by Maria Gröndal, Karl Ask, Timothy J. Luke, Stefan WinbladA rapid stream of research confirms that the COVID-19 pandemic is a global threat to mental health and psychological well-being. It is therefore important to identify both hazardous and protective individual factors during the pandemic. The current research explored the relationships between self-reported affective responding, perceived personal consequences of the COVID-19 pandemic, and subjective well-being. An online survey (N = 471) conducted in Sweden between June and September, 2020, showed that higher levels of irritability, impulsivity, and the tendency to experience and express anger were generally associated with more severe personal consequences of the pandemic, particularly in areas related to family life, work/study, and finances. While more severe impacts of the pandemic in these areas of life were directly associated with lower subjective well-being, emotion regulation through cognitive reappraisal appeared to moderate the extent to which consequences of the pandemic in other areas of life (i.e., social, free-time and physical activities) translated into decreased well-being. This suggests that cognitive reappraisal may serve to protect against some of the debilitating effects of the COVID-19 pandemic on mental health. Overall, the results indicate that the perceived consequences of the pandemic are multifaceted and that future research should examine these consequences using a multidimensional approach.
by Alvera Noviyani, Tanawin Nopsopon, Krit PongpirulBackground
Tuberculosis (TB) has contributed to a significant disease burden and economic loss worldwide. Given no gold standard for diagnosis, early identification of TB infection has been challenging. This study aimed to comparatively investigate the prevalence of TB across diagnostic approaches (sputum AFB, sputum culture, sputum genetic test, and chest x-ray) and geographical areas of Indonesia.Methods
Participant demographic variables and TB screening test results were obtained from the Tuberculosis Unit, Health Research and Development Agency, Ministry of Health (HRDA-MoH). The prevalence of pulmonary TB in populations aged 15 years and over was calculated using TB cases as a numerator and populations aged 15 years and over as a denominator. Variations across geographical areas and diagnostic approaches were expressed as prevalence and 95% confidence interval (CI).Results
A total of 67,944 records were reviewed. Based on bacteriological evidence, the prevalence of TB per 100,000 in Indonesia was 759 (95% CI: 589.7–960.8) with variations across areas: 913 (95% CI 696.7–1,176.7; Sumatra), 593 (95% CI 447.2–770.6; Java-Bali), and 842 (95% CI 634.7–1,091.8; other islands). Also, the prevalence of TB varied across diagnostic approaches: 256.5 (sputum AFB), 545 (sputum culture), 752.2 (chest x-ray), and 894.9 (sputum genetic test). Based on sputum AFB, the TB prevalence varied from 216.6 (95% CI 146.5–286.8; Java-Bali), 259.9 (95% CI 184.2–335.6; other islands) to 307.4 (95% CI 208.3–406.5; Sumatra). Based on sputum culture, the TB prevalence ranged from 487.9 (95% CI 433.6–548.6; Java-Bali), 635.9 (95% CI 564.9–715.1; Sumatra), to 2,129.8 (95% CI 1,664.0–2,735.6; other islands). Based on chest x-ray, the TB prevalence varied from 152.1 (95% CI 147.9–156.3; Java-Bali), 159.2 (95% CI 154.1–164.3; Sumatra), to 864 (95% CI 809–921.4; other islands). Based on sputum genetic test, the TB prevalence ranged from 838.7 (95% CI 748.4–900.8; Java-Bali), 875 (95% CI 775.4–934.2; Sumatra), to 941.2 (95% CI 663.6–992.3; other islands).Conclusions
The variation of TB prevalence across geographical regions could be confounded by the diagnostic approaches.Trial registration
This study was approved by the Institutional Review Board of Chulalongkorn University (IRB No. 684/63).
by Yohanis Alemeshet Asefa, Bezatu Mengistie Alemu, Negga Baraki, Dinku Mekbib, Dechasa Adare MengistuBackground
Biological deterioration of drinking water is the major cause of waterborne disease globally. However, there is a paucity of information on identifying the point where deterioration of the bacteriological quality of drinking water occurs (source or point of use) and associated factors among households in developing countries, especially in Ethiopia.Method
A community based cross-sectional study design was conducted among 425 households in Eastern Ethiopia. Households with at least one child under-five years of age were included in the study. A total of 448 Water samples (425 from households and 23 from water sources) were collected and analyzed by the membrane filtration method to identify Thermotolerant coliform. Binary logistic regression was performed to assess the association between each independent and dependent variable. Adjusted Odd Ratios along with 95% Confidence intervals were estimated to identify factors associated with the outcome variable.Result
This study revealed that 21.7%; 95% CI (4.5%, 39.1%) of water sources and 83.3%; 95% CI (79.8%, 87.1%) of households’ drinking water were contaminated by thermotolerant coliform. Drinking water samples from households with poor wealth index [AOR = 9.63; 95%CI (2.92, 31.69)], households with unimproved sanitation facility [AOR = 2.81; 95%CI (1.31, 6.01)], households which shares their house with animal [AOR = 3.73; 95%CI (1.66, 8.37)], households that didn’t practice household water treatment [AOR = 3.42; 95%CI (1.60, 7.31)] and not washing hands before water collection [AOR = 7.04; 95%CI (2.22, 22.30)] were significantly associated with deterioration of bacteriological quality of household drinking water.Conclusion
This study indicates that the bacteriological quality of drinking water deteriorates from source to point of use. Thus, health education programs on water, sanitation, hygienic practice must be enhanced to improve the quality of drinking water.
by Tze Chiew Christie Soo, Subha BhassuDiseases have remained the major issue for shrimp aquaculture industry for decades by which different shrimp species demonstrated alternative disease resistance or tolerance. However, there had been insufficient studies on the underlying host mechanisms of such phenomenon. Hence, in this study, the main objective involves gaining a deeper understanding into the functional importance of shrimp STAT gene from the aspects of expression, sequence, structure, and associated genes. STAT gene was selected primarily because of its vital signalling roles in stress, endocrine, and immune response. The differential gene expressions of Macrobrachium rosenbergii STAT (MrST) and Penaeus monodon STAT (PmST) under White Spot Syndrome Virus (WSSV) and Vibrio parahaemolyticus/VpAHPND infections were identified through qPCR analysis. Notably, during both pathogenic infections, MrST demonstrated significant gene expression down-regulations (during either early or later post-infection time points) whereas PmST showed only significant gene expression up-regulations. Important sequence conservation or divergence was highlighted through STAT sequence comparison especially amino acid alterations at 614 aa [K (Lysine) to E (Glutamic Acid)] and 629 aa [F (Phenylalanine) to V (Valine)] from PmST (AY327491.1) to PmST (disease tolerant strain). There were significant differences observed between in silico characterized structures of MrST and PmST proteins. Important functional differentially expressed genes (DEGs) in the aspects of stress, endocrine, immune, signalling, and structural were uncovered through comparative transcriptomic analysis. The DEGs associated with STAT functioning were identified including inositol 1,4,5-trisphosphate receptor, hsp90, caspase, ATP binding cassette transmembrane transporter, C-type Lectin, HMGB, ALF1, ALF3, superoxide dismutase, glutathione peroxidase, catalase, and TBK1. The main findings of this study are STAT differential gene expression patterns, sequence divergence, structural differences, and associated functional DEGs. These findings can be further utilized for shrimp health or host response diagnostic studies. STAT gene can also be proposed as a suitable candidate for future studies of shrimp innate immune enhancement.
by Taeyoung Kong, Hye Sun Lee, So Young Jeon, Je Sung You, Jong Wook Lee, Hyun Soo Chung, Sung Phil ChungBackground
Postpartum hemorrhage (PPH) constitutes a major risk for maternal mortality and morbidity. Unfortunately, the severity of PPH can be underestimated because it is difficult to accurately measure blood loss by visual estimation. The delta neutrophil index (DNI), which reflects circulating immature granulocytes, is automatically calculated in hematological analyzers. We evaluated the significance of the DNI in predicting hemorrhage severity based on the requirement for massive transfusion (MT) in patients with PPH.Methods
We retrospectively analyzed data from a prospective registry to evaluate the association between the DNI and MT. Moreover, we assessed the predictive ability of the combination of DNI and shock index (SI) for the requirement for MT. MT was defined as a transfusion of ≥10 units of red blood cells within 24 h of PPH. In total, 278 patients were enrolled in this study and 60 required MT.Results
Multivariable logistic regression revealed that the DNI and SI were independent predictors of MT. The optimal cut-off values of ≥3.3% and ≥1.0 for the DNI and SI, respectively, were significantly associated with an increased risk of MT (DNI: positive likelihood ratio [PLR] 3.54, 95% confidence interval [CI] 2.5–5.1 and negative likelihood ratio [NLR] 0.48, 95% CI 0.4–0.7; SI: PLR 3.21, 95% CI 2.4–4.2 and NLR 0.31, 95% CI 0.19–0.49). The optimal cut-off point for predicted probability was calculated for combining the DNI value and SI value with the equation derived from logistic regression analysis. Compared with DNI or SI alone, the combination of DNI and SI significantly improved the specificity, accuracy, and positive likelihood ratio of the MT risk.Conclusion
The DNI and SI can be routinely and easily measured in the ED without additional costs or time and can therefore, be considered suitable parameters for the early risk stratification of patients with primary PPH.
by Prechiel A. Barredo, Marvin Jose F. Fernandez, Christopher E. Ambe, Mannix P. BalanayThe microtubule-binding protein tau has been the center of researches concerning Alzheimer’s disease (AD) due to several clinical trials of β-amyloid therapies failing recently. The availability of the tau fibril structure from AD brain enables computational modeling studies to calculate binding affinities with different ligands. In this study, the tau paired helical filaments (PHF-Tau) (PDB ID: 5O3L) was used as receptor and interactions with the lipids: 3-alpha-cholesterol; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; and C18:1 sphingomyelin, were explored with molecular docking, molecular dynamics, and natural bond orbital analysis. Docking sites upon solvation of the protein with transferable interatomic potential-3 points reveal the amphipathic nature of PHF-Tau and molecular dynamics simulations show that the embedded phosphocholine at the tail side gives high potential energy values with some amino acids forming H-bond interactions.
by Natasha Hall, Long Le, Ishani Majmudar, Maree Teesson, Cathy MihalopoulosObjectives
To determine treatment seeking behaviour in those with opioid use disorder (OUD) in the high-income countries.Methods
Five databases were searched in November 2019 for quantitative studies that reported OUD treatment seeking behaviour. Data analysis involved determining an overall pooled proportion estimate of treatment seeking behaviour for the two base groups, lifetime treatment and past 12-month or less treatment using the IVhet effect model. Subgroup analysis included heroin OUD, prescription OUD and general OUD. The sensitivity analysis included removal of outliers, separating adults and adolescents and the metaXL sensitivity analysis (studies are excluded if outside the pooled proportion confidence interval of the base case). Systematic review Prospero database registration number [CRD42020159531].Results
There were 13 quantitative studies included in the systematic review, with all studies being from the United States of America (USA). IVhet models showed that 40% (95% CI: 23%, 58%) and 21% (95% CI: 16%, 26%) sought treatment in their lifetime and past 12 months respectively. Sub-group analysis found that lifetime treatment seeking for prescription OUD, 29% (95% CI: 27%, 31%), was less than for heroin plus combined OUD, 54% (95% CI: 26%, 82%). Most of the pooled results had high heterogeneity statistics except for results of lifetime treatment seeking for prescription OUD and past 12-month treatment seeking for prescription OUD.Conclusion
All included studies in this meta-analysis were from the USA and indicate modest levels of treatment seeking for those with OUD. In particular, this review found that in the USA one in five people with OUD sought OUD treatment in the previous 12 months and two in five people with OUD sought OUD treatment in their lifetime. Further research is urgently required to explore the barriers and facilitators that can improve this low treatment seeking in those with OUD.
by Moza Alishaq, Hanaa Nafady-Hego, Andrew Jeremijenko, Jameela Ali Al Ajmi, Mohamed Elgendy, Suni Vinoy, Sameera Bihi Fareh, Justine Veronica Plaatjies, Mariam Nooh, Nadya Alanzi, Anvar H. Kaleeckal, Ali Nizar Latif, Peter Coyle, Hamed Elgendy, Abdul-Badi Abou-Samra, Adeel Ajwad ButtBackground and objective
The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar.Methods
We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection.Results
Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection.Conclusion
Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination.
by Jianyong Dong, Chunmei Mao, Jie Xu, Yanting He, Kaiqi Zhang, Jun CuiBackground
Immediately placed implants with immediate provisionalization have become attractive options for patients and clinicians. However, there is no agreement on the esthetic advantages of immediately placed implants with immediate provisionalization. The aim of this systematic review and meta-analysis will be to assess the effect of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants in a single-tooth implant of the esthetic area.Methods
An electronic search of MEDLINE/PubMed, EMBASE, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database will be performed. The search will be carried out in the databases for articles published until May 2021. Two researchers will independently perform the literature selection, data extraction and quality assessment. Only randomized controlled trials (RCTs) reporting on the impact of immediate provisionalization on the clinical esthetic outcomes of implants immediately placed in a single-tooth implant of the aesthetic area will be included. The primary outcome of this study will be the esthetic outcome assessed by the objective index and patient satisfaction. The survival rate of implants and restorations and the changes in mucosa and bone around implants will also be analyzed. The included studies will be analyzed by Review Manager 5.3, and a meta-analysis will be performed.Results
The study will evaluate the clinical esthetic outcomes of immediately placed implants with and without immediate provisionalization in single-tooth implants of the esthetic area. The results will provide clinicians with a better treatment approach in their application.Conclusion
This systematic review and meta-analysis will provide more reliable, evidence-based data for the impact of immediate provisionalization on the clinical esthetic outcomes of immediately placed implants, which may or may not be beneficial.Registration number
PROSPERO registration number: CRD42021221669.
by Indah K. Murni, Dian C. Sulistyoningrum, Danijela Gasevic, Rina Susilowati, Madarina JuliaBackground
It has been shown that vitamin D is associated with obesity and the development of atherosclerosis. Less is known about this association among adolescents with obesity.Objectives
To determine the association of vitamin D level and metabolic risk factors with carotid intima-media thickness (CIMT) among obese adolescents.Methods
We conducted a cross-sectional study among obese children aged 15 to 17 years in Yogyakarta, Indonesia. The association of vitamin D and other metabolic risk factors (triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR)) with CIMT was explored by multivariable linear regression models.Results
Out of 156 obese adolescents, 55.8% were boys. Compared to girls, boys had higher BMI z-score, waist circumference, and HDL-cholesterol. After adjustment for age, sex and second-hand smoke exposure, high HOMA-IR, total cholesterol, LDL-cholesterol and triglyceride levels were associated with higher odds of elevated CIMT. In analyses stratified by sex, a similar trend was observed in boys, while none of the risk factors were associated with CIMT in girls. We observed no association between vitamin D and CIMT.Conclusions
Hyperinsulinemia, higher total cholesterol and LDL cholesterol were associated with greater odds of elevated CIMT among obese adolescent boys.
by Cinthia Aguilera, Elisabeth Gabau, Ariadna Ramirez-Mallafré, Carme Brun-Gasca, Jana Dominguez-Carral, Veronica Delgadillo, Steve Laurie, Sophia Derdak, Natàlia Padilla, Xavier de la Cruz, Núria Capdevila, Nino Spataro, Neus Baena, Miriam Guitart, Anna RuizAngelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with absence of speech, happy disposition, frequent laughter, hyperactivity, stereotypies, ataxia and seizures with specific EEG abnormalities. There is a 10–15% of patients with an AS phenotype whose genetic cause remains unknown (Angelman-like syndrome, AS-like). Whole-exome sequencing (WES) was performed on a cohort of 14 patients with clinical features of AS and no molecular diagnosis. As a result, we identified 10 de novo and 1 X-linked pathogenic/likely pathogenic variants in 10 neurodevelopmental genes (SYNGAP1, VAMP2, TBL1XR1, ASXL3, SATB2, SMARCE1, SPTAN1, KCNQ3, SLC6A1 and LAS1L) and one deleterious de novo variant in a candidate gene (HSF2). Our results highlight the wide genetic heterogeneity in AS-like patients and expands the differential diagnosis.
by Bryan C. Jensen, Pashmi Vaney, John Flaspohler, Isabelle Coppens, Marilyn ParsonsIn many eukaryotes, multiple protein kinases are situated in the plasma membrane where they respond to extracellular ligands. Ligand binding elicits a signal that is transmitted across the membrane, leading to activation of the cytosolic kinase domain. Humans have over 100 receptor protein kinases. In contrast, our search of the Trypanosoma brucei kinome showed that there were only ten protein kinases with predicted transmembrane domains, and unlike other eukaryotic transmembrane kinases, seven are predicted to bear multiple transmembrane domains. Most of the ten kinases, including their transmembrane domains, are conserved in both Trypanosoma cruzi and Leishmania species. Several possess accessory domains, such as Kelch, nucleotide cyclase, and forkhead-associated domains. Surprisingly, two contain multiple regions with predicted structural similarity to domains in bacterial signaling proteins. A few of the protein kinases have previously been localized to subcellular structures such as endosomes or lipid bodies. We examined the localization of epitope-tagged versions of seven of the predicted transmembrane kinases in T. brucei bloodstream forms and show that five localized to the endoplasmic reticulum. The last two kinases are enzymatically active, integral membrane proteins associated with the flagellum, flagellar pocket, or adjacent structures as shown by both fluorescence and immunoelectron microscopy. Thus, these kinases are positioned in structures suggesting participation in signal transduction from the external environment.
by Wonjun Choi, Hyunju LeeUnderstanding the role of genes in human disease is of high importance. However, identifying genes associated with human diseases requires laborious experiments that involve considerable effort and time. Therefore, a computational approach to predict candidate genes related to complex diseases including cancer has been extensively studied. In this study, we propose a convolutional neural network-based knowledge graph-embedding model (KGED), which is based on a biological knowledge graph with entity descriptions to infer relationships between biological entities. As an application demonstration, we generated gene-interaction networks for each cancer type using gene-gene relationships inferred by KGED. We then analyzed the constructed gene networks using network centrality measures, including betweenness, closeness, degree, and eigenvector centrality metrics, to rank the central genes of the network and identify highly correlated cancer genes. Furthermore, we evaluated our proposed approach for prostate, breast, and lung cancers by comparing the performance with that of existing approaches. The KGED model showed improved performance in predicting cancer-related genes using the inferred gene-gene interactions. Thus, we conclude that gene-gene interactions inferred by KGED can be helpful for future research, such as that aimed at future research on pathogenic mechanisms of human diseases, and contribute to the field of disease treatment discovery.
by Andrew Ma, Kenneth K. Lau, Dominic ThyagarajanObjective
To determine whether arytenoid cartilage position and dynamics change with advancing duration and severity (as graded by MDS-UPDRS part III scores) in Parkinson’s disease, in a cross-sectional study design, we performed laryngeal four-dimensional computed tomography (4D-CT) in people with Parkinson’s disease and controls.Methods
31 people with Parkinson’s disease covering a range of disease duration and severity and 19 controls underwent laryngeal 4D-CT whilst repeatedly vocalizing. We measured on each CT volume the glottic area (GA), inter-arytenoid distance (IAD), IAD-Area index (IAI) and arytenoid cartilage velocity (av→).Results
People with Parkinson’s disease had reductions in the mean/effective minimum IAD when compared to controls, while mean/effective minimum GA and mean/effective maximum IAI were increased. Arytenoid cartilage velocities showed no difference. On Spearman correlation analyses, advancing disease duration and severity of PD showed moderately strong and significant correlations with increasing mean/effective minimum GA, increasing mean/effective maximum IAI and decreasing effective minimum IAD. Linear mixed models which considered the effects of intra and inter-individual variation showed that both disease duration (b = -0.011, SEb = 0.053, 95% CI [-0.022, 0], t(27) = -2.10, p = 0.045) and severity (b = -0.069, SEb = 0.032, 95% CI [-0.14,-0.0039], t(27) = -2.17, p = 0.039) were significant predictors for IAD, and also for transformed values of the GA and IAI.Conclusions
There are progressive alterations in phonatory posturing as Parkinson’s disease advances. The increases in GA despite reductions in IAD are concordant with prior observations of vocal fold bowing. Our study provides a basis for using laryngeal 4D-CT to assess disease progression in Parkinson’s disease.
by Benedict O. Orindi, Abdhalah Ziraba, Luk Bruyneel, Sian Floyd, Emmanuel LesaffreIntroduction
To make valid comparisons across groups, a measurement instrument needs to be measurement invariant across those groups. The present study evaluates measurement invariance for experience of violence among adolescent girls and young women (AGYW) in two informal settlements in Nairobi, Kenya.Methods
We used survey data collected from 1,081 AGYW aged 15–22 years from two Nairobi’s informal settlements of Korogocho (n = 617) and Viwandani (n = 464) in 2017 through DREAMS (an initiative aimed at reducing HIV incidence among AGYW with a core package of evidence-based interventions) impact evaluation project. Experience of violence was measured using the 15-item WHO’s violence against women instrument, and factorial (non)invariance assessed within exploratory structural equation modeling (ESEM) framework. Cross-group measurement invariance was assessed using Bayesian Multiple Indicator Multiple Causes (MIMIC) model across site, age groups, self-reported invitation to participate in DREAMS, marital status, currently in school, education level, religion, ethnic groups, ever had sex, slept hungry at night past 4 weeks, and wealth index.Results
The mean and median ages of the AGYW were 17.9 years and 17 years, respectively. About 59% reported having had sex and 58% of AGYW were in school. The percentage reporting each act of violence varied from 1.6% (“attacked you with a weapon”) to 26.5% (“insult you or make you feel bad about yourself”). About 44% (n = 474) of participants experienced ≥1 acts of violence, and 2.7% (n = 29) experienced at least half of the 15 acts. The structure underlying the 15 items was configurally similar to that proposed by WHO, with three factors reflecting either psychological, physical, or sexual violence. Noninvariance was detected for five items—spread across the three domains. Three of five items showed noninvariance only for sleeping hungry at night in the past 4 weeks. As the majority of items did not show evidence of noninvariance, differences in latent mean scores likely reflect actual differences and may not be attributable to measurement artifacts.Conclusions
Using state-of-the-art statistical techniques on a widely used instrument for measuring exposure to violence among women, this study provides support for the subscales of psychological, physical and sexual violence in a Kenyan AGYW population. The instrument supports comparisons across groups within this population. This is crucial when comparing violence against girls/women prevalence rates and to understand challenges and exchange strategies to reduce abuse or violence experienced by AGYW, or women in general.
by Tetsuya Ishizawa, Naohiko Makino, Yasuharu Kakizaki, Akiko Matsuda, Yoshihide Toyokawa, Shun Ooyama, Masaru Tanaka, Yoshiyuki UenoCovered self-expandable metal stents (CSEMS) are often used for palliative endoscopic biliary drainage; however, the unobstructed period is limited because of sludge occlusion. The present study aimed to evaluate the biosafety of a novel poly(2-methoxyethyl acrylate)-coated CSEMS (PMEA-CSEMS) for sludge resistance and examine its biosafety in vivo. Using endoscopic retrograde cholangiopancreatography, we placed the PMEA-CSEMS into six normal porcine bile ducts and conventional CSEMS into three normal porcine bile ducts. We performed serological examination and undecalcified histological analysis at 1, 3, and 6 months during follow-up. In the bile ducts with PMEA-CSEMS or conventional CSEMS, we observed no increase in liver enzyme or inflammatory marker levels in the serological investigations and mild fibrosis but no inflammatory response in the histopathological analyses. Thus, we demonstrated the biosafety of PMEA-CSEMS in vivo.
by Yuki Takahashi, Masatoshi Saito, Haruo Usuda, Tsukasa Takahashi, Shimpei Watanabe, Takushi Hanita, Shinichi Sato, Yusaku Kumagai, Shota Koshinami, Hideyuki Ikeda, Sean Carter, Erin L. Fee, Lucy Furfaro, Sylvain Chemtob, Jeffrey Keelan, David Olson, Nobuo Yaegashi, John P. Newnham, Alan H. Jobe, Matthew W. KempBackground
Intraamniotic inflammation is associated with up to 40% of preterm births, most notably in deliveries occurring prior to 32 weeks’ gestation. Despite this, there are few treatment options allowing the prevention of preterm birth and associated fetal injury. Recent studies have shown that the small, non-competitive allosteric interleukin (IL)-1 receptor inhibitor, rytvela, may be of use in resolving inflammation associated with preterm birth (PTB) and fetal injury. We aimed to use an extremely preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela in response to established intra-amniotic (IA) lipopolysaccharide (LPS) exposure. We hypothesized that rytvela would reduce LPS-induced IA inflammation in amniotic fluid (AF) and fetal tissues.Methods
Sheep with a single fetus at 95 days gestation (estimated fetal weight 1.0 kg) had surgery to place fetal jugular and IA catheters. Animals were recovered for 48 hours before being randomized to either: i) IA administration of 2 ml saline 24 hours before 2 ml IA and 2 ml fetal intravenous (IV) administration of saline (Saline Group, n = 7); ii) IA administration of 10 mg LPS in 2 ml saline 24 hours before 2 ml IA and 2 ml fetal IV saline (LPS Group, n = 10); 3) IA administration of 10 mg LPS in 2 ml saline 24 hours before 0.3 mg/fetal kg IA and 1 mg/fetal kg fetal IV rytvela in 2 ml saline, respectively (LPS + rytvela Group, n = 7). Serial AF samples were collected for 120 h. Inflammatory responses were characterized by quantitative polymerase chain reaction (qPCR), histology, fluorescent immunohistochemistry, enzyme-linked inmmunosorbent assay (ELISA), fluorescent western blotting and blood chemistry analysis.Results
LPS-treated animals had endotoxin and AF monocyte chemoattractant protein (MCP)-1 concentrations that were significantly higher at 24 hours (immediately prior to rytvela administration) relative to values from Saline Group animals. Following rytvela administration, the average MCP-1 concentrations in the AF were significantly lower in the LPS + rytvela Group relative to in the LPS Group. In delivery samples, the expression of IL-1β in fetal skin was significantly lower in the LPS + rytvela Group compared to the LPS Group.Conclusion
A single dose of rytvela was associated with partial, modest inhibition in the expression of a panel of cytokines/chemokines in fetal tissues undergoing an active inflammatory response.
by Katsuhiro Yoshikawa, Mitsuaki Ishida, Hirotsugu Yanai, Koji Tsuta, Mitsugu Sekimoto, Tomoharu SugieBackground
Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. A recent study demonstrated the efficacy of anti-PD-L1 (anti-programmed death ligand-1) immunotherapy in patients with TNBC. However, the identification of TNBC patients who may benefit from immunotherapy is a critical issue. Several assays have been used to evaluate PD-L1 expression, and a few studies comparing PD-L1 expression using various primary antibodies in TNBC tissues have been reported. However, the expression profiles of the PD-L1 using the 73–10 assay have not yet been analyzed in TNBC tissues.Methods
We analyzed the PD-L1 immunohistochemical profiles of 62 women with TNBC using the 73–10, SP142 (companion diagnostic for atezolizumab), and E1L3N assays. PD-L1 expression on immune cells (ICs) and tumor cells (TCs) was also evaluated, and PD-L1 positivity was defined as a PD-L1-expressing ICs or TCs ≥ 1%.Results
The expression rates of PD-L1 were 79.0%, 67.7%, and 46.8% on ICs, and 17.7%, 6.5%, and 12.9% on TCs using the 73–10, SP142, and E1L3N assays, respectively. The concordance rates between the 73–10 and SP142 assays were 85.5% (on ICs) and 88.7% (on TCs), respectively, and substantial agreement on ICs (coefficient 0.634) and moderate agreement (coefficient 0.485) on TCs were noted. Sample age and tumor diameter did not influence the ratio of PD-L1 expression among the assays.Conclusions
The positive rate on ICs and TCs of the 73–10 assay was higher than that of the SP 142 and E1L3N assays. Although substantial agreement on ICs and moderate agreement on TCs between the 73–10 and SP142 assays was noted in the present cohort, further studies are needed to clarify the PD-L1 expression status using various primary antibodies in a larger patient population. This would lead to the establishment of an effective evaluation method to assess the predictive value of anti-PD-L1 immunotherapy.
by Sze-Yuen Yau, Yu-Che Chang, Meng-Yu Wu, Shu-Chen LiaoBackground
Endotracheal intubation is crucial in emergency medical care and anaesthesia. Our study employed a high-fidelity simulator to explore differences in intubation success rate and other skills between junior and senior physicians.Methods
We examined the performance of 50 subjects, including undergraduate students (UGY), postgraduate trainees (PGY), residents (R), and attending physicians (VS). Each participant performed 12 intubations (i.e. 3 devices x 4 scenarios) on a high-fidelity simulator. Main outcome measures included success rate, time for intubation, force applied on incisor and tongue, and Cormack Lehane grades.Results
There was no primary effect of seniority on any outcome measure except success rate and Cormack Lehane grades. However, VS demonstrated shorter duration than medical students using Glidescope and direct laryngoscopy, whereas VS and R applied significantly more force on the incisor in the normal airway and rigid neck scenario respectively.Discussion
Seniority does not always correlate with skill perfection in detailed processes. Our study suggests that the use of video laryngoscopy enhances the intubation success rate and speed, but the benefit only accrues to senior learners, whereby they applied more force on the incisor at a single peak under difficult scenarios. These findings are discussed in terms of psychological and cognitive perspectives.Conclusion
Speed and safety are essential for high quality critical medical procedures. A tool should be designed and implemented to educate junior physicians with an emphasis on practice and efficiency, which should also contribute to updating senior physicians’ knowledge and competence by providing instant feedback on their performance. This type of fine-grained feedback could serve as a complement to traditional training and provide a sustainable learning model for medical education.
by David Santos, Blanca Requero, Manuel Martín-FernándezThe present research examined how individuals’ thinking style (holistic vs. analytic) is associated with the way they deal with contradictory information and whether experiencing mixed emotions can mediate this relationship. Participants first completed the thinking style measure and then were exposed to two contradictory pieces of information (Studies 1 and 2). In study 2, we also measured the experience of mixed emotions to test the mediating role of this variable. Across two studies, we found that individuals with a holistic thinking style were more able to reconcile contradictory information compared to individuals with an analytic thinking style. Study 2 showed that the relationship between thinking style and dealing with contradiction was mediated by the experience of mixed emotions. This research extends previous findings on confrontation of contradiction and mixed emotions by using an individual-differences rather than a cultural-differences approach, and establishes mixed emotions as a plausible mediating variable.