bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboxymethyl-γ-cyclodextrin, a novel selective relaxant binding agent for the reversal of neuromuscular block induced by aminosteroid neuromuscular blockers: an ex vivo laboratory study
Authors: Fábián Ákos I. , Tassonyi Edömér , Csernoch Vera , Fedor Marianna , Sohajda Tamás , Szente Lajos , Fülesdi Béla
Published: August 2021

Background

Residual neuromuscular block at the end of surgery may compromise the patient’s safety. The risk of airway complications can be minimized through monitoring of neuromuscular function and reversal of neuromuscular block if needed. Effective reversal can be achieved with selective relaxant binding agents, however, sugammadex is the only clinically approved drug in this group.

We investigated the concentration–response properties of a novel selective relaxant binding agent, carboxymethyl-γ-cyclodextrin for the reversal of neuromuscular block. We evaluated the hypothesis that it is equally potent for reversing neuromuscular block as sugammadex.

Methods

Phrenic nerve – hemidiaphragm tissue preparations were isolated from male Wistar rats and suspended in a tissue holder allowing electrical stimulation of the nerve and monitoring of muscle contraction force. Concentration–response relationships were constructed for the neuromuscular blocking agents rocuronium, pipecuronium, and vecuronium. The half-effective concentrations of sugammadex and carboxymethyl-γ-cyclodextrin for reversal of neuromuscular block were determined.

Results

The half effective concentrations (95% confidence interval, CI) were 7.50 (6.93–8.12) μM for rocuronium, 1.38 (1.33–1.42) μM for pipecuronium, and 3.69 (3.59–3.80) μM for vecuronium. The half effective concentrations (95% CI) of carboxymethyl-γ-cyclodextrin and sugammadex were 35.89 (32.67–39.41) μM and 3.67 (3.43–3.92) μM, respectively, for the reversal of rocuronium-induced block; 10.14 (9.61–10.70) μM and 0.67 (0.62–0.74) μM, respectively, for the reversal of pipecuronium-induced block; and 376.1 (341.9–413.8) μM and 1.45 (1.35–1.56) μM, respectively, for the reversal of vecuronium-induced block.

Conclusions

Carboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.
Increased ratio of sST2/LVMI predicted cardiovascular mortality and heart failure rehospitalization in heart failure with reduced ejection fraction patients: a prospective cohort study
Authors: Li Fuhai , Xu Mengying , Fu Mingqiang , Cui Xiaotong , Lian Zhexun , Xin Hui , Zhou Jingmin , Ge Junbo
Published: August 2021

Background

Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction.

Methods

This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model.

Results

Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan–Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm.

Conclusion

In patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.
Mucormycosis-induced upper gastrointestinal ulcer perforation in immunocompetent patients: a report of two cases
Authors: Huang Hongyun , Xie Lang , Zheng Zheng , Yu Hanhui , Tu Lingjing , Cui Chunhui , Yu Jinlong
Published: August 2021

Background

Gastrointestinal mucormycosis (GIM) is a rare, opportunistic fungal infection with poor prognosis. Clinically, it is difficult to diagnose GIM owing to its nonspecific clinical symptoms and poor suspicion. The estimated incidence of GIM is inaccurate, and most cases are diagnosed accidentally during surgery or upon postmortem examination. GIM usually occurs in patients with immune deficiencies or diabetes. Here, we report two cases of immunocompetent young patients with GIM who had good prognosis after treatment. Compared to other case reports on GIM, our cases had unusual infection sites and no obvious predisposing factors, which make it important to highlight these cases.

Case presentation

The first case was that of a 16-year-old immunocompetent boy who was admitted with gastrointestinal bleeding and perforation due to a gastric ulcer. Strategies used to arrest bleeding during emergency gastroscopy were unsuccessful. An adhesive mass was then discovered through laparoscopy. The patient underwent type II gastric resection. Pathological examination of the mass revealed bacterial infection and GIM. The second case was of a 33-year-old immunocompetent woman with a recent history of a lower leg sprain. The patient subsequently became critically ill and required ventilatory support. After hemodynamic stabilization and extubation, she presented with hematemesis due to exfoliation and necrosis of the stomach wall. The patient underwent total gastrectomy plus jejunostomy. The pathology results revealed severe bacterial infection and fungal infection that was confirmed as GIM. The patient fully recovered after receiving anti-infective and antifungal treatments.

Conclusions

Neither patient was immunosuppressed, and both patients presented with gastrointestinal bleeding. GIM was confirmed via pathological examination. GIM is not limited to immunocompromised patients, and its diagnosis mainly relies on pathological examination. Early diagnosis, timely surgical treatment, and early administration of systemic drug treatment are fundamental to improving its prognosis.
Nosocomial sepsis and drug susceptibility pattern among patients admitted to adult intensive care unit of Ayder Comprehensive Specialized Hospital, Northern Ethiopia
Authors: Dawit Tsega Cherkos , Mengesha Reiye Esayas , Ebrahim Mohamedawel Mohamedniguss , Tequare Mengistu Hagazi , Abraha Hiluf Ebuy
Published: August 2021

Objective

Developing nosocomial sepsis within intensive care unit (ICU) is associated with increased mortality, morbidity, and length of hospital stay. But information is scarce regarding nosocomial sepsis in intensive care units of Northern Ethiopia. Hence, this study aims to determine the incidence of nosocomial sepsis, associated factors, bacteriological profile, drug susceptibility pattern, and outcome among patients admitted to the adult ICU of Ayder Comprehensive Specialized Hospital (ACSH), which is the largest tertiary hospital in Northern Ethiopia.

Method

Facility-based longitudinal study was conducted by following 278 patients who were admitted for more than 48 h to adult ICU of ACSH, from October 2016 to October 2017. Data were collected from charts, electronic medical records, and microbiology registration book using a checklist. The collected data were subjected to descriptive statistics and multivariable logistic regression using SPSS version 25. Statistical significance was declared at p < 0.05.

Result

Of all the patients, 60 (21.6%) of them acquired nosocomial sepsis. The risk of mortality was about two times higher among adult ICU patients who acquired nosocomial sepsis (RR = 2.2; 95% CI of RR = 1.3–3.5; p = 0.003). The odds of acquiring nosocomial sepsis among those who were on a mechanical ventilator (MV) and stayed more than a week were 5.7 and 9.3 times higher, respectively, than their corresponding counterparts. Among 48 isolates, Klebsiella was the most common pathogen. The isolates had a broad antibiotic resistance pattern for cephalosporins, penicillins, and methicillin.

Conclusion

The incidence of nosocomial sepsis in the adult ICU patients of ACSH was higher when compared to the incidence reported from some African and Asian countries. Mortality was higher among patients who acquired nosocomial sepsis. Use of MV and longer length of ICU stay were the significant predictors of nosocomial sepsis. The isolates were resistant to several antibiotics. Therefore, strict application of infection prevention strategies and appropriate use of antibiotics is so crucial. As well, priority should be given to patients who develop nosocomial sepsis in ICU.
Use of monitoring indicators in hospital management of antimicrobials
Authors: da Silva Ravena Melo Ribeiro , de Mendonça Simonize Cunha B. , Leão Ingrid Novaes , dos Santos Quesia Nery , Batista Alessandra Macedo , Melo Matheus Santos , Xavier Milena da Motta , Quintans Júnior Lucindo José , da Silva Wellington Barros , Lobo Iza Maria Fraga
Published: August 2021

Background

According to the literature, 25% to 50% of antimicrobials prescribed in hospitals are unnecessary or inappropriate, directly impacting antimicrobial resistance. Thus, the present study aimed to evaluate the use of antimicrobials in a university hospital in Northeast Brazil, using days of therapy (DOT) and length of therapy (LOT) indicators in accordance with the latest national and international recommendations for monitoring the use of antimicrobials.

Methods

This is an observational, prospective analytical study conducted in a teaching hospital, with 94 active beds, distributed between the intensive care unit (ICU), the surgical clinic (SUR), the medical clinic (MED), the pneumology/infectology department (PNE/INF) and pediatrics (PED). The duration of the study was from the beginning of January to the end of December 2018.

Results

During the study period, a total of 11,634 patient-days were followed up and 50.4% of the patients were found to have received some antimicrobial, with a significant reduction in use of 1% per month throughout the year. Patients were receiving antimicrobial therapy for 376 days in every 1000 days of hospitalization (LOT = 376/1000pd). Overall, the 1st-generation cephalosporins and fluoroquinolones were the most used in respect of the number of prescriptions and the duration of therapy. The calculated global DOT/LOT ratio showed that each patient received an average of 1.5 antimicrobials during the hospital stay. The incidence of antimicrobial resistance, globally, for both methicillin-resistant Staphylococcus aureus (methicillin R), Carbapenem-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii (Carbapenem R), was 1 per 1000 patient-days.

Conclusions

The results obtained from the analyses revealed that half of the patients admitted to the hospital who took part in the study were exposed to the use of antimicrobials at some point during their stay. Although moderate, it is noteworthy that there was a decline in the use of antimicrobials throughout the year. The indicators used in this study were found to be very effective for gathering data on the use of antimicrobials, and assessing the results of the initiatives taken as part of the Stewardship program.
Epidemiology of patients with central nervous system infections, mainly neurosurgical patients: a retrospective study from 2012 to 2019 in a teaching hospital in China
Authors: Zhang Zheng , Song Yan , Kang Jianbang , Duan Surong , Li Qi , Feng Fuqiang , Duan Jinju
Published: August 2021

Background

Central nervous system (CNS) infections are relatively rare but are associated with high mortality worldwide. Empirical antimicrobial therapy is crucial for the survival of patients with CNS infections, and should be based on the knowledge of the pathogen distribution and antibiotic sensitivities. The aim of this study was to investigate the features of pathogens in patients with CNS infections in North China and evaluate the risk factors for mortality and multi-drug-resistant (MDR) bacterial infections.

Methods

A retrospective study was conducted with patients with positive cerebrospinal fluid (CSF) cultures in a teaching hospital from January 2012 to December 2019. The following data were collected: demographic characteristics, laboratory data, causative organisms and antimicrobial sensitivity results. Data were analyzed with SPSS 16.0. Univariate analysis and binary logistic regression analyses were performed to identify the risk factors for mortality and MDR bacterial infections.

Results

A total of 72 patients were diagnosed with CNS infections, and 86 isolates were identified. The proportions of Gram-positive bacteria, Gram-negative bacteria and fungi were 59.3, 30.2 and 10.5%, respectively. The predominant Gram-positive bacteria was Coagulase-negativeStaphylococci.Acinetobacter baumannii,Escherichia coliandKlebsiellaspp. were the predominant Gram-negative bacteria. Compared to 2012–2015 years, the proportion of Gram-negative bacteria increased markedly during 2016–2019 years. Coagulase-negativeStaphylococci,Streptococcus pneumoniaeandEnterococcus faeciumhad 100% sensitivity to vancomycin, teicoplanin and linezolid.Acinetobacter baumanniiandKlebsiella pneumoniaewere 100% sensitive to tigecycline.Escherichia colihad 100% sensitivity to amikacin, meropenem and imipenem. The overall mortality rate in the 72 patients was 30.6%. In multivariate analysis, age > 50 years, pulmonary infections and CSF glucose level < the normal value were associated with poor outcomes. CSF adenosine deaminase level > the normal value and the presence of external ventricular drainage/lumbar cistern drainage were associated with MDR bacterial infections.

Conclusions

The mortality rate due to CNS infections reached 30.6% in our study. The proportion of Gram-negative bacteria has increased markedly in recent years. We should give particular attention to patients with risk factors for mortality and MDR bacterial infections mentioned above.
Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer
Authors: Nahand Javid Sadri , Khanaliha Khadijeh , Mirzaei Hamed , Moghoofei Mohsen , Baghi Hossein Bannazadeh , Esghaei Maryam , Khatami Ali Reza , Fatemipour Maryam , Bokharaei-Salim Farah
Published: August 2021

Background

This study aimed to evaluate the possible role of human papillomavirus (HPV) and Epstein–Barr virus (EBV) coinfection as an etiological factor for prostate cancer (PCa) development.

Methods

This case-control study was conducted on 67 patients with PCa and 40 control subjects. The expression levels of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantified, using the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assay.

Results

The EBV/HPV coinfection was reported in 14.9% of patients in the case group and 7.5% of the control subjects. The high-risk types of HPV, that is, HPV 16 and HPV 18, were responsible for 50 and 30% of HPV/EBV-coinfected PCa cases (n = 10), respectively. No significant relationship was observed between PCa and HPV/EBV coinfection (OR = 2.9, 95% CI: 0.18–45.2, P = 0.31). However, the highest percentage of HPV genome integration was found in the HPV/EBV-coinfected PCa group (8/10; 80%). Also, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS, and RNS), anti-apoptotic mediators (Bcl-2 and survivin), and anti-anoikis factors (Twist and N-cadherin) were significantly higher in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Nevertheless, the tumor-suppressor proteins (p53 and pRb) and E-cadherin (inhibitor of anoikis resistance) showed significant downregulations in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases.

Conclusion

The HPV/EBV coinfection may be an etiological factor for PCa through modulation of cellular behaviors.
Risk of hypertension in school-aged children with different parental risk: a longitudinal study from childhood to young adulthood
Authors: Amiri Parisa , Rezaei Marjan , Jalali-Farahani Sara , Karimi Mehrdad , Cheraghi Leila , Esbati Romina , Azizi Fereidoun
Published: August 2021

Background

Although previous studies have shown the relationship between different parental factors and children’s blood pressure status, there is limited data on the cumulative effect of these factors. Considering parental socio-demographic, behavioral and cardio-metabolic characteristics, the current study aimed to distinguish parental risk clusters and their impact on the incidence of hypertension in school-age children over 13 years.

Methods

Parental characteristics of 1669 children, including age, education, employment, smoking, physical activity, metabolic syndrome (MetS), hypertension (HTN), weight status, and diabetes were considered to categorize parents into low and high-risk clusters. Crude incidence rates (per 10,000 person-years) of HTN in children were assessed in each maternal and paternal cluster. Using Cox proportional hazard model, results on the association between parental risk clusters and HTN incidence in children were reported in five different models.

Results

Mean age of children was 13.96 ± 2.89 years, and 51.2% (n = 854) were girls. MetS, HTN, and weight status were the most important factors distinguishing low and high-risk parental clusters, respectively. Crude incidence rates (per 10,000 person-years) of HTN were 86 (95% CI: 71–106) and 38 (95% CI, 29–52) in boys and girls, respectively. Moreover, incidence rates (per 10,000 person-years) of HTN were 50 (95% CI, 40–63) and 80 (95% CI, 64–102) in maternal low and high-risk clusters, respectively. The incidence rates (per 10,000 person-years) of HTN in paternal low and high-risk clusters were 53 (95% CI, 41–70) and 68 (95% CI, 56–84), respectively.

Conclusion

Our findings underscore the prognostic value of maternal characteristics in predicting the incidence of HTN in their offspring. The current results could be valuable in planning related programs to prevent hypertension in similar communities.
Objectively measured physical activity and sedentary time in children with overweight, obesity and morbid obesity: a cross-sectional analysis
Authors: ten Velde Gabrielle , Plasqui Guy , Dorenbos Elke , Winkens Bjorn , Vreugdenhil Anita
Published: August 2021

Background

Limited physical activity (PA) and a high level of sedentary time (ST) are associated with childhood obesity and are a target for intervention. This study aimed to assess objectively measured PA and ST in Dutch children across weight categories, age groups and sex.

Methods

202 children with overweight, obesity and morbid obesity (55% girls, 12 ± 3y of age, BMI z-score + 3.15 ± 0.73), referred to the Centre for Overweight Adolescents and Children’s Healthcare (COACH, Maastricht UMC+) were included. PA (total PA, light PA and moderate to vigorous PA (MVPA)) and ST were measured with the GT3X Actigraph accelerometer. Wear time validation was set to include at least four days, 480 min/day, including one weekend day.

Results

PA levels in children with morbid obesity were higher compared to children with obesity, also after correction for age and sex (corrected difference (B) 118 counts per minute (cpm), p = .006). ST was lower in children with morbid obesity compared to children with obesity (B − 51 min/day, p = .018). Girls performed significantly less MVPA than boys (B − 11 min/day, p < .001) and for each year increase of age, children performed less PA (B − 46 cpm, p < .001) and ST increased (B 18 min/day, p < .001).

Conclusion

PA and ST is different in subgroups of children with overweight, obesity and morbid obesity, depending on sex, age and overweight severity. In particular, children with obesity perform less PA and more ST compared to children with morbid obesity. Future research could explore the preferences and needs for PA and ST in children in the different weight categories.

Trial registration

The trial is registered with Clinicaltrials.govNCT02091544 at March 19, 2014.
Gait biomechanics in patients with intra-articular tibial plateau fractures – gait analysis at three months compared with age- and gender-matched healthy subjects
Authors: Fändriks Anna , Tranberg Roy , Karlsson Jón , Möller Michael , Zügner Roland
Published: August 2021

Introduction

Tibial plateau fractures involve the knee joint, one of the most weight-bearing joints in the body. Studies have shown that gait asymmetries exist several years after injury. Instrumental gait analysis, generating both kinematic and kinetic data from patients with tibial plateau fractures, is uncommon.

Aim

To examine walking ability and knee range of motion in patients suffering intra-articular tibial plateau fractures.

Method

Twenty participants, eight males and 12 females, aged 44 years (range 26–60), with unilateral isolated tibial plateau fractures, were examined 12 weeks (range 7–20) after injury. The investigation consisted of passive range of motion (ROM) using a goniometer, six-minute walking test (6 MW), pain estimation using the visual analogue scale (VAS), the “Knee injury and Osteoarthritis Outcome Score” (KOOS) self-assessment questionnaire and instrumental 3-dimensional gait analysis (3DGA). 3DGA included spatiotemporal variables (speed, relative stance time, step length), kinematic variables (knee flexion, knee extension, ankle dorsiflexion) and kinetic variables (generating knee power (extension) and ankle power (plantarflexion)). A skin marker model with twenty reflective markers was used. Non-parametric tests were used for comparisons of the injured leg, the uninjured leg and a reference group.

Result

The participants walked more slowly compared with healthy references (p < 0.001). Stance time and step length was shorter for the injured side compared with the uninjured side (p < 0.014). Step length was shorter compared with the reference group (p = 0.001). The maximum knee extension in the single stance phase was worse in the injured side compared with the uninjured side and the reference group (p < 0.001) respectively. The maximum ankle dorsiflexion during stance phase was higher in the injured leg compared with the uninjured side and the reference group (p < 0.012). Maximum generated power in the knee was lower in the injured side compared with the uninjured side and the reference group (p < 0.001 respectively). The same was true of maximum power generated in the ankle (p < 0.023). The median KOOS value was lower in the study group (p < 0.001). ROM showed decreased flexion and extension in the knee joint and decreased dorsiflexion in the ankle joint compared with the uninjured side (p < 0.006). The average distance in the six-minute walking test was shorter in the study group (p < 0.001).

Conclusion

Patients who have sustained tibial plateau fractures generally display a limitation in their walking pattern 3 months after injury. These limitations are mainly related to the inability to extend the knee.
“Slipped capital femoral epiphysis in a 25-year-old hypogonadic man with a large cranial chondroma: causality or coincidence? “
Authors: Sawicka-Gutaj Nadia , Woźniak Waldemar , Naczk Jakub , Pochylski Mateusz , Kruczyński Jacek , Budny Bartłomiej , Szczepanek-Parulska Ewelina , Ruchała Marek
Published: August 2021

Background

Slipped capital femoral epiphysis (SCFE) is a hip disorder frequently occurring in adolescence. In adults it is rare and so far very few cases have been documented.

Case presentation

This report presents a 25-year-old patient diagnosed with an anterior fossa giant chondroma, hypogonadotropic hypogonadism, and SCFE. The patient underwent surgical and hormonal therapy. His symptoms revealed, and he became a father.

Conclusions

Every patient diagnosed with SCFE in adulthood should undergo endocrinological assessment based on physical examination and laboratory tests.
Predictors of self-medication with herbal remedies during pregnancy based on the theory of planned behavior in Kashan, Iran
Authors: Karimian Zahra , Sadat Zohreh , Afshar Bahareh , Hasani Maryam , Araban Marzieh , Kafaei-Atrian Mahbubeh
Published: August 2021

Background

The incidence of application of medicinal herbs during pregnancy has increased significantly among women over the past years; however, the safety and efficacy of medicinal herbs during pregnancy are still unclear. The aim of the present study was to categorize the predictors of self-medication with herbal remedies during pregnancy based on the theory of planned behavior (TPB).

Methods

The present descriptive-analytical study was conducted on 300 pregnant women referred to Kashan health center to receive prenatal care services in 2020. The study participants were randomly selected using stratified random sampling with proportional allocation. The data collection tool was a two-part researcher made questionnaire. The first part of the questionnaire included demographic information, midwifery information, and questions related to women’s awareness about herbal medicine. The second part of the questionnaire was designed based on the theory of planned behavior including attitudes, perceived behavioral control, subjective norms, intention, and behavior performance. Data were analyzed using descriptive statistics, regression analysis, and SPSS version 18.0.

Results

The mean age of participants was 28. 7±5.4 years (range, 15–45 years), the majority were housewives (88.3%) and had secondary education (39.3%). A total of 164 women (57. 1%) used medicinal herbs during pregnancy. The individual’s attitude towards herbal medicines consumption, subjective norm, and perceived behavioral control was correlated with behavioral intention (P < 0.05). Similarly, subjective norms were the most predictor of using herbal medicine among pregnant women (P < 0.05).

Conclusion

The findings revealed that more than 50 % of pregnant women used medicinal herbs during pregnancy. The present study showed that the individual’s attitude towards herbal medicines consumption, subjective norm, and perceived behavioral control was correlated with intention of herbal medicine use among pregnant women. Likewise, subjective norms were the most predictor of herbal medicine use among pregnant women. The TPB should be addressed in planning health education programs and modifying health behaviors, including self-medication, especially during pregnancy.
Barriers to accessing health care among undocumented migrants in Sweden - a principal component analysis
Authors: Mona Hatem , Andersson Lena M.C. , Hjern Anders , Ascher Henry
Published: August 2021

Background

Undocumented migrants face many hardships in their everyday life such as poor living conditions, discrimination, and lack of access to healthcare. Previous studies have demonstrated considerable health care needs for psychiatric disorders as well as physical diseases. The aim of this paper was to find out the main barriers that undocumented migrants experience in accessing the Swedish healthcare system and to explore their relation with socioeconomic factors.

Methods

A cross-sectional study with adult undocumented migrants was performed in the three largest cities of Sweden in 2014–2016. Sampling was done via informal networks. A socioeconomic questionnaire was constructed including 22 barriers to health care. Trained field workers conducted the interviews. A principal component analysis was conducted of all barriers to reveal central components. Then, Pearson’s chi-squared test was used to explore the characteristics of undocumented migrants experiencing barriers to care.

Results

Two main components/barriers were extracted: “Fear of being taken by police/authorities”, which was related to fear of disclosure by or in relation to seeking health care, and “Structural and psychosocial factors” which was related to practical obstacles or shame of being ill. Lower age (74.1 % vs 56.0 %), lower level of education (75.0 % vs. 45.1 %), and having no children (70.3 % vs. 48.1 %) were significantly related to a higher likelihood of experiencing a barrier.

Conclusion

Fear of deportation and practical and psychosocial factors constitute hinderance of access to healthcare for undocumented migrants in Sweden. This highlights the importance of clear instructions, both to undocumented migrants and health professionals about the right to health care according to the international law on human rights as well as the law of confidentiality.
Ultrafine particle levels measured on board short-haul commercial passenger jet aircraft
Authors: Michaelis Susan , Loraine Tristan , Howard C. V.
Published: August 2021

Background

Airline crew members report adverse health effects during and after inhalation exposure to engine oil fumes sourced to the air supply system onboard commercial and military aircraft. Most investigations into the causal factors of their reported symptoms focus on specific chemical contaminants in the fumes. The adverse health effects reported in aircrew exposed to the aircraft air supply, bled unfiltered off the engine or Auxiliary Power Unit (APU) may be related to particulate exposures, which are widely known to effect health. While oil contaminates the aircraft air supply, some suggest that this will only occur when there is a bearing seal failure, others document that there is low level oil contamination of the air supply during normal engine operation. This brief pilot study explores whether particulate exposure may be associated with the normal engine/APU and air supply operation and to therefore increase the understanding that UFP exposures may have on crew and passengers.

Methods

An ultrafine particle counter was utilised by an experienced airline captain in the passenger cabin of four short-haul commercial passenger aircraft. All flights were under 90 min on aircraft from two different carriers ranging from 7 months to 14 years old.

Results

UFP concentrations showed maximum concentrations ranging from 31,300 to 97,800 particles/cm3 when APU was selected on as a source of air on the ground and with engine bleed air and the air conditioning packs selected on during the climb. In 2 of the 4 flights the peaks were associated with an engine oil smell. Increases in UFP particle concentrations occurred with changes in engine/APU power and air supply configuration changes.

Conclusions

This study identified increases in UFP concentrations associated with engine and APU power changes and changes in air supply configuration. These results correlated with times when engine and APU oil seals are known to be less effective, enabling oil leakage to occur. The concentrations reached in the passenger cabins exceeded those taken in other ground-based environments. UFP exposures in aircraft cabins during normal flight indicates there will be health consequences for long serving aircrew and some passengers.
Cells of the human respiratory tract support the replication of pathogenic Old World orthohantavirus Puumala
Authors: Hägele Stefan , Nusshag Christian , Müller Alexander , Baumann Alexandra , Zeier Martin , Krautkrämer Ellen
Published: August 2021

Background

Transmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eurasia cause hemorrhagic fever with renal syndrome (HFRS) and New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS). However, cases of infection with Old World orthohantaviruses with severe pulmonary manifestations have also been observed. Therefore, human airway cells may represent initial targets for orthohantavirus infection and may also play a role in the pathogenesis of infections with Eurasian orthohantaviruses.

Methods

We analyzed the permissiveness of primary endothelial cells of the human pulmonary microvasculature and of primary human epithelial cells derived from bronchi, bronchioles and alveoli for Old World orthohantavirus Puumala virus (PUUV) in vitro. In addition, we examined the expression of orthohantaviral receptors in these cell types. To minimize donor-specific effects, cells from two different donors were tested for each cell type.

Results

Productive infection with PUUV was observed for endothelial cells of the microvasculature and for the three tested epithelial cell types derived from different sites of the respiratory tract. Interestingly, infection and particle release were also detected in bronchial and bronchiolar epithelial cells although expression of the orthohantaviral receptor integrin β3 was not detectable in these cell types. In addition, replication kinetics and viral release demonstrate enormous donor-specific variations.

Conclusions

The human respiratory epithelium is among the first targets of orthohantaviral infection and may contribute to virus replication, dissemination and pathogenesis of HFRS-causing orthohantaviruses. Differences in initial pulmonary infection due to donor-specific factors may play a role in the observed broad variance of severity and symptoms of orthohantavirus disease in patients. The absence of detectable levels of integrin αVβ3 surface expression on bronchial and small airway epithelial cells indicates an alternate mode of orthohantaviral entry in these cells that is independent from integrin β3.
Quality of life of transplanted children and their parents: a cross-sectional study
Authors: Duvant Pauline , Fillat Magali , Garaix Florentine , Roquelaure Bertrand , Ovaert Caroline , Fouilloux Virginie , Tsimaratos Michel , Auquier Pascal , Fabre Alexandre , Baumstarck Karine
Published: August 2021

Background

Transplantation is a saving therapeutic that has heavy consequences. The quality of life (QoL) of transplanted children and their parents has been little studied and should help physicians better manage these patients. The objectives of the study were to assess: (1) the QoL of transplanted children and parents and compare it with that of children with other chronic conditions associated with long-term consequences, and (2) potential variables modulating the QoL.

Methods

This cross-sectional study was performed in a multidisciplinary paediatric unit (Timone Hospital, Marseille, France). Children were less than 18 years old; had a liver, kidney or heart transplant; and had a time since transplantation of 1–10 years. Socio-demographics and clinical data were recorded from medical forms. The QoL was assessed using the VSP-A (Vécu et Santé Perçue de l’Adolescent et de l’Enfant) and the WhoQoL self-reported questionnaires.

Results

Forty-five families were included (response rate: 76%). The transplanted organs were the liver for 20 children, the kidney for 15 children, and the heart for 10 children. The QoL of transplanted children reported by their parents was better than that of children with inborn errors of metabolism and similar to that of childhood leukaemia survivors. The QoL of parents of transplanted children was better than that of parents of children with inborn errors of metabolism and did not differ from French norms. The QoL did not differ according to the nature of the transplanted organ, sex or the main sociodemographic data. The main modulators decreasing QoL were residual treatment level, medications switch and the presence of another regular treatment.

Conclusion

Transplanted children and their families reported a fairly preserved QoL compared to children with other chronic health conditions. Special attention should be given to QoL modulators related to therapeutic management (medication switches, regular treatments) that might be amenable to improve the QoL.

Trial registrationEthics committee of Aix-Marseille University, France (reference number: 2014-08-04-03, 24/4/2015;https://www.univ-amu.fr/fr/public/comite-dethique).
Identification of novel COX-2 / CYP19A1 axis involved in the mesothelioma pathogenesis opens new therapeutic opportunities
Authors: Nuvoli Barbara , Antoniani Barbara , Libener Roberta , Maconi Antonio , Sacconi Andrea , Carosi Mariantonia , Galati Rossella
Published: August 2021

Background

Based on previous studies highlighting that the induction of cyclooxygenase-2 (COX-2) and high prostaglandin E2 (PGE2) levels contribute to the pathogenesis of malignant pleural mesothelioma (MPM), and that aromatase (CYP19A1), an enzyme that plays a key role in estrogen biosynthesis, along with estradiol (E2) were expressed in MPM, this study aimed to investigate the possible interplay between COX-2 and CYP19A1 in the pathogenesis of mesothelioma, as well as the underlying mechanism.

Methods

The interaction between COX-2 and CYP19A1 was first investigated on different MPM lines upon PGE2, and COX-2 inhibitor (rofecoxib) treatment by western blot, RT-PCR. The key regulatory pathways involved in the COX-2 and CYP19A1 axis were further studied in MPM cells, after rofecoxib and exemestane (CYP19A1 inhibitor) treatment in monotherapy and in combination, by cell cycle distribution, western blot, and combination index analysis. To explore the role of COX-2/CYP19A1 axis in 3D preclinical models of MPM cells, we analyzed the effect of combination of COX-2 and CYP19A1 inhibitors in mesosphere formation. Immunohistochemical analysis of MPM mesosphere and specimens was utilized to evaluate the involvement of COX-2 on the CYP19A1 activity and the relationship between E2 and COX-2.

Results

PGE2 or rofecoxib treatment caused in MPM cells an increased or decreased, respectively, CYP19A1 expression at mRNA and protein levels. The effect of rofecoxib and exemestane combination in MPM cell proliferation was synergistic. Activation of caspase-3 and cleavage of PARP confirmed an apoptotic death for MPM cell lines. Increased expression levels of p53, p21, and p27, downregulation of cyclin D1 and inhibition of Akt activation (pAKT) were also found. The antagonistic effect of rofecoxib and exemestane combination found only in one cell line, was reverted by pretreatment with MK2206, a pAKT inhibitor, indicating pAKT as an actionable mediator in the COX-2-CYP19A1 axis. Reduction of size and sphere-forming efficiency in MPM spheres after treatment with both inhibitor and a decrease in COX-2 and E2 staining was found. Moreover, immunohistochemical analysis of 46 MPM samples showed a significant positive correlation between COX-2 and E2.

Conclusions

Collectively, the results highlighted a novel COX-2/CYP19A1 axis in the pathogenesis of MPM that can be pharmacologically targeted, consequently opening up new therapeutic options.
Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort
Authors: Magunia Harry , Lederer Simone , Verbuecheln Raphael , Gilot Bryant Joseph , Koeppen Michael , Haeberle Helene A. , Mirakaj Valbona , Hofmann Pascal , Marx Gernot , Bickenbach Johannes , Nohe Boris , Lay Michael , Spies Claudia , Edel Andreas , Schiefenhövel Fridtjof , Rahmel Tim , Putensen Christian , Sellmann Timur , Koch Thea , Brandenburger Timo , Kindgen-Milles Detlef , Brenner Thorsten , Berger Marc , Zacharowski Kai , Adam Elisabeth , Posch Matthias , Moerer Onnen , Scheer Christian S. , Sedding Daniel , Weigand Markus A. , Fichtner Falk , Nau Carla , Prätsch Florian , Wiesmann Thomas , Koch Christian , Schneider Gerhard , Lahmer Tobias , Straub Andreas , Meiser Andreas , Weiss Manfred , Jungwirth Bettina , Wappler Frank , Meybohm Patrick , Herrmann Johannes , Malek Nisar , Kohlbacher Oliver , Biergans Stephanie , Rosenberger Peter
Published: August 2021

Background

Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes.

Methods

A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported.

Results

1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy.

Conclusions

Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models.

Trial registration“ClinicalTrials” (clinicaltrials.gov) under NCT04455451.
CoCoA-diff: counterfactual inference for single-cell gene expression analysis
Authors: Park Yongjin P. , Kellis Manolis
Published: August 2021

Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables in single-cell RNA-seq data. We demonstrate that our method substantially improves statistical power in simulations and real-world data analysis of 70k brain cells collected for dissecting Alzheimer’s disease. We identify 215 differentially regulated causal genes in various cell types, including highly relevant genes with a proper cell type context. Genes found in different types enrich distinctive pathways, implicating the importance of cell types in understanding multifaceted disease mechanisms.
Characterization and evaluation of a recombinant multiepitope peptide antigen MAG in the serological diagnosis of Toxoplasma gondii infection in pigs
Authors: Song Yongle , Zhao Yongjuan , Pan Ke , Shen Bang , Fang Rui , Hu Min , Zhao Junlong , Zhou Yanqin
Published: August 2021

Background

Toxoplasmosis caused by Toxoplasma gondii is a serious disease threatening human and animal health. People can be infected with T. gondii by ingesting raw pork contaminated with cysts or oocysts. Serological test is a sensitive and specific method usually used for large-scale diagnosis of T. gondii infection in humans and animals (such as pigs). Commercial pig Toxoplasma antibody ELISA diagnostic kits are expensive, which limits their use; moreover, the wide antigen composition used in these diagnostic kits is still unclear and difficult to standardize. The multiepitope peptide antigen is a novel diagnostic marker, and it has potential to be developed into more accurate and inexpensive diagnostic kits.

Methods

The synthetic multiepitope antigen (MAG) cDNA encoding a protein with epitopes from five T. gondii-dominant antigens (SAG1, GRA1, ROP2, GRA4, and MIC3) was designed, synthesized, and expressed in Escherichia coli BL21 (DE3) strain. The recombinant protein was detected through western blot with pig anti-T. gondii-positive and -negative serum, and then IgG enzyme-linked immunosorbent assay (ELISA) named MAG-ELISA was designed. The MAG-ELISA was evaluated in terms of specificity, sensitivity, and stability. The MAG-ELISA was also compared with a commercial PrioCHECK®Toxoplasma Ab porcine ELISA (PrioCHECK ELISA). Finally, the trend of pig anti-T. gondii IgG levels after artificial infection with RH tachyzoites was evaluated using MAG-ELISA and two other ELISA methods (rMIC3-ELISA and PrioCHECK ELISA).

Results

MAG antigen could be specifically recognized by pig anti-T. gondii-positive but not -negative serum. MAG-ELISA showed high diagnostic performance in terms of specificity (88.6%) and sensitivity (79.1%). MAG-ELISA could be used for detecting anti-T. gondii IgG in the early stage of T. gondii infection in pigs (at least 7 days after artificial infection).

Conclusions

Our results suggest that MAG antigen can be applied to specifically recognize anti-T. gondii IgG in pig, and MAG-ELISA has the potential for large-scale screening tests of T. gondii infection in pig farms and intensive industries.

Graphical abstract
Reliability of ultrasound versus digital vaginal examination in detecting cervical dilatation during labor: a diagnostic test accuracy systematic review
Authors: Mohaghegh Zaynab , Jahanfar Shayesteh , Abedi Parvin , El Aziz Mohamed A. Abd
Published: August 2021

Background

This systematic review aimed to investigate the reliability of ultrasound method compared with digital vaginal examinations in detecting cervical dilation.

Methods

We searched Cochrane (CENTRAL), MEDLINE, EMBASE, CINAHL, ISI Web of Science Core Collection, Trip Database, PubMed, DARE and NHS EED, HTA, and PROSPERO. Ten observational studies with a total sample size of 856 were included in the meta-analysis.

Results

The intraclass correlation coefficient (ICC) values ranged between 0.21 and 0.69. The fixed-effect models for the ultrasound test showed an average of ICC (r = 0.32 (95% CI 0.26–0.38). Correlation between two methods was poor (r = 0.359, 95% CI 0.26–0.44). In nulliparous and multigravida participants the correlation between ultrasound measurements and digital examinations was (r = 0.349, 95% CI 0.25–0.43) and ICC (r = 0.676, 95% CI 0.419–0.833), respectively.

Conclusion

Trans-perineal ultrasonography seems to be a reliable method for assessing labor progression in multigravida women, but its usage in nulliparous women needs further studies.