bluuebunny/crossref_metadata_2025 huggingface dataset:
International consensus on the most useful assessments used by physical therapists to evaluate patients with temporomandibular disorders: A Delphi study
Authors: von Piekartz Harry , Schwiddessen Julius , Reineke Lukas , Armijo‐Olivio Susan , Bevilaqua‐Grossi Débora , Biasotto Gonzalez Daniela A. , Carvalho Gabriela , Chaput Eve , Cox Erin , Fernández‐de‐las‐Peñas Cesar , Gadotti Inae Caroline , Gil Martínez Alfonso , Gross Anita , Hall Toby , Hoffmann Marisa , Julsvoll Elisabeth Heggem , Karegeannes Micheal , La Touche Roy , Mannheimer Jeffrey , Pitance Laurent , Rocabado Mariano , Strickland Mark , Stelzenmüller Wolfgang , Speksnijder Caroline , van der Meer Hedwig Aleida , Luedke Kerstin , Ballenberger Nicolaus
Published: March 2020

Objective

To identify assessment tools used to evaluate patients with temporomandibular disorders (TMD) considered to be clinically most useful by a panel of international experts in TMD physical therapy (PT).

Methods

A Delphi survey method administered to a panel of international experts in TMD PT was conducted over three rounds from October 2017 to June 2018. The initial contact was made by email. Participation was voluntary. An e‐survey, according to the Checklist for Reporting Results of Internet E‐Surveys (CHERRIES),was posted using SurveyMonkey for each round. Percentages of responses were analysed for each question from each round of the Delphi survey administrations.

Results

Twenty‐three experts (completion rate: 23/25) completed all three rounds of the survey for three clinical test categories: 1) questionnaires, 2) pain screening tools and 3) physical examination tests. The following was the consensus‐based decision regarding the identification of the clinically most useful assessments. (1) Four of 9 questionnaires were identified: Jaw Functional Limitation (JFL‐8), Mandibular Function Impairment Questionnaire (MFIQ), Tampa Scale for Kinesiophobia for Temporomandibular disorders (TSK/TMD) and the neck disability index (NDI). (2) Three of 8 identified pain screening tests: visual analog scale (VAS), numeric pain rating scale (NRS) and pain during mandibular movements. (3) Eight of 18 identified physical examination tests: physiological temporomandibular joint (TMJ) movements, trigger point (TrP) palpation of the masticatory muscles, TrP palpation away from the masticatory system, accessory movements, articular palpation, noise detection during movement, manual screening of the cervical spine and the Neck Flexor Muscle Endurance Test.

Conclusion

After three rounds in this Delphi survey, the results of the most used assessment tools by TMD PT experts were established. They proved to be founded on test construct, test psychometric properties (reliability/validity) and expert preference for test clusters. A concordance with the screening tools of the diagnostic criteria of TMD consortium was noted. Findings may be used to guide policymaking purposes and future diagnostic research.
Identification of the blast resistance gene Picl(t) from Chaling common wild rice (Oryza rufipogon Griff.)
Authors: Zheng Chuanqin , Jiang Nan , Zhao Xinhui , Yan Tianze , Fu Jun , Li Yanfeng , Wu Zhongxiu , Hu Xiaochun , Bai Zhenan , Liu Tiangang , Xiao Gui , Zhou Yanbiao , Chen Liangbi , Wang Kai , Yang Yuanzhu
Published: March 2020

Rice blast, caused by the fungal pathogen Magnaporthe oryzae (M. oryzae), is one of the most destructive and widespread plant diseases in the world. Utilization of resistance genes in rice breeding is considered to be an effective and economical method to control this disease. To identify new sources of blast resistance, a set of 1160 introgression lines (ILs) containing chromosome segments of Chaling common wild rice (Oryza rufipogon Griff.) in the genetic background of an elite indica rice variety 93‐11 were developed and phenotyped in the blast nursery. Thirty‐three ILs displaying stable blast resistance in three consecutive years were obtained. Among them, one line, IL1043, was subsequently found to be resistant to all of the 28 M. oryzae isolates from different regions through artificial inoculation in greenhouse. By combining bulk segregant analysis coupled with next‐generation sequencing (BSA‐seq) and recessive class analysis (RCA), a major blast resistance gene in IL1043, designated Picl(t), was mapped on rice chromosome 6 flanked by the markers RM527 and Indel6 with an interval of approximately 925 kb, which covers the Pi2/9 locus. These results will facilitate fine mapping and cloning of Picl(t), and the linked markers will further provide a useful tool for rice blast resistance breeding.
Medication errors among registered nurses in Jordan
Authors: Alrabadi Nasr , Haddad Rabia , Haddad Razan , Shawagfeh Shaima , Mukatash Tareq , Al-rabadi Daher , Abuhammad Sawsan
Published: March 2020

Objectives

Medication error (ME) is like a venom dispersing in clinical practice, particularly the process of drugs’ administration. Nurses, as the direct drug administrators, are in critical defense lines to prevent its occurrence. Therefore, our aims were to explore nurses’ understanding, perception, attitude and prevalence of MEs and thereafter defining the main factors associated with its occurrence and needed for designing proper policies for its sufficient prevention.

Methods

Self-reported questionnaires were obtained from 156 nurses distributed almost equally between the 3 major teaching hospitals in Jordan. The questionnaires aimed at measuring their understanding, attitudes, and the prevalence of MEs.

Key findings

The majority of respondents were males (51.3%), young (25–34, 75%), hold a BSc degree (84.6%). Most of their experiences were less than 5 years (67.3%). The level of understanding of the definition, associated factors, and the consequences of ME was acceptable between registered nurses in Jordanian teaching hospitals. Nurses who had the lowest experience (0–5 years) were the highest in committing MEs (P-value = 0.006). Otherwise, gender, age, and education were not significantly associated with MEs. The participants reported that the most common causes of medication error were setting the infusion devices incorrectly, distraction, labeling and packaging problems. Participants declared that the incidents of MEs are underreported (Reporting rate (28.3%)) and they believed that it was most likely due to the fear of losing their job, misjudgment on the seriousness of the incidence that warrant reporting, and fear from coworkers' actions.

Conclusions

MEs are common and may be underreported among registered nurses in Jordan. National policymakers should take critical steps to encourage the nurses to report any error in medication administration and therefore reducing its occurrence.
Integrating new knowledge into everyday practices: teacher pedagogy in early grade literacy in rural Mozambique
Authors: Lee Jeongmin , D'sa Nikhit , Zuilkowski Stephanie Simmons
Published: March 2020

Improving literacy outcomes in sub‐Saharan Africa is a central focus of national governments, donors and non‐governmental organisations alike, as evidenced by the inclusion of literacy as a target in the United Nations' Sustainable Development Goal 4. Though significant international development funding has been devoted to teacher training in the region, little evidence is available on how teachers improve their literacy instruction in practice. This study profiles how 20 teachers in eight schools in rural Mozambique translated training in literacy instruction into classroom instruction. We used three domains of teacher knowledge – content knowledge, pedagogical knowledge and pedagogical content knowledge – to analyse interview and observation data. While some aspects of training translated into classroom practices, including explicit literacy instruction and use of visual aids, teachers rarely used activities for oral language development or reading comprehension, which are critical to producing skilled readers. We discuss the research and policy implications of these findings.
The role of Bells in the continuous accretion between the CM and CR chondrite reservoirs
Authors: van Kooten Elishevah , Cavalcante Larissa , Wielandt Daniel , Bizzarro Martin
Published: March 2020

CM meteorites are dominant members of carbonaceous chondrites (CCs), which evidently accreted in a region separated from the terrestrial planets. These chondrites are key in determining the accretion regions of solar system materials, since in Mg and Cr isotope space, they intersect between what are identified as inner and outer solar system reservoirs. In this model, the outer reservoir is represented by metal‐rich carbonaceous chondrites (MRCCs), including CR chondrites. An important question remains whether the barrier between MRCCs and CCs was a temporal or spatial one. CM chondrites and chondrules are used here to identify the nature of the barrier as well as the timescale of chondrite parent body accretion. We find based on high precision Mg and Cr isotope data of seven CM chondrites and 12 chondrules, that accretion in the CM chondrite reservoir was continuous lasting <3 Myr and showing late accretion of MRCC‐like material reflected by the anomalous CM chondrite Bells. We further argue that although MRCCs likely accreted later than CM chondrites, CR chondrules must have initially formed from a reservoir spatially separated from CM chondrules. Finally, we hypothesize on the nature of the spatial barrier separating these reservoirs.
Ultrasound can detect alternating vertebral artery occlusions due to hangman fracture
Authors: Ohara Keiichiro , Sato Takeo , Mitsumura Hidetaka , Arai Ayumi , Komatsu Teppei , Sakai Kenichiro , Kawamura Daichi , Ohashi Hiroki , Ishibashi Toshihiro , Murayama Yuichi , Iguchi Yasuyuki
Published: March 2020

We present a case of alternating vertebral artery occlusions due to hangman fracture which was detected by repeated ultrasound. An 89‐year‐old woman presented with sudden onset of consciousness disturbance. Magnetic resonance imaging showed bilateral cerebellar ischemic lesions and daily alternating vertebral artery occlusions. Carotid ultrasonography and transcranial color flow imaging showed blood flow changes from day to day which indicated an abnormal hemodynamic status of bilateral vertebral artery. Computed tomography angiography revealed hangman fracture and severe compression of bilateral vertebral artery with thrombi. We applied Halo‐Vest fixation and started the patient on anticoagulation therapy. Then, carotid ultrasonography and transcranial color flow imaging demonstrated improvement of bilateral vertebral artery blood flow. The patient remained free of neurological deficits after Halo‐Vest fixation and anticoagulation. This case highlights the importance of repeated ultrasonographic evaluation of cerebral arteries in patients with ischemic stroke by hangman fracture.
Urinary orosomucoid 1 protein to creatinine ratio as a potential biomarker for early screening of kidney impairment in type‐2 diabetes patients
Authors: Wang Huabin , Bao Xinyu , Ma Yongjun , Shan Xiaoyun , Huang Caiqun
Published: March 2020

Background

Early screening of diabetic kidney disease (DKD) remains a major challenge. Our aim was to evaluate the value of urinary orosomucoid 1 protein (UORM1) in early renal impairment screening in type‐2 diabetes patients.

Methods

The concentration of UORM1, the UORM1‐to‐creatinine ratio (UORM1CR), the urinary albumin‐to‐creatinine ratio (ACR), the alpha‐1‐microglobulin‐to‐creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were measured in 406 type‐2 diabetes patients. Any positive values for ACR, A1MCR and/or eGFR were considered as indicative of renal impairment.

Results

On average, the levels of UORM1 and UORM1CR were about seven times higher in subjects with renal injury than in those without. Both UORM1 and UORM1CR, when adjusted via logarithm‐transformation, were significantly related to ACR, A1MCR and eGFR levels. The highest correlation was observed between UORM1CR and A1MCR (r = 0.85, P < .001). The cut‐off values for UORM1 (2.53 mg/L) and UORM1CR (3.69 mg/g) for the early diagnosis of kidney impairment were obtained from receiver operating characteristic curves. UORM1CR obviously had higher diagnostic efficiency corresponding to 83.26% sensitivity and 90.32% specificity than UORM1. Likewise, its sensitivity was higher than those of ACR, A1MCR and eGFR. Bad glycaemic control had the highest risk of increased UORM1CR (odds ratio [OR] = 2.81, P < .001), while high HDL‐C (high‐density lipoprotein cholesterol) decreased the risk of increased UORM1CR (OR = 0.38, P = .017).

Conclusion

The UORM1CR (>3.69 mg/g) has the high diagnostic efficiency for the early screening of renal impairment in type‐2 diabetes patients. Furthermore, good glycaemic control and high HDL‐C might be protective factors against UORM1CR increase.
Life‐threatening ventricular arrhythmia as first presentation of Tuberculosis—Early diagnosis and successful treatment: A case series
Authors: Nair Mohan , Bhagirath Pranav , Gothi Rajesh , Singal Gautum , Kitey Pritam , Chopra Deepak , Ahluwalia Navjeet , Kataria Vikas
Published: March 2020

Background

Tuberculosis of the myocardium is an extremely rare entity with few published case reports. Diagnosis is often delayed, and outcomes are unfavorable: particularly when cardiac involvement has been the presenting entity.

Methods

Four patients, aged 24‐51 years, presented with life‐threatening ventricular arrhythmia (VA). None had a previous history of tuberculosis or any structural heart disease. Electrocardiogram during sinus rhythm and Echocardiography did not show any gross abnormality. All patients underwent contrast‐enhanced computer tomography of thorax and cardiac magnetic resonance imaging. Attempts to obtain tissue (cardiac or associated mediastinal lymph nodes) were associated with increased risk to the patients thus indirect evidence of Mantoux skin test and interferon gamma release assay results were used to aid diagnosis.

Results

Based on clinicoradiological findings, patients were put on antitubercular therapy (ATT). Supportive therapy included antiarrhythmic drugs (all patients), catheter ablation (two patients), and implantable cardioverter defibrillator (one patient). Arrhythmia suppression was achieved in all patients predischarge. On a follow‐up of 2‐24 months, none of the patients has had any recurrence of arrhythmia. ATT and antiarrhythmic drug therapy have been stopped in two patients who have completed the 6 months of ATT. Their radiological lesions showed resolution.

Conclusions

Myocardial tuberculosis presenting as life‐threatening VA in a rare but definite clinical entity. A high index of suspicion and cardiac imaging can lead to early diagnosis and appropriate treatment that ensures survival in all patients.
Long‐term efficacy and safety of topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Post hoc pediatric subgroup analysis from a 44‐week open‐label extension study
Authors: Hebert Adelaide A. , Glaser Dee Anna , Green Lawrence , Hull Cheryl , Cather Jennifer , Drew Janice , Gopalan Ramanan , Pariser David M.
Published: March 2020

Background/Objectives

Glycopyrronium tosylate (GT) cloth, 2.4% is a topical anticholinergic approved in the United States for primary axillary hyperhidrosis in patients ≥9 years. This post hoc analysis evaluated long‐term response (efficacy and safety) in pediatric patients (≥9 to ≤16 years) to GT in the 44‐week, open‐label extension (NCT02553798) of two, phase 3, double‐blind, vehicle‐controlled, 4‐week trials (NCT02530281, NCT02530294).

Methods

In the double‐blind trials, patients ≥9 years with primary axillary hyperhidrosis were randomized 2:1 to once‐daily GT:vehicle. Those who completed the study could receive open‐label GT for up to an additional 44 weeks. Safety assessments included treatment‐emergent adverse events (TEAEs) and local skin reactions (LSRs). Descriptive efficacy assessments included gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale response (≥2‐grade improvement), and Children's Dermatology Life Quality Index.

Results

Of 43 pediatric patients completing either double‐blind trial, 38 (88.4%) entered the open‐label extension (age, years: 9 [n = 1], 12 [n = 2], 13 [n = 7], 14 and 15 [n = 9 each], 16 [n = 10]). The safety profile observed was similar to the double‐blind trials. Most TEAEs (>95%) were mild/moderate, related to anticholinergic activity, and infrequently led to discontinuation (n = 1/38 [2.6%]). No pediatric patients experienced a serious TEAE. Most anticholinergic TEAEs did not require a dose modification and resolved within 7 days. Approximately, one‐third of patients (n = 13/38 [34.2%]) had LSRs; most were mild/moderate in severity. Improvements in efficacy measures were maintained from the double‐blind trials.

Conclusions

Long‐term, once‐daily GT for up to 48 weeks (4‐week double‐blind plus 44 week open label) provides a noninvasive, well‐tolerated treatment option for pediatric patients with primary axillary hyperhidrosis.
Shedding light on the ‘black hole’ of small airways physiology in asthma
Authors: Thien Francis
Published: March 2020

See related article
Labor protection laws and the drain on productivity: Evidence from India
Authors: Schwab Daniel
Published: March 2020

Employment protection legislation (EPL) is designed to promote securityers by placing restrictions on firing, but it generates unintended consequences. With India as a setting, I argue that EPL shifts jobs from younger to older workers in two ways: by discouraging the hiring of unproven young workers and by preventing the firing of low‐productivity workers. The identification strategy is motivated by Rajan and Zingales (1998): I assume that EPL is more binding in those manufacturing sectors where the involuntary separation rate in other countries is high. The data show that older workers are more likely to have formal jobs, and the effect is strongest in high‐firing sectors, which indicates that EPL shifts jobs from young to old. Additionally, EPL reduces plant‐level total factor productivity, and this effect is seen only in plants which are large enough to fall within the purview of EPL, which provides a useful placebo test.
Progressive Taxation and Economic Stability*
Authors: Alessandrini Diana
Published: March 2020

Recent empirical evidence finds that progressive taxation is an effective economic stabilizer, but theoretical results disagree. This paper shows that a lifecycle model with total factor productivity shocks can match the empirical evidence. If the US economy switched from progressive to proportional taxation, output volatility would increase by 5 percent. Progressive taxes act as stabilizers by reducing income volatility among the young and soon‐to‐be retirees. Thus, incorporating a rich lifecycle structure in the model is important to match the data. The model is then used to study the welfare implications of reducing tax progressivity.
Traumatizing Oneself—Deep Wrist Injuries Self‐Inflicted with Suicidal Intention are Associated with More Severe PTSD Symptomatology than Similar Injuries from Accidents
Authors: Westermair Anna Lisa , Matzkeit Nico , Waldmann Annika , Stang Felix , Mailänder Peter , Schweiger Ulrich , Kisch Tobias
Published: March 2020

Objective

As suicide attempts by definition entail at least some threat to physical integrity and life, they theoretically qualify as an A1 criterion for posttraumatic stress disorder (PTSD). This study uses the unique opportunity of deep wrist injuries to quantify the effect of intentionality on PTSD rates by comparing suicide attempt survivors with patients who sustained accidental injuries similar in mechanism, localization, and extent.

Method

Patients who had been admitted with an acute deep wrist injury from 2008 to 2016 filled out the revised Impact of Event Scale and reported other known PTSD risk factors. Mental morbidity and intentionality of the injury were determined by psychiatric consultation during the index hospitalization.

Results

Fifty‐one patients were followed up (72.5% male, 92.2% Caucasian, mean age at injury 42.3 ± 17.5 years, 72.5% accidental injuries), on average 4.2 ± 2.9 years after their injury. The intentionality of the injury alone predicted the severity of intrusions, avoidance, hyperarousal, and probable PTSD (aOR = 14.0).

Conclusions

Traumatization in the context of a suicide attempt may be a hitherto unknown PTSD risk factor. Patients after suicide attempts, especially medically serious attempts, should be monitored for PTSD symptoms.
School Environment as a Determinant of Organizational Learning Support
Authors: Šuťáková Valentína , Ferencová Janka , Kosturková Martina
Published: March 2020

Organizational learning as a strategic tool for organizational change and stabilization of success has been discussed in a school environment since the 1990s. Its importance is increasing in the context of dynamic development of the society and the need to flexibly adapt to constant changes. Organizational learning research focuses on analyzing factors that are important to organizational learning and adaptability. The study aim was to examine a school environment as a determinant of organizational learning support. We chose a design of qualitative research, in which a group interview with 32 teachers from four schools was carried out. Based on the interviews we specified five categories of organizational learning support – psychological safety, open communication, cooperation, openness to new ideas, engagement and participation. Through an analysis of participants‘ responses, we identified the most significant barriers to organizational learning in the environment of selected schools. Their recognition has made it possible to formulate recommendations related to school management and to the promotion of organizational learning at schools.
La cuestión misionera en Medellín
Authors: Raschietti Stefano
Published: March 2020

Al revisar los documentos de la II Conferencia General del Episcopado Latinoamericano (1968) se constata la falta de una reflexión específicamente misionera. Sin embargo, Medellín ofrece elementos esenciales para un debate misionológico propiamente latinoamericano. Son objetivos de este trabajo rescatar los aportes del Documento de Melgar en preparación de Medellín, rememorar la ponencia de monseñor Samuel Ruiz “La evangelización en América Latina” en la Conferencia, y plantear consideraciones sobre las líneas maestras que permean el Documento final. De esta indagación es posible entrever problemáticas emergentes, perspectivas misioneras, algunas lagunas y, particularmente, ejes fundamentales sobre los cuales configurar una teología de la misión a partir de América Latina.
The Associations Between Self-Perceived Actual and Ideal Body Sizes and Physical Activity Among Early Adolescents
Authors: Solomon-Krakus Shauna , Sabiston Catherine M. , Brunet Jennifer , Castonguay Andree L. , Henderson Mélanie
Published: March 2020

Purpose: This study examined the association between self-perceived actual and ideal body sizes and objectively assessed moderate-to-vigorous physical activity (MVPA) among adolescents, controlling for puberty, fat mass index, and sex. A secondary objective was to explore the association between objectively assessed fat mass index and MVPA. Methods: Participants were 438 early adolescents (Mage = 11.61, SD = 0.92). Participants selected body sizes that represented their self-perceived actual and ideal bodies. Participants then wore an accelerometer for 1 week to assess MVPA. Polynomial regression analysis with response surface methods was used to explore MVPA in relation to the discrepancy and agreement (ie, no discrepancy) between self-perceived actual and ideal body sizes. Results: When self-perceived actual and ideal body sizes were in agreement and represented smaller and larger bodies, MVPA was low. Participants with similar self-perceived actual and ideal bodies in the middle of the body-size spectrum demonstrated the highest levels of MVPA. The direction and degree of the discrepancy between self-perceived actual and ideal bodies were not significantly associated with MVPA. Fat mass index was significantly and negatively associated with MVPA. Conclusions: These findings may inform physical activity promotion programs and provide methodological contributions to the study of how body image and MVPA are related.
Porphyromonas gingivalis
Fimbriae Use β
2
Integrin (CD11/CD18) on Mouse Peritoneal Macrophages as a Cellular Receptor, and the CD18 β Chain Plays a Functional Role in Fimbrial Signaling
Authors: Takeshita Akira , Murakami Yukio , Yamashita Yoshinori , Ishida Masami , Fujisawa Seiichiro , Kitano Shigeo , Hanazawa Shigemasa
Published: March 2020

In this study, we demonstrate that
Porphyromonas gingivalis
fimbriae use molecules of β
2
integrin (CD11/CD18) on mouse peritoneal macrophages as cellular receptors and also show that the β chain (CD18) may play a functional role in signalling for the fimbria-induced expression of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) genes in the cells. Using a binding assay with
125
I-labeled fimbriae, we observed that fimbrial binding to the macrophages was inhibited by treatment with CD11a, CD11b, CD11c, or CD18 antibody but not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of β
2
integrin (CD11/CD18) on the macrophages. Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1β and TNF-α genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment. Interestingly, intracellular adhesion molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial binding to the cells in a dose-dependent manner. In addition, ICAM-1 clearly inhibited the fimbria-induced expression of IL-1β and TNF-α genes in the cells. However, such inhibitory action was not observed with laminin treatment. These results suggest the importance of β
2
integrin (CD11/CD18) as a cellular receptor of
P. gingivalis
fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease.
Murine Macrophages Use Oxygen- and Nitric Oxide-Dependent Mechanisms To SynthesizeS-Nitroso-Albumin and To Kill Extracellular Trypanosomes
Authors: Gobert Alain P. , Semballa Silla , Daulouede Sylvie , Lesthelle Sophie , Taxile Murielle , Veyret Bernard , Vincendeau Philippe
Published: March 2020

Reactive nitrogen intermediates were synthesized spontaneously in cultures of macrophages fromTrypanosoma brucei brucei-infected mice by an inducible nitric oxide (NO) synthase. This was inhibited by the addition of nitro-l-arginine. In this paper, we report the kinetics of the fixation of macrophage-derived NO on bovine serum albumin by using an enzyme-linked immunosorbent assay. S nitrosylation was confirmed by the Saville reaction, using mercuric chloride. It is known that reactive oxygen intermediates (ROI) are also synthesized by stimulated macrophages. The fact that NO is able to bind cysteine only under aerobic conditions led us to investigate the role of macrophage-derived ROI in the formation of S-nitrosylated proteins by activated macrophages. The immunoenzymatic signal decreased by 66 and 30% when superoxide dismutase and catalase, respectively, were added to the culture medium of macrophages from infected mice. In addition, the decrease in S-nitrosylated albumin formation correlated with the protection of extracellular trypanosomes from the cytostatic and cytotoxic activity of NO. Melatonin, a hydroxyl radical scavenger resulting from the decomposition of peroxynitrous acid, had no effect. All these data support the concept that an interaction between NO and ROI promoted the production ofS-nitroso-albumin by activated macrophages from infected mice.
Cloned Lines ofPlasmodium bergheiANKA Differ in Their Abilities To Induce Experimental Cerebral Malaria
Authors: Amani Véronique , Boubou Mariama Idrissa , Pied Sylviane , Marussig Myriam , Walliker David , Mazier Dominique , Rénia Laurent
Published: March 2020

Infection withPlasmodium bergheiANKA is usually lethal. The parasite causes in some mouse strains a neurovascular syndrome, experimental cerebral malaria (ECM), involving immunopathological reactions. The effects on the development of ECM of the mouse genetic background have been clearly demonstrated, but nothing is known about the effects of the clonal diversity of the parasite. We showed that various cloned lines derived from a polyclonal line ofP. bergheiANKA caused ECM but that the extent of ECM induction was dependent on the amount of inoculum. Subtle differences in ECM characteristics (survival time and hypothermia) were also observed. We also confirmed, using the 1.49L cloned line, that the mouse genetic background strongly affects ECM.
Identification and Characterization of a Newly Isolated Shiga Toxin 2-Converting Phage from Shiga Toxin-Producing
Escherichia coli
Authors: Watarai Masahisa , Sato Toshio , Kobayashi Midori , Shimizu Takeshi , Yamasaki Shinji , Tobe Toru , Sasakawa Chihiro , Takeda Yoshifumi
Published: March 2020

Shiga toxins 1 (Stx1) and 2 (Stx2) are encoded by toxin-converting bacteriophages of Stx-producing
Escherichia coli
(STEC), and so far two Stx1- and one Stx2-converting phages have been isolated from two STEC strains (A. D. O’Brien, J. W. Newlands, S. F. Miller, R. K. Holmes, H. W. Smith, and S. B. Formal, Science 226:694–696, 1984). In this study, we isolated two Stx2-converting phages, designated Stx2Φ-I and Stx2Φ-II, from two clinical strains of STEC associated with the outbreaks in Japan in 1996 and found that Stx2Φ-I resembled 933W, the previously reported Stx2-converting phage, in its infective properties for
E. coli
K-12 strain C600 while Stx2Φ-II was distinct from them. The sizes of the plaques of Stx2Φ-I and Stx2Φ-II in C600 were different; the former was larger than the latter. The restriction maps of Stx2Φ-I and Stx2Φ-II were not identical; rather, Stx2Φ-II DNA was approximately 3 kb larger than Stx2Φ-I DNA. Furthermore, Stx2Φ-I and Stx2Φ-II showed different phage immunity, with Stx2Φ-I and 933W belonging to the same group. Infection of C600 by Stx2Φ-I or 933W was affected by environmental osmolarity differently from that by Stx2Φ-II. When C600 was grown under conditions of high osmolarity, the infectivity of Stx2Φ-I and 933W was greatly decreased compared with that of Stx2Φ-II. Examination of the plating efficiency of the three phages for the defined mutations in C600 revealed that the efficiency of Stx2Φ-I and 933W for the
fadL
mutant decreased to less than 10
−7
compared with that for C600 whereas the efficiency of Stx2Φ-II decreased to 0.1% of that for C600. In contrast, while the plating efficiency of Stx2Φ-II for the
lamB
mutant decreased to a low level (0.05% of that for C600), the efficiencies of Stx2Φ-I and 933W were not changed. This was confirmed by the phage neutralization experiments with isolated outer membrane fractions from C600,
fadL
mutant, or
lamB
mutant or the purified His
6
-tagged FadL and LamB proteins. Based on the data, we concluded that FadL acts as the receptor for Stx2Φ-I and Stx2Φ-II whereas LamB acts as the receptor only for Stx2Φ-II.
Fas (CD95)-Dependent Cell-Mediated Immunity toListeria monocytogenes
Authors: Jensen Eric R. , Glass Alison A. , Clark William R. , Wing Edward J. , Miller Jeff F. , Gregory Stephen H.
Published: March 2020

Two distinct and complementary pathways, one mediated by perforin and the other dependent upon CD95 (Fas), effect cell-mediated cytotoxicity. We examined the relative roles of these pathways in host defenses against the intracellular bacterial pathogenListeria monocytogenesby using murine listeriosis as a model system. Mice which lacked both perforin and Fas (P0L0) were generated, and their responses to primary and secondary listeriosis were compared to those of wild-type (WT), Fas-deficient (L0), and perforin knockout (P0) mice. Relative to WT mice during primary listeriosis, P0 mice exhibited a reduced capacity to clear the infection from their spleens but not their livers whereas L0 mice had elevated bacterial titers in their livers and a modestly increased titer in their spleens. In contrast, bacterial titers in P0L0 mice were increased approximately 50- to 560-fold in their spleens and 230- to 1,000-fold in their livers; eventual clearance of listeriae from both organs was significantly delayed. Furthermore, the resistance of P0L0 mice to secondary listeriosis was significantly reduced in their spleens and livers compared to that of WT, P0, or L0 mice. In vitro experiments indicated that immune cytotoxic T lymphocytes (CTL) lysedL. monocytogenes-infected hepatocytes primarily via a Fas-dependent, perforin-independent mechanism. The absence of Fas severely abrogated the lysis of infected hepatocytes by immune CD8+CTL. Taken together, these results provide the first evidence for Fas-dependent CTL-mediated lysis ofL. monocytogenes-infected hepatocytes and demonstrate complementary roles for Fas and perforin in host defenses against an intracellular bacterial pathogen.
Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of FourPlasmodium falciparumDNA Plasmids
Authors: Wang Ruobing , Doolan Denise L. , Charoenvit Yupin , Hedstrom Richard C. , Gardner Malcolm J. , Hobart Peter , Tine John , Sedegah Martha , Fallarme Victoria , Sacci John B. , Kaur Manjit , Klinman Dennis M. , Hoffman Stephen L. , Weiss Walter R.
Published: March 2020

CD8+T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8+T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8+T-cell responses against multipleP. falciparumproteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding fourP. falciparumproteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8+T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8+T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.
Identification of an Erythrocyte Binding Peptide from the Erythrocyte Binding Antigen, EBA-175, Which Blocks Parasite Multiplication and Induces Peptide-Blocking Antibodies
Authors: Jakobsen P. H. , Heegaard P. M. H. , Koch C. , Wasniowska K. , Lemnge M. M. , Jensen J. B. , Sim B. K. L.
Published: March 2020

A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) ofPlasmodium falciparumbound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes as demonstrated by flow cytometry analysis. The peptide, EBA(aa1076–96), also bound to desialylated glycophorin A and glycophorin B when tested by ELISA. The peptide blocked parasite multiplication in vitro. The glycophorin A binding sequence was further delineated to a 12-aa sequence, EBA(aa1085–96), by testing the binding of a range of truncated peptides to immobilized glycophorin A. Our data indicate that EBA(aa1085–96) is part of a ligand on the merozoite for binding to erythrocyte receptors. This binding suggests that the EBA(aa1085–96) peptide is involved in a second binding step, independent of sialic acid. Antibody recognition of this peptide sequence may protect against merozoite invasion, but only a small proportion of sera from adults from different areas of malaria transmission showed antibody reactivities to the EBA(aa1076–96) peptide, indicating that this sequence is only weakly immunogenic duringP. falciparuminfections in humans. However, Tanzanian children with acute clinical malaria showed high immunoglobulin G reactivity to the EBA(aa1076–96) peptide compared to children with asymptomaticP. falciparuminfections. The EBA(aa1076–96) peptide sequence from EBA-175 induced antibody formation in mice after conjugation of the peptide with purified protein derivative. These murine sera inhibited EBA(aa1076–96) peptide binding to glycophorin A.
Expression of the Peptide Antibiotic Human β-Defensin 1 in Cultured Gingival Epithelial Cells and Gingival Tissue
Authors: Krisanaprakornkit Suttichai , Weinberg Aaron , Perez Christopher N. , Dale Beverly A.
Published: March 2020

Human β-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia. Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples. Cell cultures were challenged with cell wall extracts of
Porphyromonas gingivalis
or
Fusobacterium nucleatum
,
Escherichia coli
lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate. hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1. Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA. The sequence of the PCR product was identical to that of hBD-1. hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested. Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR. hBD-1 mRNA was expressed in all tissue samples. The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis. However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression. Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts. These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health.
Interleukin-4 Enhances Pulmonary Clearance ofPseudomonas aeruginosa
Authors: Jain-Vora Shilpa , LeVine Ann Marie , Chroneos Zissis , Ross Gary F. , Hull William M. , Whitsett Jeffrey A.
Published: March 2020

To determine the effects of interleukin-4 (IL-4) on bacterial clearance from the mouse lung, transgenic mice expressing IL-4 in respiratory epithelial cells under the control of the Clara cell secretory protein promoter (CCSP-IL-4 mice) were infected intratracheally withPseudomonas aeruginosa. Survival of CCSP-IL-4 mice following bacterial administration was markedly improved compared with that of control mice. While bacteria proliferated in lungs of wild-type mice, a rapid reduction in the number of bacteria was observed in the IL-4 mice as early as 6 h postinfection. Similarly, intranasal administration of IL-4 enhanced bacterial clearance from the lungs of wild-type mice. While acute and chronic IL-4 increased the numbers of neutrophils in bronchoalveolar lavage fluid, bacterial infection was associated with acute neutrophilic pulmonary infiltration, and this response was similar in the presence or absence of IL-4. Local administration or expression of IL-4 in the mouse lung enhanced pulmonary clearance ofP. aeruginosain vivo and decreased mortality following infection.
Comparison of Loss of Serum Resistance by Defined Lipopolysaccharide Mutants and an Acapsular Mutant of UropathogenicEscherichia coliO75:K5
Authors: Burns Stacy M. , Hull Sheila I.
Published: March 2020

In order to determine the importance of the O75 O antigen versus the K5 capsular antigen and the bimodal distribution of lipopolysaccharides (LPSs) in protection from complement-mediated lysis, mutants were made by insertion of acator anaphAgene in or in place of genes necessary for the synthesis of LPS and/or the K antigen of an O75+K5+uropathogenicEscherichia colistrain, GR-12. Mutations were made in the following genes: therfbDgene (required for the synthesis of TDP-rhamnose), therfbKMgenes (necessary for the synthesis of GDP-mannose), therolgene (regulating O-antigen length), thekfiCgene (encoding a putative glycosyltransferase), and thekfiC-rfbDgenes. The resulting phenotypes were rough (O75−), core plus one partial O-antigen subunit, random distribution of O-antigen chain lengths, acapsular (K5−), and O75−K5−, respectively. All five mutants and GR-12 were analyzed for survival in 80% serum. The GR-12 parent was resistant, exhibiting a 500% increase in numbers. Therol,rfbKM,rfbD, andkfiC-rfbDmutants were sensitive, experiencing 99%, 99.9%, 99.9%, and at least 99.999% killing, respectively, in the first hour. ThekfiCmutant, however, increased in numbers in the first hour but experienced delayed sensitivity, decreasing in viability by 80% in the third hour. Single mutants were complemented with the wild-type gene intrans, showing restoration of the wild-type phenotype and serum resistance. Therefore, the O75 antigen is more important for survival in serum than the K5 antigen, and regulation of the O75 O-antigen chain length is crucial for protection of the bacteria from complement-mediated lysis.
Cloning and Characterization of
tdhA
, a Locus Encoding a TonB-Dependent Heme Receptor from
Haemophilus ducreyi
Authors: Thomas Christopher E. , Olsen Bonnie , Elkins Christopher
Published: March 2020

Haemophilus ducreyi
is unable to synthesize heme and must acquire it from its only known host, humans. We cloned and sequenced a gene encoding an outer membrane receptor for heme. It was designated
tdhA
(for TonB-dependent heme receptor A) since it was related by sequence homology to the family of TonB-dependent receptors. TdhA was strikingly similar to open reading frame HI0113 from the genome of
Haemophilus influenzae
Rd and also shared homology with five other heme receptors, including HxuC, HemR, HmuR, ChuA, and ShuA, from gram-negative bacteria. An
Escherichia coli hemA tonB
mutant strongly expressing
H. ducreyi tdhA
grew on low levels of heme as a source of heme only when an intact
H. ducreyi
Ton system plasmid was present, formally demonstrating functional TonB dependence.
tdhA
was expressed poorly in vitro by
H. ducreyi
and only under conditions of heme limitation. A survey of
H. ducreyi
revealed that all tested strains but one synthesized small amounts of TdhA in vitro under heme-limiting conditions. Surprisingly, an isogenic mutant of
tdhA
as well as its parent, 35000, both required the same high levels of heme for growth (50 μg/ml [77 μM] on agar medium). This result, together with previous findings, suggests that in vitro, the uptake of heme by
H. ducreyi
is mediated by a TonB- and TdhA-independent mechanism, possibly diffusion.
Humoral Immunity to Commensal Oral Bacteria in Human Infants: Salivary Antibodies Reactive with
Actinomyces naeslundii
Genospecies 1 and 2 during Colonization
Authors: Cole Michael F. , Bryan Stacey , Evans Mishell K. , Pearce Cheryl L. , Sheridan Michael J. , Sura Patricia A. , Wientzen Raoul , Bowden George H. W.
Published: March 2020

The secretory immune response in saliva to colonization by
Actinomyces naeslundii
genospecies 1 and 2 was studied in 10 human infants from birth to 2 years of age.
Actinomyces
species were not recovered from the mouths of the infants until approximately 4 months after the eruption of teeth. However, low levels of secretory immunoglobulin A1 (SIgA1) and SIgA2 antibodies reactive with whole cells of
A. naeslundii
genospecies 1 and 2 were detected within the first month after birth. Although there was a fivefold increase in the concentration of SIgA between birth and age 2 years, there were no differences between the concentrations of SIgA1 and SIgA2 antibodies reactive with
A. naeslundii
genospecies 1 and 2 over this period. When the concentrations of SIgA1 and SIgA2 antibodies reactive with whole cells of
A. naeslundii
genospecies 1 and 2 were normalized to the concentrations of SIgA1 and SIgA2 in saliva, the
A. naeslundii
genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies showed a significant decrease from birth to 2 years of age. The fine specificities of
A. naeslundii
genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies were examined by Western blotting of envelope proteins. Similarities in the molecular masses of proteins recognized by SIgA1 and SIgA2 antibodies, both within and between subjects over time, were examined by cluster analysis and showed considerable variability. Taken overall, our data suggest that among the mechanisms
Actinomyces
species employ to persist in the oral cavity are the induction of a limited immune response and clonal replacement with strains differing in their antigen profiles.
Involvement of C3a and C5a in Interleukin-8 Secretion by Human Polymorphonuclear Cells in Response to Capsular Material ofCryptococcus neoformans
Authors: Vecchiarelli Anna , Retini Cinzia , Casadevall Arturo , Monari Claudia , Pietrella Donatella , Kozel Thomas R.
Published: March 2020

In a previous paper we demonstrated that human polymorphonuclear cells (PMN) in the presence of normal human serum (NHS) secrete proinflammatory cytokines in response toCryptococcus neoformansor its major capsular component, glucuronoxylomannan (GXM). The hypothesis that activation of the complement system could be responsible for the observed phenomenon is supported by the fact that encapsulated and acapsularC. neoformansisolates are activators of the complement system and, in particular, large encapsulated isolates are powerful activators. In the present study we demonstrate that (i) interleukin-8 (IL-8) release in response to acapsular or encapsulated strains ofC. neoformansis significantly reduced in the presence of heat-inactivated serum rather than NHS and is completely abrogated in the absence of human serum; (ii) GXM-induced IL-8 release is strictly dependent on the presence of NHS, is inhibited by specific antibodies to either C3a and C5 complement components, and is completely abrogated by the combined use of these antibodies; (iii) the addition of purified C3a and C5a directly stimulates IL-8 release by PMN; and (iv) monoclonal antibody to GXM in combination with GXM or encapsulatedC. neoformanspotentiates IL-8 release by PMN. These data shed light on the mechanism involved in GXM-induced IL-8 secretion by PMN, provide an additional potential role for complement in the control ofC. neoformansinfections, and suggest a complex interplay between the complement system, humoral immunity, and cytokine regulation.