bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal subdural hematoma and subdural anesthesia following combined spinal–epidural anesthesia: a case report
Authors: Bi Yanmei , Zhou Junying
Published: April 2021

Background

Subdural anesthesia and spinal subdural hematoma are rare complications of combined spinal-epidural anesthesia. We present a patient who developed both after multiple attempts to achieve combined spinal–epidural anesthesia.

Case presentation

A 21-year-old parturient, gravida 1, para 1, with twin pregnancy at gestational age 34+ 5 weeks underwent cesarean delivery. Routine combined spinal–epidural anesthesia was planned; however, no cerebrospinal fluid outflow was achieved after several attempts. Bupivacaine (2.5 mL) administered via a spinal needle only achieved asymmetric blockade of the lower extremities, reaching T12. Then, epidural administration of low-dose 2-chlorprocaine caused unexpected blockade above T2 as well as tinnitus, dyspnea, and inability to speak. The patient was intubated, and the twins were delivered. Ten minutes after the operation, the patient was awake with normal tidal volume. The endotracheal tube was removed, and she was transferred to the intensive care unit for further observation. Postoperative magnetic resonance imaging suggested a spinal subdural hematoma extending from T12 to the cauda equina. Sensory and motor function completely recovered 5 h after surgery. She denied headache, low back pain, or other neurologic deficit. The patient was discharged 6 days after surgery. One month later, repeat MRI was normal.

Conclusions

All anesthesiologists should be aware of the possibility of SSDH and subdural block when performing neuraxial anesthesia, especially in patients in whom puncture is difficult. Less traumatic methods of achieving anesthesia, such as epidural anesthesia, single-shot spinal anesthesia, or general anesthesia should be considered in these patients. Furthermore, vital signs and neurologic function should be closely monitored during and after surgery.
Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function
Authors: Campbell Duncan J. , Coller Jennifer M. , Gong Fei Fei , McGrady Michele , Boffa Umberto , Shiel Louise , Liew Danny , Stewart Simon , Owen Alice J. , Krum Henry , Reid Christopher M. , Prior David L.
Published: April 2021

Background

Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual’s kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors.

Methods

We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years.

Results

In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60–69 years, with similar sensitivities for men and women.

Conclusions

In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women.

Trial registration

ClinicalTrials.gov NCT00400257, NCT00604006, and NCT01581827.
Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model
Authors: Mimouni Myriam , Richard Christophe , Adenot Pierre , Letheule Martine , Tarrade Anne , Sandra Olivier , Dahirel Michèle , Lilin Thomas , Lecuelle Benoit , Gélin Valérie , Cohen Julien , Fauconnier Arnaud , Vialard François , Huchon Cyrille , Chavatte-Palmer Pascale
Published: April 2021

Background

Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model.

Methods

Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure (“group 12”) and N = 3 with 20 mmHg (“group 20”). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei.

Results

DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20.

Conclusions

This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.
Combined effect of hypertension and hyperuricemia on ischemic stroke in a rural Chinese population
Authors: Sun Peng , Chen Mengqi , Guo Xiaofan , Li Zhao , Zhou Ying , Yu Shasha , Yang Hongmei , Sun Guozhe , Zheng Liqiang , Sun Yingxian
Published: April 2021

Background

To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population.

Methods

The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis.

Results

After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment.

Conclusions

This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.
Adverse body composition and lipid parameters in patients with prolactinoma: a case-control study
Authors: Posawetz Anna Sophia , Trummer Christian , Pandis Marlene , Aberer Felix , Pieber Thomas R. , Obermayer-Pietsch Barbara , Pilz Stefan , Theiler-Schwetz Verena
Published: April 2021

Background

Hyperprolactinaemia might cause adverse metabolic effects. The aim of our study was to compare parameters of body composition, glucose and lipid metabolism between untreated patients with prolactinoma and controls and to assess changes after initiation of cabergoline.

Methods

Case-control study with a retrospectively analyzed follow-up in patients with prolactinoma after initiation of cabergoline therapy.

Results

21 patients with prolactinoma (9 micro- and 12 macroprolactinomas; 7 females) and 30 controls were analyzed. Patients with prolactinoma had significantly higher BMI than controls; fat mass did not differ between groups. Only men - but not women - with prolactinoma had significantly higher fat mass at all six sites measured compared to controls. Levels of LDL (130 (107–147.5) vs. 94.5 (80–127.5) mg/dl, p < 0.001) were significantly higher, levels of HDL (56 ± 16.7 vs. 69.2 ± 14.6 mg/dl, p = 0.004) significantly lower than in controls. Fasting glucose, HOMA-IR, HbA1c, adiponectin, CRP, and homocysteine did not differ between groups.

After a median of 10 weeks (IQR 7–18 weeks) after initiation of cabergoline, total (from 212.5 ± 36.2 to 196.9 ± 40.6 mg/dl, p = 0.018) and LDL cholesterol (130 (107–147.5) to 106.5 (94.3–148) mg/dl, p = 0.018) had significantly decreased. Analyzing men and women separately, this change occurred in men only.

Conclusions

Reasons for the association between prolactin and metabolic parameters include direct effects of prolactin on adipose tissue, hyperprolactinaemia-triggered hypogonadism and dopamine-agonist therapy per se. Altered lipid metabolism in patients with prolactinoma might imply an increased cardiovascular risk, highlighting the necessity to monitor metabolic parameters in these patients.
Lists of potential diagnoses that final-year medical students need to consider: a modified Delphi study
Authors: Urushibara-Miyachi Yuka , Kikukawa Makoto , Ikusaka Masatomi , Otaki Junji , Nishigori Hiroshi
Published: April 2021

Background

Contrastive learning is known to be effective in teaching medical students how to generate diagnostic hypotheses in clinical reasoning. However, there is no international consensus on lists of diagnostic considerations across different medical disciplines regarding the common signs and symptoms that should be learned as part of the undergraduate medical curriculum. In Japan, the national model core curriculum for undergraduate medical education was revised in 2016, and lists of potential diagnoses for 37 common signs, symptoms, and pathophysiology were introduced into the curriculum. This study aimed to validate the list of items based on expert consensus.

Methods

The authors used a modified Delphi method to develop consensus among a panel of 23 expert physician-teachers in clinical reasoning from across Japan. The panel evaluated the items on a 5-point Likert scale, based on whether a disease should be hypothesized by final-year medical students considering given signs, symptoms, or pathophysiology. They also added other diseases that should be hypothesized. A positive consensus was defined as both a 75% rate of panel agreement and a mean of 4 or higher with a standard deviation of less than 1 on the 5-point scale. The study was conducted between September 2017 and March 2018.

Results

This modified Delphi study identified 275 basic and 67 essential other than basic items corresponding to the potential diagnoses for 37 common signs, symptoms, and pathophysiology that Japanese medical students should master before graduation.

Conclusions

The lists developed in the study can be useful for teaching and learning how to generate initial hypotheses by encouraging students’ contrastive learning. Although they were focused on the Japanese educational context, the lists and process of validation are generalizable to other countries for building national consensus on the content of medical education curricula.
Perceptions of Ghanaian traditional health practitioners, primary health care workers, service users and caregivers regarding collaboration for mental health care
Authors: Nyame Solomon , Adiibokah Edward , Mohammed Yasmin , Doku Victor C. , Othieno Caleb , Harris Benjamin , Gureje Oye , Soraya Seedat , Appiah-Poku John
Published: April 2021

Background

In low- and middle-income countries, the paucity of conventional health services means that many people with mental health problems rely on traditional health practitioners (THPs). This paper examines the possibility of forging partnerships at the Primary Health Care (PHC) level in two geopolitical regions of Ghana, to maximize the benefits to both health systems.

Methods

The study was a qualitative cross-sectional survey. Eight (8) focus group discussions (FGDs) were conducted between February and April 2014. The views of THPs, PHC providers, service users (i.e. patients) and their caregivers, on the perceived benefits, barriers and facilitators of forging partnerships were examined. A thematic framework approach was employed for analysis.

Results

The study revealed that underlying the widespread approval of forging partnerships, there were mutual undertones of suspicion. While PHC providers were mainly concerned that THPs may incur harms to service users (e.g., through delays in care pathways and human rights abuses), service users and their caregivers highlighted the failure of conventional medical care to meet their healthcare needs. There are practical challenges to these collaborations, including the lack of options to adequately deal with human rights issues such as some patients being chained and exposed to the vagaries of the weather at THPs. There is also the issue of the frequent shortage of psychotropic medication at PHCs.

Conclusion

Addressing these barriers could enhance partnerships. There is also a need to educate all providers, which should include sessions clarifying the potential value of such partnerships.
Electronic patient record and its effects on social aspects of interprofessional collaboration and clinical workflows in hospitals (eCoCo): a mixed methods study protocol
Authors: Beckmann Marina , Dittmer Kerstin , Jaschke Julia , Karbach Ute , Köberlein-Neu Juliane , Nocon Maya , Rusniok Carsten , Wurster Florian , Pfaff Holger
Published: April 2021

Background

The need for and usage of electronic patient records within hospitals has steadily increased over the last decade for economic reasons as well as the proceeding digitalization. While there are numerous benefits from this system, the potential risks of using electronic patient records for hospitals, patients and healthcare professionals must also be discussed. There is a lack in research, particularly regarding effects on healthcare professionals and their daily work in health services. The studyeCoCoaims to gain insight into changes in interprofessional collaboration and clinical workflows resulting from introducing electronic patient records.

Methods

eCoCois a multi-center case study integrating mixed methods from qualitative and quantitative social research. The case studies include three hospitals that undergo the process of introducing electronic patient records. Data are collected before and after the introduction of electronic patient records using participant observation, interviews, focus groups, time measurement, patient and employee questionnaires and a questionnaire to measure the level of digitalization. Furthermore, documents (patient records) as well as structural and administrative data are gathered. To analyze the interprofessional collaboration qualitative network analyses, reconstructive-hermeneutic analyses and document analyses are conducted. The workflow analyses, patient and employee assessment analyses and classification within the clinical adoption meta-model are conducted to provide insights into clinical workflows.

Discussion

This study will be the first to investigate the effects of introducing electronic patient records on interprofessional collaboration and clinical workflows from the perspective of healthcare professionals. Thereby, it will consider patients’ safety, legal and ethical concerns and quality of care. The results will help to understand the organization and thereby improve the performance of health services working with electronic patient records.

Trial registration

The study was registered at the German clinical trials register (DRKS00023343, Pre-Results) on November 17, 2020.
The effects of competition and bundled payment on patient reported outcome measures after hip replacement surgery
Authors: Goude Fanny , Kittelsen Sverre A. C. , Malchau Henrik , Mohaddes Maziar , Rehnberg Clas
Published: April 2021

Background

Competition-promoting reforms and economic incentives are increasingly being introduced worldwide to improve the performance of healthcare delivery. This study considers such a reform which was initiated in 2009 for elective hip replacement surgery in Stockholm, Sweden. The reform involved patient choice of provider, free establishment of new providers and a bundled payment model. The study aimed to examine its effects on hip replacement surgery quality as captured by patient reported outcome measures (PROMs) of health gain (as indicated by the EQ-5D index and a visual analogue scale (VAS)), pain reduction (VAS) and patient satisfaction (VAS) one and six years after the surgery.

Methods

Using patient-level data collected from multiple national registers, we applied a quasi-experimental research design. Data were collected for elective primary total hip replacements that were carried out between 2008 and 2012, and contain information on patient demography, the surgery and PROMs at baseline and at one- and six-years follow-up. In total, 36,627 observations were included in the analysis. First, entropy balancing was applied in order to reduce differences in observable characteristics between treatment groups. Second, difference-in-difference analyses were conducted to eliminate unobserved time-invariant differences between treatment groups and to estimate the causal treatment effects.

Results

The entropy balancing was successful in creating balance in all covariates between treatment groups. No significant effects of the reform were found on any of the included PROMs at one- and six-years follow-up. The sensitivity analyses showed that the results were robust.

Conclusions

Competition and bundled payment had no effects on the quality of hip replacement surgery as captured by post-surgery PROMs of health gain, pain reduction and patient satisfaction. The study provides important insights to the limited knowledge on the effects of competition and economic incentives on PROMs.
Antimicrobial resistance and genotyping of Staphylococcus aureus obtained from food animals in Sichuan Province, China
Authors: Gan Ting , Shu Gang , Fu Hualin , Yan Qigui , Zhang Wei , Tang Huaqiao , Yin Lizi , Zhao Ling , Lin Juchun
Published: April 2021

Background

Staphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is considered a common zoonotic pathogen, causing severe infections. The objective of this study was to investigate the antimicrobial susceptibility, resistance genes and molecular epidemiology among MRSA and methicillin-susceptible Staphylococcus aureus (MSSA) isolated from food animals in Sichuan Province, China.

Methods

This study was conducted on 236 S. aureus isolates. All isolates were subjected to antimicrobial susceptibility testing by using a standard microbroth dilution method. The Polymerase Chain Reaction (PCR) was performed to identify genes encoding the β-lactams resistance (blaZ, mecA), macrolides (ermA, ermB, ermC) and aminoglycosides (aacA-aphD). The molecular structures and genomic relatedness of MRSA isolates were determined by staphylococcal chromosome cassette mec (SCCmec) typing and pulsed-field gel electrophoresis (PFGE), respectively.

Results

Among 236 isolates, 24 (10.17 %) were recognized as MRSA. MRSA isolates showed different resistance rates to 11 antimicrobials ranging from 33.33 to 100 %, while for MSSA isolates the rates varied from 8.02 to 91.51 %. Multi-drug resistance phenotype was found in all MRSA isolates. The ermC gene encoding macrolides-lincosamides-streptogramin B was the most prevalent gene detected in 87.29 % of the S. aureus isolates, followed by ermB (83.05 %), blaZ (63.98 %), aacA-aphD (44.07 %), ermA (11.44 %) and mecA (11.02 %) genes. The prevalence of resistance genes in MRSA isolates was significantly higher than that of MSSA. Regarding the molecular morphology, SCCmec III (12/24, 50 %) was the most common SCCmec type. Furthermore, the PFGE typing showed that 24 MRSA were divided into 15 cluster groups (A to O), the major pulsotype J encompassed 25 % of MRSA isolates.

Conclusions

The S. aureus isolates from food animals in Sichuan province of China have severe antimicrobials resistance with various resistance genes, especially MRSA isolates. Additionally, the genetic pool of MRSA isolates is diverse and complex, and further investigation is necessary.
Correction to: Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease
Authors: Karki Hem Prakash , Jang Yeongseok , Jung Jinmu , Oh Jonghyun
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Evaluation of E. coli Nissle1917 derived metabolites in modulating key mediator genes of the TLR signaling pathway
Authors: Damoogh Sheyda , Vosough Mehrad , Hadifar Shima , Rasoli Masoumeh , Gorjipour Ali , Falsafi Sarvenaz , Behrouzi Ava
Published: April 2021

Objective

Gut-microbiota plays key roles in many aspects like the health and illness of humans. It's well proved that modification of gut microbiota by probiotics is useful for improving inflammatory bowel disease (IBD) conditions. According to recent studies, different types of bacterial metabolites can affect immune cells and inflammation conditions. The present study aimed to evaluate the anti-inflammatory effects of metabolites ofE. coliNissle1917.

Results

The cell-free supernatant could modulate TNF-α production and affected many crucial mediators in the Toll-like receptor (TLR) signaling pathway. Also, supernatant showed significant dose-dependent properties in this regard. In this study, the TLR signaling pathway was found among probable mechanisms by which probiotics can affect inflammatory situations. These findings provide additional evidence on the use of probiotic metabolites for inhibiting and down-regulating numerous key mediator factors in the TLR signaling pathway. Aberrant or dysfunctional TLR signaling contributes to the development of acute and chronic intestinal inflammatory pathways in IBD. Therefore, finding a component that can affect this process might be considered for therapeutic targets in IBD patients.
The role of DNA methylation in syndromic and non-syndromic congenital heart disease
Authors: Cao Jiali , Wu Qichang , Huang Yanru , Wang Lingye , Su Zhiying , Ye Huiming
Published: April 2021

Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.
Tissue-specific role and associated downstream signaling pathways of adiponectin
Authors: Roy Bipradas , Palaniyandi Suresh Selvaraj
Published: April 2021

According to the World Health Organization, metabolic syndrome (MetS) can be defined as a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. The incidence of MetS keeps rising, as at least 35% of the USA population suffers from MetS. One of the worst comorbidities of metabolic syndrome are cardiovascular diseases that significantly amplifies the mortality associated with this syndrome. There is an urgent need to understand the pathophysiology of MetS to find novel diagnosis, treatment and management to mitigate the MetS and associated complications. Altered circulatory adiponectin levels have been implicated in MetS. Adiponectin has numerous biologic functions including antioxidative, anti-nitrative, anti-inflammatory, and cardioprotective effects. Being a pleiotropic hormone of multiple tissues, tissue-specific key signaling pathways of adiponectin will help finding specific target/s to blunt the pathophysiology of metabolic syndrome and associated disorders. The purpose of this review is to elucidate tissue-specific signaling pathways of adiponectin and possibly identify potential therapeutic targets for MetS as well as to evaluate the potential of adiponectin as a biomarker/therapeutic option in MetS.
Critical illness-related corticosteroid insufficiency during difficult weaning from mechanical ventilation
Authors: Bagate François , Bedet Alexandre , Tomberli Françoise , Boissier Florence , Razazi Keyvan , de Prost Nicolas , Carteaux Guillaume , Mekontso Dessap Armand
Published: April 2021

Background

Critical illness-related corticosteroid insufficiency (CIRCI) is common during critical illness and is usually associated with poor outcomes, as prolonged duration of mechanical ventilation (MV) and higher mortality. CIRCI may alter cardiac and vascular functions. Weaning-induced pulmonary oedema (WiPO) is a major mechanism of weaning failure. The aim of this study was to evaluate the role of CIRCI in patients with difficult ventilator weaning and its possible relation with WiPO.

Methods

This is a prospective study conducted in the intensive care of a university hospital in France. Patients under MV for more than 24 h, meeting weaning criteria and having failed the first spontaneous breathing trial (SBT) underwent a corticotropin stimulation test, with assessment of total blood cortisol levels immediately before (T0) 0.25 mg iv of tetracosactrin and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0. CIRCI was defined as T0 < 10 μg/dL (276 nmol/L) and/or Δmax < 9 μg/dL (248 nmol/L) and inadequate adrenal reserve as Δmax < 9 μg/dL. Biomarkers (natriuretic peptide and protidemia) sampling and echocardiograms were performed during the second SBT and were used to diagnose WiPO, which was defined according to two definitions (one liberal and one conservative) derived from recent publications on the topic. Successful extubation was defined as patient alive without reintubation 7 days after extubation. A competing risk analysis was used to assess extubation failure and mortality.

Results

Seventy-six consecutive patients (63 ± 14 years; 49 men) with difficult weaning were enrolled. CIRCI and inadequate adrenal reserve occurred in 25 (33%) and 17 (22%) patients, respectively. The probability of successful extubation was significantly decreased in patients with CIRCI or inadequate adrenal reserve, as compared to their counterparts, and this association persisted after adjustment on severity (SOFA score at first SBT). WiPO occurred in 44 (58%) and 8 (11%) patients, according to the liberal and conservative definition, respectively. WiPO was not associated with CIRCI nor with inadequate adrenal reserve.

Conclusion

CIRCI was common during difficult weaning and was associated with its prolongation. We did not find a significant association between CIRCI and WiPO.
Infinite number of solutions for some elliptic eigenvalue problems of Kirchhoff-type with non-homogeneous material
Authors: Yan Baoqiang , O’Regan Donal , Agarwal Ravi P.
Published: April 2021

In this paper, using variational method, we study the existence of an infinite number of solutions (some are positive, some are negative, and others are sign-changing) for a non-homogeneous elliptic Kirchhoff equation with a nonlinear reaction term.
Caregivers: the potential infection resources for the sustaining epidemic of hand, foot, and mouth disease/herpangina in Guangdong, China?
Authors: Liu Jundi , Chen Yan , Hu Peipei , Gan Lin , Tan Qimin , Huang Xinqiao , Ma Zhanzhong , Lin Cuiji , Wu Dawei , Zhu Xun , Zhang Dingmei
Published: April 2021

Background

Although several measures have been taken to control hand foot and mouth disease (HFMD) and herpangina (HA), these two diseases have been prevalent in China for 10 years with high incidence. We suspected that adults’ inapparent infection might be the cause of the continued prevalence of HFMD/HA infection in mainland China.

Methods

To explore the role of adults (especially caregivers) in the transmission process of HFMD/HA among children, 330 HFMD/HA cases and 330 healthy children (controls) were selected for a case–control study. Then, data were analyzed by logistic regression.

Results

Single-variable analyses revealed that caregivers who tested positive for enterovirus was a significant risk factor of HFMD/HA transmission to children (adjusted odds ratio (OR) = 9.22; 95% CI, 1.16 to 73.23). In the final multivariable model, caregiver behavior, such as cooling children’s food with mouth (OR = 1.85; 95% CI, 1.11 to 3.08) and feeding children with their own tableware (OR = 2.19; 95% CI, 1.07 to 4.45), significantly increased the risk of transmitting HFMD/HA to children. On the contrary, washing hands before feeding children reduced such risk.

Conclusions

These results implied that the caregivers might be the infectious source or carriers of enterovirus. Therefore, preventing or treating the caregivers’ enterovirus infection and improving their hygiene habits, especially when they are in contact with children, could provide a breakthrough for the effective control of HFMD/HA.
The influence of late retirement on health outcomes among older adults in the policy context of delayed retirement initiative: an empirical attempt of clarifying identification bias
Authors: Li Jiannan , Yuan Bocong , Lan Junbang
Published: April 2021

Background

The deepening population aging is urging policy makers to launch delayed retirement initiative, when the society is faced with unprecedented challenges of shrinking labor supply, heavier pension burdens and slowing economic growth. However, the health outcomes of late retirees receive scarce attention due to the intrinsic identification difficulties (i.e., (1) self-selection bias – older adults with predetermined ill-health are less likely to delay retirement. (2) there can be situations where the status of late retirement has terminated at the time of interview, although he/she has ever delayed retirement). To fill in this research gap, this study examines the effect of late retirement on the difficulty in physical functioning and problems of cognitive status among older adults.

Method

Using the data from China Health and Retirement Longitudinal Study (CHARLS-2015 harmonized, and CHARLS-2018), this study investigates the influence of late retirement (year 2015) on the difficulty in physical functioning and problems of cognitive status (year 2018) among older adults. A series of robustness checks are also conducted.

Results

Empirical results show that late retirement is associated with better physical functioning and cognitive status. The influence remains robust after considering potential self-selection bias and the sensitivity of including/excluding older adults who have past late retirement experience but have no longer been late retirees at the time of survey.

Conclusion

This study suggests that older adults might benefit from the engagement in late careers in their physical and cognitive functioning.
Multiresidue analysis of 184 pesticides in high-fat fish feed using a new generic extraction method coupled with gas and liquid chromatography-tandem mass spectrometry
Authors: Eyring Philipp Rudolf Michael Peter , Herrmann Susan Strange , Poulsen Mette Erecius
Published: April 2021

Animal feed is typically plant-based and can contain pesticide residues. Methods for testing food and feed samples, such as the Quick Easy Cheap Effective Rugged Safe (QuEChERS) method or the Swedish Ethyl Acetate (SweEt) method, successfully extract many pesticide residues. However, nonpolar pesticides, such as organochlorine pesticides, show poor recovery when extracted from lipid-rich samples. The previously developed water-acetonitrile-heptane-solid-phase-extraction (WAHSPE) method shows better recoveries for the nonpolar pesticides but requires two injections per sample and per instrument. Here, we present a modified version of the WAHSPE method for pesticides in fish feed using one injection per sample and per instrument. Of the 184 pesticides tested, 179 met the European Union Legislation’s validation criteria at a spike level of 50 μg/kg, showing recoveries between 70 and 120% and a relative standard deviation (RSD) below 20%. Organochlorine pesticides accounted for 14 of the tested compounds.
Molecular epidemiology of mosquito-borne viruses at the China–Myanmar border: discovery of a potential epidemic focus of Japanese encephalitis
Authors: Fang Yuan , Li Xi-Shang , Zhang Wei , Xue Jing-Bo , Wang Jia-Zhi , Yin Shou-Qin , Li Sheng-Guo , Li Xin-He , Zhang Yi
Published: April 2021

Background

Mosquito-based arbovirus surveillance can serve as an early warning in evaluating the status of mosquito-borne virus prevalence and thus prevent local outbreaks. Although Tengchong County in Yunnan Province—which borders Myanmar—is abundant and diverse in mosquitoes, very few mosquito-based arbovirus investigations have been conducted in the recent decade. Herein, this study aims to evaluate the presence and the diffusion of mosquito-borne pathogens, currently prevalent in this region.

Methods

We collected 9486 mosquitoes, representing eight species, with Culex tritaeniorhynchus and Anopheles sinensis as the dominant species, during high mosquito activity seasons (July–October) in Tengchong, in 2018. Samples collected from 342 pools were tested using reverse-transcription PCR to determine the species, distribution, and infection rates of virus and parasite, and further analyze their genotypes, phylogenetic relationships, infection rate, and potential pathogenicity.

Results

Fifteen Japanese encephalitis virus (JEV) strains from Cx. tritaeniorhynchus pools were detected. Seven strains of insect-specific flaviviruses (ISFVs), including two Aedes flavivirus (AeFV) and Yunnan Culex flavivirus strains each, one Culex theileri flavivirus, Yamadai flavivirus (YDFV) and Anopheles-associated flavivirus (AAFV) strains each were detected in Aedes albopictus, Cx. tritaeniorhynchus, Cx. vagans, Cx. pseudovihnui, and An. sinensis pools, respectively. The whole-genome was successfully amplified in one strain of JEV and AeFV each. Phylogenetic analysis using the E gene placed all the newly detected JEV strains into the GI-b genotype. They showed highly nucleotide identities, and were most closely related to the strain detected in Tengchong in 2010. The comparison of the E protein of JEV strains and vaccine-derived strain, showed six amino residue differences. The bias-corrected maximum likelihood estimation values (and 95% confidence interval) for JEV in Cx. tritaeniorhynchus collected in Tengchong in 2018 were 2.4 (1.4–3.9).

Conclusions

A potential Japanese encephalitis epidemic focus with the abundance of host mosquitoes and high JEV infection rate was observed in Tengchong. In addition, at least five species of ISFVs co-circulate in this area. This study highlights the importance of widespread and sustained mosquito-based arbovirus surveillance in local areas to prevent the transmission of JEV, and other emerging/re-emerging mosquito-borne pathogens.

Graphic Abstract
Demand for longer quarantine period among common and uncommon COVID-19 infections: a scoping review
Authors: Li Zhi-Yao , Zhang Yu , Peng Liu-Qing , Gao Rong-Rong , Jing Jia-Rui , Wang Jia-Le , Ren Bin-Zhi , Xu Jian-Guo , Wang Tong
Published: April 2021

Background

As one of the non-pharmacological interventions to control the transmission of COVID-19, determining the quarantine duration is mainly based on the accurate estimates of the incubation period. However, patients with coarse information of the exposure date, as well as infections other than the symptomatic, were not taken into account in previously published studies. Thus, by using the statistical method dealing with the interval-censored data, we assessed the quarantine duration for both common and uncommon infections. The latter type includes the presymptomatic, the asymptomatic and the recurrent test positive patients.

Methods

As of 10 December 2020, information on cases have been collected from the English and Chinese databases, including Pubmed, Google scholar, CNKI (China National Knowledge Infrastructure) and Wanfang. Official websites and medias were also searched as data sources. All data were transformed into doubly interval-censored and the accelerated failure time model was applied. By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients, we obtain the large percentiles for determining and suggesting the quarantine policies. For symptomatic and presymptomatic COVID-19 patients, the incubation time is the duration from exposure to symptom onset. For the asymptomatic, we substitute the date of first positive result of nucleic acid testing for that of symptom onset. Furthermore, the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients.

Results

A total of 1920 laboratory confirmed COVID-19 cases were included. Among all uncommon infections, 34.1% (n = 55) of them developed symptoms or were identified beyond fourteen days. Based on all collected cases, the 95th and 99th percentiles were estimated to be 16.2 days (95% CI 15.5–17.0) and 22.9 days (21.7‒24.3) respectively. Besides, we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days (14.4‒15.7) and 21.1 days (20.0‒22.2).

Conclusions

There are a certain number of infected people who require longer quarantine duration. Our findings well support the current practice of the extended active monitoring. To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine, properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.
In-depth characterization of a mouse model of post-traumatic epilepsy for biomarker and drug discovery
Authors: Di Sapia Rossella , Moro Federico , Montanarella Marica , Iori Valentina , Micotti Edoardo , Tolomeo Daniele , Wang Kevin K. W. , Vezzani Annamaria , Ravizza Teresa , Zanier Elisa R.
Published: April 2021

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies and 10–20% of the acquired forms. The latency between traumatic brain injury (TBI) and epilepsy onset in high-risk patients offers a therapeutic window for intervention to prevent or improve the disease course. However, progress towards effective treatments has been hampered by the lack of sensitive prognostic biomarkers of PTE, and of therapeutic targets. There is therefore a pressing clinical need for preclinical PTE models suitable for biomarker discovery and drug testing. We characterized in-depth a model of severe TBI induced by controlled cortical impact evolving into PTE in CD1 adult male mice. To identify sensitive measures predictive of PTE development and severity, TBI mice were longitudinally monitored by video-electrocorticography (ECoG), examined by MRI, and tested for sensorimotor and cognitive deficits and locomotor activity. At the end of the video-ECoG recording mice were killed for brain histological analysis. PTE occurred in 58% of mice with frequent motor seizures (one seizure every other day), as determined up to 5 months post-TBI. The weight loss of PTE mice in 1 week after TBI correlated with the number of spontaneous seizures at 5 months. Moreover, the recovery rate of the sensorimotor deficit detected by the SNAP test before the predicted time of epilepsy onset was significantly lower in PTE mice than in those without epilepsy. Neuroscore, beam walk and cognitive deficit were similar in all TBI mice. The increase in the contusion volume, the volume of forebrain regions contralateral to the lesioned hemisphere and white matter changes over time assessed by MRI were similar in PTE and no-PTE mice. However, brain histology showed a more pronounced neuronal cell loss in the cortex and hippocampus contralateral to the injured hemisphere in PTE than in no-PTE mice. The extensive functional and neuropathological characterization of this TBI model, provides a tool to identify sensitive measures of epilepsy development and severity clinically useful for increasing PTE prediction in high-risk TBI patients. The high PTE incidence and spontaneous seizures frequency in mice provide an ideal model for biomarker discovery and for testing new drugs.
Sex-specific DNA methylation differences in Alzheimer’s disease pathology
Authors: Zhang Lanyu , Young Juan I. , Gomez Lissette , Silva Tiago C. , Schmidt Michael A. , Cai Jesse , Chen Xi , Martin Eden R. , Wang Lily
Published: April 2021

Sex is an important factor that contributes to the clinical and biological heterogeneities in Alzheimer’s disease (AD), but the regulatory mechanisms underlying sex disparity in AD are still not well understood. DNA methylation is an important epigenetic modification that regulates gene transcription and is known to be involved in AD. We performed the first large-scale sex-specific meta-analysis of DNA methylation differences in AD neuropathology, by re-analyzing four recent epigenome-wide association studies totaling more than 1000 postmortem prefrontal cortex brain samples using a uniform analytical pipeline. For each cohort, we employed two complementary analytical strategies, a sex-stratified analysis that examined methylation-Braak stage associations in male and female samples separately, and a sex-by-Braak stage interaction analysis that compared the magnitude of these associations between different sexes. Our analysis uncovered 14 novel CpGs, mapped to genes such as TMEM39A and TNXB that are associated with the AD Braak stage in a sex-specific manner. TMEM39A is known to be involved in inflammation, dysregulated type I interferon responses, and other immune processes. TNXB encodes tenascin proteins, which are extracellular matrix glycoproteins demonstrated to modulate synaptic plasticity in the brain. Moreover, for many previously implicated genes in AD neuropathology, such as MBP and AZU1, our analysis provided the new insights that they were predominately driven by effects in only one sex. These sex-specific DNA methylation differences were enriched in divergent biological processes such as integrin activation in females and complement activation in males. Our study implicated multiple new loci and biological processes that affected AD neuropathology in a sex-specific manner.
A survey on artificial intelligence assurance
Authors: Batarseh Feras A. , Freeman Laura , Huang Chih-Hao
Published: April 2021

Artificial Intelligence (AI) algorithms are increasingly providing decision making and operational support across multiple domains. AI includes a wide (and growing) library of algorithms that could be applied for different problems. One important notion for the adoption of AI algorithms into operational decision processes is the concept of assurance. The literature on assurance, unfortunately, conceals its outcomes within a tangled landscape of conflicting approaches, driven by contradicting motivations, assumptions, and intuitions. Accordingly, albeit a rising and novel area, this manuscript provides a systematic review of research works that are relevant to AI assurance, between years 1985 and 2021, and aims to provide a structured alternative to the landscape. A new AI assurance definition is adopted and presented, and assurance methods are contrasted and tabulated. Additionally, a ten-metric scoring system is developed and introduced to evaluate and compare existing methods. Lastly, in this manuscript, we provide foundational insights, discussions, future directions, a roadmap, and applicable recommendations for the development and deployment of AI assurance.
Dual edge classifier for robust cloth unfolding
Authors: Gabas Antonio , Kita Yasuyo , Yoshida Eiichi
Published: April 2021

Compared with more rigid objects, clothing items are inherently difficult for robots to recognize and manipulate. We propose a method for detecting how cloth is folded, to facilitate choosing a manipulative action that corresponds to a garment’s shape and position. The proposed method involves classifying the edges and corners of a garment by distinguishing between edges formed by folds and the hem or ragged edge of the cloth. Identifying the type of edges in a corner helps to determinate how the object is folded. This bottom-up approach, together with an active perception system, allows us to select strategies for robotic manipulation. We corroborate the method using a two-armed robot to manipulate towels of different shapes, textures, and sizes.
Occurrence of Salmonella Typhimurium and its monophasic variant (4, [5],12:i:-) in healthy and clinically ill pigs in northern Italy
Authors: D’Incau Mario , Salogni Cristian , Giovannini Stefano , Ruggeri Jessica , Scali Federico , Tonni Matteo , Formenti Nicoletta , Guarneri Flavia , Pasquali Paolo , Alborali Giovanni Loris
Published: April 2021

Background

The serovar Typhimurium (4, [5],12:i:1,2), is the most frequently isolated serovar in case of salmonellosis in pigs in Europe and its monophasic variant (4, [5],12:i:-) has been increasingly responsible for Salmonella outbreaks in humans. A total of 25,215 samples were collected, during the years 2002–2017, from 1359 pig farms located in Northern Italy. Samples were collected from different material sources including fecal samples, rectal swabs, gut content and different organs.

Results

Salmonella was isolated in 15.80% of samples and, among the isolates, 733 were typed as Salmonella Typhimurium (ST) or its monophasic variant (MST). Over time, there was an increase of isolation of MST which outnumbered ST. Most of the strains were isolated in animals during the weaning stage and the growing – fattening period whereas the clinical cases were mainly present in young pigs after weaning.

Conclusions

This study confirms the presence of ST and MST in pig farms although, considering the total of isolated serotypes, with lower percentages than previously reported.

In the last few years, ST has increasingly been replaced by MST suggesting that MST has a competitive advantage over ST, probably due to its different antigenicity and pathogenicity which renders the infection stealthier to recognize and control.