expenditures , Humans , Income , India/epidemiology , Tuberculosis/drug therapy , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiologyABSTRACT
The detection and quantification of low-abundance molecular biomarkers in biological samples is challenging. Here, we show that a plasmonic nanoscale construct serving as an 'add-on' label for a broad range of bioassays improves their signal-to-noise ratio and dynamic range without altering their workflow and readout devices. The plasmonic construct consists of a bovine serum albumin scaffold with approximately 210 IRDye 800CW fluorophores (with a fluorescence intensity approximately 6,700-fold that of a single 800CW fluorophore), a polymer-coated gold nanorod acting as a plasmonic antenna and biotin as a high-affinity biorecognition element. Its emission wavelength can be tuned over the visible and near-infrared spectral regions by modifying its size, shape and composition. It improves the limit of detection in fluorescence-linked immunosorbent assays by up to 4,750-fold and is compatible with multiplexed bead-based immunoassays, immunomicroarrays, flow cytometry and immunocytochemistry methods, and it shortens overall assay times (to 20 min) and lowers sample volumes, as shown for the detection of a pro-inflammatory cytokine in mouse interstitial fluid and of urinary biomarkers in patient samples.
Subject(s)
Biological Assay/methods , Fluorescent Dyes/chemistry , Nanoparticles/chemistry , Animals , Bone Marrow Cells/cytology , Cell Line, Tumor , Colloids/chemistry , Dendritic Cells/cytology , Female , Flow Cytometry , Fluorescence , Humans , Immunoassay , Lipopolysaccharides/pharmacology , Mice, Inbred C57BL , Microspheres , Proteomics , Reference StandardsABSTRACT
Management of cancer pain among children is a difficult process due to the way they perceive pain, their dependence on parents, complexity of assessment, and limited availability of safe analgesics. Pain among children with cancer is still a less explored problem in India. This descriptive study was carried out in a tertiary cancer center to explore the characteristics of pain and its management among the children with cancer. We analyzed children diagnosed with hematologic malignancies, aged 4-18 years, admitted between January 2013 and December 2017. This retrospective cohort study involved the review of patient records available at the medical records department. During the study period, there were 290 admission episodes, of which 93 (32.1%) episodes were associated with pain. Of these 93 episodes, 14 (15%) were primarily for pain management. Step I analgesic was utilized in the majority (83%) of the admission episodes involving younger age group (4-9 years) children, whereas for the older age group (10-18 years) Step 2 analgesic (tramadol) was utilized in 29 (58%) episodes, and this was found to be statistically significant (P < .001). Only in 9 (9.7%) episodes Step 3 analgesic was utilized. A significant proportion of children with hematologic malignancies had pain episodes, and these episodes in older age group children were managed with weak opioids.