Non-invasive iron deficiency diagnosis: a saliva-based approach using capillary flow microfluidics.

Iron deficiency anemia (IDA) is a condition characterized by lower-than-average iron (Fe) levels in the body, affecting a substantial number of young children and pregnant women globally. Existing diagnostic methods for IDA rely on invasive analysis of stored Fe in ferritin from blood samples, posing challenges, especially for toddlers and young children. To address this issue, saliva has been proposed as a non-invasive sample matrix for IDA diagnosis. However, conventional Fe analysis techniques often necessitate complex and costly instrumentation. This study presents the first non-invasive, saliva-based preliminary screening test for IDA using a nitrocellulose lateral flow system. In this study, we introduce a novel approach using the ferroin reaction with bathophenanthroline (Bphen) and ferrous (Fe2+) ions to quantify Fe levels in saliva. Our methodology involves a capillary flow-driven microfluidic device integrated into a lateral flow system utilizing nitrocellulose membranes. Here, we present the first instance of saliva on a nitrocellulose substrate to detect salivary Fe levels. The optimized system yielded a linear response over the 1-200 ppm range in buffer solution, with a limit of detection (LoD) of 5.6 ppm. Furthermore, the system demonstrated a linear response in pooled saliva samples across the 1-1000 ppm range, with a LoD of 55.1 ppm. These results underscore the potential of our capillary flow-driven microfluidic device as a viable non-invasive diagnostic tool for IDA, particularly in remote and resource-limited settings.

Microfluidics in environmental analysis: advancements, challenges, and future prospects for rapid and efficient monitoring.

Microfluidic devices have emerged as advantageous tools for detecting environmental contaminants due to their portability, ease of use, cost-effectiveness, and rapid response capabilities. These devices have wide-ranging applications in environmental monitoring of air, water, and soil matrices, and have also been applied to agricultural monitoring. Although several previous reviews have explored microfluidic devices' utility, this paper presents an up-to-date account of the latest advancements in this field for environmental monitoring, looking back at the past five years. In this review, we discuss devices for prominent contaminants such as heavy metals, pesticides, nutrients, microorganisms, per- and polyfluoroalkyl substances (PFAS), etc. We cover numerous detection methods (electrochemical, colorimetric, fluorescent, etc.) and critically assess the current state of microfluidic devices for environmental monitoring, highlighting both their successes and limitations. Moreover, we propose potential strategies to mitigate these limitations and offer valuable insights into future research and development directions.

Ethnomedicinal plants in Champadevi rural municipality, Okhaldhunga district, Nepal.

BACKGROUND: Okhaldhunga is a hilly district with fragile socioeconomic conditions, limited access to health care, social stigma, and poor resource management, where most people rely on medicinal plants for primary health care. The use of medicinal plants for primary health care varies with socioeconomic attributes. Following the intra-cultural analysis, we documented and tested the hypothesis that use of medicinal plants in Champadevi, Okhaldhunga, Nepal, depends on socioeconomic variables. METHODS: We interviewed 224 respondents, 53.12% female and 46.88% male, including 31 Brahmin, 157 Chhetri, 13 Dalit, and 23 Janajati, and conducted three focused group discussions and seven key informant interviews to record the ethnomedicinal plants used in Champadevi rural municipality, Okhaldhunga District. The relative frequency of citation (RFC) was computed to know the importance of the species. A generalized linear model (GLM) was used to see the relationship between medicinal plants reported with the sociocultural variables, which include age, gender, occupation, education, ethnicity, and religion. RESULTS: We documented 149 medicinal plants, including 69 herbs, 22 shrubs, nine climbers, 48 trees, and one parasitic plant, belonging to 68 families and 130 genera, and used to treat 48 distinct diseases and ailments. Plant parts, leaf, and digestive disorders were frequently treated during healing. Curcuma angustifolia was the most cited species with RFC 0.9554. The respondents' knowledge of medicinal plant use varied significantly with age (p = 0.0001) and occupation (p = 0.003). Changes in land use, population decline of medicinal plant species, and unsustainable harvesting practices constituted the local threats to medicinal plants and associated knowledge. Elders died without passing on their knowledge to the younger generations during sociocultural transformation, and youth disinterest coupled with the free availability of allopathic medicine led to knowledge erosion. CONCLUSIONS: The use of medicinal plants in Champadevi, Okhaldhunga, was significantly depended on two socioeconomic variables age and occupation. Ethnomedicinal plants are essential in the primary healthcare system in Nepal; however, their availability and practices are declining. Thus, plans regulating land use change and human migration, acknowledging traditional healthcare practices, and raising awareness of the significance of traditional medical practices as complementary healthcare practices should be strengthened.

Capillary Flow-Driven Microfluidics Combined with a Paper Device for Fast User-Friendly Detection of Heavy Metals in Water.

Human exposure to heavy metals is a concerning global problem because of its detrimental effect on our health and ecosystem. Assessing the levels of these metals is cost- and labor-intensive and nonuser friendly because current analysis approaches typically rely on heavy instrumentations like inductively coupled plasma-mass spectrometry, which is only possible in centralized labs. Hence, simple economical detection methods are in high demand in developing countries and areas with insufficient infrastructure, professional experts, and appropriate environmental treatment. Several microfluidic paper-based analytical devices have been reported as promising alternatives to conventional testing methods for on-site heavy metal detection. Paper-based microfluidics are advantageous because of their simple fabrication, biodegradability, low cost, and ability to operate without pumps. However, typical assay times for current platforms are slow, and they typically rely on pipetting a fixed volume into the assay cards. This adds complexity in actual field scenarios. Here, we report a novel, inexpensive, and straightforward capillary-driven microfluidic device combined with paper for rapid and user-friendly detection of Ni(II), Cu(II), and Fe(III) in water. A colorimetric approach was adopted to quantify these metals. The device was able to produce a homogeneous color signal within 8 s of sample insertion. The limit of detection and limit of quantification were calculated to be 2 and 6.67 ppm for nickel, 0.3 and 1 ppm for Cu, and 1.1 and 3.67 ppm for Fe, respectively. The majority (>90%) of the collected samples showed recovery in the 80-110% range with acceptable accuracy and precision (<15% RSD) for a colorimetric device. This technique can be beneficial for rapidly assessing heavy metal exposure in drinking and surface water at drastically reduced assay time and is the first example of capillary flow-driven microfluidic devices as a transport medium for heavy metal detection.

Depredation loss drives human-wildlife conflict perception in the Trans-Himalayas.

Communities in and around protected areas are exposed to a higher level of human-wildlife interactions. The conservation practice with persistently adverse local livelihood outcomes can potentially aggravate such interactions leading to conflict. In our study, we examined how perceptions of HWC have formed in a protected area of the Trans-Himalayas whose conservation program collides with a centuries-long tradition of transhumance pastoralism. To examine determinants of depredation and how conflict perception has developed there, along with the socioeconomic and ecological interactions underlying those trends, we collected data using household surveys, key informant interviews, and focus group discussions. We employed Poisson-logit maximum-likelihood hurdle, binary logit, and multinomial ordered logit regressions in order to explore the determinants of annual livestock depredation, predator attacks on the shed, and household-level perceptions of HWC, respectively. Depredation and encounters with wildlife were the principal causes of perceived HWC, and depredation caused an average household-level loss of US $422.5, up to 23.28% of annual income in some households. Predators' attacks on high-quality sheds were relatively infrequent but more common in areas with perceived habitat degradation. Social customs, pastoral practices, and the present compensation mechanism were identified as being antithetical to conflict reduction and sustainable pastureland management. Further analysis revealed that a diversity of livelihoods, however, lowered conflict perception formation. The identified socio-ecological factors will continue to increase depredation, exacerbate perceived HWC, and degrade pastureland unless local conservation authorities take appropriate remedial measures.

The use of medicinal plants to prevent COVID-19 in Nepal.

BACKGROUND: Medicinal plants are the fundamental unit of traditional medicine system in Nepal. Nepalese people are rich in traditional medicine especially in folk medicine (ethnomedicine), and this system is gaining much attention after 1995. The use of medicinal plants has increased during the COVID-19 pandemic as a private behavior (not under the control of government). A lot of misinterpretations of the use of medicinal plants to treat or prevent COVID-19 have been spreading throughout Nepal which need to be managed proactively. In this context, a research was needed to document medicinal plants used, their priority of use in society, their cultivation status, and the source of information people follow to use them. This study aimed to document the present status of medicinal plant use and make important suggestion to the concerned authorities. METHODS: This study used a web-based survey to collect primary data related to medicinal plants used during COVID-19. A total of 774 respondents took part in the survey. The study calculated the relative frequencies of citation (RFC) for the recorded medicinal plants. The relationship between plants recorded and different covariates (age, gender education, occupation, living place, and treatment methods) was assessed using Kruskal-Wallis test and Wilcoxon test. The relationship between the information sources people follow and the respondent characteristics was assessed using chi-square test. RESULTS: The study found that the use of medicinal plants has increased during COVID-19 and most of the respondents recommended medicinal plants to prevent COVID-19. This study recorded a total of 60 plants belonging to 36 families. The leaves of the plants were the most frequently used. The Zingiber officinale was the most cited species with the frequency of citation 0.398. Most of the people (45.61%) were getting medicinal plants from their home garden. The medicinal plants recorded were significantly associated with the education level, location of home, primary treatment mode, gender, and age class. The information source of plants was significantly associated with the education, gender, method of treatment, occupation, living with family, and location of home during the lockdown caused by COVID-19. CONCLUSIONS: People were using more medicinal plants during COVID-19 claiming that they can prevent or cure COVID-19. This should be taken seriously by concerned authorities. The authorities should test the validity of these medicinal plants and control the flow of false information spread through research and awareness programs.

Clinical Profile of COVID-19 Patients Admitted in a COVID Designated Hospital.

BACKGROUND: Pandemic of COVID-19 has engulfed Nepal as well. In this paper, we studied the demographic, clinical, laboratory findings as well as the treatment modalities, prognostic factors and outcome of patients admitted with COVID-19. METHODS: This was an observational cross-sectional study that included all patients admitted to the General Medicine Department of College of Medical Sciences, Bharatpur, during the first wave of COVID-19 from April 2020 to February 2021 after obtaining the ethical clearance. Data analysis was done using statistical packages for social sciences version 16. RESULTS: A total of 119 patients with mean age of 61.5 years were admitted. They had a mean duration of onset of symptoms of 7.1 days. Commonest symptoms were fever (70.6%), cough (67.2%) and dyspnea (64.7%). Severe COVID-19 at admission with a median CT severity score of 15 was found in 49.7% of them. Total 83.2% patients required ICU care and 10.9% required mechanical ventilation. ARDS and secondary infection occurred in 17.6% each. Median length of hospital stay was 6 days. In total, 56.3% recovered 27.7% left against medical advice and 16.0% expired. Severity of COVID at admission, CT severity score at presentation and D-dimer at admission were found to be significantly associated with mortality (P<0.05).Neither of the age, duration of illness, CRP at admission nor the use of remdesivir or convalescent plasma had significant relation with the mortality (P>0.05). CONCLUSIONS: Severity of illness at presentation, CT severity score and D-dimer level at admission are significantly associated with mortality of the patients admitted with COVID-19.

Outpatient template-guided permanent interstitial brachytherapy using 131Cs in gynecologic malignancies: Initial report.

PURPOSE: Optimal curative intent brachytherapy for certain gynecologic cancers requires interstitial brachytherapy, often using template-guided techniques such as a Syed-Neblett implant. Whether high or low dose rate (LDR), these procedures pose significant risks to patients, partly attributable to the prolonged period of bed rest. Published results of free-handed permanent interstitial brachytherapy (PIB) with 131Cs demonstrate it to be an effective modality for the management of small volume gynecologic cancers. This report is the first to describe a permanent template-guided interstitial technique using 131Cs for gynecologic cancers, performed as an LDR outpatient procedure. METHODS AND MATERIALS: Five sequential patients with recurrent or primary gynecologic malignancies underwent template-guided PIB using 131Cs. A posttreatment planning CT was obtained immediately after the procedure and again 3-4 weeks later. Both CT data sets were fused and the relative positions compared to assess for migration in the x, y, and z planes. Seed positions as well as dosimetric parameters including D90, D100, V100, and the dose to 2 cc of rectum and bladder were compared to quantify migration of sources and the resulting effect, if any, on the treatment. RESULTS: The median age was 69 years (range 64-85). All patients received a template-guided 131Cs PIB implant to treat gross disease. All 5 patients had significant medical comorbidities that limited treatment options. Considering all 5 patients, a total of 40 interstitial needles were placed. Ten needles carried only Vicryl-stranded sources, and 30 needles carried a combination of stranded 131Cs seeds and free seeds. Needle count was between 6 and 10 needles per patient, with active lengths of 4-10 cm. The median dose was 30 Gy (range 25-55 Gy) to permanent decay, enabling a cumulative median biological effective dose 91.5 Gy (range 60.9-92.1 Gy) and equivalent dose at 2 Gy per fraction 75.9 Gy (range 50.7-76.8 Gy). All implants were performed as outpatient procedures with only the first patient admitted for 23-hour observation. All calculated median migration distances were less than 1 cm in the axial, sagittal, or coronal planes. In 69.2% cases, the individual seed migration was <5 mm. Strand migration appeared directly related to peripheral placement and the use of stranded sources. The median D90, D100, and V100 were compared between study sets, and no significant differences were identified. No Grade 3 or higher complications occurred. CONCLUSIONS: Permanent LDR template-guided PIB using 131Cs can be safely performed on an outpatient basis. Compared to currently used template-guided techniques, the use of 131Cs avoids prolonged bed rest and hospitalization, significantly lowers cost, and enables a higher cumulative dose. Seed migration is minimal with this technique. Early experience suggests that the technique is safe and merits further study.

Independent dosimetric assessment of the model EP917 episcleral brachytherapy plaque.

PURPOSE: To investigate the influence of slot design on dose distributions and dose-volume histograms (DVHs) for the model EP917 plaque for episcleral brachytherapy. METHODS: Dimensions and orientations of the slots were measured for three model EP917 plaques and compared to data in the Plaque Simulator (PS) treatment planning software (version 5.7.6). These independently determined coordinates were incorporated into the MCNP Monte Carlo simulation environment to obtain dose from the plaques in a water environment and in a clinical environment with ocular structures. A tumor volume was simulated as 5 mm in apical height and 11 mm in basal diameter. Variations in plaque mass density and composition; slot length, width, and depth; seed positioning; and Ag-marker rod positioning were simulated to examine their influence on plaque central axis (CAX) and planar dose distributions, and DVHs. RESULTS: Seed shifts in a single slot toward the eye and shifts of the(125)I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution. A shift of 0.0994 mm toward the eye increased dose by 14%, 9%, 4.3%, and 2.7% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. When examining the fully-modeled plaque in the ocular geometry, the largest dose variations were caused by shifting the Ag rods toward the sclera and shifting the seeds away from the globe when the slots were made 0.51 mm deeper, causing +34.3% and -69.4% dose changes to the outer sclera, respectively. At points along the CAX, dose from the full plaque geometry using the measured slot design was 2.4%±1.1% higher than the manufacturer-provided slot design and 2.2%±2.3% higher than the homogeneous calculation of PS treatment planning results. The ratio of D10 values for the measured slot design to the D10 values for the manufacturer-provided slot design was higher by 9%, 10%, and 19% for the tumor, inner sclera, and outer sclera, respectively. In comparison to the measured slot design, a theoretical plaque having narrower and deeper slots delivered 30%, 37%, and 62% lower D10 doses to the tumor, inner sclera, and outer sclera, respectively. CONCLUSIONS: While the measured positions of the slots on the model EP917 plaque were in close agreement (<0.7 mm) with the PS values, small differences in the slot shape caused substantial differences in dose distributions and DVH metrics. Increasing slot depth by 0.1 mm decreased outer scleral dose by 20%, yet shifting the Ag rods in the seeds toward the globe by 0.1 mm increased outer scleral dose by 35%. The clinical medical physicist is advised to measure these types of plaques upon acceptance testing before clinical use to inspect slot shape and position for comparison with data used for treatment planning purposes.

Implementation and early clinical results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies.

OBJECTIVE: Permanent interstitial brachytherapy is an ideal yet underutilized treatment modality for accessible, small volume gynecological malignancies. We present early clinical results utilizing a new permanent isotope, Cs-131. METHODS: A retrospective review was performed evaluating patients treated with Cs-131 permanent interstitial radiation at our institution from July 2011 through June 2013. Doses were most commonly prescribed and calculated to a depth of 5mm using Paterson-Parker planar implant rules for Au-198. This activity was converted to air-kerma strength (U). A conversion factor of 1.1 was applied based on RBE calculations, clinical observation and experience. RESULTS: 14 patients were identified among whom 17 Cs-131 implants were performed. Seven patients were implanted as sole therapy, and a median dose of 50 Gy was delivered. Ten implants were performed as boost within a more extensive radiation treatment plan. In these patients, a median implant dose of 27.5 Gy was used and the median total dose delivered in combination was 78.25 Gy. After a median follow up of 12 months, the actuarial local control rate was 84.4%. A very low level of grade 1-3 reactions was observed with no fistula formations or other severe side effects. CONCLUSIONS: Permanent interstitial brachytherapy with Cs-131 was well tolerated with favorable early results compared to other series. Cs-131 has multiple favorable properties, including minimal radiation exposure to treating staff, and should be considered as a therapeutic option in appropriately selected patients. A methodology for dose prescription, calculation of radioactivity required and distribution of the isotope is also presented.

A modern Monte Carlo investigation of the TG-43 dosimetry parameters for an 125I seed already having AAPM consensus data.

PURPOSE: To investigate potential causes for differences in TG-43 brachytherapy dosimetry parameters in the existent literature for the model IAI-125A(125)I seed and to propose new standard dosimetry parameters. METHODS: The MCNP5 code was used for Monte Carlo (MC) simulations. Sensitivity of dose distributions, and subsequently TG-43 dosimetry parameters, was explored to reproduce historical methods upon which American Association of Physicists in Medicine (AAPM) consensus data are based. Twelve simulation conditions varying(125)I coating thickness, coating mass density, photon interaction cross-section library, and photon emission spectrum were examined. RESULTS: Varying(125)I coating thickness, coating mass density, photon cross-section library, and photon emission spectrum for the model IAI-125A seed changed the dose-rate constant by up to 0.9%, about 1%, about 3%, and 3%, respectively, in comparison to the proposed standard value of 0.922 cGy h(-1) U(-1). The dose-rate constant values by Solberg et al. ["Dosimetric parameters of three new solid core (125)I brachytherapy sources," J. Appl. Clin. Med. Phys. 3, 119-134 (2002)], Meigooni et al. ["Experimental and theoretical determination of dosimetric characteristics of IsoAid ADVANTAGE™ (125)I brachytherapy source," Med. Phys. 29, 2152-2158 (2002)], and Taylor and Rogers ["An EGSnrc Monte Carlo-calculated database of TG-43 parameters," Med. Phys. 35, 4228-4241 (2008)] for the model IAI-125A seed and Kennedy et al. ["Experimental and Monte Carlo determination of the TG-43 dosimetric parameters for the model 9011 THINSeed™ brachytherapy source," Med. Phys. 37, 1681-1688 (2010)] for the model 6711 seed were +4.3% (0.962 cGy h(-1) U(-1)), +6.2% (0.98 cGy h(-1) U(-1)), +0.3% (0.925 cGy h(-1) U(-1)), and -0.2% (0.921 cGy h(-1) U(-1)), respectively, in comparison to the proposed standard value. Differences in the radial dose functions between the current study and both Solberg et al. and Meigooni et al. were <10% for r ≤ 5 cm, and increased for r > 5 cm with a maximum difference of 29% at r = 9 cm. In comparison to Taylor and Rogers, these differences were lower (maximum of 2% at r = 9 cm). For the similarly designed model 6711 (125)I seed, differences did not exceed 0.5% for 0.5 ≤ r ≤ 10 cm. Radial dose function values varied by 1% as coating thickness and coating density were changed. Varying the cross-section library and source spectrum altered the radial dose function by 25% and 12%, respectively, but these differences occurred at r = 10 cm where the dose rates were very low. The 2D anisotropy function results were most similar to those of Solberg et al. and most different to those of Meigooni et al. The observed order of simulation condition variables from most to least important for influencing the 2D anisotropy function was spectrum, coating thickness, coating density, and cross-section library. CONCLUSIONS: Several MC radiation transport codes are available for calculation of the TG-43 dosimetry parameters for brachytherapy seeds. The physics models in these codes and their related cross-section libraries have been updated and improved since publication of the 2007 AAPM TG-43U1S1 report. Results using modern data indicated statistically significant differences in these dosimetry parameters in comparison to data recommended in the TG-43U1S1 report. Therefore, it seems that professional societies such as the AAPM should consider reevaluating the consensus data for this and others seeds and establishing a process of regular evaluations in which consensus data are based upon methods that remain state-of-the-art.

Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction.

PURPOSE: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. METHODS: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescription doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (Fr: with resensitization, Fn: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, ß, and relative biological effectiveness for different types of tumors were used for the calculation. RESULTS: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (Fr) and without (Fn) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of Fr/Fn were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of Fr/Fn were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of Fr/Fn were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of Fr was 1.07/1.11 (rounded to 1.1), and the averaged value of Fn was 1.75/1.18. Fr of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. CONCLUSIONS: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.