Background
Physicians routinely encounter diagnostic uncertainty in practice. Despite its impact on health care utilization, costs and error, measurement of diagnostic uncertainty is poorly ...understood. We conducted a systematic review to describe how diagnostic uncertainty is defined and measured in medical practice.
Methods
We searched OVID Medline and PsycINFO databases from inception until May 2017 using a combination of keywords and Medical Subject Headings (MeSH). Additional search strategies included manual review of references identified in the primary search, use of a topic-specific database (AHRQ-PSNet) and expert input. We specifically focused on articles that (1) defined diagnostic uncertainty; (2) conceptualized diagnostic uncertainty in terms of its sources, complexity of its attributes or strategies for managing it; or (3) attempted to measure diagnostic uncertainty.
Key Results
We identified 123 articles for full review, none of which defined diagnostic uncertainty. Three attributes of diagnostic uncertainty were relevant for measurement: (1) it is a subjective perception experienced by the clinician; (2) it has the potential to impact diagnostic evaluation—for example, when inappropriately managed, it can lead to diagnostic delays; and (3) it is dynamic in nature, changing with time. Current methods for measuring diagnostic uncertainty in medical practice include: (1) asking clinicians about their perception of uncertainty (surveys and qualitative interviews), (2) evaluating the patient–clinician encounter (such as by reviews of medical records, transcripts of patient–clinician communication and observation), and (3) experimental techniques (patient vignette studies).
Conclusions
The term “diagnostic uncertainty” lacks a clear definition, and there is no comprehensive framework for its measurement in medical practice. Based on review findings, we propose that diagnostic uncertainty be defined as a “subjective perception of an inability to provide an accurate explanation of the patient’s health problem.” Methodological advancements in measuring diagnostic uncertainty can improve our understanding of diagnostic decision-making and inform interventions to reduce diagnostic errors and overuse of health care resources.
The effects of methyl jasmonate (MeJA), an elicitor of plant defense mechanisms, on the biosynthesis of diosgenin, a steroidal saponin, were investigated in six fenugreek (Trigonella foenum-graecum) ...varieties (Gujarat Methi-2, Kasuri-1, Kasuri-2, Pusa Early Branching, Rajasthan Methi and Maharashtra Methi-5). Treatment with 0.01% MeJA increased diosgenin levels, in 12 days old seedlings, from 0.5%-0.9% to 1.1%-1.8%. In addition, MeJA upregulated the expression of two pivotal genes of the mevalonate pathway, the metabolic route leading to diosgenin: 3-hydroxy-3-methylglutaryl-CoA reductase (HMG) and sterol-3-β-glucosyl transferase (STRL). In particular, MeJA increased the expression of HMG and STRL genes by 3.2- and 22.2-fold, respectively, in the Gujarat Methi-2 variety, and by 25.4- and 28.4-fold, respectively, in the Kasuri-2 variety. Therefore, MeJA may be considered a promising elicitor for diosgenin production by fenugreek plants.
This work involves fluorescent probe which is composed of carbon dots (CD) and cadmium sulfide quantum dots (CdS QD) for the sensitive and selective fluorescence detection of chromium(
vi
) ions. The ...blue fluorescent carbon dots were synthesized by hydrothermal method from natural precursor apricot. The carbon dots-cadmium sulfide quantum dots (CD-CdS QD) nanocomposite was synthesized and all as-synthesized products were characterized using different characterization techniques. It showed white fluorescence under UV light which was quenched selectively in the presence of chromium(
vi
) ions due to the inner filter effect (IFE). The linear decrease in the white fluorescence was observed in the concentration range 2-120 μM of chromium(
vi
) ions with the limit of detection 2.07 μM. This is novel probe for the sensitive, selective and rapid detection of chromium(
vi
) ions.
This work involves fluorescent probe which is composed of carbon dots (CD) and cadmium sulfide quantum dots (CdS QD) for the sensitive and selective fluorescence detection of chromium(
vi
) ions.
Conflict with humans is a significant source of mortality for large carnivores globally. With rapid loss of forest cover and anthropogenic impacts on their habitats, large carnivores are forced to ...occupy multi-use landscapes outside protected areas. We investigated 857 attacks on livestock in eastern Himalaya and 375 attacks in western Himalaya by leopards between 2015 and 2018. Multivariate analyses were conducted to identify the landscape features which increased the probability of livestock depredation by leopards. The risk of a leopard killing livestock increased within a heterogeneous landscape matrix comprising of both closed and open habitats (very dense forests, moderate dense forests, open forests, scrubland and non-forests). We used the results to map potential human-leopard conflict hotspots across parts of the Indian Himalayan region. Our spatial risk maps indicate pockets in the eastern, central and western part of eastern Himalaya and the central, northern part of western Himalaya as hotspots of human-leopard conflicts. Most of the attacks occurred when livestock were grazing freely within multi-use areas without supervision of a herder. Our results suggest that awareness about high risk areas, supervised grazing, and removing vegetation cover around human settlements should be initiated to reduce predation by leopards.
Background:
Collusion in cancer care is the diplomatic concealment of information between a triad of the health care professional (HCP), patient, and caregiver. Free and expressive communication is ...determined by multiple factors, which establishes a healthy balance between ‘patient-centric’ and ‘family-centric’ decision making. The lack of a universal approach to prognostic disclosure techniques emphasizes the need for a systematic review of contemporary practice.
Methods:
A systematic review of the literature was conducted till June 2020 using themes based on cancer, communication, prognostic disclosure, and collusion by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results:
Fifty-three studies involving 10,569 subjects were studied for their utility on prognostic disclosure using different communication methods and interfaces. Twenty-three studies used a face-to-face interview with subjects while in-person telephonic interviews were conducted in two studies, 16 studies implicated semi-structured questionnaires, and 6 studies mentioned the development of a new technique/tool for disclosure. The duration of a session for prognosis-disclosure ranged from 22 min to 1 h. The involvement of palliative care specialists and mental health professionals was limited during the disclosure of the prognosis.
Conclusion:
The findings of the review indicate that patients in cancer care are aware of their diagnosis and to a certain extent of prognosis despite nondisclosure by their family members and treating teams. This review emphasizes the assessment of ‘disclosure wishes’ among patients and caregivers in separate interviews rather than simply relying on one specific method of interviewing. The nonconfrontational approach and training among HCPs are of utmost importance to build therapeutic resilience among the treating team involved in cancer care. Since many factors such as family wishes, cultural dissonance, medical model, and patient perception could become barriers to prognostic disclosure, there is a need to develop a universal approach to prognostic disclosure and handling associated collusion.
Lethal measures are widely adopted by local communities and governments to manage human-wildlife conflicts. Such measures lead to large scale decline of carnivore populations globally with trophic ...cascades on ecosystems and questionable impacts on human-wildlife conflicts. Mitigating human-carnivore conflicts through non-lethal measures will protect endangered predators and secure livelihoods. However, information on the effectiveness of such measures are extremely limited and hence cannot be applied in developing scientific evidence. Further to develop human-carnivore coexistence models, it is important for local community members, biologists and wildlife managers to actively participate in conservation programs. We evaluated the response of a non-lethal visual deterrent (i.e. fox lights) to deter leopard attacks on livestock within a multiple-use landscape of western Himalaya through community engagement. We monitored 16 experimental sites and 17 control sites within 27 villages and recorded data on livestock depredation by leopards between April 2018 to April 2019. A multivariate analysis was conducted to determine the influence of landscape predictors and animal husbandry practices on livestock depredation by leopards within the vicinity of human settlements. We found that visual deterrents discouraged common leopards to predate on livestock (cows and goats). We also demonstrated that community based conservation initiatives are successful in mitigating human-carnivore conflicts within large semi-natural landscapes. We suggest developing site specific coexistence strategies and adopting non-lethal measures to safeguard carnivores, livestock and humans within shared landscapes.
The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized ...that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heatstressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stressinduced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.
Our study was designed to screen the antibacterial potency of Princepia utilis leaf and seed extract and to measure their antioxidant effects, total phenol content, total flavonoid content, and total ...carbohydrate content. Collected samples were extracted by cold maceration. Hexane, ethyl acetate, methanol, and distilled water were used as extraction solvents. In the disc diffusion method, P. utilis ethyl acetate leaf extract was most prominent against Staphylococcus epidermis with a zone of inhibition (ZOI) of 13.83 mm. Similarly, methanolic leaf extract was most prominent against Staphylococcus aureus (ZOI-12.33 mm). Furthermore, the methanolic seed extract was most sensitive against Klebsiella pneumoniaee (ZOI-11.66 mm) Escherichia coli (ZOI-9.0 mm). The lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.5 mg/mL and 0.6 mg/mL, respectively, were shown by ethyl acetate leaf extract against S. epidermis. Similarly, the highest values of MIC and MBC, i.e., 20.8 mg/mL and 33.3 mg/mL, respectively, were shown by hexane leaf extract against S. epidermidis. On the other hand, evaluation of antioxidant capacity revealed that ethyl acetate leaf extract showed the maximum antioxidant effect (IC50: 66.69 μg/mL). The total flavonoid contents of different extracts were measured in the range of 37 ± 0.74 μg QE/mg dry extract weight (methanolic seed extract) to 321.84 ± 4.82 μg QE/mg dry extract weight (hexane seed extract). Likewise, the total polyphenol content ranged from the hexane leaf extract (17.33 ± 0.642 μg GAE/mg dry extract weight) to ethyl acetate leaf extract (62.56 ± 1.284 μg GAE/mg dry extract weight). We found a variation in total carbohydrate content in the range of 23.55 ± 1.125 μg glucose/mg dry extract weight (hexane leaf extract) to 96.63 ± 2.253 μg glucose/mg dry extract weight (aqueous leaf extract). Overall, this study revealed that leaf and seed extract of P. utilis exhibited noteworthy antibacterial effects against diverse pathogenic microorganisms.
The most frequently reported symptom of exposure to high altitude is loss of body mass and decreased performance which has been attributed to altered protein metabolism affecting skeletal muscles ...mass. The present study explores the mechanism of chronic hypobaric hypoxia mediated skeletal muscle wasting by evaluating changes in protein turnover and various proteolytic pathways. Male Sprague–Dawley rats weighing about 200 g were exposed to hypobaric hypoxia (7,620 m) for different durations of exposure. Physical performance of rats was measured by treadmill running experiments. Protein synthesis, protein degradation rates were determined by
14
C-Leucine incorporation and tyrosine release, respectively. Chymotrypsin-like enzyme activity of the ubiquitin–proteasome pathway and calpains were studied fluorimetrically as well as using western blots. Declined physical performance by more than 20%, in terms of time taken in exhaustion on treadmill, following chronic hypobaric hypoxia was observed. Compared to 1.5-fold increase in protein synthesis, the increase in protein degradation was much higher (five-folds), which consequently resulted in skeletal muscle mass loss. Myofibrillar protein level declined from 46.79 ± 1.49 mg/g tissue at sea level to 37.36 ± 1.153 (
P
< 0.05) at high altitude. However, the reduction in sarcoplasmic proteins was less as compared to myofibrillar protein. Upregulation of Ub-proteasome pathway (five-fold over control) and calpains (three-fold) has been found to be important factors for the enhanced protein degradation rate. The study provided strong evidences suggesting that elevated protein turnover rate lead to skeletal muscle atrophy under chronic hypobaric hypoxia via ubiquitin–proteasome pathway and calpains.
Abstract
Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify ...single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%–90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs.
In-silico
expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs,
qRWC1.1
and
qYLD7.1
, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in
qYLD7.1
associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.
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