bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors for ARDS: clinical, physiological and atypical immunodeficiency
Authors: Song Min , Liu Yijie , Lu Zhiwen , Luo Hong , Peng Hong , Chen Ping
Published: April 2020

Background

Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency.

Methods

ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis.

Results

In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO2/FiO2(P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008,P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO2/FiO2ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO2/FiO2ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log10years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057).

Conclusions

Age (per log10years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.
Patellar sleeve avulsion fracture in a patient with Sinding-Larsen-Johansson syndrome: a case report
Authors: Schmidt-Hebbel Andrés , Eggers Felipe , Schütte Vincent , Achtnich Andrea , Imhoff Andreas B.
Published: April 2020

Background

Patellar sleeve avulsion (PSA) fractures are rare injuries that occur in in skeletally immature patients. Initial diagnosis is key to a successful outcome, as these injuries are easily overlooked on plain radiographs with poor results well documented from delayed management. High index of suspicion from the mechanism of injury, thorough clinical examination and Magnetic Resonance Imaging (MRI) help to avoid misdiagnosis.

Case presentation

The case of a 12-year-old male athlete with an acute PSA after a conservative treatment of a SLJ syndrome is described. The patient was referred to our clinic due to severe pain and loss of function after performing a high jump. Plain radiographs (X-ray) and MRI confirmed an inferior pole PSA which was fixed with double trans osseous ultra-high strength tapes. At the 3-month follow- up visit the patient was able to ambulate brace free. At 2-years follow up the patient was able to play soccer and ice hockey. To our knowledge, there are no case reports of inferior pole PSA with prior SLJ syndrome described in literature.

Conclusions

Early clinical suspicion and distinguishing this PSA from other enchondral ossification disorders around the knee is critical to avoid misdiagnosis. Whether SLJ syndrome increases the risk of sustaining a PSA is still not clear. Trans osseous fixation with suture tapes leads to good functional results in a young athlete with inferior pole PSA.
Non-health outcomes affecting self-care behaviors and medical decision-making preference in patients with type 2 diabetes: a cross-sectional study
Authors: Wang Ming-Jye , Lin Hung-Ming , Hung Li-Chen , Lo Yi-Ting
Published: April 2020

Background

The effects of patient sustained self-care behaviors on glycemic control are even greater than the effects of medical treatment, indicating the value of identifying the factors that influence self-care behaviors. To date, these factors have not been placed in a single model to clarify the critical path affecting self-care behaviors. The aims of this study were to explore the relationships of these factors and the differences in patient preference for medical decision-making.

Methods

A cross-sectional study was conducted among outpatients with type 2 diabetes at a regional teaching hospital. Purposive sampling was adopted to recruit 316 eligible patients via self-administered questionnaires. Partial least squares structural equation modeling was used for analysis.

Results

Significant direct pathways were identified from health literacy to self-efficacy, patient empowerment, and self-care behaviors; from self-efficacy to self-care behaviors; and from patient empowerment to self-care behaviors. Indirect pathways were from health literacy to self-care behaviors via self-efficacy or patient empowerment. The pathway from health literacy to self-efficacy was significantly stronger in those preferring shared decision-making than in those who preferred physician decision-making.

Conclusions

Health literacy is a critical factor in improving self-care behaviors in patients with type 2 diabetes, and the effect of health literacy on self-efficacy was more significant in the shared decision-making than in the physician decision-making. Therefore, developing an effective health strategy to strengthen health literacy awareness and designing friendly, diverse health literacy materials, and application tools is the most important factor to facilitate self-care behaviors in this population.
Assessing the youth-friendliness of youth clinics in northern Sweden: a survey analyzing the perspective of the youth
Authors: Waenerlund Anna-Karin , San Sebastian Miguel , Hurtig Anna-Karin , Wiklund Maria , Christianson Monica , Goicolea Isabel
Published: April 2020

Background

Sweden has nearly 300 youth clinics that have been offering services since the 1970s. However, no evaluation has been done to assess their youth-friendliness. This study aims to assess: i) to what extent youth clinics are perceived as youth-friendly by the young people using them; and ii) if the level of youth friendliness is equally perceived across different sociodemographic groups of users.

Methods

The four northernmost counties of Sweden were included in the study. Of the total identified 22 youth clinics, 20 participated by giving out questionnaires to the youth after their visits to the respective youth clinics. In total 1110 youth participated in the study and answered questions according to the World Health Organization’s criteria of accessibility, equity, respect, privacy and confidentiality, no judgement, and quality. Means and frequencies were calculated, and t-test and ANOVA were used to compare means by sociodemographic variables.

Results

Participants perceived the youth clinics as very youth friendly across the measured domains, with scores as high as 4.8 and 4.9 (of a maximum of 5). Youth clinics were perceived in a similar way regardless of gender, but other sociodemographic factors influenced some of the domains, especially ethnic background.

Conclusions

The perception of youth friendliness in youth clinics was very high. Nonetheless, younger users; users who did not categorize themselves as either heterosexual, homosexual, or bisexual; users with trans-experiences; and users with non-Swedish backgrounds gave youth clinics lower scores for certain domains.
‘Wait and wait, that is the only thing they can say’: a qualitative study exploring experiences of immigrated Syrian doctors applying for medical license in Germany
Authors: Loss Julika , Aldoughle Yamen , Sauter Alexandra , von Sommoggy Julia
Published: April 2020

Background

Due to the civil war in Syria, many Syrian citizens have had to flee their country during recent years, among them many physicians. Germany is among the preferred immigration countries. Immigrant Syrian physicians could help overcome the prevailing shortage of medical specialists in Germany. This study explores the experiences and perceptions of Syrian physicians of the licensure process and job application. The study aims at understanding barriers in integrating Syrian doctors into the German health care system.

Methods

We conducted 20 semi standardized interviews with Syrian doctors (n = 17 m; n = 3 f) living in different federal states in Germany. The interviews dealt with the procedure of the accreditation process, its speed and challenges, the interactions with authorities, and the job application process; they were transcribed verbatim. A detailed content analysis was performed.

Results

All interviewees described the licensure process as a complex, lengthy, ever-changing and non-transparent procedure, which is perceived as a partly unfair, sometimes arbitrary bureaucracy. They often feel at mercy of Government employees and report experiences with reviewers who ask for absurd and impossible accomplishments, refuse to give information, and act at random. As a consequence, the interviewees describe themselves as depressed, irritated and/or in despair. According to the interviews, informational and practical support from official institutions was scarce. Instead, the Syrian doctors relied on peers or, in some cases, German friends to understand the requirements and seek information about the licensure process. To find a job placement, it was very helpful, if not essential, to have a German acquaintance establishing contact with possible employers. All three interviewed female doctors reported that their wearing a Hijab led to episodes of discrimination in their job search.

Conclusions

The study points towards the necessity to establish an official information source which provides immigrant doctors with accurate and detailed information about the licensure process, e.g. required documents, estimated waiting times, regulation for courses and exams, criteria regarding credentials, sources of help, etc. Additionally, it seems advisable to consider providing help with regard to the job search and sensitize hospital management for cultural and religious diversity to avoid discrimination.
A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis
Authors: Bedeschi Maria Francesca , Crippa Beatrice Letizia , Colombo Lorenzo , Buscemi Martina , Rossi Cesare , Villa Roberta , Gangi Silvana , Picciolini Odoardo , Cinnante Claudia , Fergnani Viola Giulia Carlina , Ajmone Paola Francesca , Scola Elisa , Triulzi Fabio , Mosca Fabio
Published: April 2020

Background

An early diagnosis of CHARGE syndrome is challenging, especially for the primary care physicians who often take care of neonates with multiple congenital anomalies. Here we report eight cases of CHARGE syndrome whose diagnosis was made early in life with the intent to identify the most helpful features allowing a prompt clinical diagnosis.

Methods

Medical records of patients with CHARGE syndrome whose diagnosis was made at the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico in Milan, Italy were retrospectively reviewed.

Results

Taken together, these patients reflect the considerable phenotypic variability of the syndrome; in one patient, the diagnosis was made immediately after birth because all the major criteria were met. In six patients, presenting with relatively nonspecific defects, a temporal bone computerized tomography scan was essential to achieve the correct diagnosis. In one patient, the diagnosis was made later than the others were. A careful examination revealed the presence of outer, middle, and inner ear anomalies: these elements, in the absence of any additional major criteria, represented for us an important diagnostic clue.

Conclusions

This article suggests that an accurate evaluation of the ear should be made every time CHARGE syndrome is considered as a likely diagnosis even when the standard criteria are not fulfilled.
RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells
Authors: Bai Zhenzi , Zhao Xiaonan , Li Chenghua , Sheng Chuanlun , Li Hongyan
Published: April 2020

Background

Emerging evidence closely links Enterovirus 71 (EV71) infection with the generation of reactive oxygen species (ROS). Excess ROS results in apoptosis and exacerbates inflammatory reactions. The Keap1–Nrf2 axis serves as an essential oxidant counteracting pathway.

Methods

The present study aimed to elucidate the role of the Keap1–Nrf2 pathway in modulating apoptosis and inflammatory reactions triggered by oxidative stress in Vero and RD cells upon EV71 infection.

Results

Elevated ROS production was identified in EV71 infected Vero and RD cells. The percentage of dead cells and expression of inflammation-promoting cytokines were increased in these cells. EV71 infected cells also displayed reinforced Keap1 expression and abrogated Nrf2 expression. Keap1 silencing resulted in the downstream aggregation of the Nrf2 protein and heme oxygenase-1 HO-1. Keap1 silencing repressed ubiquitination and reinforced Nrf2 nuclear trafficking. Furthermore, silencing Keap1 expression repressed ROS production, cell death, and inflammatory reactions in EV71 infected RD and Vero cells. In contrast, silencing of both Keap1 and Nrf2 restored ROS production, cell death, and inflammatory reactions. Nrf2 and Keap1 modulated the stimulation of the Akt sensor and extrinsic as well as intrinsic cell death pathways, resulting in EV71-triggered cell death and inflammatory reactions.

Conclusions

EV71 infection can trigger ROS production, cell death, and inflammatory reactions by modulating the Nrf2 and Keap1 levels of infected cells.
Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
Authors: Kalange Muhamudu , Nansunga Miriam , Kasozi Keneth Iceland , Kasolo Josephine , Namulema Jackline , Atusiimirwe Jovile Kasande , Ayikobua Emmanuel Tiyo , Ssempijja Fred , Munanura Edson Ireeta , Matama Kevin , Semuyaba Ibrahim , Zirintunda Gerald , Okpanachi Alfred Omachonu
Published: April 2020

Objective

Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats.

Results

Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.
Thyrotoxic periodic paralysis presenting in an African-American teenage male: case report
Authors: Glass Joshua , Osipoff Jennifer
Published: April 2020

Background

Thyrotoxic periodic paralysis is a rare complication of hyperthyroidism and is associated with hypokalemia and muscle paralysis. This condition is most commonly seen in Asian men.

Case presentation

We report on a 14-year-old African American male with Graves’ disease and intermittent asthma who presented with bilateral leg weakness. The patient demonstrated signs of thyrotoxicosis and laboratory evaluation revealed hypokalemia and hyperthyroidism. Following the administration of potassium supplementation clinical status improved and the patient was discharged home on a high dose of methimazole and propranolol. At a 6-month follow up visit, he was found to be clinically euthyroid and demonstrated no signs of hyperthyroidism or muscle weakness.

Conclusion

Children presenting with weakness and hypokalemia should be investigated for thyroid dysfunction. Correction of hypokalemia improves acute presentation, but the patient will remain at risk for paralysis until euthyroid state is achieved.
Examining the impact of a social skills training program on preschoolers’ social behaviors: a cluster-randomized controlled trial in child care centers
Authors: Larose Marie-Pier , Ouellet-Morin Isabelle , Vergunst Francis , Vitaro Frank , Girard Alain , E. Tremblay Richard , Brendgen Mara , M. Côté Sylvana
Published: April 2020

Background

Preschoolers regularly display disruptive behaviors in child care settings because they have not yet developed the social skills necessary to interact prosocially with others. Disruptive behaviors interfere with daily routines and can lead to conflict with peers and educators. We investigated the impact of a social skills training program led by childcare educators on children’s social behaviors and tested whether the impact varied according to the child’s sex and family socio-economic status.

Methods

Nineteen public Child Care Centers (CCC, n = 361 children) located in low socio-economic neighborhoods of Montreal, Canada, were randomized into one of two conditions: 1) intervention (n = 10 CCC; 185 children) or 2) wait list control (n = 9 CCC; 176 children). Educators rated children’s behaviors (i.e., disruptive and prosocial behaviors) before and after the intervention. Hierarchical linear mixed models were used to account for the nested structure of the data.

Results

At pre-intervention, no differences in disruptive and prosocial behaviors were observed between the experimental conditions. At post-intervention, we found a significant sex by intervention interaction (β intervention by sex = − 1.19, p = 0.04) indicating that girls in the intervention condition exhibited lower levels of disruptive behaviors compared to girls in the control condition (f2 effect size = − 0.15). There was no effect of the intervention for boys.

Conclusions

Girls may benefit more than boys from social skills training offered in the child care context. Studies with larger sample sizes and greater intervention intensity are needed to confirm the results.

Trial registration

Current clinical trial number is ISRCTN84339956 (Retrospectively registered in March 2017). No amendment to initial protocol.
In vitro and in vivo effects of flubendiamide and copper on cyto-genotoxicity, oxidative stress and spleen histology of rats and its modulation by resveratrol, catechin, curcumin and α-tocopherol
Authors: Mandil Rajesh , Prakash Atul , Rahal Anu , Singh S. P. , Sharma Deepak , Kumar Rahul , Garg Satish Kumar
Published: April 2020

Background

Living organisms are frequently exposed to more than one xenobiotic at a time either by ingestion of contaminated food/fodder or due to house-hold practices, occupational hazards or through environment. These xenobiotics interact individually or in combination with biological systems and act as carcinogen or produce other toxic effects including reproductive and degenerative diseases. Present study was aimed to investigate the cyto-genotoxic effects of flubendiamide and copper and ameliorative potential of certain natural phyotconstituent antioxidants.

Method

In vitro cytogenotoxic effects were evaluated by employing battery of assays including Propidium iodide staining, Tunel assay, Micronuclei, DNA fragmentation and Comet assay on isolated splenocytes and their prevention by resveratrol (5 and 10 μM), catechin (10 and 20 μM), curcumin (5 and 10 μM) and α-tocopherol (5, 10 and 20 μM). In vivo study was also undertaken daily oral administration of flubendiamide (200 mg/kg) or copper (33 mg/kg) and both these in combination, and also all these concurrently with of α-tocopherol to Wistar rats for 90 days.

Results

Flubendiamide and copper produced concentration-dependent cytotoxic effects on splenocytes and at median lethal concentrations, flubendiamide (40 μM) and copper (40 μM) respectively produced 71 and 81% nonviable cells, higher number of Tunel+ve apoptotic cells, 7.86 and 9.16% micronucleus and 22.90 and 29.59 comets/100 cells and DNA fragmentation. In vivo study revealed significant (P < 0.05) increase in level of lipid peroxidation (LPO) and decrease in glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities in groups exposed to flubendiamide or copper alone or both these in combination. Histopathological examination of rat spleens revealed depletion of lymphoid tissue, separation of splenocytes and rarification in splenic parenchyma of xenobiotic(s) treated groups.

Conclusion

Flubendiamide and copper induce oxidative stress and produce cytogenotoxic effects along with histoarchitectural changes in spleen. All four tested natural antioxidants (resveratrol, catechin, curcumin and α-tocopherol) reduced flubendiamide and copper-induced cytotoxic effects in rat splenocytes. Rat splenocytes are very sensitive to flubendiamide and copper-induced cytogenotoxicity, therefore, these can be effectively employed for screening of compounds for their cytogenotoxic potential. α-tocopherol was effective in restoring alterations in oxidative stress biomarkers and preventing histoarchitectural lesions in spleen.
Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG
Authors: Chiang Jason , Diaz Alexander K. , Makepeace Lydia , Li Xiaoyu , Han Yuanyuan , Li Yimei , Klimo Paul , Boop Frederick A. , Baker Suzanne J. , Gajjar Amar , Merchant Thomas E. , Ellison David W. , Broniscer Alberto , Patay Zoltan , Tinkle Christopher L.
Published: April 2020

Diffuse intrinsic pontine glioma (DIPG) is most commonly diagnosed based on imaging criteria, with biopsy often reserved for pontine tumors with imaging features not typical for DIPG (atypical DIPG, ‘aDIPG’). The histopathologic and molecular spectra of the clinical entity aDIPG remain to be studied systematically. In this study, thirty-three patients with newly diagnosed pontine-centered tumors with imaging inconsistent with DIPG for whom a pathologic diagnosis was subsequently obtained were included. Neoplasms were characterized by routine histology, immunohistochemistry, interphase fluorescence in situ hybridization, Sanger and next-generation DNA/RNA sequencing, and genome-wide DNA methylome profiling. Clinicopathologic features and survival outcomes were analyzed and compared to those of a contemporary cohort with imaging features consistent with DIPG (typical DIPG, ‘tDIPG’). Blinded retrospective neuroimaging review assessed the consistency of the initial imaging-based diagnosis and correlation with histopathology. WHO grade II-IV infiltrating gliomas were observed in 54.6% of the cases; the remaining were low-grade gliomas/glioneuronal tumors or CNS embryonal tumors. Histone H3 K27M mutation, identified in 36% of the cases, was the major prognostic determinant. H3 K27M–mutant aDIPG and H3 K27M–mutant tDIPG had similar methylome profiles but clustered separately from diffuse midline gliomas of the diencephalon and spinal cord. In the aDIPG cohort, clinicoradiographic features did not differ by H3 status, yet significant differences in clinical and imaging features were observed between aDIPG without H3 K27M mutation and tDIPG. Neuroimaging review revealed discordance between the classification of aDIPG and tDIPG and did not correlate with the histology of glial/glioneuronal tumors or tumor grade. One patient (3.1%) developed persistent neurologic deficits after surgery; there were no surgery-related deaths. Our study demonstrates that surgical sampling of aDIPG is well-tolerated and provides significant diagnostic, therapeutic, and prognostic implications, and that neuroimaging alone is insufficient to distinguish aDIPG from tDIPG. H3 K27M-mutant aDIPG is epigenetically and clinically similar to H3 K27M-mutant tDIPG.
Lipid-coated ZnO nanoparticles synthesis, characterization and cytotoxicity studies in cancer cell
Authors: Cao Dingding , Shu Xugang , Zhu Dandan , Liang Shengli , Hasan Murtaza , Gong Sheng
Published: April 2020

ZnO nanoparticles are widely used in biological, chemical, and medical fields, but their toxicity impedes their wide application. In this study, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) and lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) with different morphologies were prepared by chemical method and characterized by TEM, XRD, HRTEM, FTIR, and DLS. Our results showed that the lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) groups improved the colloidal stability, prevented the aggregation and dissolution of nanocrystal particles in the solution, inhibited the dissolution of ZnO NPs into Zn2+cations, and reduced cytotoxicity more efficiently than the pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm). Compared to the lipid-coated ZnO NPs, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) could dose-dependently destroy the cells at low concentrations. At the same concentration, ZnO NPs (~ 7 nm) exhibited the highest cytotoxicity. These results could provide a basis for the toxicological study of the nanoparticles and direct future investigations for preventing strong aggregation, reducing the toxic effects of lipid-bilayer and promoting the uptake of nanoparticles by HeLa cells efficiently.
Unsteady shock front waviness in shock-buffet of transonic aircraft
Authors: Apetrei Razvan Marian , Ciobaca Vlad , Curiel-Sosa Jose Luis , Qin Ning
Published: April 2020

The unsteady transonic aerodynamics of a wing-body configuration is investigated by solving the Unsteady Reynolds-averaged Navier-Stokes equations closed with the full Reynolds Stress Model. This work presents the prediction of flow field characteristics during deep shock-buffet penetration of a transport aircraft-representative geometry. Mach number of 0.85, and Reynolds number of 5 million based on the mean chord, are selected to reproduce experimental test conditions that serve as validating datasets. The results obtained give information about both surface and flow field shock-buffet dynamics. An unsteady shock front is observed on the suction side of the wing which gives birth to the so-called buffet cells. Flow field characteristics are dominated by the presence of lambda-shaped shocks and fully separated boundary layer over a significant part of the wing.
Correction to: Post-treatment benign changes versus recurrence in non-lymphoid head and neck malignancies: can diffusion-weighted magnetic resonance imaging end up the diagnostic challenge?
Authors: Serour Dalia K. , Adel Khaled M. , Osman Ayman M. A.
Published: April 2020

Following publication of the original article [1], the author reported that the institution Cairo University Hospitals (Cairo, Egypt) is not added in the Methods section
Comparison of short-term (saliva) and long-term (hair) cortisol levels in out-patients with melancholic and non-melancholic major depression
Authors: Herane-Vives Andrés , Young Allan H. , Wise Toby , Aguirre Juan , de Angel Valeria , Arnone Danilo , Papadopoulos Andrew , Cleare Anthony J.
Published: April 2020

Background

Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration.

Method

Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva – the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) – were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures.

Results

The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs.

Conclusions

The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.
CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes
Authors: Capello Michela , Fahrmann Johannes F. , Rios Perez Mayrim V. , Vykoukal Jody V. , Irajizad Ehsan , Tripathi Satyendra C. , Roife David , Bantis Leonidas E. , Kang Ya’an , Kundnani Deepali L. , Xu Hanwen , Prakash Laura R. , Long James P. , Katayama Hiroyuki , Fleury Alia , Ferri-Borgogno Sammy , Baluya Dodge L. , Dennison Jennifer B. , Aguilar-Bonavides Clemente , Casabar Julian P. , Celiktas Muge , Do Kim-Anh , Fiehn Oliver , Maitra Anirban , Wang Huamin , Feng Ziding , Chiao Paul J. , Katz Matthew H. , Fleming Jason B. , Hanash Samir M.
Published: April 2020

PURPOSE

The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC.

METHODS

PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment.

RESULTS

High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment ( P = .04).

CONCLUSION

To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.
Relevance and Effectiveness of Molecular Tumor Board Recommendations for Patients With Non–Small-Cell Lung Cancer With Rare or Complex Mutational Profiles
Authors: Koopman Bart , van der Wekken Anthonie J. , ter Elst Arja , Hiltermann T. Jeroen N. , Vilacha Juliana F. , Groves Matthew R. , van den Berg Anke , Hiddinga Birgitta I. , Hijmering-Kappelle Lucie B. M. , Stigt Jos A. , Timens Wim , Groen Harry J. M. , Schuuring Ed , van Kempen Léon C.
Published: April 2020

PURPOSE

Molecular tumor boards (MTBs) provide physicians with a treatment recommendation for complex tumor-specific genomic alterations. National and international consensus to reach a recommendation is lacking. In this article, we analyze the effectiveness of an MTB decision-making methodology for patients with non–small-cell lung cancer (NSCLC) with rare or complex mutational profiles as implemented in the University Medical Center Groningen (UMCG).

METHODS

The UMCG-MTB comprises (pulmonary) oncologists, pathologists, clinical scientists in molecular pathology, and structural biologists. Recommendations are based on reported actionability of variants and molecular interpretation of pathways affected by the variant and supported by molecular modeling. A retrospective analysis of 110 NSCLC cases (representing 106 patients) with suggested treatment of complex genomic alterations and corresponding treatment outcomes for targeted therapy was performed.

RESULTS

The MTB recommended targeted therapy for 59 of 110 NSCLC cases with complex molecular profiles: 24 within a clinical trial, 15 in accordance with guidelines (on label) and 20 off label. All but 16 recommendations involved patients with an EGFR or ALK mutation. Treatment outcome was analyzed for patients with available follow-up (10 on label and 16 off label). Adherence to the MTB recommendation (21 of 26; 81%) resulted in an objective response rate of 67% (14 of 21), with a median progression-free survival of 6.3 months (interquartile range, 3.2-10.6 months) and an overall survival of 10.4 months (interquartile range, 6.3-14.6 months).

CONCLUSION

Targeted therapy recommendations resulting from the UMCG-MTB workflow for complex molecular profiles were highly adhered to and resulted in a positive clinical response in the majority of patients with metastatic NSCLC.
Improving inverse Compton sources by avoiding non-linearities
Authors: Terzić B. , Krafft G. A. , Petrillo V. , Drebot I. , Ruijter M.
Published: April 2020

We present a new, more nuanced understanding of non-linear effects in inverse Compton sources. Deleterious non-linear effects can arise even at low laser intensities, a regime previously viewed as linear. After laying out a survey of non-linear phenomena which degrade the effectiveness of inverse Compton sources, we discuss two powerful techniques designed to avoid these non-linearities. Starting with the known technique of non-linear longitudinal chirping of the laser pulse in the high laser field regime, we show that the simple stretching of the laser pulse, while keeping the energy constant, can significantly increase the spectral density of the scattered radiation in many operating regimes. Our numerical simulations show that combining these two techniques avoids detrimental non-linearities and improves the performance of inverse Compton sources over an order of magnitude.
Reliability and Validity of Performance Evaluations of Pain Medicine Clinical Faculty by Residents and Fellows Using a Supervision Scale
Authors: Dexter Franklin , Hadlandsmyth Katherine , Pearson Amy C. S. , Hindman Bradley J.
Published: April 2020

BACKGROUND:

Annual and/or semiannual evaluations of pain medicine clinical faculty are mandatory for multiple organizations in the United States. We evaluated the validity and psychometric reliability of a modified version of de Oliveira Filho et al clinical supervision scale for this purpose.

METHODS:

Six years of weekly evaluations of pain medicine clinical faculty by resident physicians and pain medicine fellows were studied. A 1–4 rating (4 = “Always”) was assigned to each of 9 items (eg, “The faculty discussed with me the management of patients before starting a procedure or new therapy and accepted my suggestions, when appropriate”).

RESULTS:

Cronbach α of the 9 items equaled .975 (95% confidence interval [CI], 0.974–0.976). A G coefficient of 0.90 would be expected with 18 raters; the N = 12 six-month periods had mean 18.8 ± 5.9 (standard deviation [SD]) unique raters in each period (median = 20).

Concurrent validity was shown by Kendall τb = 0.45 (P < .0001) pairwise by combination of ratee and rater between the average supervision score and the average score on a 21-item evaluation completed by fellows in pain medicine. Concurrent validity also was shown by τb = 0.36 (P = .0002) pairwise by combination of ratee and rater between the average pain medicine supervision score and the average operating room supervision score completed by anesthesiology residents.

Average supervision scores differed markedly among the 113 raters (η2 = 0.485; CI, 0.447–0.490). Pairings of ratee and rater were nonrandom (Cramér V = 0.349; CI, 0.252–0.446).

Mixed effects logistic regression was performed with rater leniency as covariates and the dependent variable being an average score equaling the maximum 4 vs <4. There were 3 of 13 ratees with significantly more averages <4 than the other ratees, based on P < .01 criterion; that is, their supervision was reliably rated as below average. There were 3 of 13 different ratees who provided supervision reliably rated as above average.

Raters did not report higher supervision scores when they had the opportunity to perform more interventional pain procedures.

CONCLUSIONS:

Evaluations of pain medicine clinical faculty are required. As found when used for evaluating operating room anesthesiologists, a supervision scale has excellent internal consistency, achievable reliability using 1-year periods of data, concurrent validity with other ratings, and the ability to differentiate among ratees. However, to be reliable, routinely collected supervision scores must be adjusted for rater leniency.
The Effect of the No Pain Labor & Delivery-Global Health Initiative on Cesarean Delivery and Neonatal Outcomes in China: An Interrupted Time-Series Analysis
Authors: Drzymalski Dan M. , Guo Jun-Cai , Qi Xue-Qin , Tsen Lawrence C. , Sun Yingyong , Ouanes Jean-Pierre P. , Xia Yun , Gao Wei Dong , Ruthazer Robin , Hu Fengling , Hu Ling-Qun
Published: April 2020

BACKGROUND:

The proportion of live births by cesarean delivery (CD) in China is significant, with some, particularly rural, provinces reporting up to 62.5%. The No Pain Labor & Delivery-Global Health Initiative (NPLD-GHI) was established to improve obstetric and neonatal outcomes in China, including through a reduction of CD through educational efforts. The purpose of this study was to determine whether a reduction in CD at a rural Chinese hospital occurred after NPLD-GHI. We hypothesized that a reduction in CD trend would be observed.

METHODS:

The NPLD-GHI program visited the Weixian Renmin Hospital, Hebei Province, China, from June 15 to 21, 2014. The educational intervention included problem-based learning, bedside teaching, simulation drill training, and multidisciplinary debriefings. An interrupted time-series analysis using segmented logistic regression models was performed on data collected between June 1, 2013 and May 31, 2015 to assess whether the level and/or trend over time in the proportion of CD births would decline after the program intervention. The primary outcome was monthly proportion of CD births. Secondary outcomes included neonatal intensive care unit (NICU) admissions and extended NICU length of stay, neonatal antibiotic and intubation use, and labor epidural analgesia use.

RESULTS:

Following NPLD-GHI, there was a level decrease in CD with an estimated odds ratio (95% confidence interval [CI]) of 0.87 (0.78–0.98), P = .017, with odds (95% CI) of monthly CD reduction an estimated 3% (1–5; P < .001), more in the post- versus preintervention periods. For labor epidural analgesia, there was a level increase (estimated odds ratio [95% CI] of 1.76 [1.48–2.09]; P < .001) and a slope decrease (estimated odds ratio [95% CI] of 0.94 [0.92–0.97]; P < .001). NICU admissions did not have a level change (estimated odds ratio [95% CI] of 0.99 [0.87–1.12]; P = .835), but the odds (95% CI) of monthly reduction in NICU admission was estimated 9% (7–11; P < .001), greater in post- versus preintervention. Neonatal intubation level and slope changes were not statistically significant. For neonatal antibiotic administration, while the level change was not statistically significant, there was a decrease in the slope with an odds (95% CI) of monthly reduction estimated 6% (3–9; P < .001), greater post- versus preintervention.

CONCLUSIONS:

In a large, rural Chinese hospital, live births by CD were lower following NPLD-GHI and associated with increased use of labor epidural analgesia. We also found decreasing NICU admissions. International-based educational programs can significantly alter practices associated with maternal and neonatal outcomes.
Thoracolumbar Interfascial Plane Block for Spinal Cord Stimulator System Implantation: A Case Series
Authors: Hoydonckx Yasmine , Kumar Pranab , Chin Ki Jinn , Bhatia Anuj
Published: April 2020

Thoracolumbar interfascial plane block (TLIPB) has recently been described for postoperative analgesia after thoracolumbar spine surgery. This block is minimally invasive, relatively safe, and easy to perform. TLIPB can potentially decrease opioid requirements and enhance recovery following spine surgery. We describe the sonoanatomic landmarks of this technique, and we report results of this retrospective case series on analgesic impact of this block in patients undergoing implantation of spinal cord stimulation systems. Clinical studies are required to investigate the analgesic role of TLIPB for spinal thoracolumbar surgery.
The Conditions of Mercy
Authors: Revere William
Published: April 2020

This article examines John Bunyan’s relationship to traditions of representing labor reaching back before the Reformation, from Piers Plowman and its imitators through to a range of “plowman” satires, complaints, and reformist dialogues in the sixteenth and seventeenth centuries. Bunyan’s provocative rejection of the virtues of labor in part one of The Pilgrim’s Progress brings together theological convictions about justification by faith with a vision of mechanic mobility and schooling in the Spirit that disrupts a range of social forms and hierarchies. Yet in part two of The Pilgrim’s Progress, particularly in the figure of Mercie, Bunyan offers up a new valuation of the exemplarist potentials of labor. Part two expands rather than contracts Bunyan’s exploration of the active life of dissent, reimagining questions of embodiment, habituation, imitation, and community. Mercie’s labors are performed in continuity with a late medieval tradition linking work and virtue. Her example prompts reconsideration both of Bunyan’s own dissenting allegories and of the uses of literary forms and ethical traditions across conventional period boundaries and confessional identities.
F-BAR domain protein Syndapin regulates actomyosin dynamics during apical cap remodeling in syncytial Drosophila embryos
Authors: Sherlekar Aparna , Mundhe Gayatri , Richa Prachi , Dey Bipasha , Sharma Swati , Rikhy Richa
Published: April 2020

Branched actin networks driven by Arp2/3 interact with actomyosin filaments in processes such as cell migration. Similar interactions occur in the syncytial Drosophila blastoderm embryo where expansion of apical caps by Arp2/3-driven actin polymerization occurs in interphase, and cap buckling at contact edges by Myosin II to form furrows takes place in metaphase. Here, we study the role of Syndapin (Synd), an F-BAR domain-containing protein, in apical cap remodeling prior to furrow extension. We found that depletion of synd resulted in larger apical caps. Super-resolution and TIRF microscopy showed that control embryos had long apical actin protrusions in caps during interphase and short protrusions during metaphase, whereas synd depletion led to formation of sustained long protrusions, even during metaphase. Loss of Arp2/3 function in synd mutants partly reverted defects in apical cap expansion and protrusion remodeling. Myosin II levels were decreased in synd mutants, an observation consistent with the expanded cap phenotype previously reported for Myosin II mutant embryos. We propose that Synd function limits branching activity during cap expansion and affects Myosin II distribution in order to bring about a transition in actin remodeling activity from apical cap expansion to lateral furrow extension.
Kinesin-14 family proteins and microtubule dynamics define S. pombe mitotic and meiotic spindle assembly, and elongation
Authors: Loncar Ana , Rincon Sergio A. , Lera Ramirez Manuel , Paoletti Anne , Tran Phong T.
Published: April 2020

To segregate the chromosomes faithfully during cell division, cells assemble a spindle that captures the kinetochores and pulls them towards opposite poles. Proper spindle function requires correct interplay between microtubule motors and non-motor proteins. Defects in spindle assembly or changes in spindle dynamics are associated with diseases, such as cancer or developmental disorders. Here, we compared mitotic and meiotic spindles in fission yeast. We show that, even though mitotic and meiotic spindles underwent the typical three phases of spindle elongation, they have distinct features. We found that the relative concentration of the kinesin-14 family protein Pkl1 is decreased in meiosis I compared to mitosis, while the concentration of the kinesin-5 family protein Cut7 remains constant. We identified the second kinesin-14 family protein Klp2 and microtubule dynamics as factors necessary for proper meiotic spindle assembly. This work defines the differences between mitotic and meiotic spindles in fission yeast Schizosaccharomyces pombe, and provides prospect for future comparative studies.

This article has an associated First Person interview with the first author of the paper.