Protein evolution with an expanded genetic code

We have devised a phage display system in which an expanded genetic code is available for directed evolution. This system allows selection to yield proteins containing unnatural amino acids should such sequences functionally outperform ones containing only the 20 canonical amino acids. We have optimized this system for use with several unnatural amino acids and provide a demonstration of its utility through the selection of anti-gp120 antibodies. One such phage-displayed antibody, selected from a naïve germline scFv antibody library in which six residues in V_H CDR3 were randomized, contains sulfotyrosine and binds gp120 more effectively than a similarly displayed known sulfated antibody isolated from human serum. These experiments suggest that an expanded “synthetic” genetic code can confer a selective advantage in the directed evolution of proteins with specific properties.     

The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19

Introduction

Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU).

Methods

In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia.

Results

Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00–8.08, p = 0.050; HR = 3.87, 95% CI = 1.12–13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively.

Conclusion

VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.     

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background

Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy.

Objectives

We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population.

Methods

The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy.

Results

Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy.

Conclusions

In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk.

Citation

Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472     

A systematic review of medical science students' knowledge and related factors towards burns first aids

This systematic review aims to examine the knowledge of medical science students about burn first aid. A comprehensive, systematic search was performed in different international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as “Knowledge”, “First aid”, “Medical science student” and “Burn” from the earliest to February 1, 2023. The quality of the studies included in this systematic review was evaluated by using the appraisal tool for cross-sectional studies (AXIS tool). Thirteen studies had a total of 5046 students studying medical sciences. Among them, 62.24% were female and 77.67% were medical students. The studies included in this systematic review were conducted in Saudi Arabia, Pakistan, Syria, Egypt, and Malaysia. Medical science students' average knowledge of first aid for burns is 56.92 out of 100, which is considered to be a moderate level of knowledge. Factors such as the experience of first aid training, academic year, clinical experience, and economic status had a significant positive relationship with the knowledge of medical science students about first aid for burns. Also, factors such as age, academic specialisation, academic year, information sources, and fathers' occupation had a significant relationship with the knowledge of medical students about first aid for burns. Therefore, it is suggested that healthcare managers and policymakers make the necessary plans to ensure that first aid training courses are implemented during medical science students' studies as a part of their curriculum.     

Perceived stigmatisation and reliability of questionnaire in the survivors with burns wound: A systematic review and meta-analysis

Perceived stigmatisation (PS) can cause different effects on burns survivors such as depression, low self-esteem, body image disturbance, and social anxiety. Current systematic review and meta-analysis aimed to determine the average PS among the burns survivor population and the average reliability of the PS questionnaire (PSQ). A comprehensive systematic search was conducted in various international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as “Stigmatisation”, “Burns”, “Reliability”, and “Questionnaire” from the earliest to February 1, 2023. The COSMIN and the Joanna Briggs Institute (JBI) checklists were applied to evaluate the risk of bias. Data analysis was performed in STATA V.14 and JAMOVI v 2.3.24 software. The analysis consisted of two sections. Firstly, the overall weighted average of PS was calculated based on mean and standard deviation. Then, the reliability average of PSQ was calculated with the reliability generalisation method based on the alpha coefficient, questionnaire items, and sample size of each study. Finally, eight articles were included in the quantitative analysis. The results showed the weighted average of PS was 2.14 (ES: 2.14, 95%CI: 1.77-2.51, Z = 11.40, I²:97.8%, P < 0.001). The average of PS in the factors of confused/staring behaviour, absence of friendly behaviour, and hostile behaviour was 2.36 (ES: 2.36, 95%CI: 2.05-2.67, Z = 14.86, I²:92.7%, P < 0.001), 2.13 (ES: 2.13, 95%CI: 1.87-2.39, Z = 16.22, I²:93.8%, P < 0.001) and 2.07 (ES: 2.07, 95%CI: 1.67-2.47, Z = 10.05, I²:96.5%, P < 0.001), respectively. The analysis showed that the overall coefficient alpha of the PSQ was 0.88 (ES: 0.88, 95%CI: 0.851-0.910, Z = 58.7, I²: 95.04%, P < 0.001). Also, the alpha coefficient of factors including confused/staring behaviour, absence of friendly behaviour, and hostile behaviour were 0.847 (ES: 0.847, 95%CI: 0.770-0.924, Z = 21.6, I²:99.13%, P < 0.001), 0.860 (ES: 0.860, 95%CI: 0.808-0.912, Z = 32.4, I²:98.02%, P < 0.001) and 0.899 (ES: 0.899, 95%CI: 0.829-0.968, Z = 21.33, I²: 0.0%, P < 0.001), respectively. In sum, the current study showed that the average PS was 2.14 out of 5 points. Most survivors and parents reported confused/starring behaviour as a common perceived behaviour from different individuals. Also, the average reliability of PSQ was 0.88, and it had acceptable reliability. More studies are required to better judge the level of PS among different age groups. Also, the psychometric properties of PSQ in different cultures are an essential issue.     

A systematic review of life satisfaction and related factors among burns patients

This systematic review aimed to examine the life satisfaction and related factors among burns patients. A comprehensive systematic search was conducted at the international electronic databases such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as ‘Burns’, ‘Life satisfaction’, ‘Personal satisfaction’, and ‘Patient satisfaction’ from the earliest to the 1 October 2022. The quality of the studies included in this review was evaluated using the appraisal tool for cross-sectional studies (AXIS tool). A total of 3352 burn patients in the nine cross-sectional studies were included in this systematic review. 70.52% of burn patients were male. The mean age of burn patients was 37.47 (SD = 14.73). The mean score of life satisfaction in burn patients based on SWLS was 23.02 (SD = 7.86) out of 35, based on LSI-A was 12.67 (SD = 4.99) out of 20, and based on the life satisfaction questionnaire was 4.81 (SD = 1.67) out of 7. Factors including time since burn, religion, and constant had a positive and significant relationship with life satisfaction in burn patients. Whereas, factors such as single marital status, age at injury, length of hospital stay, presence of pain, larger total body surface area burn, head and neck burn, functional impairment, family satisfaction, satisfaction with appearance, and previous psychiatric treatment had a negative and significant relationship with life satisfaction in burn patients. In sum, this systematic review showed that burn patients were slightly satisfied with their life. Therefore, health managers and policymakers can improve the quality of life of burn victims by planning psychological counselling and behavioural therapy, and consequently increase their life satisfaction.     

Effects of massage therapy on pain and anxiety intensity in patients with burns: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to examine the effects of massage therapy on pain and anxiety intensity in patients with burns. A comprehensive, systematic search was conducted in various international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as ‘Massage therapy’, ‘Musculoskeletal manipulations’, ‘Acute pains’, ‘Burning pain’, and ‘Burn’ from the earliest to October 17, 2022. Cochran's tool is used to check the risk of bias for randomised clinical trial (RCT) articles. The methodological index for non-randomised studies was used to assess the risk of bias in quasi-experimental studies. STATA version 14 software was used to perform the meta-analysis. A 95% confidence interval (CI) was used to determine statistical significance. Heterogeneity was investigated with I². A P-value less than .1 was considered statistically significant for publication bias value. A total of 733 patients with burns were included in seven studies. Five studies had an RCT design and two studies had a quasi-experimental design. The duration of the study was reported in five studies, with a mean of 42.40 weeks. The duration of the intervention was reported in seven studies with a mean of 22.86 minutes. The results of the meta-analysis showed using various types of massage therapy interventions significantly reduced pain intensity in the intervention group compared with the control group (weighted mean difference: −2.08, 95% CI: −2.55 to −1.62, Z = 8.77, I²: 67.1%, P < .001). Massage therapy intervention significantly reduced the intensity of anxiety in burn patients (standard mean difference: −7.07, 95% CI: −10.13 to −4.01, Z = 4.53, I²: 98.2, P < .001). Overall, the present systematic review and meta-analysis showed that massage therapy can reduce the intensity of pain and anxiety in burn patients. Therefore, it is recommended that health managers and policymakers pay special attention to massage therapy as a simple, low-cost, and efficient non-pharmacological treatment to relieve pain and anxiety in burn patients.     

Effects of non-pharmacological interventions on pain intensity of children with burns: A systematic review and meta-analysis

Pain is one of the complications associated with burns, which can lead to anxiety and sleeplessness in children. Various studies evaluated the effects of non-pharmacological interventions on burn wound care. The present study was conducted to determine the effects of non-pharmacological interventions on pain intensity of children with burns. A comprehensive systematic search was conducted in various international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as ‘Non-pharmacological’, ‘Virtual reality’, ‘Pain’, ‘Burn’, ‘Wound’ and ‘Child’ from the earliest to December 1, 2022. The risk of bias in the final articles was also assessed with the Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Finally, a total of 1005 burn patients were included in 19 studies. The age range of the patients was from 0.5 to 19 years. Of the participants, 50.05% were in the intervention group. All studies had a randomised clinical trial design. The results found that non-pharmacological interventions significantly reduced pain intensity in children (ES: −0.73, 95% CI: −1.08 to −0.38, Z = 4.09, I²:79.8, P < .001). Virtual reality (VR) (ES: −0.54, 95% CI: −1.19 to −0.18, Z = 2.90, I²:72.9%, P = .004) and non-VR (ES: -0.86, 95% CI: −1.45 to −0.27, Z = 2.86, I²:91.4%, P = .04) interventions decreased pain intensity significantly in children based sub-group analysis. Non-pharmacological interventions significantly reduced the pain intensity of dressing removal (ES: −0.77, 95% CI: −1.34 to −0.20, Z = 66.3, I²:91.8%, P = .008), dressing application (ES: −0.53, 95% CI: −0.97 to −0.09, Z = 2.37, I²:60.8%, P = .02), and physical therapy (ES: −1.18, 95% CI: −2.10 to −0.26, Z = 2.51, I²:88.0%, P = .01). Also, interventions reduced the pain of burn wound care (ES: −0.29, 95% CI: −1.01 to 0.44, Z = 0.78, I²:72.6%, P = .43), but it was statistically insignificant. In sum, the result of the present study indicated that using non-pharmacological interventions significantly reduced pain intensity in children. The reduction of pain intensity was greater in non-VR than in VR interventions. Future studies should focus on comparing VR interventions with non-VR and single versus multi-modal distraction to clarify the effectiveness of each.     

Pemphigus and pemphigoids: Clinical presentation,diagnosis and therapy

Pemphigus and pemphigoid are two potentially life-threatening groups of autoimmune diseases, characterized by autoantibodies targeting structural components of desmosomes or hemidesmosomes, respectively. Affected patients typically show itchy/painful plaques or blistering skin lesions and/or impairing mucosal blistering and erosions, which may strongly impact their quality of life. Since the milestone work of Walter Lever in 1953, who differentiated these two groups of diseases by histopathological analysis of the level of antibody-mediated skin cleavage, enormous progresses occurred. Achievements made in laboratory diagnostics now allow to identify antigen specific structural proteins of the skin that are targeted by pathogenic autoantibodies. These progresses were accompanied by an increased understanding of the pathogenesis of these diseases thanks to the establishment of animal models reproducing disease and on studies on skin and blood of affected individuals, which have been leading to novel and disease-specific treatments. Yet, given their phenotypical overlap with more common dermatological diseases, correct diagnosis and appropriate treatment are often delayed, in some cases leading to irreversible sequelae, including organ dysfunction (i.e., loss of vision in mucous membrane pemphigoid). Here, we provide a concise overview of the clinical appearance, diagnosis and therapeutic management of pemphigus and pemphigoid diseases.