Precautions on Contact Dermatoscopy and Other Practices in the Pandemic of COVID-19

In the age of the pandemic of COVID-19, there is a considerable need for hospitals that triggers many challenges for health care providers to keep themselves and their patients protected from any nosocomial infections, including viral, fungal and bacterial infections. Among health care providers, dermatologists play a vital role in performing dermatoscopy free from Staphylococcus epidermidis, Micrococcus, and Corynebacterium species reported to be identified on the dermoscopic lenses and their adaptors. There is also a possibility for SARS-CoV-2, a member of coronaviruses, to be transmissible from patient to a physician or vice versa or even from a physician to one of her or his family members. SARS-CoV-2 can be transferred through the mucus membranes of the human eyes. This chapter will flag the importance of having a detailed list of precautions for dermatologists and patients to make clinical practice as safe as possible

Visual feature extraction from dermoscopic colour images for classification of melanocytic skin lesions

The early diagnosis of Melanoma is a challenging task for dermatologists, because of the characteristic similarities of Melanoma with other skin lesions such as typical moles and dysplastic nevi. Aims: This work aims to help both experienced and non-experienced dermatologists in the early detection of cutaneous Melanoma through the development of a computational helping tool based on the “ABCD” rule of dermoscopy. Moreover, it aims to decrease the need for invasive biopsy procedure for each tested abnormal skin lesion. Methods: This is accomplished through the utilization of MATLAB programming language to build a feature extraction tool for the assessment of lesion asymmetry, borders irregularity, and colors variation in the tested lesion. Results: The helping tool obtained a sensitivity of 81.48%, a specificity of 52.83% and accuracy of 62.50% in the assessment of the Asymmetry Index. A new metric for the borders irregularity index was built. Finally, for the Colors Variation Index algorithm a sensitivity of 51.37%, a specificity of 61.51% and accuracy of 57.80% was achieved. Conclusions: This work created a computational tool based on the ABCD-rule, which is helpful for both experienced and non-experienced dermatologists in the early discrimination of Melanoma than other types of skin lesions and to eliminate the need of the biopsy procedure. A new metric for the Borders Irregularity Index was established depending on the number of inflection points in the lesion’s borders

Knowledge, Misconceptions and Attitudes towards Labor Regional Analgesia in a University Hospital: A Cross-Sectional Study

Background: Pain relief in labor is considered an important concern in the management of pregnant females in childbirth. The aim of this study is to assess the knowledge and attitudes of Jordanian females towards various regional analgesic techniques. Methods: We conducted a cross-sectional survey on 652 Jordanian women with a mean age of 32.9 (±8.17). Data collection took place at the gynecological and obstetrics clinics between December, 2017 and September, 2018. Results: Subjects with higher educational levels tend to have better knowledge about regional analgesia (p-value = 0.003), are less likely to ask for general anesthesia (GA) (p < 0.001), and have more previous regional analgesia 47.9% (p < 0.001). Moreover, multiparous women had better knowledge about regional analgesia and higher tendency to ask for it as an efficacious analgesic method during delivery (p < 0.05). Conclusions: In conclusion, even though higher educational levels and multiparty were significantly associated with better knowledge and acceptance rate of regional analgesia, sources of information about regional analgesia plays an important role, emphasizing on the significant role of anesthesiologists and obstetricians in increasing the awareness levels in our society

Binding of Transcription Factor GabR to DNA Requires Recognition of DNA Shape at a Location Distinct from its Cognate Binding Site

Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding. In silico predictions suggest that the bridging DNA sequence is likely to be bendable in one direction and kinetic analysis of mutant DNA sequences with biolayer interferometry, allowed the independent quantification of the relative contribution of DNA base and shape recognition in the GabR–DNA interaction. These indicate that the two cognate binding sites as well as the bendability of the DNA sequence in between these sites are required to form a stable complex. The mechanism of GabR–DNA interaction provides an example where the correct shape of DNA, at a clearly distinct location from the cognate binding site, is required for transcription factor binding and has implications for bioinformatics searches for novel binding sites

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

miRNA target prediction might explain the reduced transmission of SARS-CoV-2 in Jordan, Middle East

MicroRNAs (miRNAs) are non-coding RNAs that control many functions within the human cells by controlling protein levels through binding to messenger RNA (mRNA) translation process or mRNA abundance. Many pieces of evidence show that miRNAs affect the viral RNA replication and pathogenesis through direct binding to the RNA virus to mediate changes in the host transcriptome. Many previous studies have been studying the interaction between human cells' miRNA and viral RNA to predict many targets along the viral genome. In this work, via the miRDB database, we determined the target scores of predicted human miRNA to bind with the ss-RNA of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in general and its spike gene in specific. Our predicted miRNA targets of the ss-RNA of SARS-CoV-2 might destabilize the ss-RNA translation of SARS-CoV-2 that has been established by more than 80% of asymptomatic infected cases in Jordan due to host miRNA interactions. In respiratory epithelial cells, the high prediction scoring for miRNAs covers the RNA from 5′ to 3′ that explains successful antiviral defenses against ss-RNA of SARS-CoV-2 and might lead to new nucleotide deletion mechanisms. The exciting findings here that the nucleotide substitution 1841A > G at the viral genomic RNA level, which is an amino acid substation D614G at the spike protein level showed a change in the predicted miRNA sequence from hsa-miR-4793-5p to hsa-miR-3620-3p with an increase in the target score from 91 to 92

Mechanism of DNA binding of an unusual bacterial transcription regulator.

GabR is a chimeric transcription factor from Bacillus subtilis belonging to the GntR family of transcription factors and controls genes involved in the metabolism of gamma-aminobutyric acid (GABA). The crystal structure of GabR reveals a head-to-tail domain swap homodimer whereby the C-terminal aminotransferase I-like domains form a dimeric core with the N-terminal winged helix-turn-helix DNA (wHTH) binding domains located at opposing sides of the dimer. This unusual structure has raised the questions about the structural changes required for DNA binding and the switch from transcription repressor state to activator state upon binding of the effector molecule GABA. Here, we show that GabR binds to its cognate direct repeat sequence in the promoter region as a dimer to form both the repressive and the activating complex and ruled out changes in stoichiometry as part of regulatory mechanism. Small angle X-ray scattering (SAXS) showed that the solution structure of the GabR dimer is consistent with the crystal structure and that binding of GABA resulted in small structural changes contrary to models predicting large conformational changes for DNA binding. The SAXS data of the GabR-DNA complex were consistent with a model in which the DNA duplex undergoes an unexpected conformational change during complex formation: The DNA molecule bends around the dimeric core such that the direct repeat sequences can simultaneously contact the helix-turn-helix domains on opposite sides of the GabR dimer without the need for major conformational changes of the protein. Analysis of the binding and unbinding kinetics of the GabR to wild type DNA and a range of mutants showed that (1) the complex is only stable when both helix-turn-helix domains can bind to their cognate direct repeat sequences and (2) the sequence of DNA in between the repeat sequences has evolved to contain a particular pattern of alternating regions of high and low bendability that generates intrinsic curvature in the DNA in the correct direction to facilitate GabR binding. Thus, both direct readout mechanisms involving the contacts of the helix-turn-helix domains with the bases in the repeat sequences and indirect readout mechanisms relying on the shape complementarity of the DNA to the protein are essential for GabR-DNA complex formation

Stability Study of Etoricoxib a Selective Cyclooxygenase-2 Inhibitor by a New Single and Rapid Reversed Phase HPLC Method

Cyclooxygenase-2 (COX-2) is an enzyme responsible for inflammation and pain. Etoricoxib is the most recent selective (COX-2) inhibitor that has a higher COX-2 selectivity than the other COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs), which significantly improves its gastric safety profile. The current therapeutic indications of etoricoxib includes the treatment of several painful conditions, such as osteoarthritis, acute gout, ankylosing spondylitis, and rheumatoid arthritis. To the best of found knowledge, no decent method has been reported that can be used for the routine determination of etoricoxib and additives in pharmaceutical suspensions by a single, rapid and cost-effective run of HPLC, using an UV-Vis detector. Earlier reported methods, such as liquid chromatography-mass spectrometry (LC-MS), high performance thin layer chromatography (HPTLC), capillary zone electrophoresis, and ultra performance liquid chromatography (UPLC), are all tedious and time consuming. A reversed phase high performance liquid chromatography (RP-HPLC) was used as a first reported single run method to achieve developed and validated simultaneous determination for sodium saccharin, vanillin, methyl paraben, etoricoxib, and butyl paraben, in prepared oral suspensions of etoricoxib. Reversed phase column of octadecylsilane (ODS) C18 with isocratic mobile phase containing methanol, and phosphate buffer of pH 6 in a ratio of 70:30 (v/v). Celecoxib is used as an internal standard at a detection wavelength of 215 nm. This method separates the analytes in a total running time less than 13 min. Linearity is obtained in the calibration curve for all analytes with a R2 value of &gt; 0.999. Furthermore, beta-cyclodextrin (&beta;-CD) and 2-hydroxypropyl-&beta;-cyclodextrin (HP-&beta;-CD) were added, either alone or combined, to prevent the crystal formation, and any unpleasant taste of etoricoxib in oral formulations. After testing both HP-&beta;-CD and &beta;-CD at 3% w/w for each, the results showed that HP-&beta;-CD is more efficient in preventing the crystal formation of etoricoxib in suspensions at room temperature than &beta;-CD is

THE IMPACT OF URANIUM NEAR A PHOSPHATE MINING PORT ON THE ENVIRONMENT (GULF OF AQABA, JORDAN)

Uranium has three isotopes in nature, the 238U, 235U and 234U. The presence of uranium isotopes in marine sediment at relatively high concentrations was the drivebehind several studies to determine the radionuclides levels in marine ecosystems to assess the potentially negative effects on environment. By using alpha spectroscopy, this study determined the activity concentrations of uranium isotopes in marine sediment and seagrasses from the northern Gulf of Aqaba in Jordan. Samples were collected from a phosphate mining port located at the northern coastline Gulf of Aqaba in Jordan. In marine sediment of the phosphate port, the activity concentrations of alpha emitters were (783.47 - 836.17, 29.43 - 30.43, and 804.56 - 847.80 Bq kg -1) for 238U, 235U and234U, respectively, and (158.19 Bq kg -1) in seagrasses samples. Our results show that the determined levels of uranium radioactive isotopes are more than the internationally accepted limit byapproximately two folds. In conclusion, raw phosphate dusts might be one of the main pollution sources for marine ecosystems in the Gulf of Aqaba