Abstract
Dengue is the world’s most common arboviral infection, with almost 4 billion people estimated to be living at risk of dengue infection. A recently introduced vaccine is currently recommended ...only for seropositive individuals in a restricted age range determined by transmission intensity. With no effective dengue vaccine for the general population or any antiviral therapy, dengue control continues to rely heavily on vector control measures. Early and accurate diagnosis is important for guiding appropriate management and for disease surveillance to guide prompt dengue control interventions. However, major uncertainties exist in dengue diagnosis and this has important implications for all three. Dengue can be diagnosed clinically against predefined lists of signs and symptoms and by detection of dengue-specific antibodies, non-structural 1 antigen or viral RNA by reverse transcriptase–polymerase chain reaction. All of these methods have their limitations. This review aims to describe and quantify the advantages, uncertainties and variability of the various diagnostic methods used for dengue and discuss their implications and applications for dengue surveillance and control.
Dengue is the world's most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported ...figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines.
PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77-98) and 93% (95% CI: 86-96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8-65) and 31% (95% CI: 18-48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy.
Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.
Metformin (MET), an oral antidiabetic drug, was reported to possess promising anticancer effects. We hypothesized that MET encapsulation in unique nanospanlastics would enhance its anticancer ...potential against HEP-2 cells. Our results showed the successful fabrication of Nano-MET spanlastics (d = 232.10 ± 0.20 nm; PDI = 0.25 ± 0.11; zeta potential = (−)44.50 ± 0.96; drug content = 99.90 ± 0.11 and entrapment efficiency = 88.01 ± 2.50%). MTT assay revealed the enhanced Nano-MET cytotoxicity over MET with a calculated IC50 of 50 μg/mL and > 500 μg/mL, respectively. Annexin V/PI apoptosis assay showed that Nano-MET significantly decreased the percentage of live cells from 95.49 to 93.70 compared to MET and increased the percentage of cells arrested in the G0/G1 phase by 8.38%. Moreover, Nano-MET downregulated BCL-2 and upregulated BAX protein levels by 1.57 and 1.88 folds, respectively. RT-qPCR revealed that Nano-MET caused a significant 13.75, 4.15, and 2.23-fold increase in caspase-3, −8, and − 9 levels as well as a 100 and 43.47-fold decrease in cyclin D1 and mTOR levels, respectively. The proliferation marker Ki67 immunofluorescent staining revealed a 3-fold decrease in positive cells in Nano-MET compared to the control. Utilizing the combined Pathway-Enrichment Analysis (PEA) and Reactome analysis indicated high enrichment of certain pathways including nucleotides metabolism, Nudix-type hydrolase enzymes, carbon dioxide hydration, hemostasis, and the innate immune system. In summary, our results confirm MET cytotoxicity enhancement by its encapsulation in nanospanlastics. We also highlight, using PEA, that MET can modulate multiple pathways implicated in carcinogenesis.
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The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.bone.2019.01.007. The duplicate article has therefore ...been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Klark is a novel online medical education tool (www.klark-cases.com) where students take histories from virtual patients with common presentations from multiple specialities. We investigated whether ...Klark could enhance student confidence and competence in history-taking, and whether students find Klark helpful.
A single cohort of first-year clinical medical students had access to Klark for three weeks. At both ends of the trial, participants were asked to complete feedback forms and participate in two mock Objective Structured Clinical Examination (OSCE) history stations. Outcome measures included self-reported confidence and competence in history-taking, performance in OSCE stations, and qualitative user experience data.
Seventy participants successfully completed a case on Klark (mean 18.7), of which 63 (90% user retention) completed ≥ 2 cases. Self-reported competence (
< 0.001) and confidence (
< 0.001) improved. Participants found Klark to be helpful, impactful, and would recommend it to other students. OSCE scores improved for medical (57% vs. 69%,
< 0.001) and surgical (58% vs. 70%,
< 0.001) histories.
Klark improved competence and confidence in history-taking. Students found it helpful and chose to continue using the platform. By developing confidence and competence at their own pace in the Klark simulated environment, students can then maximise benefit from in-person clinical opportunities.
Infants in neonatal intensive care units frequently experience clinically necessary painful procedures, which elicit a range of behavioral, physiological, and neurophysiological responses. However, ...the measurement of pain in this population is a challenge and no gold standard exists. The aim of this study was to investigate how noxious‐evoked changes in facial expression, reflex withdrawal, brain activity, heart rate, and oxygen saturation are related and to examine their accuracy in discriminating between noxious and non‐noxious stimuli. In 109 infants who received a clinically required heel lance and a control non‐noxious stimulus, we investigated whether combining responses across each modality, or including multiple measures from within each modality improves our ability to discriminate the noxious and non‐noxious stimuli. A random forest algorithm was used to build data‐driven models to discriminate between the noxious and non‐noxious stimuli in a training set which were then validated in a test set of independent infants. Measures within each modality were highly correlated, while different modalities showed less association. The model combining information across all modalities had good discriminative ability (accuracy of 0.81 in identifying noxious and non‐noxious stimuli), which was higher than the discriminative power of the models built from individual modalities. This demonstrates the importance of including multiple modalities in the assessment of infant pain.
Abstract
Background
Anopheles pharoensis
has a major role in transmitting several human diseases, especially malaria, in Egypt?. Controlling
Anopheles
is considered as an effective strategy to ...eliminate the spread of malaria worldwide.
Galaxaura rugosa
is a species of red algae found in tropical to subtropical marine environments. The presence of
G. rugosa
is indicative of the ecosystem's overall health. The current work aims to investigate UPLC/ESI/MS profile of
G. rugosa
methanol and petroleum ether extracts and its activity against
An. pharoensis
and non-target organisms,
Danio rerio
and
Daphnia magna
.
Methods
Galaxaura rugosa
specimens have been identified using DNA barcoding for the COI gene and verified as
G. rugosa.
The UPLC/ESI/MS profiling of
G. rugosa
collected from Egypt was described. The larvicidal and repellent activities of
G. rugosa
methanol and petroleum ether extracts against
An. pharoensis
were evaluated, as well as the toxicity of tested extracts on non-target organisms,
Dan. rerio
and
Dap. magna.
Results
The UPLC/ESI/MS analysis of methanol and petroleum ether extracts led to the tentative identification of 57 compounds belonging to different phytochemical classes, including flavonoids, tannins, phenolic acids, phenyl propanoids
.
Larval mortality was recorded at 93.33% and 90.67% at 80 and 35 ppm of methanol and petroleum ether extracts, respectively, while pupal mortality recorded 44.44 and 22.48% at 35 and 30 ppm, respectively. Larval duration was recorded at 5.31 and 5.64 days by methanol and petroleum ether extracts at 80 and 35 ppm, respectively. A decrease in acetylcholinesterase (AChE) level and a promotion in Glutathione-S-transferase (GST) level of
An. pharoensis
3rd instar larvae were recorded by tested extracts. The petroleum ether extract was more effective against
An. pharoensis
starved females than methanol extract. Also, tested extracts recorded LC
50
of 1988.8, 1365.1, and 11.65, 14.36 µg/mL against
Dan. rerio,
and
Dap. magna,
respectively.
Conclusions
Using red algae derivatives in
An. pharoensis
control could reduce costs and environmental impact and be harmless to humans and other non-target organisms.
Background
Nonalcoholic fatty liver disease (NAFLD) is a worldwide epidemic with global prevalence estimated at 25%. Although NAFLD is usually associated with obesity, patients who are not obese can ...also present with NAFLD; this is known as “lean NAFLD.” Lean NAFLD is defined as NAFLD that develops in patients with a body mass index (BMI) <25 kg/m2. The prevalence of lean NAFLD varies from 7% in the United States to as high as 19% in Asia. Unfortunately, being lean (not overweight) does not necessarily lead to better health. A recent large meta analysis by Sookoian and Pirola of almost 2,000 patients with NAFLD who were lean demonstrated that patients with NAFLD who are lean or obese share a common altered metabolic and cardiovascular profile, which in turn may lead to collective risk for adverse cardiometabolic outcomes, including diabetes and ischemic heart disease. Indeed, atherosclerotic cardiovascular disease remains the most common cause of death in all weight categories.
NAFLD comprises a wide pathological spectrum ranging from simple steatosis to steatohepatitis (NASH) with variable degrees of fibrosis and cirrhosis. The strongest predictor of fibrosis progression in NAFLD is the presence of steatohepatitis (Trenell et al., 2017).
The diagnosis of NASH mandates a liver biopsy, yet the risks and costs associated with a liver biopsy preclude its widespread use. Pain is almost universal, and there is bleeding in approximately 1 in 500 liver biopsies and death in 1 in 10,000, dissuading patients from undergoing the procedure. Moreover, the disproportionately increasing incidence of NAFLD calls for practical and costeffective care and monitoring (Estes et al.,2018). Methods for non-invasive assessment of fatty liver disease and studies in the field have exponentially appeared over the last three decades, offering a safe and more non-invasive practical approach to hepatic fibrosis and steatosis quantification (Castera et al.,2019).
Aim of the study
Determining the correlation of Fib-4 score and NAFL diagnosed by liver biopsy in lean Egyptian patients
Patients and Methods
This study had been carried out on 30 subjects, age range above 18 years old, with BMI (18.5-24.9) selected from transplantation donor outpatient clinic at Ain shams university specialized hospital in Cairo after informed consent were taken from the patients Subjects were divided as follow:
•Group I: 15 adult patients with NAFLD.
•Group II: 15 adult patient with normal liver biopsy who will be educated about lean NAFLD and how to prevent it.
Results
In the current study we concluded that FIB-4 score is not significant with degree of fibrosis while it has a negative correlation with steatosis assessed by biopsy. FIB-4 failed to discriminate advanced fibrosis. Conversely, it showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients in other studies. (FATIH et al., 2020)
Conclusion
FIB-4 failed to discriminate advanced fibrosis. Conversely, it showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients. so fib 4 score can’t be used as a marker of fibrosis nor steatosis in lean NAFLD patients but more like a prognostic value.
End-stage renal disease (ESRD) patients, including those on hemodialysis, possess a high risk for cardiovascular diseases, as the first leading cause of death among them. Traditional risk factors do ...not utterly elucidate this. Throughout the last two decades, CD4+CD28null T cells; an unusual subset of T lymphocytes, was detected high with excess cardiovascular (CV) mortality. We aimed to investigate the circulating CD4+CD28null T cells frequency in ESRD patients on hemodialysis and to evaluate their relationship with atherosclerotic changes. High-resolution carotid ultrasonography was done to assess the common carotid artery intima media thickness in a number of ESRD patients, accordingly patients were selected and subdivided into two groups; 30 with atherosclerosis (mean SD age, 51.6 6.3 years) and 30 without (mean SD age, 48.9 5.5 years). Another 30 healthy individuals (mean SD age, 48.5 6.8 years) were enrolled. Analysis of CD4+CD28null T-cells frequency by flow-cytometry was performed in all studied subjects. CD4+CD28null T cell percentage was significantly higher in ESRD patients, (mean SD, 7.3 2.7 %) compared to healthy individuals (mean SD, 3.0 0.8 %), (p < 0.001). Additionally, the expansion of these unusual T lymphocytes was significantly higher in ESRD patients with atherosclerotic changes (mean SD, 9.47 0.75 %) compared to those without atherosclerosis (mean SD, 5.22 2.14 %), (p < 0.001). In conclusion circulating CD4+CD28null T lymphocyte population showed expansion in ESRD patients, and of interest in correlation to preclinical atherosclerotic changes.
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